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Markopoulos C - PubMed - NCBI Display Settings: Abstract, 200 per page, Sorted by Pub Date Filter your results:All (109)
Results: 109
c Lancet. 2011 Aug 27;378(9793):771-84. Epub 2011 Jul 28.
1. Relevance of breast cancer hormone receptors and
other factors to the efficacy of adjuvant tamoxifen:
patient-level meta-analysis of randomised trials.
Early Breast Cancer Trialists' Collaborative Group (EBCTCG), Davies C,
Godwin J, Gray R, Clarke M, Cutter D, Darby S, McGale P, Pan HC, Taylor
C, Wang YC, Dowsett M, Ingle J, Peto R.
Collaborators (693)
Abstract
BACKGROUND:
As trials of 5 years of tamoxifen in early breast cancer
mature, the relevance of hormone receptor measurements (and other patient
characteristics) to long-term outcome can be assessed increasingly reliably.
We report updated meta-analyses of the trials of 5 years of adjuvant
tamoxifen.
METHODS: We undertook a collaborative meta-analysis of individual patient
data from 20 trials (n=21,457) in early breast cancer of about 5 years of
tamoxifen versus no adjuvant tamoxifen, with about 80% compliance.
Recurrence and death rate ratios (RRs) were from log-rank analyses by
allocated treatment.
FINDINGS: In oestrogen receptor (ER)-positive disease (n=10,645),
allocation to about 5 years of tamoxifen substantially reduced recurrence
rates throughout the first 10 years (RR 0·53 [SE 0·03] during years 0-4 and
RR 0·68 [0·06] during years 5-9 [both 2p<0·00001]; but RR 0·97 [0·10] during
years 10-14, suggesting no further gain or loss after year 10). Even in
marginally ER-positive disease (10-19 fmol/mg cytosol protein) the
recurrence reduction was substantial (RR 0·67 [0·08]). In ER-positive
disease, the RR was approximately independent of progesterone receptor
status (or level), age, nodal status, or use of chemotherapy. Breast cancer
mortality was reduced by about a third throughout the first 15 years (RR 0·71
[0·05] during years 0-4, 0·66 [0·05] during years 5-9, and 0·68 [0·08] during
years 10-14; p<0·0001 for extra mortality reduction during each separate
time period). Overall non-breast-cancer mortality was little affected, despite
small absolute increases in thromboembolic and uterine cancer mortality
(both only in women older than 55 years), so all-cause mortality was
substantially reduced. In ER-negative disease, tamoxifen had little or no
effect on breast cancer recurrence or mortality.
INTERPRETATION: 5 years of adjuvant tamoxifen safely reduces 15-year
risks of breast cancer recurrence and death. ER status was the only
recorded factor importantly predictive of the proportional reductions. Hence,
the absolute risk reductions produced by tamoxifen depend on the absolute
breast cancer risks (after any chemotherapy) without tamoxifen.


Markopoulos C - PubMed - NCBI Cancer Research UK, British Heart Foundation, and Medical Research Council. Copyright 2011 Elsevier Ltd. All rights reserved. Comment in
Lancet. 2011 Aug 27;378(9793):747-9.
PMID: 21802721 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms, Substances, Grant Support
c Am J Clin Pathol. 2011 Aug;136(2):266-74.
2. Heterogeneous HER2 gene amplification: impact on
patient outcome and a clinically relevant definition.
Bartlett AI, Starcyznski J, Robson T, Maclellan A, Campbell FM, van de
Velde CJ, Hasenburg A, Markopoulos C, Seynaeve C, Rea D, Bartlett JM.
Endocrine Cancer Group, Edinburgh University, Edinburgh, Scotland.
Abstract
Heterogeneous expression or amplification is a challenge to HER2
diagnostics. A guideline defines heterogeneity as the presence of between
5% and 50% cells with HER2/CEP17 ratios of more than 2.20. We audited
the frequency of such cells and their clinical impact in the results from 2
pathology laboratories combined with data from the TEAM [Tamoxifen vs
Exemestane Adjuvant Multicentre] pathology study. HER2 reports were
scanned and the percentages of amplified cells reported. Of 6,461 eligible
cases, 754 (11.7%) exhibited 50% or more cells with ratios of more than
2.20, which is "amplified" by College of American Pathologists guidelines. Of
the cases, 2,166 (33.5%) exhibited more than 5% but less than 50% of cells
with HER2/CEP17 ratios of more than 2.20, or "heterogeneous
amplification." No prognostic impact was observed when fewer than 30% of
cells exhibited ratios of more than 2.20. All amplified cases with 30% to 50%
of cells with ratios more than 2.20 were identified as such by United Kingdom
guidelines. The percentage of tumor cells with HER2/CEP17 ratios more
than 2.20 does not identify cases with heterogeneous amplification or poor
outcome. A modified approach for identification of true heterogeneous
amplification is suggested.
PMID: 21757600 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms, Substances
c J Clin Oncol. 2011 Apr 20;29(12):1531-8. Epub 2011 Mar 21.
3. Estrogen receptor and progesterone receptor as


Markopoulos C - PubMed - NCBI predictive biomarkers of response to endocrine
therapy: a prospectively powered pathology study in
the Tamoxifen and Exemestane Adjuvant
Multinational trial.
Bartlett JM, Brookes CL, Robson T, van de Velde CJ, Billingham LJ,
Campbell FM, Grant M, Hasenburg A, Hille ET, Kay C, Kieback DG, Putter
H, Markopoulos C, Kranenbarg EM, Mallon EA, Dirix L, Seynaeve C, Rea
D.
Endocrine Cancer Group, Edinburgh Cancer Research Centre, Western General
Hospital, Crewe Rd South, Edinburgh, EH4 2XR, United Kingdom. John.Bartlett@ed.ac.uk Abstract
PURPOSE:
The Tamoxifen and Exemestane Adjuvant Multinational (TEAM)
trial included a prospectively planned pathology substudy testing the
predictive value of progesterone receptor (PgR) expression for outcome of
estrogen receptor-positive (ER-positive) early breast cancer treated with
exemestane versus tamoxifen.
PATIENTS AND METHODS: Pathology blocks from 4,781 TEAM patients
randomly assigned to exemestane versus tamoxifen followed by exemestane
for 5 years of total therapy were collected centrally, and tissue microarrays
were constructed from samples from 4,598 patients. Quantitative analysis of
hormone receptors (ER and PgR) was performed by using image analysis
and immunohistochemistry, and the results were linked to outcome data from
the main TEAM trial and analyzed relative to disease-free survival and
treatment.
RESULTS:
4,325 eligible ER-positive patients, 23% were PgR-poor (Allred < 4) and 77% were PgR- rich (Allred ≥ 5). No treatment-by-marker effect for PgR was observed for exemestane versus tamoxifen (PgR-rich hazard ratio [HR], 0.83; 95% CI, 0.65 to 1.05; PgR-poor HR, 0.85; 95% CI, 0.61 to 1.19; P = .88 for interaction). Both PgR and ER expression were associated with patient prognosis in univariate (PgR HR, 0.53; 95% CI, 0.43 to 0.65; P < .001; ER HR, 0.66; 95% CI, 0.51 to 0.86; P = .002), and multivariate analyses (P < .001 and P = .001, respectively). A trend toward a treatment-by-marker effect for ER-rich patients was observed. CONCLUSION: Preferential exemestane versus tamoxifen treatment benefit
was not predicted by PgR expression; conversely, patients with ER-rich
tumors may derive additional benefit from exemestane. Quantitative analysis
of ER and PgR expression provides highly significant information on risk of
early relapse (within 1 to 3 years) during treatment.
Comment in
J Clin Oncol. 2011 Apr 20;29(12):1504-6.
PMID: 21422407 [PubMed - indexed for MEDLINE] PMCID: PMC3082973[Available on 2012/4/20] Markopoulos C - PubMed - NCBI Publication Types, MeSH Terms, Substances, Grant Support
c Lancet. 2011 Jan 22;377(9762):321-31.
4. Adjuvant tamoxifen and exemestane in early breast
cancer (TEAM): a randomised phase 3 trial.
van de Velde CJ, Rea D, Seynaeve C, Putter H, Hasenburg A, Vannetzel
JM, Paridaens R, Markopoulos C, Hozumi Y, Hille ET, Kieback DG, Asmar
L, Smeets J, Nortier JW, Hadji P, Bartlett JM, Jones SE.
Leiden University Medical Centre, Leiden, Netherlands. c.j.h.van_de_velde@lumc.nl
Abstract
BACKGROUND:
Aromatase inhibitors improved disease-free survival
compared with tamoxifen when given as an initial adjuvant treatment or after
2-3 years of tamoxifen to postmenopausal women with hormone-receptor-
positive breast cancer. We therefore compared the long-term effects of
exemestane monotherapy with sequential treatment (tamoxifen followed by
exemestane).
METHODS:
Tamoxifen Exemestane Adjuvant Multinational (TEAM) phase 3 trial was conducted in hospitals in nine countries. Postmenopausal women (median age 64 years, range 35-96) with hormone-receptor-positive breast cancer were randomly assigned in a 1:1 ratio to open-label exemestane (25 mg once a day, orally) alone or following tamoxifen (20 mg once a day, orally) for 5 years. Randomisation was by use of a computer-generated random permuted block method. The primary endpoint was disease-free survival (DFS) at 5 years. Main analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, NCT00279448, NCT00032136, and NCT00036270; NTR 267; Ethics Commission Trial27/2001; and UMIN, C000000057. FINDINGS: 9779 patients were assigned to sequential treatment (n=4875) or
exemestane alone (n=4904), and 4868 and 4898 were analysed by intention
to treat, respectively. 4154 (85%) patients in the sequential group and 4186
(86%) in the exemestane alone group were disease free at 5 years (hazard
ratio 0·97, 95% CI 0·88-1·08; p=0·60). In the safety analysis, sequential
treatment was associated with a higher incidence of gynaecological
symptoms (942 [20%] of 4814 vs 523 [11%] of 4852), venous thrombosis (99
[2%] vs 47 [1%]), and endometrial abnormalities (191 [4%] vs 19 [<1%]) than
was exemestane alone. Musculoskeletal adverse events (2448 [50%] vs
2133 [44%]), hypertension (303 [6%] vs 219 [5%]), and hyperlipidaemia (230
[5%] vs 136 [3%]) were reported more frequently with exemestane alone.
INTERPRETATION: Treatment regimens of exemestane alone or after
tamoxifen might be judged to be appropriate options for postmenopausal
women with hormone-receptor-positive early breast cancer.
FUNDING: Pfizer.
Copyright  2011 Elsevier Ltd. All rights reserved. Comment in
Lancet. 2011 Jan 22;377(9762):280-1.


Markopoulos C - PubMed - NCBI PMID: 21247627 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms, Substances, Secondary
Source ID

c Cancer Metastasis Rev. 2010 Dec;29(4):581-94.
5. Minimizing early relapse and maximizing treatment
outcomes in hormone-sensitive postmenopausal
breast cancer: efficacy review of AI trials.
Markopoulos CJ.
Athens University Medical School, 8, Iassiou str, 11521 Athens, Greece.
Abstract
Breast cancer is one of the leading causes of cancer-related deaths in
women. Regardless of prognosis, all women with breast cancer are at risk for
early recurrence. Nearly 50% of early recurrences occur within 5 years of
surgery, and they peak at 2 years after surgery in women treated with
adjuvant tamoxifen. Most early recurrences are distant metastases, which
strongly correlate with increased mortality. Treatments that mitigate the risk
of early distant metastases (DM) are, therefore, likely to improve overall
survival in women with early breast cancer (EBC). Aromatase inhibitors (AIs)-
-anastrozole, letrozole, and exemestane-have been investigated as
alternatives to tamoxifen for adjuvant treatment of hormone receptor-positive
(HR+) EBC in postmenopausal women (PMW). AIs are better at minimizing
risk of early relapse compared with tamoxifen. However, it is not clear if
preferential use of AIs over tamoxifen will benefit all PMW with HR+ EBC.
The ability to subtype HR+ breast cancer on the basis of biomarkers
predictive of response to AIs and tamoxifen would likely be key to
determining the most beneficial hormonal treatment within patient
subpopulations, but this process requires thorough investigation. Until then,
adjuvant therapies that provide the greatest reduction in risk of DM should be
considered for all PMW with HR+ EBC. This article reviews the clinical trials
of AI adjuvant therapies for hormone-sensitive breast cancer, particularly in
the context of how they compare with tamoxifen in minimizing the risk of
relapse, occurrence of DM, and breast cancer-related deaths.
PMID: 20830503 [PubMed - indexed for MEDLINE] PMCID: PMC2962795
Free PMC Article
Publication Types, MeSH Terms, Substances
c J Transl Med. 2010 Nov 3;8:108. 6.



Markopoulos C - PubMed - NCBI Evaluation of six CTLA-4 polymorphisms in high-risk
melanoma patients receiving adjuvant interferon
therapy in the He13A/98 multicenter trial.
Gogas H, Dafni U, Koon H, Spyropoulou-Vlachou M, Metaxas Y, Buchbinder
E, Pectasides E, Tsoutsos D, Polyzos A, Stratigos A, Markopoulos C,
Panagiotou P, Fountzilas G, Castana O, Skarlos P, Atkins MB, Kirkwood JM.
First Department of Medicine, University of Athens, Medical School, Athens, Greece.
Abstract
PURPOSE:
Interferon is approved for adjuvant treatment of patients with
stage IIb/III melanoma. The toxicity and uncertainty regarding survival
benefits of interferon have qualified its acceptance, despite significant
durable relapse prevention in a fraction of patients. Predictive biomarkers
that would enable selection of patients for therapy would have a large impact
upon clinical practice. Specific CTLA-4 polymorphisms have previously
shown an association with response to CTLA-4 blockade in patients with
metastatic melanoma and the development of autoimmunity.
EXPERIMENTAL DESIGN: 286 melanoma patients and 288 healthy controls
were genotyped for six CTLA-4 polymorphisms previously suggested to be
important (AG 49, CT 318, CT 60, JO 27, JO30 and JO 31). Specific allele
frequencies were compared between the healthy and patient populations, as
well as presence or absence of these in relation to recurrence. Alleles related
to autoimmune disease were also investigated.
RESULTS: No significant differences were found between the distributions of
CTLA-4 polymorphisms in the melanoma population compared with healthy
controls. Relapse free survival (RFS) and overall survival (OS) did not differ
significantly between patients with the alleles represented by these
polymorphisms. No correlation between autoimmunity and specific alleles
was shown. The six polymorphisms evaluated where strongly associated
(Fisher's exact p-values < 0.001 for all associations) and significant linkage
disequilibrium among these was indicated.
CONCLUSION: No polymorphisms of CTLA-4 defined by the SNPs studied
were correlated with improved RFS, OS, or autoimmunity in this high-risk
group of melanoma patients.
PMID: 21044351 [PubMed - indexed for MEDLINE] PMCID: PMC2988721
Free PMC Article
Publication Types, MeSH Terms, Substances, Grant Support
c Psychiatry Res. 2010 Oct 30;179(3):333-7. Epub 2010 May 21.
7. Phantom breast syndrome: The effect of in situ
breast carcinoma.
Markopoulos CJ, Spyropoulou AC, Zervas IM, Christodoulou GN,
Markopoulos C - PubMed - NCBI Papageorgiou C. Second Department of Propedeutic Surgery, University of Athens, Athens, Greece. Abstract
Phantom breast syndrome (PBS) represents the experience of the continued
presence of the breast, after mastectomy. Our aim was to assess PBS
appearance by means of a structured questionnaire and to look into possible
associations to disease and treatment parameters, in 105 women with breast
cancer treated by mastectomy. PBS was recorded in 22.9% of the patients.
In the majority of cases phantom experience had the size (88.9%), shape
(76.5%) and weight (64.7%) of the normal breast and was localised in the
entire breast (50%). Concerning disease parameters, no association with
primary tumour size (T) or lymph node status was detected, but interestingly,
in situ breast cancer (DCIS) was found to be more frequently associated with
PBS, compared with invasive tumours. No significant associations of PBS
with previous sensory experiences of the breast, radiotherapy or systemic
treatment were assessed. The results are interpreted within the frame of
Melzack's theory of a neuromatrix, assuming that PBS represents the
continued existence, even after amputation, of a sensory engram of the
breast. The absence of infiltration in primary tumour histology, probably
through an unknown pathophysiological mechanism, might play a role for the
significantly higher incidence of PBS in women undergoing mastectomy for
DCIS.
Copyright 2009 Elsevier Ireland Ltd. All rights reserved. PMID: 20493554 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms
c Cancer. 2010 Sep 15;116(18):4326-33.
8. Correlation of molecular human leukocyte antigen
typing and outcome in high-risk melanoma patients
receiving adjuvant interferon.
Gogas H, Kirkwood JM, Falk CS, Dafni U, Sondak VK, Tsoutsos D, Stratigos
A, Markopoulos C, Pectasides D, Spyropoulou-Vlachou M.
First Department of Medicine, University of Athens, Medical School, Athens, Greece.
Abstract
BACKGROUND:
Interferon is approved for adjuvant treatment of patients
with stage IIB/III melanoma. The identification of predictive markers that
would permit selection of patients would be beneficial. Specific human
leukocyte antigen (HLA) class I and II antigens have previously shown an
association with response to therapy or overall survival of patients with
metastatic melanoma.
METHODS:
tal of 284 high-risk melanoma patients participating in a randomized trial and 246 healthy controls were molecularly typed for HLA


Markopoulos C - PubMed - NCBI class I and II. Specific allele frequencies were compared between the healthy and patient populations, as well as presence or absence of these in relation to recurrence. Alleles related to autoimmune disease were also investigated. RESULTS:
significant differences were found between the distribution of HLA genotype in the melanoma population compared with healthy controls. Correlations between nonrecurrence and the presence of HLA-Cw 06 allele were noted present in 19.3% of melanoma patients. The median relapse-free survival of the Cw 06-positive cohort was 100.2 months versus 37.3 months in the Cw 06-negative cohort (P = .013). The median overall survival for the Cw 06-positive cohort has not yet been reached, versus 78.9 months in the Cw 06-negative cohort (P = .025). HLA-Cw 06 was present in 29.79% of patients in the autoimmunity group and 15.38% of patients in the nonautoimmunity group (P = .049). was associated with absence of recurrence in patients receiving adjuvant interferon with the exception of HLA-Cw 06, an allele correlated with psoriasis. HLA-Cw 06-positive patients have better relapse-free and overall survival. 2010 American Cancer Society. PMID: 20549830 [PubMed - indexed for MEDLINE] PMCID: PMC2970916
Free PMC Article
Publication Types, MeSH Terms, Substances, Grant Support
c Br J Surg. 2010 May;97(5):671-9.
9. Variations in locoregional therapy in postmenopausal
patients with early breast cancer treated in different
countries.
van Nes JG, Seynaeve C, Jones S, Markopoulos C, Putter H, van de Velde
CJ; Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trialists,
Hasenburg A, Rea DW, Vannetzel JM, Dirix L, Hozumi Y, Kerin MJ, Kieback
DG, Meershoek-Klein Kranenbarg WM, Hille ET, Nortier JW.
Department of Surgery, Leiden University Medical Centre, Leiden, The Netherlands.
Abstract
BACKGROUND:
The Tamoxifen and Exemestane Adjuvant Multinational
(TEAM) trial is an international randomized trial evaluating the efficacy and
safety of exemestane, alone or following tamoxifen. The large number of
patients already recruited offered the opportunity to explore locoregional
treatment practices between countries.
METHODS:
were enrolled in Belgium, France, Germany, Greece, Ireland, Japan, the Netherlands, the UK and the USA. The core protocol had minor differences in eligibility criteria between countries, reflecting variations in national guidelines and practice regarding adjuvant endocrine therapy. RESULTS:
2001 and 2006, 9779 patients of mean(s.d.) age 64(9)



Markopoulos C - PubMed - NCBI years were randomized. Some 58.4 per cent had T1 tumours (range between countries 36.8-75.9 per cent; P < 0.001) and 47.3 per cent were axillary node positive (range 25.9-84.6 per cent; P < 0.001). Independent factors for type of breast surgery were country, age, tumour status and calendar year of surgery. After breast-conserving surgery, radiotherapy was given to 93.2 per cent of patients, 86.0 per cent in the USA and 100 per cent in France. Axillary lymph node dissection was performed in 82.0 (range 74.6-99.1) per cent. CONCLUSION: Despite international consensus guidelines, wide global
variations were observed in treatment practices of early breast cancer. There
should be further efforts to optimize locoregional treatment for breast cancer
worldwide.
Copyright 2010 British Journal of Surgery Society Ltd. PMID: 20393978 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms, Substances
c Breast Cancer Res. 2010;12(4):403. Epub 2010 Aug 3.
10. Managing bone health in women with breast cancer
under adjuvant treatment with aromatase inhibitors:
pretreatment bone mineral density is important.

Markopoulos C.
Comment on
Breast Cancer Res. 2010;12(3):110.
PMID: 20727234 [PubMed - indexed for MEDLINE] PMCID: PMC2949639
Free PMC Article
Publication Types, MeSH Terms, Substances
c Breast Cancer Res. 2010;12(2):R24. Epub 2010 Apr 16.
11. Management of anastrozole-induced bone loss in
breast cancer patients with oral risedronate: results
from the ARBI prospective clinical trial.

Markopoulos C, Tzoracoleftherakis E, Polychronis A, Venizelos B, Dafni U,
Xepapadakis G, Papadiamantis J, Zobolas V, Misitzis J, Kalogerakos K,
Sarantopoulou A, Siasos N, Koukouras D, Antonopoulou Z, Lazarou S,
Gogas H.
Hellenic Society of Breast Surgeons, 6 Eslin Street, Athens, Greece.
Markopoulos C - PubMed - NCBI Abstract
INTRODUCTION:
The aim of this multicenter, phase III, prospective open
label clinical trial was to investigate the effect of risedronate (R) on bone
mineral density (BMD) in postmenopausal, early breast cancer (BC) patients
scheduled to receive anastrozole (A).
METHODS:
BMD of 213 patients with hormone receptor- positive BC was evaluated at lumbar spine (LS) and hip (HP). Patients were categorized according to their baseline BMD T-score as being at low, moderate and high risk of osteoporosis. Low risk patients received anastrozole only (A), moderate risk were randomized to anastrozole +/- risedronate (A+/-R) administration and high risk patients received anastrozole + risedronate (A+R). Anastrozole was given at a dosage of 1 mg/day while oral risedronate was given at 35 mg/week. BMD was then assessed at 12 and 24 months. All patients received daily supplements of calcium (1000 mg/day) and vitamin D (400 IU/day). At 24 months, in RESULTS:
the moderate risk group, treatment with A+R resulted in a significant increase in BMD at LS and HP compared to treatment with A only (5.7% v -1.5%, Wilcoxon test P = 0.006, and 1.6% v -3.9% Wilcoxon test P = 0.037, respectively), while no significant difference was found at 12 months; 24.3% of the patients moved to normal BMD region. In the high risk group, a significant increase for LS was detected both at 12 and 24 months (6.3% and 6.6%, P < 0.001) but not for HP; BMD in 14% of patients improved to the osteopenic region. In the low risk group, a significant decrease of BMD was detected at 12 months for LS and HP (-5.3% P < 0.001 and -2.4% P < 0.001, respectively,); at 24 months, a significant decrease of BMD was detected only for LS (-2.5%, P < 0.001). However, 22% of patients became osteopenic and only 4% became osteoporotic. addition of oral risedronate in post-menopausal breast cancer patients receiving anastrozole has a favorable effect on BMD. Patients with pre-treatment osteopenic to osteoporotic status should be treated with a combination of both therapies in order to avoid bone loss induced by aromatase inhibition. Patients with normal BMD before starting treatment with anastrozole have a very low risk to develop osteoporosis. Comment in
Breast Cancer Res. 2010;12(3):110.
PMID: 20398352 [PubMed - indexed for MEDLINE] PMCID: PMC2879572
Free PMC Article
Publication Types, MeSH Terms, Substances, Secondary
Source ID

c J Natl Cancer Inst Monogr. 2010;2010(41):162-77.
12. Overview of the randomized trials of radiotherapy in
Markopoulos C - PubMed - NCBI ductal carcinoma in situ of the breast.
Early Breast Cancer Trialists' Collaborative Group (EBCTCG), Correa C,
McGale P, Taylor C, Wang Y, Clarke M, Davies C, Peto R, Bijker N, Solin L,
Darby S.
Collaborators (610)
Abstract
Individual patient data were available for all four of the randomized trials that
began before 1995, and that compared adjuvant radiotherapy vs no
radiotherapy following breast-conserving surgery for ductal carcinoma in situ
(DCIS). A total of 3729 women were eligible for analysis. Radiotherapy
reduced the absolute 10-year risk of any ipsilateral breast event (ie, either
recurrent DCIS or invasive cancer) by 15.2% (SE 1.6%, 12.9% vs 28.1% 2
P <.00001), and it was effective regardless of the age at diagnosis, extent of
breast-conserving surgery, use of tamoxifen, method of DCIS detection,
margin status, focality, grade, comedonecrosis, architecture, or tumor size.
The proportional reduction in ipsilateral breast events was greater in older
than in younger women (2P < .0004 for difference between proportional
reductions; 10-year absolute risks: 18.5% vs 29.1% at ages <50 years,
10.8% vs 27.8% at ages ≥ 50 years) but did not differ significantly according
to any other available factor. Even for women with negative margins and
small low-grade tumors, the absolute reduction in the 10-year risk of
ipsilateral breast events was 18.0% (SE 5.5, 12.1% vs 30.1%, 2P = .002).
After 10 years of follow-up, there was, however, no significant effect on
breast cancer mortality, mortality from causes other than breast cancer, or
all-cause mortality.
PMID: 20956824 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms, Substances, Grant Support
c Anticancer Res. 2009 Jul;29(7):2851-6.
13. Salvage chemotherapy with oxaliplatin and
capecitabine for breast cancer patients pretreated
with anthracyclines and taxanes.
Polyzos A, Gogas H, Markopoulos C, Tsavaris N, Papadopoulos O,
Polyzos K, Giannopoulos A.
Department of Propaedeutic Medicine, Medical Oncology Unit, Laiko General
Hospital, Athens University School of Medicine, Athens, Greece. panoraiap@med.uoa.gr Abstract
There is no standard treatment for breast cancer patients whose tumors
have been exposed both to anthracyclines and taxanes. Oxaliplatin shows
synergism with 5-fluorouracil (5-FU) and capecitabine is an oral prodrug of
5-FU with known efficacy in pretreated patients. This phase II trial studied
the efficacy and toxicity of the oxaliplatin-capecitabine combination as
Markopoulos C - PubMed - NCBI salvage treatment in breast cancer patients pretreated with anthracyclines and taxanes. Patients received oxaliplatin 80 mg/m(2) on day 1 followed by oral capecitabine 1800 mg/m(2) divided in two doses for 7 days every two weeks for a maximum of twelve courses or until disease progression. Twenty-eight patients were evaluable for efficacy and toxicity. Objective responses (all partial) were documented in 9 patients [32%; 95% confidence interval (CI): 13-51.2%]. Responses were documented at all metastatic sites. The median response duration was 5 months (range 3-9), median time to progression was 4.5 months (range 2-10) and median overall survival was 10 months (range 2-18). Myelotoxicity was minimal with grade 3 thrombocytopenia as the main toxicity. Hand-foot syndrome was well tolerated. The present regimen was well tolerated with a rather moderate effectiveness but very significant for this group of patients. Further studies where the combination could be compared with single agent capecitabine are warranted. PMID: 19596973 [PubMed - indexed for MEDLINE] MeSH Terms, Substances
c Eur J Surg Oncol. 2009 Mar;35(3):333. Epub 2008 May 1.
14. Aromatase inhibitors in the management of early
breast cancer: the TEAM trial.
Markopoulos C.
Comment on
Eur J Surg Oncol. 2008 Nov;34(11):1199-207.
PMID: 18455358 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms, Substances
c J Pharm Pharmacol. 2009 Feb;61(2):143-9.
15. Stability of oleuropein in the human proximal gut.
Markopoulos C, Vertzoni M, Agalias A, Magiatis P, Reppas C.
Department of Pharmaceutical Technology, Faculty of Pharmacy, National & Kapodistrian University of Athens, Zografou, Greece. Abstract
OBJECTIVES:
assess the intralumenal stability of oleuropein in human gastric and small intestinal contents. We additionally aimed to assess the stability characteristics of oleuropein in media simulating the intralumenal conditions. METHODS: The intralumenal stability of oleuropein was assessed in
aspirates from the stomach and the upper small intestine of healthy
volunteers collected under both fasted and fed state conditions and in media
Markopoulos C - PubMed - NCBI simulating the intralumenal environment. KEY FINDINGS: Oleuropein degraded in aspirates collected in the fasted
state. When the initial concentration was about 50 microg/ml (close to
expected intragastric concentration after single dose of commercially
available products of oleuropein) the mean zero-order half-life of oleuropein
in aspirates collected from the fasted small intestine was estimated to be
3.14 +/- 0.08 h at 37 degrees C (i.e. after oral administration in the fasted
state, a substantial fraction of oleuropein degrades before reaching the
intestinal mucosa). In contrast, oleuropein was stable in aspirates collected
from the fed stomach; in small intestinal contents aspirated in the fed state
the estimated zero-order degradation half-life was at least 12 h.
data suggest that oleuropein should not have substantial intralumenal stability problems when administered in the fed state. Data collected in media simulating the intragastric and intraintestinal environment suggest that pH affects the stability of oleuropein only at low pH values (of about 2). At higher pHs degradation characteristics are at least partly affected by the presence of other scavengers of reactive oxygen species in the medium. PMID: 19178760 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms, Substances
c Ann Oncol. 2009 Jan;20(1):49-55. Epub 2008 Aug 4.
16. Lipid changes in breast cancer patients on
exemestane treatment: final results of the TEAM
Greek substudy.

Markopoulos C, Polychronis A, Dafni U, Koukouras D, Zobolas V,
Tzorakoleftherakis E, Xepapadakis G, Gogas H.
Department of Breast Surgery, Medical School, University of Athens, Athens,
Greece. cmarkop@hol.gr Abstract
BACKGROUND:
The Greek substudy of the Tamoxifen and Exemestane
Adjuvant Multicenter International trial compared the effect of exemestane
on the lipid profile of postmenopausal, breast cancer patients to that of
tamoxifen in the adjuvant setting.
PATIENTS AND METHODS: Lipidemic profile changes were studied in 142
postmenopausal patients randomized to receive either adjuvant
exemestane (n=77) or tamoxifen (n=65). Total cholesterol (TC), high-density
lipoprotein (HDL), low-density lipoprotein (LDL) and serum triglyceride
(TRG) levels were measured at baseline and then every 3 months for the
first 12 months of treatment and at 18 and 24 months.
RESULTS: trend for a reduction in TC was found in both treatment arms;
however, TC and LDL levels were consistently and significantly decreased
in tamoxifen arm only. The mean HDL level was higher for the tamoxifen
Markopoulos C - PubMed - NCBI arm compared with the exemestane arm across time. No significant trend was detected throughout the study period on TRG levels on either arm. Unlike tamoxifen's beneficial effect on TC and LDL levels, exemestane appears to have a neutral effect on lipidemic profile of postmenopausal, breast cancer patients. These data offer additional information with regard to the safety and tolerability of exemestane treatment in the adjuvant setting. PMID: 18678766 [PubMed - indexed for MEDLINE] Free full text
Publication Types, MeSH Terms, Substances
c Breast Cancer Res. 2009;11(3):R35. Epub 2009 Jun 16.
17. Extended adjuvant hormonal therapy with
exemestane has no detrimental effect on the lipid
profile of postmenopausal breast cancer patients:
final results of the ATENA lipid substudy.

Markopoulos C, Dafni U, Misitzis J, Zobolas V, Tzoracoleftherakis E,
Koukouras D, Xepapadakis G, Papadiamantis J, Venizelos B, Antonopoulou
Z, Gogas H.
Hel enic Society of Breast Surgeons, Athens, Greece. cmarkop@hol.gr
Abstract
INTRODUCTION:
Extended adjuvant endocrine therapy for breast cancer
with aromatase inhibitors may potentially alter the lipid profile of
postmenopausal patients and thus increase the risk of developing
cardiovascular disease. In this study, a subprotocol of the ATENA (Adjuvant
post-Tamoxifen Exemestane versus Nothing Applied) trial, we compared the
effect of the steroidal aromatase inactivator exemestane on the lipid profile
of postmenopausal patients with operable breast cancer, in the adjuvant
setting, with that of observation alone after completion of 5 to 7 years of
primary treatment with tamoxifen.
METHODS:
this open-label, randomized, parallel-group study, 411 postmenopausal patients with operable breast cancer, who had been treated with tamoxifen for 5 to 7 years, were randomized to either 5 additional years of exemestane (25 mg/day; n = 211) or observation only (n = 200). Assessments of total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total serum triglycerides (TRG) were performed at baseline and then during each follow-up visit, performed at either 6 or 12 months, according to the center's clinical practice, until completing 24 months in the study. RESULTS:
and LDL levels increased significantly across time for both arms; TC increase was more pronounced for the observation arm, and that was sustained up to 24 months. HDL levels decreased significantly across time for the exemestane arm, whereas no significant change was detected across time for the observation arm. Triglyceride levels decreased Markopoulos C - PubMed - NCBI significantly across time on both arms, with no difference detected in changes from baseline between the exemestane and the observation arms. lacks the beneficial effect of tamoxifen on lipids; however, sequential adjuvant treatment with exemestane in postmenopausal breast cancer patients after cessation of 5 to 7 years of tamoxifen does not appear to alter the lipid profile significantly compared with that of an observational arm. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT00810706.
PMID: 19531217 [PubMed - indexed for MEDLINE] PMCID: PMC2716503
Free PMC Article
Publication Types, MeSH Terms, Substances, Secondary
Source ID

c J Int Med Res. 2009 Jan-Feb;37(1):182-8.
18. Impact of breast cancer surgery on the self-esteem
and sexual life of female patients.
Markopoulos C, Tsaroucha AK, Kouskos E, Mantas D, Antonopoulou Z,
Karvelis S.
Breast Unit, Second Department of Surgery, Athens University Medical School -
'Laiko' General Hospital, Athens, Greece. Abstract
Patient satisfaction with cosmetic outcome and the psychological impact of
breast cancer surgery were evaluated. A total of 207 patients with primary
breast cancer, treated with either breast-conserving surgery (n = 83),
modified radical mastectomy without reconstruction (n = 108), or
mastectomy with delayed breast reconstruction (n = 16) rated their cosmetic
outcome and satisfaction following surgery, and the impact of surgery on
their self-esteem and sexual life, by questionnaire. Patients undergoing
breast-conserving surgery were most satisfied with their surgery and body
image, followed by those treated with mastectomy with delayed
reconstruction. Although diagnosis of breast cancer had a negative impact
on the psychology of all patients, those undergoing breast-conserving
surgery or mastectomy with delayed reconstruction were more satisfied and
reported a lower impact on their self-esteem and sexual life versus those
who only had mastectomy. Diagnosis of breast cancer has a negative
psychological impact on the patient, but the type of surgery has a significant
role in post-operative self-esteem and sexual life.
PMID: 19215689 [PubMed - indexed for MEDLINE] MeSH Terms
Markopoulos C - PubMed - NCBI c J Hazard Mater. 2008 Sep 15;157(2-3):579-86. Epub 2008 Jan 20.
19. Titanium leaching from red mud by diluted sulfuric
acid at atmospheric pressure.
Agatzini-Leonardou S, Oustadakis P, Tsakiridis PE, Markopoulos Ch.
Department of Mining and Metallurgical Engineering, Laboratory of Metallurgy,
National Technical University of Athens, Zografou, Athens, Greece. Abstract
Laboratory-scale research has focused on the recovery of titanium from red
mud, which is obtained from bauxite during the Bayer process for alumina
production. The leaching process is based on the extraction of this element
with diluted sulfuric acid from red mud under atmospheric conditions and
without using any preliminary treatment. Statistical design and analysis of
experiments were used, in order to determine the main effects and
interactions of the leaching process factors, which were: acid normality,
temperature and solid to liquid ratio. The titanium recovery efficiency on the
basis of red mud weight reached 64.5%. The characterization of the initial
red mud, as well as this of the leached residues was carried out by X-ray
diffraction, TG-DTA and scanning electron microscopy.
PMID: 18295399 [PubMed - indexed for MEDLINE] MeSH Terms, Substances
c Surg Oncol. 2008 Aug;17(2):113-28. Epub 2008 Jan 4.
20. Safely promoting breast-conserving surgery and
preventing early relapses with an aromatase
inhibitor.

Markopoulos C.
Athens Medical School, University of Athens, GR-11521 Athens, Greece. Abstract
Neoadjuvant therapy improves patient outcomes substantially by increasing
the rate of breast-conserving surgery. Following primary surgery, women
with hormone-sensitive early breast cancer remain at risk for loco-regional
and systemic recurrence. The most common relapse event, distant
metastases, is associated with the poorest outcomes. As a neoadjuvant
therapy, anastrozole, letrozole, and exemestane have been investigated in
phase 3 studies and have shown efficacy in this setting. All three aromatase
inhibitors (AIs) significantly improved the rate of breast-conserving surgery.
As initial adjuvant therapy, the third-generation AIs anastrozole and
letrozole more effectively reduce recurrence risk compared with tamoxifen
following surgery, especially in the first 2 years, when the risk is greatest.
Tamoxifen, once the standard initial therapy, is associated with improved
disease-free survival but may be more effective at reducing loco-regional
recurrence than distant metastases. Initial adjuvant letrozole therapy has
Markopoulos C - PubMed - NCBI also shown a pronounced reduction in the risk of distant metastases early on in the course of therapy. If AIs are not used upfront, sequential use of exemestane or anastrozole following tamoxifen provides greater protection against relapse than continuing on tamoxifen. Side effects associated with estrogen deprivation of AIs are less serious than those of tamoxifen and are easily managed. Various molecular markers are under study as surrogates to predict response to neoadjuvant therapy, which may in turn predict responsiveness to adjuvant therapy. Surgeons treating breast cancer patients and prescribing endocrine therapy should be aware of all treatment strategies, including neoadjuvant and adjuvant hormonal therapy, and inform their patients of the benefits and the potential side effects. Early and long-term-risk reduction with AI treatment should be discussed with patients, as should the management of common AI-associated adverse events. PMID: 18178077 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms, Substances
c Ann Oncol. 2008 May;19(5):853-60. Epub 2007 Nov 27.
21. Postoperative dose-dense sequential chemotherapy
with epirubicin, paclitaxel and CMF in patients with
high-risk breast cancer: safety analysis of the
Hellenic Cooperative Oncology Group randomized
phase III trial HE 10/00.
Fountzilas G, Dafni U, Gogas H, Linardou H, Kalofonos HP, Briasoulis E,
Pectasides D, Samantas E, Bafaloukos D, Stathopoulos GP, Karina M,
Papadimitriou C, Skarlos D, Pisanidis N, Papakostas P, Markopoulos C,
Tzorakoeleftherakis E, Dimitrakakis K, Makrantonakis P, Xiros N,
Polichronis A, Varthalitis I, Karanikiotis C, Dimopoulos AM; Hellenic
Cooperative Oncology Group.
Department of Medical Oncology, Papageorgiou Hospital, School of Medicine,
Aristotle University of Thessaloniki, Thessaloniki, Greece. fountzil@med.auth.gr Abstract
BACKGROUND:
A randomized phase III trial in high-risk breast cancer
patients was conducted, to further explore the impact of dose-density in the
adjuvant treatment for breast cancer. The safety analysis is presented.
PATIENTS AND METHODS: From October 2000 until June 2005, 1121
node-positive patients were randomized to sequential dose-dense epirubicin
110 mg/m(2) and paclitaxel (Taxol, Bristol Myers-Squibb, Princeton, New
Jersey, USA) 250 mg/m(2) (group A), or concurrent epirubicin 83 mg/m(2)
and paclitaxel 187 mg/m(2) (group B), both followed by three cycles of
'intensified' combination chemotherapy with cyclophosphamide,
methotrexate and fluorouracil (CMF). Granulocyte colony-stimulating factor
was given prophylactically with the dose-dense treatments.
Median dose intensity RESULTS:
of epirubicin and paclitaxel was double in Markopoulos C - PubMed - NCBI group A, as designed, with significantly less cycles administered at full dose (P < 0.001). Median cumulative dose of all drugs and total treatment duration, however, were identical between groups. Severe taxane-related toxic effects were more frequent in group A, while severe thrombocytopenia was low and present only in group A. There were no differences in the rates of other hematological toxic effects, including febrile neutropenia. The rates of secondary malignancies were low. CONCLUSION: Both regimens as used in the present study are well
tolerated and safe. The rates of severe taxane-related toxic effects and
thrombocytopenia, although low overall, are significantly increased with the
dose-dense sequential regimen.
PMID: 18042835 [PubMed - indexed for MEDLINE] Free full text
Publication Types, MeSH Terms, Substances,
Supplementary Concepts

c World J Surg Oncol. 2008 Apr 29;6:44.
22. Glycogen-rich clear cell carcinoma of the breast.
Markopoulos C, Mantas D, Philipidis T, Kouskos E, Antonopoulou Z,
Hatzinikolaou M, Gogas H.
Breast Unit, 2nd Propedeutic Department of Surgery, Athens University Medical
School, Greece. cmarkop@hol.gr Abstract
BACKGROUND:
Glycogen-rich carcinoma of the breast is a rare
histological subtype of breast cancer, usually reported to have poor
prognosis.
CASE PRESENTATION: We present the case of a 59-year-old woman who
underwent a mastectomy for a 3.5 cm clinically palpable left breast
carcinoma, originally diagnosed as fibroadenoma on a screening
mammogram four years before presentation. Diagnosis of clear cell
carcinoma was based on certain histological characteristics of the tumour
and immunohistochemical analysis (PAS staining, keratins AE1/AE3, EMA,
cytokeratin 7, cytokeratin 20, melanosomes, vimentin, Chromogranin,
Synaptophysin, S-100, SMA). No lymph node metastasis was found and as
the tumour was ER positive and PgR negative, patient was treated only with
an aromatase inhibitor upfront and remains free of disease 48 months now
since operation.
CONCLUSION: Glycogen-rich clear cell carcinoma of the breast is a rare
tumor, its clinical behavior reported to be rather aggressive so far, might
varies depending on special characteristics such as low grade and strongly
positive ER expression.
PMID: 18442419 [PubMed - indexed for MEDLINE] PMCID: PMC2386120
Free PMC Article
Markopoulos C - PubMed - NCBI Publication Types, MeSH Terms, Substances
c Eur Arch Psychiatry Clin Neurosci. 2008 Apr;258(3):165-70.
23. Depressive symptomatology correlates with
phantom breast syndrome in mastectomized women.
Spyropoulou AC, Papageorgiou C, Markopoulos C, Christodoulou GN,
Soldatos KR.
Department of Psychiatry, Eginition Hospital, University of Athens, Athens, Greece.
arspyrop@yahoo.com Abstract
OBJECTIVE:
Phantom breast syndrome (PBS) after mastectomy has been
hypothesized to represent a complex psychological reaction to mastectomy,
but psychological studies concerning PBS are few and inconclusive. This
study aimed to assess possible correlations of PBS to current
psychopathology and personality dimensions, as well as to examine
subjectively experienced provoking and relieving factors for the experience
of PBS.
METHOD: total of 105 women who had undergone modified radical
mastectomy were interviewed by a structured questionnaire after breast
surgery. Moreover, they completed a set of self-administered psychometric
scales consisting of Symptom Checklist-90-R, Eysenck personality
questionnaire, Zung depression scale, State-Trait Anxiety Inventory and
Whiteley Index of hypochondriasis.
RESULTS:
rienced by 24 women (22.9%). The majority of them thought that PBS did not interfere with their everyday life. Women with PBS scored significantly higher on the Zung depression scale. Multiple logistic regression analysis revealed that women aged more than 66 years were 82% less likely to have PBS compared to those aged less than 51 years. CONCLUSION: These findings provide evidence that PBS is associated
with higher scores of depressive symptomatology and younger age. The
nature of such an association remains unclear and calls for further
investigation.
PMID: 18000636 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms
c Breast Cancer Res Treat. 2008 Feb;107(3):431-41. Epub 2007 Apr 24.
24. Greek BRCA1 and BRCA2 mutation spectrum: two
BRCA1 mutations account for half the carriers found
Markopoulos C - PubMed - NCBI among high-risk breast/ovarian cancer patients.
Konstantopoulou I, Rampias T, Ladopoulou A, Koutsodontis G, Armaou S,
Anagnostopoulos T, Nikolopoulos G, Kamakari S, Nounesis G, Stylianakis
A, Karanikiotis C, Razis E, Gogas H, Keramopoulos A, Gaki V,
Markopoulos C, Skarlos D, Pandis N, Bei T, Arzimanoglou I, Fountzilas G,
Yannoukakos D.
Molecular Diagnostics Laboratory, I/R-RP, National Center for Scientific Research
"Demokritos", Athens, Greece. Abstract
127 Greek breast/ovarian cancer families were screened for germline
BRCA1/2 mutations by dHPLC followed by direct sequencing. Our results
indicated 16 and 5 breast/ovarian cancer families bearing deleterious
mutations in the BRCA1 and BRCA2 genes, respectively. Two novel
BRCA2 germline mutations (G4X and 3783del10) are reported here for the
first time. Subsequent compilation of our present findings with previously
reported mutation data reveals that in a total of 287 Greek breast/ovarian
cancer families, 46 and 13 carry a deleterious mutation in BRCA1 and
BRCA2, respectively. It should be noted that two BRCA1 mutations,
5382insC and G1738R, both located in exon 20, account for 46% of the
families found to carry a mutation. Based on our mutation analysis results,
we propose here a hierarchical, cost-effective BRCA1/2 mutation screening
protocol for individuals of Greek ethnic origin. The suggested protocol can
impact on the clinical management of breast-ovarian cancer families on a
national healthcare system level.
PMID: 17453335 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms
c Stem Cells. 2008 Feb;26(2):431-9. Epub 2007 Nov 29.
25. Connexin expression and functional analysis of gap
junctional communication in mouse embryonic stem
cells.
Wörsdörfer P, Maxeiner S, Markopoulos C, Kirfel G, Wulf V, Auth T,
Urschel S, von Maltzahn J, Willecke K.
Division of Molecular Genetics, Institute of Genetics, University of Bonn, Bonn,
Abstract
Gap junctional intercellular communication (GJIC) has been suggested to
be necessary for cellular proliferation and differentiation. We wanted to
investigate the function of GJIC in mouse embryonic stem (ES) cells using
pharmacological inhibitors or a genetic approach to inhibit the expression of
connexins, that is, the subunit proteins of gap junction channels. For this
purpose, we have analyzed all known connexin genes in mouse ES cells
but found only three of them, Cx31, Cx43, and Cx45, to be expressed as
Markopoulos C - PubMed - NCBI proteins. We have demonstrated by coimmunoprecipitation that Cx31 and Cx43, as well as Cx43 and Cx45, probably form heteromeric gap junction channels, whereas Cx31 and Cx45 do not. The pharmacological inhibitors reduced GJIC between ES cells to approximately 3% and initiated apoptosis, suggesting an antiapoptotic effect of GJIC. In contrast to these results, reduction of GJIC to approximately 5% by decreased expression of Cx31 or Cx45 via RNA interference in homozygous Cx43-deficient ES cells did not lead to apoptosis. Additional studies suggested that apoptotic death of ES cells and adult stem cells reported in the literature is likely due to a cytotoxic side effect of the inhibitors and not due to a decrease of GJIC. Using the connexin expression pattern in mouse ES cells, as determined in this study, multiple connexin-deficient ES cells can now be genetically engineered in which the level of GJIC is further decreased, to clarify whether the differentiation of ES cells is qualitatively or quantitatively compromised. PMID: 18055446 [PubMed - indexed for MEDLINE] Free full text
MeSH Terms, Substances
c J Chemother. 2007 Oct;19(5):582-9.
26. Mitoxantrone plus vinorelbine in pretreated patients
with metastatic breast cancer.
Onyenadum A, Gogas H, Markopoulos C, Bafaloukos D, Aravantinos G,
Mantzourani M, Koutras A, Tzorakoelefterakis E, Xiros N, Makatsoris T,
Fountzilas G, Kalofonos HP.
Hellenic Cooperative Oncology Group, Data Office, Athens, Greece.
Abstract
Vinorelbine and mitoxantrone have both been demonstrated to have
significant antitumor activity in patients with breast cancer. The aim of this
study was to evaluate the efficacy and safety of the combination as second
or third line treatment in patients with metastatic breast cancer (MBC). Fifty-
one previously treated patients with MBC were enrolled from October 2001
to May 2004 and 48 were eligible for evaluation. Median age was 59 years
(range 33-82) and ECOG performance status was < or =2. Distant sites of
metastasis were as follows: liver 64%, bone 49%, lung 36%, lymph nodes
6%, skin 4%, brain 2% and other sites 6%. All patients received vinorelbine
20 mg/m(2), D1+8 and mitoxantrone 10 mg/m(2) D8 every 21 days for 6
cycles. All eligible patients were analyzed for toxicity and response. Two
patients (4%) achieved complete response and 12 (25.5%) partial response.
The objective overall response rate was 29.5% (95% confidence interval
[CI] 17 - 45), 9 (19%) patients had stable disease, 17 (36%) had progressive
disease and 7 (15%) were non-evaluable. After a median follow up of 18
months, overall survival was 13 months (range 0.8 - 38+) and median time
to disease progression was 5 months (range 1 - 32). A total of 280 cycles
was delivered. The relative dose intensities of mitoxantrone and vinorelbine
were 79% and 77%, respectively. Toxicities (grade III-IV) were as follows:
Markopoulos C - PubMed - NCBI leukopenia 18 (38%), neutropenia 21 (45%), thrombocytopenia 1 (2%), anemia 4 (8.5%), alopecia 2 (4%) and constipation 1 (2%). Febrile neutropenia was recorded in one patient. There were no treatment related deaths. The combination of mitoxantrone and vinorelbine is an effective regimen with manageable toxicity in pretreated patients with advanced breast cancer. PMID: 18073159 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms, Substances
c Hum Mol Genet. 2007 May 15;16(10):1216-24. Epub 2007 Apr 19.
27. The connexin31 F137L mutant mouse as a model for
the human skin disease erythrokeratodermia
variabilis (EKV).
Schnichels M, Wörsdörfer P, Dobrowolski R, Markopoulos C, Kretz M,
Schwarz G, Winterhager E, Willecke K.
Institut für Genetik, Abteilung Molekulargenetik, Universität Bonn, Bonn 53117,
Abstract
Erythrokeratodermia variabilis (EKV) is a rare autosomal dominant human
genodermatosis. Its clinical appearance varies from transient, fast moving
erythemas to persistent brown hyperkeratoses. So far, several mutations in
the Cx31 or Cx30.3 gene have been reported to cause EKV in humans. We
have generated a conditional mouse mutant that carries the human F137L
mutation in the Cx31 gene which was described to act in a transdominant
negative manner. The phenylalanine residue at position 137 is highly
conserved in several human and mouse connexin genes. Mouse embryonic
stem (ES) cells expressing one allele of the Cx31F137L mutation were
stable but showed approximately 30% decreased transfer of neurobiotin.
This is probably due to dominant negative effects of the Cx31F137L protein
on wild type Cx31 and Cx43 protein expressed in ES cells. Surprisingly, the
healing process of tail incision wounds in Cx31(+/F137L) mice was
shortened by 1 day, i.e. very similar as previously reported for mice with
decreased expression of Cx43 in the epidermis. This suggests again that
Cx31 and Cx43 proteins functionally interact, possibly by forming
heteromeric channels in the epidermis. Heterozygous Cx31(+/F137L) mice
are viable and fertile, in contrast to homozygous Cx31(F137L/F137L) mice
that die around ED 7.5. In Cx31(+/F137L) mice, the epidermal expression
pattern and level of Cx26, Cx30, Cx30.3 and Cx43 proteins were not altered
compared with wild-type mice. No erythemas were detected in young C31
(+/F137L) mice before 2 weeks of age. In contrast to human EKV patients,
hyperproliferation of the stratum germinativum was found in only 5% of the
analyzed skin area.
PMID: 17446259 [PubMed - indexed for MEDLINE] Free full text
Markopoulos C - PubMed - NCBI Publication Types, MeSH Terms, Substances
c Anticancer Res. 2007 May-Jun;27(3B):1709-13.
28. Breast cancer risk in relation to most prevalent IgE
specific antibodies: a case control study in Greece.
Petridou ET, Chavelas C, Dikalioti SK, Dessypris N, Terzidis A, Nikoulis DI,
Markopoulos C, Papadiamantis Y, Germenis AE.
Unit of Preventive Medicine, Department of Hygiene and Epidemiology and School of Medicine, University of Athens, Athens 11527, Greece. epetrid@med.uoa.gr Abstract
BACKGROUND:
This study aims to explore the debatable role of allergy in
breast cancer (BC) by using country-specific biological markers, namely
levels of the most prevalent allergen-specific immunoglobulin E in Greece.
PATIENTS AND
METHODS:
and clinical information were collected over a 30-month period from 103 women with histologically-confirmed BC and 103 controls from two university hospitals in Athens. Allergen-specific IgE, against the 12 prevailing allergens in Greece were determined; thereafter, a score comprising the sum of the individual values for this battery of serological IgE determinations was created. Bivariate and multiple logistic regression analyses were undertaken using case-control status as the outcome and IgE-scores as the predictor variable, controlling for socio-demographic, gynecological and lifestyle confounders. RESULTS:
rum IgE score seemed to be positively related to BC (OR: approximately 1.73; CI: 0.95-3.14; p-value: 0.07). A positive correlation between serological evidence and allergic history among controls was also found (p-value: 0.06). CONCLUSION: This investigation suggests an IgE-mediated allergic
response among women with BC in comparison to their controls. The
finding needs confirmation by immuno-epidemiological investigation to
clarify the directionality of this association and whether laboratory-
ascertained atopy can be considered as a risk-marker of susceptibility in the
development of BC.
PMID: 17595802 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms, Substances
c Ann Oncol. 2006 Dec;17(12):1835-41. Epub 2006 Sep 15.
29. Temozolomide in combination with celecoxib in
patients with advanced melanoma. A phase II study
of the Hellenic Cooperative Oncology Group.

Markopoulos C - PubMed - NCBI Gogas H, Polyzos A, Stavrinidis I, Frangia K, Tsoutsos D, Panagiotou P,
Markopoulos C, Papadopoulos O, Pectasides D, Mantzourani M, Middleton
M, Vaiopoulos G, Fountzilas G.
First Department of Medicine, University of Athens, Medical School, Athens,
Greece. hgogas@hol.gr Abstract
BACKGROUND:
There is now increasing evidence that a constitutive
expression of cyclooxygenase (COX)-2 plays a role in the development and
progression of malignant epithelial tumors. Expression of COX-2 is seen in
93% of melanomas, as determined by immunohistochemistry.
Temozolomide (TMZ) has demonstrated activity against melanoma and has
been investigated as single agent or in combination. We designed a phase
II study to assess the efficacy and toxicity of the combination of TMZ and
celecoxib (a COX-2 inhibitor) in patients with advanced melanoma.
PATIENTS AND
From January 2003 METHODS:
to July 2004, 52 patients were enrolled in the study. Nineteen patients were M1a, six M1b and 27 M1c. Patients received TMZ 200 mg/m(2) per day p.o. for 5 consecutive days every 4 weeks and celecoxib 400 mg b.i.d. p.o. for a maximum of six cycles. Celecoxib was continued until progression. RESULTS:
was 63 years. There were 29 males and 23 females. Among 50 assessable patients, there were 11 (21.5%) objective responses including five complete responses and six partial responses. Twenty patients (38.5%) had stabilization of their disease, and 19 (36.5%) progressed. The median time to progression was 4.6 months and the median survival 9.5 months. Twenty-two patients (41.5%) completed all cycles of treatment. Median relative dose intensity of TMZ was 0.99 (range 0.6-1.2). Most commonly seen toxic effects included anemia (27.5%), neutropenia (17.5%), thrombocytopenia (33%), nausea/vomiting (75%), gastrointestinal (52%) and fatigue (46.5%). One patient discontinued due to severe toxicity. COX-2 was determined by immunohistochemistry and was expressed in all cases. CONCLUSION: The combination of TMZ and celecoxib is safe and
potentially effective in the treatment of metastatic melanoma. Randomized
studies are needed to explore the role of celecoxib in combination with
chemotherapy or as maintenance treatment in these patients.
PMID: 16980601 [PubMed - indexed for MEDLINE] Free full text
Publication Types, MeSH Terms, Substances
c Breast. 2006 Aug;15(4):540-3. Epub 2006 Mar 20.
30. Paraffinomas of the breast or oleogranulomatous
mastitis-a rare entity.
Markopoulos C, Mantas D, Kouskos E, Antonopoulou Z, Revenas C,
Yiacoumettis A.
Markopoulos C - PubMed - NCBI Breast Unit, 2nd Propaedeutic, Department of Surgery, Faculty of Medicine, University of Athens, "Laiko" General Hospital, 8, Iassiou Street, 11521 Athens, Greece. cmarkop@hol.gr Abstract
Breast augmentation with the injection of a high-viscosity fluid has been
practiced in the past, especially in Asia, resulting in most cases in different
varieties of paraffinoma, alternatively known as oleogranulomatous mastitis,
a complication of a 'foreign body' reaction type. We report our series of four
consecutive cases of destructive paraffinomas that occurred in female
patients who had had paraffin injection for cosmetic reasons. Complications
due to paraffinoma reactions of breast tissue and skin, as well as
progression of the disease and treatment of our patients, are presented
here, together with a review of the relevant literature.
PMID: 16545569 [PubMed - indexed for MEDLINE] MeSH Terms, Substances
c Breast Cancer Res Treat. 2006 Apr;96(3):251-61.
31. Evaluation of the prognostic value of HER-2 and
VEGF in breast cancer patients participating in a
randomized study with dose-dense sequential
adjuvant chemotherapy.
Kostopoulos I, Arapantoni-Dadioti P, Gogas H, Papadopoulos S, Malamou-
Mitsi V, Scopa CD, Markaki S, Karagianni E, Kyriakou V, Margariti A,
Kyrkou E, Pavlakis K, Zaramboukas T, Skordalaki A, Bourli A,
Markopoulos C, Pectasides D, Dimopoulos MA, Skarlos D, Fountzilas G.
Aristotle University of Thessaloniki, School of Medicine, Thessaloniki, Greece. Abstract
PURPOSE:
To assess the prognostic and predictive significance of HER-2
overexpression and high expression of VEGF in high-risk patients with
breast cancer treated with dose-dense sequential chemotherapy.
PATIENTS AND METHODS: From June 1997 until November 2000, 595
patients were randomized to three cycles of epirubicin (E) 110 mg/m2
followed by three cycles of paclitaxel (T) 250 mg/m2 followed by three
cycles of "intensified" CMF (cyclophosphamide 840 mg/m2, methotrexate
47 mg/m2 and fluorouracil 840 mg/m2) or to four cycles of E, followed by
four cycles of CMF. HER-2 was assessed by immunohistochemistry (IHC) in
394 patients, and by fluorescence in situ hybridization (FISH) in cases
scored as 2+ by IHC. VEGF was evaluated in 323 patients by IHC.
HER-2 overexpression RESULTS:
was detected in 123 patients (31%) and high expression of VEGF in 233 (72%). The rate of HER-2 overexpression was significantly higher in patients with positive VEGF staining (35% vs. 21%, p=0.02). Overexpression of HER-2 was significantly associated with negative hormonal status, high histologic grade and larger tumors. HER-2 Markopoulos C - PubMed - NCBI overexpression was a significant negative predictor of DFS (p=0.002), but not of OS. Adjusting for HER-2 overexpression, DFS and OS did not significantly differ between treatment groups. Positive VEGF staining was not associated with receptor status, number of positive nodes, grade, tumor size, incidence of relapse or death. For both treatmen ts, HER-2 overexpression was a significant negative prognostic factor for DFS but not for OS, while high expression of VEGF was not significantly associated to either DFS or OS. No predictive ability of HER-2 status or VEGF overexpression for T treatment was evident. PMID: 16538542 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms, Substances
c J Chemother. 2006 Apr;18(2):192-8.
32. Mitoxantrone plus gemcitabine in pretreated patients
with metastatic breast cancer.
Onyenadum A, Gogas H, Kosmidis P, Aravantinos G, Bafaloukos D,
Bacoyiannis H, Markopoulos C, Koutras A, Tzorakoelefterakis E,
Makatsoris T, Fountzilas G, Kalofonos HP; Hellenic Cooperative Oncology
Group.
University of Patras School of Medicine, Patras, Greece.
Abstract
Gemcitabine and mitoxantrone have both shown significant antitumor
activity in patients with breast cancer. The aim of this study was to evaluate
the efficacy and safety of this combination as second or third-line treatment
in patients with metastatic breast cancer (MBC). Forty-six previously treated
patients with MBC were enrolled from June 2000 to November 2002. Mean
age was 56 years and ECOG performance status was < or =2. All patients
received mitoxantrone 10 mg/m2, D8 and gemcitabine 1000 mg/m2, D1+8
every 21 days for 6 cycles. There were no complete responders. Objective
response was observed in 12 patients (26%), 15 (33%) patients had stable
disease, 15 (33%) had progressive disease and 4 (9%) were non-evaluable.
At median follow-up of 27.8 months, overall survival was 13.3 months
(range 0.6-33.8+) and the median time to disease progression (TTP) was
4.4 months (range 0.2-33.8). Toxicities (grade 3-4) were as follows:
leukopenia 18 (39%), neutropenia 19 (41%), thrombocytopenia 4 (8.5%),
anemia 6 (13%) and alopecia 1 (2%). Febrile neutropenia was recorded in 2
(4%) patients. There were no treatment related deaths. The authors
conclude that the combination of mitoxantrone and gemcitabine is an
effective regimen in pretreated patients with metastatic breast cancer.
Toxicity was manageable.
PMID: 16736889 [PubMed - indexed for MEDLINE] Markopoulos C - PubMed - NCBI Publication Types, MeSH Terms, Substances
c N Engl J Med. 2006 Feb 16;354(7):709-18.
33. Prognostic significance of autoimmunity during
treatment of melanoma with interferon.
Gogas H, Ioannovich J, Dafni U, Stavropoulou-Giokas C, Frangia K,
Tsoutsos D, Panagiotou P, Polyzos A, Papadopoulos O, Stratigos A,
Markopoulos C, Bafaloukos D, Pectasides D, Fountzilas G, Kirkwood JM.
First Department of Medicine, Laiko Hospital, Athens, Greece. hgogas@hol.gr Abstract
BACKGROUND:
Immunotherapy for advanced melanoma induces
serologic and clinical manifestations of autoimmunity. We assessed the
prognostic significance of autoimmunity in patients with stage IIB, IIC, or III
melanoma who were treated with high-dose adjuvant interferon alfa-2b.
METHODS:
patients in a substudy of a larger, ongoing randomized trial. Blood was obtained before the initiation of intravenous interferon therapy, after 1 month of therapy, and at 3, 6, 9, and 12 months. Serum was tested for antithyroid, antinuclear, anti-DNA, and anticardiolipin autoantibodies, and patients were examined for vitiligo. The median duration RESULTS:
of follow-up was 45.6 months. Relapse occurred in 115 patients, and 82 patients died. The median relapse-free survival was 28.0 months, and the median overall survival was 58.7 months. Autoantibodies and clinical manifestations of autoimmunity were detected in 52 patients (26 percent). The median relapse-free survival was 16.0 months among patients without autoimmunity (108 of 148 had a relapse) and was not reached among patients with autoimmunity (7 of 52 had a relapse). The median survival was 37.6 months among patients without autoimmunity (80 of 148 died) and was not reached among patients with autoimmunity (2 of 52 died). In univariate and multivariate regression analyses, autoimmunity was an independent prognostic marker for improved relapse-free survival and overall survival (P<0.001). arance of autoantibodies or clinical manifestations of autoimmunity during treatment with interferon alfa-2b is associated with statistically significant improvements in relapse-free survival and overall survival in patients with melanoma. Copyright 2006 Massachusetts Medical Society. Comment in
N Engl J Med. 2006 Feb 16;354(7):758-60.
PMID: 16481638 [PubMed - indexed for MEDLINE] Free full text
Markopoulos C - PubMed - NCBI Publication Types, MeSH Terms, Substances
c Eur J Gynaecol Oncol. 2006;27(3):275-8.
34. Surgical management of nipple discharge.
Markopoulos C, Mantas D, Kouskos E, Antonopoulou Z, Lambadariou K,
Revenas K, Papachristodoulou A.
Breast Unit, 2nd Department of Propedeutic Surgery, Athens University School of
Medicine, Laiko General Hospital, Athens, Greece. Abstract
PURPOSE:
Nipple discharge is reported in 2.5-3% of women with breast
carcinoma. Breast carcinoma is found in approximately 8% of surgically
treated patients presenting with bloody nipple discharge (ND).
METHODS:
present study 110 women with ND as a presenting symptom were examined. The discharge was spontaneous in 76 and elicited in 11 patients. RESULTS:
rgical intervention benign breast disease was found in 85% of patients. Thirteen women (15%) were found to have malignancy and underwent additional surgery. Cytology of the discharge was positive or suspicious for malignancy in only seven out of 13 patients found to have in situ or invasive carcinoma. CONCLUSION: Women with spontaneous, single duct ND, especially when
it is darkish or bloody, should have cytological examination of the fluid and
mammography according to their age or additional clinical findings. Most of
them will require a microdochectomy, as the possibility of finding a
carcinoma among those women is between 10-15%. However, single duct
papilloma is the most common cause of bloody discharge.
PMID: 16800258 [PubMed - indexed for MEDLINE] MeSH Terms
c Eur J Gynaecol Oncol. 2006;27(3):262-6.
35. Wire localisation biopsy of non-palpable breast
lesions: reasons for unsuccessful excision.
Kouskos E, Gui GP, Mantas D, Revenas K, Rallis N, Antonopoulou Z,
Lampadariou E, Gogas H, Markopoulos C.
Surgical Department, Vostanio General Hospital of Mytilene, Lesvos Island Greece.
Abstract
Surgical excision following needle-wire localization of nonpalpable,
mammographically detected breast lesions is a very valuable diagnostic and
therapeutic procedure. No further treatment is usually required after
establishing an accurate histological benign diagnosis of indeterminate
lesions on preoperative assessment. On the other hand, ductal carcinoma
in-situ (DCIS) and early invasive cancer, properly excised, may sometimes
Markopoulos C - PubMed - NCBI require further management depending on specific histologic findings. An uncommon problem of this procedure is the failure to identify, localize or excise the breast lesion. In this review article, factors that contribute to the failed needle localization procedure are presented. PMID: 16800254 [PubMed - indexed for MEDLINE] MeSH Terms
c Oncology. 2006;70(4):301-5. Epub 2006 Oct 12.
36. Duration of tamoxifen effect on lipidemic profile of
postmenopausal breast cancer patients following
deprivation of treatment.

Markopoulos C, Chrissochou M, Antonopoulou Z, Xepapadakis G,
Papadiamantis J, Tzoracoleftherakis E, Gogas H.
Hellenic Breast Surgeons Society, Athens, Greece. cmarkop@hol.gr
Abstract
OBJECTIVE:
It was the aim of this study to investigate the effect of
tamoxifen withdrawal on markers of lipid metabolism in postmenopausal
women with breast cancer who completed tamoxifen therapy and received
no further treatment.
METHODS:
profile changes were studied in 190 postmenopausal patients with operable breast cancer, following cessation of 5-7 years of tamoxifen treatment. Assessments of total cholesterol, high-density lipoprotein, low-density lipoprotein and total serum triglycerides were performed at baseline, 6 months and 12 months. By 6 months, both total choles RESULTS:
terol and low-density lipoprotein levels were significantly increased, and total triglyceride levels were significantly reduced compared with baseline values and maintained to 12 months. There was no significant alteration observed for high-density lipoprotein levels over the study period. CONCLUSION: The beneficial effect of tamoxifen on the lipidemic profile of
postmenopausal breast cancer patients seems to be lost in less than 12
months time following cessation of 5-7 years of tamoxifen treatment. A
'rebound effect' on the lipidemic parameters should be expected and those
patients should be monitored carefully.
Copyright (c) 2006 S. Karger AG, Basel. PMID: 17047401 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms, Substances
c Ann Oncol. 2005 Dec;16(12):1861-6. Epub 2005 Jun 24.
37. Should women be advised to take prophylactic
Markopoulos C - PubMed - NCBI endocrine treatment outside of a clinical trial
setting?
Gogas H, Markopoulos C, Blamey R.
First Department of Internal Medicine, Athens Medical School, National and
Kapodistrian University of Athens, Athens, Greece. hgogas@hol.gr Abstract
Epidemiological, experimental and clinical data strongly support the
possibility that breast cancer can be prevented by using anti-estrogenic
interventions in healthy women. Four trials involving over 25,000 women
have so far been reported using tamoxifen 20 mg/day or placebo in healthy
women to chemoprevent breast cancer, and several trials utilizing raloxifene
or aromatase inhibitors are underway. Interim analyses of the Royal
Marsden tamoxifen trial and the Italian national trial showed no effect on the
early incidence of breast cancer. The NSABP-P1 showed a 49% reduction
in early incidence of breast cancer. This was associated with a reduction in
osteoporotic fractures but increases in the risks of endometrial cancer,
cataract and thromboembolism. The IBIS trial showed a 32% reduction with
a two-fold increase in endometrial cancer and in thromboembolic events.
Mortality rates of breast cancer in women receiving tamoxifen
prophylactically should be monitored and further follow-up of these trials is
needed to determine whether tamoxifen provides an overall health benefit or
increase specific or overall survival of breast cancer. High-risk women
should not be advised to take anti-estrogens outside of a clinical trial setting.
PMID: 15980159 [PubMed - indexed for MEDLINE] Free full text
Publication Types, MeSH Terms, Substances
c Acta Chir Belg. 2005 Nov-Dec;105(6):660-1.
38. Development of early malignant bilateral breast
disease in relation to antidepressant treatment.
Markopoulos C, Kouskos E, Phillipidis T.
Breast Unit-2nd Department of Propedeutic Surgery, Athens University Medical School, Laiko General Hospital, Athens, Greece. Abstract
The aim of this study is to present two rare cases of young female patients
who were under antidepressant medication and developed bilateral breast
disease; histology confirmed the noninvasive, malignant nature. The role of
that type of agents in the breast pathology is briefly discussed, based on the
data of the current literature.
PMID: 16438082 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms, Substances
Markopoulos C - PubMed - NCBI c Ann Oncol. 2005 Nov;16(11):1762-71. Epub 2005 Sep 7.
39. Postoperative dose-dense sequential chemotherapy
with epirubicin, followed by CMF with or without
paclitaxel, in patients with high-risk operable breast
cancer: a randomized phase III study conducted by
the Hellenic Cooperative Oncology Group.
Fountzilas G, Skarlos D, Dafni U, Gogas H, Briasoulis E, Pectasides D,
Papadimitriou C, Markopoulos C, Polychronis A, Kalofonos HP, Siafaka V,
Kosmidis P, Timotheadou E, Tsavdaridis D, Bafaloukos D, Papakostas P,
Razis E, Makrantonakis P, Aravantinos G, Christodoulou C, Dimopoulos
AM.
Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece.
fountzil@med.auth.gr Abstract
PURPOSE:
The aim of this study was to explore the effect of dose-dense
sequential chemotherapy with or without paclitaxel primarily on disease-free
survival (DFS) and secondarily on overall survival (OS) in patients with high-
risk operable breast cancer.
PATIENTS AND METHODS: From June 1997 until November 2000, 604
patients with T1-3N1M0 or T3N0M0 tumors were randomized to three
cycles of epirubicin 110 mg/m2 followed by three cycles of paclitaxel 250
mg/m2 followed by three cycles of 'intensified' CMF (cyclophosphamide 840
mg/m2, methotrexate 47 mg/m2 and fluorouracil 840 mg/m2) (group A), or
to four cycles of epirubicin followed by four cycles of CMF, as in group A
(group B). All cycles were given every 2 weeks with granulocyte colony-
stimulating factor support.
RESULTS: total of 595 patients were eligible. Median follow-up was 61.7
months for group A and 62 months for group B. The 3-year DFS was 80% in
group A and 77% in group B. Survival rates were 93% and 90%,
respectively. The effect of treatment on the hazard of death was different
according to hormonal receptor status. More specifically, in patients with
negative receptor status the hazard of death was significantly higher for
group B (hazard ratio 2.42). Both regimens were well tolerated and severe
acute side-effects were infrequent. No cases of severe cardiotoxicity or
acute leukemia were recorded.
present study failed to demonstrate a significant difference in DFS or OS between the two treatment groups. However, our study has shown clearly that high-dose paclitaxel can be safely incorporated to dose-dense sequential chemotherapy. PMID: 16148021 [PubMed - indexed for MEDLINE] Free full text
Publication Types, MeSH Terms, Substances,
Supplementary Concepts

Markopoulos C - PubMed - NCBI c Anticancer Drugs. 2005 Sep;16(8):879-83.
40. Effect of exemestane on the lipidemic profile of post-
menopausal operable breast cancer patients
following 5-7 years of adjuvant tamoxifen:
preliminary results of the ATENA substudy.

Markopoulos C, Chrissochou M, Michailidou A, Tzoracoleftherakis E,
Xepapadakis G, Papadiamantis J, Misitzis J, Zobolas V, Bafaloukos D,
Gogas H.
Hellenic Breast Surgeons Society, Greece. cmarkop@hol.gr
Abstract
Long-term endocrine therapy for breast cancer may have clinical
implications as drugs that potentially alter the lipid profile may increase the
risk of developing cardiovascular disease. In this study, a companion
subprotocol to the ATENA (Adjuvant post-Tamoxifen Exemestane versus
Nothing Applied) trial, we compared the effect of the steroidal aromatase
inactivator exemestane on the lipid profile of post-menopausal women with
operable breast cancer in the adjuvant setting to that of observation alone
following deprivation of 5-7 years primary treatment with tamoxifen. In this
open-label, randomized, parallel group study, 340 post-menopausal patients
with operable breast cancer who had been treated with tamoxifen for 5-7
years were randomized to either 5 additional years of exemestane (25
mg/day; n=172) or observation alone (n=168). Assessments of total
cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL)
and total serum triglycerides (TRG) were performed at baseline, and at 6
and 12 months. Total TRG levels were significantly reduced compared with
baseline for the exemestane and the observational arm. Both total
cholesterol and LDL levels were significantly increased above that of
baseline values by 6 months, maintained through to 12 months, with no
significant difference between the two treatment arms. There was no
significant alteration observed for HDL over time or between the two arms.
We conclude that sequential adjuvant treatment with exemestane in post-
menopausal operable breast cancer patients following cessation of 5-7
years of tamoxifen does not appear to significantly alter the lipidemic profile
for at least 12 months compared with an observational arm.
PMID: 16096437 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms, Substances
c Breast Cancer Res Treat. 2005 Sep;93(1):61-6.
41. The effect of exemestane on the lipidemic profile of
postmenopausal early breast cancer patients:
preliminary results of the TEAM Greek sub-study.

Markopoulos C, Polychronis A, Zobolas V, Xepapadakis G, Papadiamantis
J, Koukouras D, Lappas H, Gogas H.
Markopoulos C - PubMed - NCBI Hellenic Breast Surgeons Society (HBSS), 8 Iassiou Street, Athens, Attica 11521, Greece. cmarkop@hol.gr Abstract
INTRODUCTION:
Long-term endocrine therapy for breast cancer may have
clinical implications as drugs that potentially alter the lipid profile may
increase the risk of developing cardiovascular disease. In this study, a
companion sub-protocol to the TEAM (Tamoxifen and Exemestane Adjuvant
Multicenter) International trial, we compared the effect of the steroidal
aromatase inactivator exemestane on the lipid profile of postmenopausal
women with early breast cancer in the adjuvant setting to that of tamoxifen.
PATIENTS AND METHODS: In this open-label, randomized, parallel group
study, 176 postmenopausal patients with estrogen and/or progesterone
receptor positive early breast cancer were randomized to either adjuvant
exemestane (25 mg/day; n = 90) or tamoxifen (20 mg/day; n = 86).
Assessments of total cholesterol, high-density lipoprotein (HDL), low-density
lipoprotein (LDL) and serum triglycerides (TRG) were performed at baseline
and every 3 months for the first 12 months.
Serum triglyceride RESULTS:
levels were consistently increased above baseline throughout the study in the tamoxifen arm, while there was a trend towards reduction in the exemestane arm. There was also an overall trend for tamoxifen to decrease the levels of LDL throughout the study period. Exemestane did not demonstrate any other significant change in HDL levels; however, there was a consistent trend for a reduction in total cholesterol in both treatment arms. The atherogenic risk determined by the TC:HDL ratio remained stable in both arms throughout the treatment period. appears to have a neutral effect on total cholesterol and HDL levels. Unlike tamoxifen's positive effect on LDL levels, exemestane does not significantly alter LDL levels. Tamoxifen on the other hand increases triglyceride levels, while exemestane results in a beneficial reduction in TRG levels. These data offer additional information with regard to the safety and tolerability of exemestane in postmenopausal breast cancer patients and support further investigation of its potential usefulness in the adjuvant setting. PMID: 16184460 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms, Substances
c Breast Cancer Res Treat. 2005 Jul;92(1):1-9.
42. Paclitaxel and carboplatin as first-line chemotherapy
combined with gefitinib (IRESSA) in patients with
advanced breast cancer: a phase I/II study
conducted by the Hellenic Cooperative Oncology
Group.
Fountzilas G, Pectasides D, Kalogera-Fountzila A, Skarlos D, Kalofonos
Markopoulos C - PubMed - NCBI HP, Papadimitriou C, Bafaloukos D, Lambropoulos S, Papadopoulos S,
Kourea H, Markopoulos C, Linardou H, Mavroudis D, Briasoulis E, Pavlidis
N, Razis E, Kosmidis P, Gogas H.
AHEPA Hospital, School of Medicine, Aristotle University of Thessaloniki, Nea
Efkarpia, 56249 Thessaloniki, Greece. fountzil@med.auth.gr Abstract
Paclitaxel (Taxol) and carboplatin are an effective combination regimen for
treating advanced breast cancer. Gefitinib (IRESSA) is the first epidermal
growth factor receptor tyrosine kinase inhibitor to be approved for cancer
treatment. This multicenter phase II trial treated 68 patients with advanced
breast cancer with paclitaxel (175 mg/m(2) over 3 h) and 3-weekly
carboplatin (area under the curve of 6) for six cycles, and 250 mg/day
gefitinib orally. Median age was 57 (range 35-77) years, patients had
performance status 0 (69.1%), 1 (27.9%) 2 (2.9%), 82.4% of patients had
visceral metastases and 63.2% had received adjuvant chemotherapy. Forty-
eight (70.6%) patients completed six cycles of chemotherapy and 20
(29.4%) patients discontinued treatment (seven [10.3%] due to disease
progression, seven [10.3%] due to toxicity, five [7.4%] withdrew consent and
one [1.5%] died after the first cycle). Sixty-three (92.7%) patients were
evaluable for response; nine (13.2%) had complete responses, 30 (44.1%)
had partial responses, 21 (30.9%) had stable disease and three (4.4%) had
disease progression. Grade 3/4 adverse events in > or =5% of patients
except of alopecia, included neutropenia (17.7%), anemia (10.3%), diarrhea
(7.4%), thrombocytopenia (5.9%) and peripheral neuropathy (5.9%). Of
those tumor biopsies available for immunohistochemical analysis (n=60),
5.0% were positive and 35.0% negative for expression of all HER-family
receptors. Comparable numbers of tumor biopsies were nuclear p27(kipl)
positive and negative (39.7 and 42.7%, respectively), with the majority
(72.1%) negative for cytoplasmic p27(kipl). The observed efficacy data in
this study were similar to those reported for the combination of paclitaxel
and carboplatin alone.
PMID: 15980985 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms, Substances
c Clin Genet. 2005 Apr;67(4):322-9.
43. Identification of germline BRCA1 and BRCA2 genetic
alterations in Greek breast cancer moderate-risk and
low-risk individuals--correlation with
clinicopathological data.
Kataki A, Gomatos I, Pararas N, Armakolas A, Panousopoulos D,
Karantzikos G, Voros D, Zografos G, Markopoulos C, Leandros E,
Konstadoulakis M.
Laboratory of Surgical Research, Hippokarteion Hospital of Athens, Athens,
Greece. labsures@med.uoa.gr Markopoulos C - PubMed - NCBI Abstract
The current study was designed to evaluate the prevalence of BRCA1 and
BRCA2 germline mutations in Greek moderate- and low-risk individuals with
respect to clinicopathological phenotype and clinical outcome of breast
cancer. Ninety-four consecutive individuals were prospectively recruited
from two University Breast Cancer Clinics (Hippokrateion Hospitan and
Laikon Hospital) between 1989 and 1999 and were categorized as
moderate-risk and low-risk individuals for carrying BRCA1/2 germline
mutations. To identify the underlying mutations, protein-truncation test and
single-strand conformation polymorphism methods were used, followed by
direct sequencing. Three novel BRCA1 missense mutations, one novel
BRCA1 intronic deletion, three novel (previously reported) BRCA2
truncating mutations, and one novel BRCA2 missense mutation were
identified in the moderate-risk group of individuals studied. The BRCA1/2
missense mutations as well as the single intronic variant identified were
designated as unclassified genetic variants. Two BRCA1 unclassified
genetic variants (missense mutations) were detected in two of the three
(66.7%) male breast cancer patients analyzed, while the third one was
identified in a sporadic (low-risk) breast cancer patient. Clinicopathological
characteristics of breast carcinomas originating from BRCA1/2
heterozygotes were consistent with those already reported and not different
from those observed in BRCA1/2 mutation (-) breast cancer patients.
Furthermore, BRCA1/2 mutation carriers presented an excellent 4.5-year
overall survival (100%). Our results reveal the unique characteristics of
BRCA1/2 mutation status, genotype-phenotype correlations, and prognosis,
in moderate- and low-risk individuals of Greek ancestry. Breast cancer due
to mutations in BRCA1 and BRCA2 genes appears to be a heterogeneous
syndrome in the Greek population.
PMID: 15733268 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms, Substances
c Eur J Gynaecol Oncol. 2005;26(3):311-4.
44. Open surgical biopsy for nonpalpable breast lesions
detected on screening mammography.
Markopoulos C, Kouskos E, Revenas K, Mantas D, Antonopoulou Z,
Kontzoglou K, Nikiteas N, Kyriakou V.
Breast Unit, 2nd Department of Propedeutic Surgery, Athens Medical School, Laiko
General Hospital, Greece. Abstract
The aim of this retrospective clinical study was the analysis of histologic
findings of nonpalpable breast lesions managed by open surgical biopsy. A
series of 630 women underwent 664 preoperative localizations of
nonpalpable, mammographically detected breast lesions during the last 10-
year period. Indications for biopsy were (1) clustered microcalcifications, (2)
Markopoulos C - PubMed - NCBI solid mass, and (3) radiologic parenchymal distortion. The lesions were localized preoperatively using hook-wire methods, and all biopsies were performed under general anesthesia. Histopathology revealed carcinoma in 172 (25.9%) cases; noninvasive in 114 (66.3%) cases and infiltrating in 58 (33.7%) cases. The highest malignancy rate was found in cases with microcalcifications (112 carcinomas out of 323 cases, 34.7%). Lymph node invasion was present in 25% of patients with invasive cancers. The hook-wire localization of nonpalpable breast lesions is a simple, accurate and safe method for detection of early breast cancers. Frozen section is feasible and accurate in the majority of these lesions, and therefore, diagnostic and therapeutic one-step surgical procedures could be performed. PMID: 15991535 [PubMed - indexed for MEDLINE] MeSH Terms
c Eur J Gynaecol Oncol. 2005;26(2):213-4.
45. Mondor's disease of the breast: is there any relation
to breast cancer?
Markopoulos C, Kouskos E, Mantas D, Kakisis J, Antonopoulou Z,
Kontzoglou K, Nikiteas N.
Breast Unit--2nd Department of Propedeutic Surgery, Athens University Medical
School, Laiko General Hospital, Athens, Greece. Abstract
Ten cases of Mondor's disease of the breast (9 females, 1 male) are
described. The diagnosis was based mainly on clinical examination, while
breast imaging, used in five cases, was complementary. Most of our cases
(9) had complete restoration of the thrombosed subcutaneous breast vein,
either spontaneously (4), or after anti-inflammatory medication (5). Only one
of our patients had surgical management (vein excision) due to delayed
remission. None of our cases was related to breast cancer.
PMID: 15857034 [PubMed - indexed for MEDLINE] MeSH Terms
c Acta Radiol. 2004 Nov;45(7):726-9.
46. Breast arterial calcifications as an indicator of
systemic vascular disease.
Markopoulos C, Mantas D, Revenas K, Kouskos E, Tzonou A, Liapis C,
Kostakis A.
Breast Unit, 2nd Department of Propedeutic Surgery, Athens University School of
Medicine, Laiko General Hospital, Athens, Greece. cmarkop@hol.gr Abstract
PURPOSE:
To evaluate the association between mammographically
detected arterial calcifications and systemic vascular disease.
Markopoulos C - PubMed - NCBI MATERIAL AND METHODS: The medical records of 77 women who had
either breast arterial calcifications or underwent surgery for carotid stenosis,
abdominal aortic aneurysm, or femoropopliteal bypass (study groups A and
B) were evaluated and compared with 33 women without breast arterial
calcifications (group C). Patients in both arms of the study underwent
additional vascular tests or mammography.
Currently availab RESULTS:
le data indicate that there is a statistically significant correlation between the presence of arterial calcifications on the mammogram and atheromatosis of the carotid or femoral arteries. CONCLUSION: Screening mammograms might be useful in the detection of
women at risk for systemic vascular disease.
PMID: 15624515 [PubMed - indexed for MEDLINE] MeSH Terms
c J Clin Endocrinol Metab. 2004 Mar;89(3):1102-7.
47. Adiponectin and breast cancer risk.
Mantzoros C, Petridou E, Dessypris N, Chavelas C, Dalamaga M, Alexe
DM, Papadiamantis Y, Markopoulos C, Spanos E, Chrousos G,
Trichopoulos D.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Beth
Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA. Abstract
Adiponectin, an adipocyte-secreted hormone, is closely and inversely
associated with insulin resistance and was recently found to be inversely
and independently associated with endometrial cancer. Because insulin
resistance in the setting of obesity has also been associated with the
development of breast cancer, we have hypothesized that decreased
adiponectin levels might underlie the association between breast cancer
and obesity/insulin resistance. We evaluated the association of adiponectin
with the occurrence of breast cancer in a case-control study comprising 174
women with newly diagnosed, histologically confirmed breast cancer and
167 controls. We found an inverse, fairly strong, and statistically significant
association of serum adiponectin with breast cancer (odds ratio, 0.84; 95%
confidence interval, 0.71-0.99). Importantly, despite a fairly robust inverse
association of adiponectin with breast cancer risk among postmenopausal
women (odds ratio, 0.82; 95% confidence interval, 0.67-1.00), no such
significant association between adiponectin and breast cancer was found
among premenopausal women. The observed associations were
independent of possible effects of major components of the IGF system,
leptin, body mass index, sociodemographic variables, and known risk
factors for breast cancer. Future studies are needed to prove causality and
provide further insights into both the mechanisms underlying the actions of
this hormone and its potential role in breast cancer.
Markopoulos C - PubMed - NCBI PMID: 15001594 [PubMed - indexed for MEDLINE] Free full text
MeSH Terms, Substances
c Eur J Gynaecol Oncol. 2004;25(4):495-7.
48. Fibroadenomas of the breast: is there any
association with breast cancer?
Markopoulos C, Kouskos E, Mantas D, Kontzoglou K, Antonopoulou K,
Revenas Z, Kyriakou V.
Breast Unit-2nd Surgical Department, School of Medicine-Laiko Hospital, Athens,
Abstract
PURPOSE:
The experience of our Breast Unit in the diagnosis and
treatment of fibroadenomas is presented in this retrospective study,
focusing specifically in cancer development within these common benign
tumors of young age.
histologically verified breast fibroadenomas who had surgical management in our Unit over the last 14 years were included in the study. RESULTS:
(n: 255) presented with palpable lesions and had triple assessment preoperatively, while the remaining 55 had nonpalpable lesions and underwent needle-wire localization biopsies. Nine cases had cancer development, usually in situ, within the fibroadenomas (2.9%). CONCLUSION: Coexistence of fibroadenomas and breast cancer is
relatively rare, but it should not be ignored by breast surgeons, and patients
should be properly informed.
PMID: 15285313 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms
c Eur J Gynaecol Oncol. 2004;25(3):391-3.
49. Solitary spleen metastasis and amyloidosis in a
patient with endometrial cancer.
Gogas H, Ignatiadis T, Markopoulos Ch, Karageorgopoulou S, Floros D,
Vaiopoulos G.
1st Department of Medicine, National and Kapodistrian University of Athens, Laikon
General Hospital, Athens, Greece. Abstract
BACKGROUND:
In contrast to autopsy findings, solitary splenic metastases
from solid tumors are extremely rare. It may occasionally be the first
manifestation of recurrent solid cancers, and in particular of gynecologic
Markopoulos C - PubMed - NCBI malignancies. Secondary amyloidosis is also found in malignancy. CASE: A 52-year-woman originally diagnosed with a Stage IB, grade 2
endometrial carcinoma presented two and a half years later with a
paroxysmal non-productive cough, weakness, loss of appetite and daily
afternoon fever. On clinical examination wheezing on forced exhalation and
painful splenomegaly was found. After an extensive work-up the patient
underwent an explorative laparotomy and a splenectomy was performed.
Histologic examination showed solitary spleen metastasis with amyloidosis.
All symptoms resolved. As the patient had received a full course of
postoperative irradiation after a total abdominal hysterectomy, six cycles of
combination chemotherapy were administered. The patient remains free of
recurrence, 46 months later.
CONCLUSION: A case of solitary spleen metastasis with amyloidosis in a
patient with endometrial cancer is presented.
PMID: 15171329 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms
c Eur J Gynaecol Oncol. 2004;25(2):230-2.
50. Missed cancers on mammograms: causes and
measures of prevention.
Kouskos E, Markopoulos C, Mantas D, Revenas K, Antonopoulou Z,
Kontzoglou K, Gogas J.
Breast Unit, 2nd Department of Propedeutic Surgery, Medical School-Laiko General
Hospital of Athens, Greece. Abstract
Mammographically missed breast cancers remain a major medical and legal
issue. In order to clarify causes and methods of the limitations, we present
the experience of our Unit on this field. During the years 1999 and 2000,
319 breast cancer patients were admitted for surgical treatment to our Unit.
Their files were reviewed in order to identify cases with mammography-
related delayed diagnosis. Thirty-three cases of mammographically missed
cancers were found (10.3%). The usual reasons for the delayed diagnoses
were: retrospectively visible cancers, in benign looking lesions no further
action was taken, and lesions with a rather malignant appearance were
reported as benign. Missed cancers could be reduced by simple measures
such as the full assessment of breast patients with clinical, radiologic, and
cytologic-histologic evaluation, the double screening of mammograms, and
improvement of the mammographic equipment and technique.
PMID: 15032289 [PubMed - indexed for MEDLINE] MeSH Terms
c J Chemother. 2003 Dec;15(6):607-12.
51. Full dose paclitaxel plus vinorelbine as salvage
Markopoulos C - PubMed - NCBI chemotherapy in anthracycline-resistant advanced
breast cancer: a phase II study.
Polyzos A, Tsavaris N, Kosmas C, Gogas H, Toufexi H, Kosmidis C,
Markopoulos C, Giannopoulos A, Papadopoulos O, Stamatiadis D,
Kouraklis G.
Medical Oncology Unit, Laikon General Hospital, Athens University School of
Medicine, 17 Agiou Thoma Street, Goudi, Athens, Greece. Abstract
This phase II trial studied the efficacy and toxicity of full dose paclitaxel plus
vinorelbine, as salvage chemotherapy in patients with metastatic breast
cancer resistant to anthracyclines. Patients received vinorelbine (30 mg/m2)
followed 1 hour later by full dose paclitaxel (175 mg/m2) every 3 weeks for a
maximum of 8 cycles or until disease progression. Because of the heavy
pretreatment of the patients, prophylactic granulocyte-colony stimulating
factor (5 microg/kg) was administered daily for 5-10 days. To minimize
potentially cumulative neurotoxicity due to both agents, amifostine was
given prior to chemotherapy. Thirty-four patients: 8 with tumors primary
resistant and 26 with tumors recurring within 3-6 months after anthracycline
treatment, were evaluable for efficacy and toxicity. Objective responses
occurred in 11 patients [32%; 95% confidence interval (CI): 16.3-47.7%), all
partial responses. Responses were observed in lung and liver. The median
response duration was 4 months (range 3-7), median time to progression
was 5 months (range 3-9) and median overall survival was 8 months (range
4-24). Neutropenia was dose limiting (35% grade 3-4 toxicity). The left
ventricular ejection fraction, measured and followed in 18 patients, fell less
than 20% below baseline level in 9 patients (50%), but only one patient
developed congestive cardiac failure. The paclitaxel-vinorelbine regimen
was moderately tolerated and moderately effective in poor prognosis breast
cancer patients with visceral metastases and tumors resistant to
anthracyclines. The combination at these doses and schedules should be
considered in the design of regimens for advanced breast cancer.
PMID: 14998089 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms, Substances
c Acta Chir Belg. 2003 Nov-Dec;103(6):626-30.
52. Pre-operative Tc-99m-sestamibi scanning and intra-
operative nuclear mapping: are they accurate in
localizing parathyroid adenomas?
Gogas J, Kouskos E, Mantas D, Markopoulos C, Kyriaki D, Tseleni-
Balafouta S, Gogas H, Kostakis A.
2nd Department of Propedeutic Surgery, 1st Department of Internal Medicine,
Departments of Nuclear Medicine and Pathology, Athens University Medical School-Laiko General Hospital, 17 Ag. Thomas Str.-115 27 Athens, Greece. Markopoulos C - PubMed - NCBI Abstract
PURPOSE:
Presentation of the results of Tc-99m-sestamibi imaging in the
pre-operative localization of parathyroid adenomas and the intra-operative
localization of those lesions using a gamma detector (prospective study).
PATIENTS & METHODS: Eighteen consecutive patients aged 27-75
years with primary hyperparathyroidism (PHPT) underwent Tc-99m-
sestamibi scanning 1-2 hours before the operation and the presence of a
single adenoma was recognized. All our patients underwent bilateral neck
exploration based on pre-operative scanning and intra-operative gamma
detector guidance and the adenoma was detected in the positions shown by
both methods.
RESULTS:
16 patients we found a single adenoma localized in the same position shown by pre-operative scanning, while the intra-operative method accurately revealed all abnormal glands. In one of the two patients where an inaccurate pre-operative localization technique had been carried out, we performed thyroid lobectomy (the adenoma proved to be intrathyroidal), while the other one had an adenoma which was not close to the site indicated by the pre-operative scintigraphy. Serum calcium reverted to normal within a few days postoperatively. CONCLUSION: Patients with true-positive scans for single parathyroid
adenoma could be eligible for minimally invasive operations since the
abnormal gland is easily identified by the above-mentioned methods.
PMID: 14743573 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms, Substances
c Breast. 2003 Jun;12(3):172-8.
53. Immunohistochemical evaluation of immune
response in invasive ductal breast cancer of not-
otherwise-specified type.
Vgenopoulou S, Lazaris AC, Markopoulos C, Boltetsou E, Kyriakou V,
Kavantzas N, Patsouris E, Davaris PS.
Department of Pathology, School of Medicine, The Athens National and
Kapodistrian University, 75 Mikras Asias Str., Goudi, GR-115 27, Athens, Greece. Abstract
We investigated endotumoral and peritumoral lymphocytic subsets [natural
killer cells (NK), B-cells and cytotoxic/suppressor (CD(8)+) T-cells], and
expression of MUC1 and MUC6 glycoprotein with regard to various
clinicopathological parameters in invasive breast cancer tissues. The study
population consisted of 64 female patients with invasive ductal breast
cancer of not-otherwise-specified type. Thirty-five women with benign breast
lesions served as controls. High-grade carcinomas exhibited higher
numbers of endotumoral NK cells and B-cell aggregates than the rest of the
tumors examined (P=0.0003 and 0.027, respectively). Cases with more than
three positive lymph nodes and with tumors over 2 cm in diameter exhibited
higher numbers of endotumoral NK cells (P=0.047 and 0.023, respectively).
Markopoulos C - PubMed - NCBI Increased numbers of peritumoral CD(8)+ T-cells were detected in cases with lymph node metastases (P=0.045). MUC1 was expressed with weaker staining intensity in the control group than in the group with breast cancer (P=0.011). Grade III carcinomas exhibited significantly stronger expression of MUC6 glycoprotein (P=0.001) than the control group. In conclusion, tumors with markers of poor prognosis exhibited increased numbers of lymphocytic infiltrates, and of NK cells in particular, and stronger MUC1 and MUC6 glycoprotein immunoreactivity than did the other tumors. PMID: 14659323 [PubMed - indexed for MEDLINE] MeSH Terms, Substances
c Anticancer Res. 2003 May-Jun;23(3C):2917-23.
54. Docetaxel and epirubicin supported by granulocyte
colony-stimulating factor first-line in advanced
breast cancer.
Polyzos A, Tsavaris N, Kosmas C, Gogas H, Vadiaka M, Markopoulos C,
Giannopoulos A, Kalahanis N, Stamatiadis D, Kouraklis G, Karatzas G,
Liapis C, Syrigos K.
Medical Oncology Unit, Laikon General Hospital, Athens University School of
Medicine, 17 Agiou Thoma Street, Goudi, GR 11527, Athens, Greece. Abstract
This phase II trial studied the efficacy and toxicity of docetaxel-epirubicin,
supported by granulocyte colony-stimulating factor, as first-line
chemotherapy in metastatic breast cancer. Patients received epirubicin (60
mg/m2) followed 1 hour later by docetaxel (80 mg/m2) every 3 weeks for a
maximum of 8 cycles or until disease progression. Prophylactic granulocyte
colony-stimulating factor (5 micrograms/kg) was administered daily for 5
days. Sixty-nine patients were evaluable for efficacy and toxicity. Objective
responses occurred in 45 patients (65%; 95% confidence interval: 53-76%),
with 11 (16%) complete responses and 34 (49%) partial responses.
Responses were observed at all metastatic sites. The median response
duration was 8 months (range 4-68), median time to progression was 10
months (range 4-68) and median overall survival was 24 months (range 7-
68): neutropenia was dose limiting (46% grade 3-4 toxicity). The left
ventricular ejection, fraction measured in 50 patients, fell below normal in 14
patients (28%), 8 patients had grade 1 and 6 grade 2 cardiotoxicity, but
none developed congestive cardiac failure. The docetaxel-epirubicin
regimen is extremely effective in poor prognosis breast cancer patients with
visceral metastases, with significant overall and complete responses,
followed by prolonged survival in responders. Although myelosuppression
remains the major toxicity, prophylactic GCSF administration was
associated with a small percentage of neutropenic fever.
PMID: 12926135 [PubMed - indexed for MEDLINE] Markopoulos C - PubMed - NCBI Publication Types, MeSH Terms, Substances
c Breast J. 2003 May-Jun;9(3):255-6.
55. Adenosis tumor of the breast.
Markopoulos C, Kouskos E, Phillipidis T, Floros D.
PMID: 12752642 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms
c Acta Radiol. 2003 Jan;44(1):43-6.
56. Computer-aided preoperative diagnosis of
microcalcifications on mammograms.
Kouskos E, Markopoulos C, Revenas K, Koufopoulos K, Kyriakou V,
Gogas J.
Breast Unit, 2nd Department of Propedeutic Surgery, University Medical School,
Laiko General Hospital of Athens, Greece. skouskos@hotmail.com Abstract
PURPOSE:
To evaluate of a computer-aided method for differentiating
malignant from benign clustered microcalcifications.
MATERIAL AND METHODS: Our material was 350 suspicious
microcalcifications on mammograms from 330 female patients who
underwent breast biopsy (after hook wire localization and under
mammographic guidance). The histologic findings were malignant in 140
cases (40%) and benign in 210 cases (60%). Those clusters were manually
detected, computer-aided analyzed and quantitatively estimated. Besides
computer analysis, 3 physicians-observers (2 radiologists and 1 breast
surgeon) evaluated the malignant or benign nature of the clustered
microcalcifications. The performance of the artificial network, each observer
and the three observers as a group was evaluated by receiver operating
characteristics (ROC) curves.
RESULTS: Comparison of the ROC curves revealed the following AUC
values (area under the curve): computer - 0.950, physician 1 - 0.815,
physician 2 - 0.830, physician 3 - 0.830, and physicians as a group - 0.825.
The results, compared by the student t-test for paired data, showed a
statistically significant difference between computer analysis and physicians'
performance, independently and as a group.
CONCLUSION: Our study showed that computer analysis achieved
statistically significantly better performance than that of physicians in the
classification of malignant and benign calcifications.
PMID: 12630997 [PubMed - indexed for MEDLINE] Markopoulos C - PubMed - NCBI Publication Types, MeSH Terms
c Eur J Gynaecol Oncol. 2003;24(1):93-5.
57. Carcinosarcoma of the breast: report of two cases.
Gogas J, Kouskos E, Markopoulos C, Mantas D, Antonopoulou Z,
Kontzoglou K, Stamoulis J, Kyriakou V.
2" Department of Propedeutic Surgery, Athens University Medical School, "Laiko "
General Hospital, Athens, Greece. Abstract
Carcinosarcoma is a rare, malignant tumor of the breast, consisting of
intraductal or infiltrating carcinoma contiguous or subtly merged with a
highly cellular, mitotically active pleomorphic spindle cell stroma (sarcoma).
It is a form of the metaplastic mammary carcinomas and it is probably
derived of myoepithelial cells. We report two cases of breast
carcinosarcoma in two white women. The patients, following a frozen
section positive for malignancy, had had a modified radical mastectomy.
Paraffin sections and positive immunohistochemical cell staining (in our first
case) confirmed the diagnosis of carcinosarcoma. This tumor should be
distinguished from other forms of metaplastic carcinomas because it is very
aggressive and has an ominous prognosis.
PMID: 12691330 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms
c Surg Today. 2003;33(2):135-7.
58. Metastatic melanoma in the gallbladder: report of a
case.
Gogas J, Mantas D, Gogas H, Kouskos E, Markopoulos C, Vgenopoulou
S.
Second Department of Propedeutic Surgery, Athens University School of Medicine,
Laiko General Hospital, Ag. Thomas Str. 17, 115-27 Goudi, Athens, Greece. Abstract
Both primary and secondary gallbladder melanomas are rare and, when a
solitary melanoma is found in the gallbladder, it is difficult to determine if it is
primary or metastatic disease. We report the case of a young woman found
to have a single metastatic gallbladder melanoma. Surgical removal of a
solitary metastatic focus remains the treatment of choice for isolated
metastasis of a malignant melanoma; however, the effectiveness of
complementary chemotherapy and immunotherapy is still being examined.
PMID: 12616378 [PubMed - indexed for MEDLINE] Markopoulos C - PubMed - NCBI Publication Types, MeSH Terms
c Ann Oncol. 2002 Nov;13(11):1737-42.
59. Neoadjuvant chemotherapy with a combination of
pegylated liposomal doxorubicin (Caelyx) and
paclitaxel in locally advanced breast cancer: a phase
II study by the Hellenic Cooperative Oncology Group.
Gogas H, Papadimitriou C, Kalofonos HP, Bafaloukos D, Fountzilas G,
Tsavdaridis D, Anagnostopoulos A, Onyenadum A, Papakostas P,
Economopoulos T, Christodoulou C, Kosmidis P, Markopoulos C.
First Department of Medicine, Laiko Hospital, University of Athens, Greece.
Abstract
BACKGROUND:
To determine the activity and safety of the combination of
paclitaxel and pegylated liposomal doxorubicin (Caelyx) in patients with
locally advanced breast cancer.
PATIENTS AND
METHODS:
a multicenter phase II study. Thirty- five newly diagnosed patients with locally advanced breast cancer were included in the study. Histological or cytological diagnosis was necessary for inclusion. Median age was 54 years (range 26-73 years). Fifteen patients were premenopausal and 20 postmenopausal. Paclitaxel was administered at a dose of 175 mg/m(2) and pegylated liposomal doxorubicin 35 mg/m(2) every 3 weeks for six cycles. Twenty-five patients (71% RESULTS:
) responded. Six (17%) had a complete response, 19 (54%) had a partial response, four remained stable, two progressed and four were not evaluated for response due to discontinuation of chemotherapy. Three patients had a pathologically complete response. A total of 173 cycles were administered. The primary toxicity observed was skin toxicity. Grade 3 skin toxicity was noted in four patients (11%). Palmar-plantar erythrodysesthesia (PPE) grade 3 was experienced by three (9%). Two patients presented with PPE and skin toxicity. Hematological toxicities included grade 3 leukopenia in four patients (3%). Other grade 3 toxicities were uncommon and included only alopecia in 29 patients (83%). Grade 3 or 4 neurotoxicity was not observed in any patient. Dose reduction was necessary in seven patients; in six due to skin toxicity and in one due to neutropenia. Four patients discontinued treatment due to skin toxicity. There were no treatment-related deaths. combination of pegylated liposomal doxorubicin and paclitaxel was active in locally advanced breast cancer. The primary toxicity was cutaneous toxicity and it was manageable. PMID: 12419745 [PubMed - indexed for MEDLINE] Free full text
Markopoulos C - PubMed - NCBI Publication Types, MeSH Terms, Substances
c Am Surg. 2002 Sep;68(9):783-6.
60. Diagnosis and treatment of intracystic breast
carcinomas.
Markopoulos C, Kouskos E, Gogas H, Kakisis J, Kyriakou V, Gogas J,
Kostakis A.
Second Department of Propedeutic Surgery, Athens University Medical School,
Laiko General Hospital, Greece. Abstract
Cystic breast masses are very common in female patients attending breast
clinics. Most of them are benign and managed by simple aspiration. We
reviewed histology records for the last 12 years to find patients with cystic
breast carcinomas and to evaluate special clinical signs that may help to
identify patients with this rare entity. Eighteen patients with cystic breast
carcinomas were found among 1510 new breast cancer patients (1.19%)
who were seen at our Breast Unit during this period. Ten had intracystic
papillary carcinoma (0.66% of all breast cancers), seven had cystic
degeneration of ductal carcinoma, and one had a mucinous carcinoma. The
diagnosis of intracystic papillary carcinoma was based on cyst fluid cytology
and breast imaging in most patients and on open breast biopsy in two cases
only. The prognosis of our cystic breast carcinoma patients was excellent
regardless of the specific histologic type of the tumor. We conclude that
cysts in postmenopausal women should be viewed with suspicion.
Bloodstained aspirated cyst fluid should be sent for cytology and breast
imaging should be carried out in all these cases. Residual mass after cyst
aspiration is also an indication for open biopsy.
PMID: 12356150 [PubMed - indexed for MEDLINE] MeSH Terms, Substances
c Cancer. 2002 May 1;94(9):2454-65.
61. High expression levels of p27 correlate with lymph
node status in a subset of advanced invasive breast
carcinomas: relation to E-cadherin alterations,
proliferative activity, and ploidy of the tumors.
Kouvaraki M, Gorgoulis VG, Rassidakis GZ, Liodis P, Markopoulos C,
Gogas J, Kittas C.
Laboratory of Histology and Embryology, University of Athens School of Medicine,
Abstract
BACKGROUND:
The cyclin-dependent kinase inhibitor p27 plays a central
role in cell cycle progression and is deregulated in breast carcinomas.
Although its levels are inversely associated with tumor proliferation,
Markopoulos C - PubMed - NCBI overexpression of p27 has been reported in a subset of rapidly proliferating breast carcinoma cell lines. METHODS:
determined by immunohistochemistry in a series of 52 sporadic invasive breast carcinomas consisting of 47 ductal, 2 lobular, and 3 mixed; most tumors were Grade 2 or 3 (46 of 52) and Tumor Node Metastasis (TNM) Stage II-IV (46 of 52). E-cadherin expression and its gene alterations at 16q22.1 were also studied, because in vitro evidence suggests a biologic association between p27 and E-cadherin-mediated growth suppression. RESULTS:
labeling index (LI; percentage of p27 positive tumor cells) was 33.3% +/- 25.3% (range, 0.1-85%). High p27 levels (p27 LI, > 50%) were observed in 14 (26.9%) of 52 carcinomas and were significantly associated with metastatic disease in axillary lymph nodes (14 of 33 vs. 0 of 19; P = 0.0007 by Fisher exact test). In addition, p27 LI was higher in the group of lymph node positive vs. lymph node negative tumors (mean p27 LI, 40.9% vs. 20.1%; P = 0.008 by Mann-Whitney test). Reduced or absent E-cadherin expression was found in 27 of 45 (60%) informative cases. Allelic imbalance of the 16q22.1 locus was found in 14 (27.5%) of 51 cases by using the microsatellite markers D16S503, D16S752, and D16S512. p27 LI and E-cadherin alterations were not statistically related. CONCLUSIONS: In summary, high p27 levels detected in a subset of
advanced breast carcinomas correlate with lymph node metastasis,
suggesting that other mechanisms may bypass the cell cycle inhibitory role
of p27 and provide growth advantage in these tumors.
Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10505 PMID: 12015771 [PubMed - indexed for MEDLINE] Free full text
MeSH Terms, Substances
c Eur J Gynaecol Oncol. 2002;23(4):333-4.
62. Granular cell tumor of the breast: a rare lesion
resembling breast cancer.
Gogas J, Markopoulos C, Kouskos E, Gogas H, Mantas D, Antonopoulou
Z, Kontzoglou K.
2nd Department of Propedeutic Surgery, Athens University Medical School, Laiko
General Hospital, Greece. Abstract
Granular cell tumor (GCT) is an uncommon, usually benign tumor that
occasionally involves the breast. It is possibly of neural origin (Schwann
cells) and usually occurs in premenopausal black women. Physical
examination, mammographic, ultrasonographic findings and pathologic
examination may suggest breast malignancy. Positive immunohistochemical
staining of the cells for S-100 protein, NSE, and CEA is indicative of GCT.
Surgical treatment of choice is wide local excision. We report a case of
Markopoulos C - PubMed - NCBI granular cell tumor of a female breast. A 52-yr-old white woman had a palpable mass close to her right axilla. Computer tomography (CT) showed a 3.74 cm mass in the mammary tail of Spencer. The findings were suspicious for malignancy and the lesion was widely resected. Pathologic examination showed granular cell tumor. PMID: 12214737 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms
c Eur J Surg. 2002;168(10):572-4.
63. Mucosa-associated lymphoid tissue thyroid
lymphoma: a rare and not aggressive tumour.
Gogas J, Kouskos E, Markopoulos C, Androulakis A, Mantas D, Gogas H,
Kostakis A.
Second Department of Propedeutic Surgery, Athens University Medical School,
Laikoe General Hospital of Athens, Athens, Greece. PMID: 12666700 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms
c Hum Mutat. 2002 Jan;19(1):81-2.
64. BRCA2 gene mutations in Greek patients with
familial breast cancer.
Armakolas A, Ladopoulou A, Konstantopoulou I, Pararas B, Gomatos IP,
Kataki A, Konstadoulakis MM, Stathopoulos GP, Markopoulos C, Leandros
E, Gogas I, Yannoukakos D, Androulakis G.
Laboratory of Surgical Research, A' Propaedeutic Surgical Clinic, Athens Medical
School, Hippokrateion Hospital, Athens, Greece. Abstract
Family history is a well-recognized risk factor for the development of breast
cancer. The isolation of BRCA1 and BRCA2 genes, the two major
predisposing genes in familial and to early onset breast and ovarian cancer,
has resulted to the identification of a large number of families with mutations
in these two genes. Despite the large number of distinct mutations detected
in both genes, several mutations have been found to recur in unrelated
families of diverse geographical origin. We have analyzed 27 Greek patients
with familial breast cancer the majority of those having one first and one
second degree relatives affected and 28 patients with sporadic breast
cancer for BRCA2 germline mutations. The techniques used were single-
strand conformation polymorphism analysis (SSCP) followed by
sequencing. Furthermore, the clinical presentation and prognosis of BRCA2
associated breast cancer cases was compared to 20 adequately matched
for age and date of diagnosis (within one year) sporadic breast cancer
patients. We identified three novel BRCA2 mutations (3058delA,
6024delTA, and 4147delG) in the ovarian cancer cluster region (OCCR) and
Markopoulos C - PubMed - NCBI one already known (2024del5) germline BRCA2 gene mutation in five different breast cancer families. The 4147delG mutation was detected in two unrelated patients. BRCA2 germline mutations were correlated with early-onset breast cancer RR=4.77 (95% CI: 0.666-34.463). Although patients with BRCA2 germline mutations did not have a distinct histological phenotype they had an improved overall survival (100% vs 65%). Our findings suggest that there is a cluster of novel mutations in exons 10 and 11 in Greek patients with familial breast cancer. These mutations appear to have a milder clinical phenotype when compared to the rest of the study group. Copyright 2001 Wiley-Liss, Inc. PMID: 11754111 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms
c Int Surg. 2002 Jan-Mar;87(1):19-24.
65. Local recurrence after radical surgery for colorectal
cancer.
Papachristodoulou A, Kouskos E, Markopoulos C, Karatzas G, Kouraklis
G, Kostakis A.
Second Department of Propedeutic Surgery, Athens University Medical School,
Laiko General Hospital, Greece. Abstract
Local recurrence of colorectal cancer after curative surgery is a major
clinical problem. The aim of our study was to present our experience in this
field. Between January 1990 and December 2000, 572 patients underwent
resection for colorectal cancer in our department; 66 of them had local
recurrence within the first 2 years. Most of those patients had Dukes' stage
B (n = 24) or stage C (n = 37) tumors, which were located mainly in the
rectum (n = 40) and sigmoid colon (n = 18). The incidence of local
recurrence was 11% and 15.9% for tumors that were Dukes' stages B and
C, respectively. Thirty-five of 66 patients received palliative treatment, and
28 of them died within 9 months. The remaining 31 patients underwent
radical excision of the recurrent tumor: 11 of these patients died within 2
years, and 20 were still alive after 30 months. The only hope for long-term
survival for patients presenting with local recurrence from colorectal cancer
after primary radical treatment is to identify local recurrence at an early
stage and treat it in a radical manner.
PMID: 12144185 [PubMed - indexed for MEDLINE] MeSH Terms
c Eur J Surg Oncol. 2001 Nov;27(7):626-30. 66. Markopoulos C - PubMed - NCBI Autoimmune thyroid disease in women with breast
carcinoma.
Gogas J, Kouskos E, Tseleni-Balafouta S, Markopoulos C, Revenas K,
Gogas G, Kostakis A.
Breast Unit, 2nd Department of Propedeutic Surgery, Athens University Medical
School, Laiko General Hospital, 17 Ag. Thomas Street, 115 27 Athens, Greece. Abstract
AIMS:
Estimation of pre
valence of autoimmune thyroid disorders in Greek breast cancer patients (prospective study). METHODS:
f autoimmune thyroiditis was estimated in 310 Greek breast cancer patients, in 100 women with benign breast disease and in 190 women without any breast disease, by submitting them to clinical examination, ultrasound thyroid evaluation, serum thyroid antibody determination and fine needle aspiration (FNA) of the thyroid gland. Autoimmune thyroiditis was found RESULTS:
in 136/310 (43.9%) breast cancer women: 95 were diagnosed by positive autoantibodies, 19 had positive FNA findings and 22 had both positive autoantibodies and positive FNA findings. In 117 cases, thyroid autoantibodies were positive (37.7% whereas the control groups had respective rates of 19% and 18.4% autoantibody positivity). There is evidence of high incidence of autoimmune thyroiditis in Greek breast cancer patients, increasing in relation to cancer stage. Copyright 2001 Harcourt Publishers Limited. PMID: 11669589 [PubMed - indexed for MEDLINE] MeSH Terms
c Eur J Surg. 2001 Sep;167(9):715-8.
67. Metastatic retroperitoneal and mediastinal fibrosis
as first sign of recurrence of breast cancer.
Gogas J, Markopoulos C, Kouskos E, Gogas H, Kiriakou V.
Breast Unit-2nd Department of Propedeutic Surgery, Laiko General Hospital,
PMID: 11759746 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms
c J Infect. 2001 Aug;43(2):159-60.
68. Primary actinomycosis of the greater omentum.
Papachristodoulou AJ, Angouras DC, Papavassiliou VG, Delladetsima JK, Markopoulos C - PubMed - NCBI Markopoulos CJ, Gogas JG. PMID: 11676528 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms, Substances
c Eur J Radiol. 2001 Jul;39(1):60-5.
69. Use of artificial neural networks (computer analysis)
in the diagnosis of microcalcifications on
mammography.

Markopoulos C, Kouskos E, Koufopoulos K, Kyriakou V, Gogas J.
Breast Unit, Second Department of Propedeutic Surgery, Athens University Medical School, Laiko General Hospital of Athens, 8 Iassiou street 115218, Athens, Greece. Abstract
INTRODUCTION/OBJECTIVE:
The purpose of this study was to evaluate a
computer based method for differentiating malignant from benign clustered
microcalcifications, comparing it with the performance of three physicians.
METHODS AND MATERIAL: Materials for the study are 240 suspicious
microcalcifications on mammograms from 220 female patients who
underwent breast biopsy, following hook wire localization under
mammographic guidance. The histologic findings were malignant in 108
cases (45%) and benign in 132 cases (55%). Those clusters were analyzed
by a computer program and eight features of the calcifications (density,
number, area, brightness, diameter average, distance average, proximity
average, perimeter compacity average) were quantitatively estimated by a
specific artificial neural network. Human input was limited to initial
identification of the calcifications. Three physicians-observers were also
evaluated for the malignant or benign nature of the clustered
microcalcifications.
RESULTS:
ce of the artificial network was evaluated by receiver operating characteristics (ROC) curves. ROC curves were also generated for the performance of each observer and for the three observers as a group. The ROC curves for the computer and for the physicians were compared and the results are:area under the curve (AUC) value for computer is 0.937, for physician-1 is 0.746, for physician-2 is 0.785, for physician-3 is 0.835 and for physicians as a group is 0.810. The results of the Student's t-test for paired data showed statistically significant difference between the artificial neural network and the physicians' performance, independently and as a group. DISCUSSION AND CONCLUSION: Our study showed that computer
analysis achieves statistically significantly better performance than that of
physicians in the classification of malignant and benign calcifications. This
method, after further evaluation and improvement, may help radiologists
and breast surgeons in better predictive estimation of suspicious clustered
microcalcifications and reduce the number of biopsies for non-palpable
Markopoulos C - PubMed - NCBI PMID: 11439232 [PubMed - indexed for MEDLINE] MeSH Terms
c J Am Geriatr Soc. 2001 Jul;49(7):1004-5.
70. Breast cancer in older women.
Markopoulos C, Kouskos E, Dimitrios M, Kontzoglou K, Pappis H, Galanos
A, Gogas H.
PMID: 11527500 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms, Substances
c Cytopathology. 2001 Jun;12(3):197-202.
71. p53 protein expression and oestrogen and
progesterone receptor status in invasive ductal
breast carcinomas.
Ioakim-Liossi A, Karakitsos P, Markopoulos C, Aroni K, Athanassiadou P,
Delivelioti K, Athanassiades P, Vaiopoulos G.
Department of Clinical Cytology, 'Laikon' Hospital, Greece.
Abstract
p53 protein expression and oestrogen and progesterone receptor status in
invasive ductal breast carcinomas The p53 protein expression and
oestrogen and progesterone receptors status was investigated in correlation
to the grade of malignancy of primary breast carcinomas. Our material
constituted imprints from surgical biopsies of 75 invasive ductal breast
cancer cases. The p53 protein expression was investigated
immunocytologically using the monoclonal antibody p53 DO-7 (DAKO). A
biochemical DCC method was applied for the detection of oestrogen and
progesterone receptors for all tumours. Fifty-one percent of breast cancer
cases were p53 protein positive. A statistically significant association of p53
protein expression and high tumour grade was found (chi2=23.72, d.f.=2, P
< 0.001). A statistically significant association was also found between
oestrogen and progesterone receptor positive cases and the grade of
malignancy (P < 0.001). A negative association between p53 protein
expression and oestrogen (ER) and progesterone receptors (PgR) positivity
was found. From our results it appears that it is possible to distinguish from
grade II tumours two subgroups of cases, one with low malignancy potential
and p53 (-), ER (+), PgR (+), and another subgroup with high malignancy
potential and phenotype p53 (+), ER (-), PgR (-). The last subset of patients
could actually benefit from adjuvant therapy.
Markopoulos C - PubMed - NCBI PMID: 11380561 [PubMed - indexed for MEDLINE] MeSH Terms, Substances
c Anticancer Res. 2001 Mar-Apr;21(2A):991-9.
72. Alterations of the 16q22.1 and 16q24.3 chromosomal
loci in sporadic invasive breast carcinomas:
correlation with proliferative activity, ploidy and
hormonal status of the tumors.
Kouvaraki M, Gorgoulis VG, Rassidakis GZ, Liodis P, Koutroumbi E,
Markopoulos C, Gogas J, Kittas C.
Laboratory of Histology and Embryology, University of Athens School of Medicine, Abstract
BACKGROUND:
Breast cancer is characterized by complex genetic
alterations found in multiple chromosomal regions, most commonly losses
of 17p, 16q, 8p and others. A number of tumor suppressor genes mapped
on these loci have been investigated in mammary tumors, whereas other
gene products are of unclear function and await identification.
MATERIALS AND METHODS: We analyzed the loss of heterozygosity
(LOH) of two chromosomal loci: a. 16q24.3 using the genetic markers
D16S303, D16S3026 and D16S3407 and b. 16q22.1, the locus of E-
cadherin gene, using the microsatelite markers D16S503, D16S752 and
D16S512, in a series of 63 sporadic invasive breast carcinomas consisting
of 56 ductal, 4 lobular and 3 tumors of mixed type. Our findings were
correlated with proliferative activity, ploidy and hormonal status of the
tumors.
RESULTS: Fourteen (22.2%) tumors demonstrated LOH of 16q24.3. Allelic
imbalance of the 16q22.1 locus was found in 19 of 61 informative cases
(31%) and commonly coexisted with LOH of 16q24.3. A significant
association was observed between LOH of D16S752 and the absence of
progesterone receptors in tumor cells (p = 0.005).
and 16q22.1 are frequent genetic alterations in breast cancer and they do not seem to correlate with tumor cell proliferation or ploidy. The statistical association between LOH of 16q24.3 and progesterone receptors need to be further investigated in larger series. PMID: 11396193 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms, Substances
c Eur J Gynaecol Oncol. 2001;22(2):157-9. 73. Markopoulos C - PubMed - NCBI Breast cancer in ectopic breast tissue.
Markopoulos C, Kouskos E, Kontzoglou K, Gogas G, Kyriakou V, Gogas J.
2nd Department of Propedeutic Surgery, Athens University Medical School and Laiko Hospital, Greece. Abstract
Ectopic breasts usually develop along the mammary ridges. Their incidence
has been reported as up to 5-6%. Development of malignancy is rare. We
report three cases of postmenopausal female patients with breast cancer
which developed in the axillary accessory breast. They were all successfully
treated by surgery and adjuvant therapy. A review of the literature on the
incidence and pathology of ectopic mammary tissue is also presented.
PMID: 11446485 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms
c Am Surg. 2000 Nov;66(11):1011-3.
74. Factors affecting axillary lymph node metastases in
patients with T1 breast carcinoma.
Markopoulos C, Kouskos E, Gogas H, Mandas D, Kakisis J, Gogas J.
2nd Department of Propedeutic Surgery, Athens University Medical School, Laiko General Hospital, Greece. Abstract
The purpose of this study was to determine factors associated with the
incidence of axillary lymph node metastases (ALNM) in T1 tumors and
cases in which axillary dissection could be omitted. Data from 195 patients
with T1 primary invasive breast cancer (size < or = 2 cm) who underwent
either mastectomy or wide local excision of the tumor and axillary dissection
were reviewed. ALNM was found in 59 of 195 patients with T1 tumors
(30.3%). Tumor size was found to be the only independent predictor of
ALNM, having a directly analogous relationship with the probability of
invaded nodes: T1a (< or = 5 mm) tumors had 0 per cent ALNM, whereas
T1b (5 mm < T1b < or = 10 mm) and T1c (10 mm < T1c < or = 20 mm)
tumors had 25.7 per cent and 33.8 per cent ALNM respectively. Among the
other factors studied (patient age, tumor site, hormone receptor status,
histologic type, and grade of the tumor) only the histologic grade of the
tumor cells appeared to correlate with the incidence of lymph node
involvement, but this was not statistically significant. In conclusion only
tumor size has statistically significant correlation with the incidence of
ALNM. Routine axillary dissection could be omitted only in patients at
minimal risk of ALNM (ductal carcinoma in situ and T1a) and when
treatment decisions were not influenced by lymph node status (e.g., elderly
patients with clinically negative axilla). Axillary dissection (at least levels I
and II) should be performed in all cases with primary invasive breast cancer
with tumor size > 5 mm.
PMID: 11090007 [PubMed - indexed for MEDLINE] Markopoulos C - PubMed - NCBI MeSH Terms
c Cancer Causes Control. 2000 May;11(5):383-8.
75. Leptin and insulin growth factor I in relation to breast
cancer (Greece).
Petridou E, Papadiamantis Y, Markopoulos C, Spanos E, Dessypris N,
Trichopoulos D.
Department of Hygiene and Epidemiology, Athens University Medical School,
Greece. epetrid@atlas.uoa.gr Abstract
OBJECTIVES:
breast cancer and the hormone leptin are associated with obesity and reproductive phenomena in women, we have examined whether there is a relationship between leptin and breast cancer among premenopausal and postmenopausal women. We have also evaluated in this dataset the association of IGF-I with breast cancer. Seventy-five cases, METHODS:
diagnosed during mammographic screening, with incident breast cancer were matched for age and type of permanent residence with seventy-five controls from those screened negative in the same study base. RESULTS:
was no evidence for an association between IGF-I and either premenopausal or postmenopausal breast cancer risk or between leptin and postmenopausal breast cancer. Among premenopausal women, however, there was a strong and statistically significant inverse association of leptin with breast cancer. CONCLUSION: We did not confirm the positive association, reported from
other investigations, of IGF-I with premenopausal breast cancer risk. We
have found evidence, however, that leptin may be inversely related to breast
cancer risk among premenopausal women. The latter finding is not
biologically implausible and deserves to be examined in additional datasets.
PMID: 10877331 [PubMed - indexed for MEDLINE] MeSH Terms, Substances
c Eur J Surg Oncol. 1999 Jun;25(3):333-5.
76. Carcinosarcoma of the submandibular salivary
gland.
Gogas J, Markopoulos C, Karydakis V, Gogas G, Delladetsima J.
2nd Propedeutic Department of Surgery, Athens University and Medical School,
Laikon Hospital, Greece. Abstract
We report a rare case of submandibular salivary gland carcinosarcoma
Markopoulos C - PubMed - NCBI ('true' malignant mixed tumour) which occurred in a 77-year-old man. Microscopic examination showed a neoplasm comprised of sarcomatous elements (chondrosarcoma, rhabdomyosarcoma and osteosarcoma) with tabular salivary ductal adenocarcinoma. A short review of the literature is also presented and the poor prognosis of these tumours, in spite of complete surgical removal and additional radiation therapy and chemotherapy, is discussed. PMID: 10383250 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms
c World J Surg. 1999 May;23(5):434-8.
77. Management of nonpalpable, mammographically
detectable breast lesions.
Markopoulos C, Kakisis J, Kouskos S, Kontzoglou K, Koufopoulos K,
Gogas J.
Breast Unit, 2nd Department of Propedeutic Surgery, Athens University Medical
School, Laiko General Hospital, 17 Ag. Thoma Avenue, 11527 Athens, Greece. Abstract
A series of 151 women underwent 156 preoperative localizations of
nonpalpable, mammographically detected breast lesions. Indications for
biopsy were (1) a cluster of more than five fine microcalcifications; (2) a
solid lump found by ultrasound investigation; and (3) a radiologic
abnormality of the breast parenchyma. The lesions were localized
preoperatively using the hook-wire method (Frank needle), and all biopsies
were performed under general anesthesia. Carcinoma was discovered in 34
(21.8%) cases; in 22 (64.7%) it was a noninvasive cancer (9 with
microinvasions) and in 12 (35.3%) an invasive carcinoma with a mean
tumor diameter of 0.8 cm. The highest malignancy rate was found among
those with microcalcifications (21 of 81 cancers, or 25.9%). Lymph node
involvement was seen in 25% of patients with invasive carcinomas. In
conclusion, the needle localization of nonpalpable breast lesions is a simple,
accurate method for early detection of small cancers with favorable
prognosis.
PMID: 10085389 [PubMed - indexed for MEDLINE] MeSH Terms
c Cancer Genet Cytogenet. 1999 Apr;110(1):34-40.
78. Changes of chromosomes 1, 3, 6, and 11 in
metastatic effusions arising from breast and ovarian
cancer.
Ioakim-Liossi A, Gagos S, Athanassiades P, Athanassiadou P, Gogas J,
Markopoulos C - PubMed - NCBI Davaris P, Markopoulos C.
Department of Pathology, Athens School of Medicine, University of Athens, Greece.
Abstract
This cytogenetic study deals with cell material obtained from 15 pleural
fluids from 11 patients with breast cancer and 27 ascitic fluids from 16
patients with ovarian cancer; in addition, 8 pleural, 5 ascitic, and 1
pericardial fluid from patients with tuberculosis, liver cirrhosis, and heart
insufficiency, were studied. Using mainly direct methods, as well as short-
term cell cultures, the chromosome spreads were GTG-banded. Cancerous
biopsies showed a plethora of numerical and structural chromosome
anomalies and exhibited broad aneuploidy. Chromosomes participating
more often in numerical and structural aberrations were 1, 3, 6, 7, 8, 9, 11,
12, and 17. This study provides further cytogenetic evidence for the
involvement of these chromosomes in breast and ovarian malignancy.
PMID: 10198620 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms
c Eur J Gynaecol Oncol. 1999;20(1):53-5.
79. Senology: the urgent need for establishing rules for
expert training and organization of multidisciplinary
breast units.
Markopoulos CJ.
2nd Propeduetic Department of Surgery, Athens University Medical School and
Laiko General Hospital, Greece. PMID: 10422683 [PubMed - indexed for MEDLINE] MeSH Terms
c Eur J Gynaecol Oncol. 1999;20(2):147-9.
80. Radial scar of the breast.
Markopoulos C, Kakisis J, Koufopoulos K, Alevras P, Gogas H, Tziortziotis
D, Floros D.
2nd Department of Propedeutic Surgery, Athens University Medical School, Laiko
General Hospital, Greece. Abstract
Four cases of radial scar of the breast, primarily diagnosed as carcinoma
are presented; the patients were found among 858 patients who were
operated on at our Breast Unit over the last 4 years. The lesion was
revealed on routine mammographic examination in 4 of our patients, while
in the fourth it was found by palpation. In two of our patients mammographic
examination revealed architectural distortion, in one patient micro-
Markopoulos C - PubMed - NCBI calcifications and in the fourth patient a stellate lesion was found. In the last two patients the lesion was localized before surgery with a hook wire. Diagnosis was established by histopathologic examination in all cases. The surgeon, the radiologist and the pathologist should be aware of this clinical entity which, in spite of its benign character, has the ability to simulate invasive carcinoma clinically, mammographically and histopathologically. PMID: 10376436 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms
c Mol Med. 1998 Dec;4(12):807-22.
81. Alterations of p16-pRb pathway and chromosome
locus 9p21-22 in sporadic invasive breast
carcinomas.
Gorgoulis VG, Koutroumbi EN, Kotsinas A, Zacharatos P, Markopoulos C,
Giannikos L, Kyriakou V, Voulgaris Z, Gogas I, Kittas C.
Department of Histology and Embryology, School of Medicine, University of Athens,
Abstract
The p16-pRb pathway represents a vital cell-cycle checkpoint. In the
present study we investigated the alterations of this G1-phase protein
pathway using immunohistochemical and molecular methods in a series of
55 breast carcinomas and correlated the findings with clinicopathological
features of the patients. Furthermore, we examined its relationship with the
status of the chromosomal region 9p21-22 performing a deletion map
analysis because there are indications that, in addition to CDKN2 and
MTS2/p15(INK4B) tumor suppressor genes (TSGs), this area harbors other
TSG(s). Aberrant expression (Ab) of p16 and pRb was observed in 26
(47%) and 16 (29%) of the carcinomas, respectively. A statistical trend
pointing out an inverse relationship between p16 and pRb expression was
found (p = 0.079). Analysis of the region that encodes for p16 by deletion
mapping, a PCR-based methylation assay and PCR-SSCP, revealed that
deletions and transcriptional silencing by methylation might represent the
main mechanisms of CDKN2/p16(INK4A) inactivation in breast carcinomas.
The results of deletion mapping also suggest that another TSG(s) may
reside at the 9p21-22 area particularly at the D9S162 loci and that co-
deletion of this putative gene with CDKN2/p16(INK4A) may play a role in
breast carcinogenesis. In addition, microsatellite instability (MI), a marker of
replication error phenotype (RER+), was observed with a frequency of 16%
in the area examined and was inversely related with loss of heterozygosity
(LOH). Interestingly, most cases with MI at the region encoding for p16 were
aggregated in a subgroup of breast carcinomas with no other obvious
genetic and/or epigenetic CDKN2/p16(INK4A) alterations. We speculate
that there is an additional mechanism of CDKN2/p16(INK4A) inactivation.
The relationship of p16 protein level pRb, status, the p16-pRb combined
immunoprofiles, and the microsatellite alterations detected at the 9p21-22
locus with the patients' clinicopathological parameters revealed two
significant correlations: one between normal pRb expression and lymph
Markopoulos C - PubMed - NCBI node involvement (p = 0.0263), and the other between microsatellite alterations (LOH and or MI) and tumor size (p = 9.2 x 10(-3)). In view of the heterogenous nature of breast cancer, we suggest that in a significant proportion of breast carcinomas, deregulation of the p16-pRb pathway in association with another, as-yet unidentified, TSG(s) of the 9p21-22 region may play a role in initiating or progressing the oncogenic procedure, while in other subgroups, alternative molecules may play this role. PMID: 9990866 [PubMed - indexed for MEDLINE] PMCID: PMC2230392
Free PMC Article
Publication Types, MeSH Terms, Substances
c Eur J Surg Oncol. 1998 Aug;24(4):332-4.
82. Association of breast cancer with meningioma.
Markopoulos C, Sampalis F, Givalos N, Gogas H.
2nd Propedeutic Department of Surgery, Medical School, University of Athens, Abstract
We report a case of meningioma subsequently developed in a patient with
bilateral breast carcinoma, which was originally thought to be single brain
metastases. A brief review of the literature is presented with emphasis on
the unique association between the two neoplasms, which suggests a
possible hormonal relationship. The knowledge of this association is
important in the differential diagnosis of patients with breast cancer who
develop central nervous system manifestations.
PMID: 9725004 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms
c Acta Cytol. 1998 Jul-Aug;42(4):918-22.
83. p53 protein expression in benign and malignant
breast lesions.
Ioakim-Liossi A, Markopoulos C, Karakitsos P, Safioleas M, Gogas J,
Vaiopoulos G.
Department of Pathology, Medical School, University of Athens, Greece.
Abstract
OBJECTIVE:
To investigate p53 protein expression in imprints from benign
and ductal breast carcinoma cases in relation to the histologic grade of
malignancy and clinical stage.
STUDY DESIGN: The study group consisted of 60 cases of primary ductal
breast carcinomas and 20 benign lesions. For the demonstration of p53
protein expression, an immunocytochemical avidin-extravidin complex
Markopoulos C - PubMed - NCBI technique was applied. Monoclonal antibody p53 was used as the primary antibody, diaminobenzidine as the chromogen and hematoxylin as the counterstain. Forty-five percent of breast RESULTS:
cancer cases showed positive expression of p53. A statistically significant difference in p53 protein expression was observed between grade 1, 2 and 3 carcinomas and stage I, II and III cases. All benign lesions were negative for p53 protein expression. CONCLUSION: Immunocytochemical p53 protein expression in cytologic
material is a simple method that can be applied in routine cytologic
laboratories for the identification of genetic alterations in primary ductal
breast cancer.
PMID: 9684577 [PubMed - indexed for MEDLINE] MeSH Terms, Substances
c Anticancer Res. 1998 May-Jun;18(3A):1501-8.
84. The prognostic value of alpha-thymosins in breast
cancer.
Tsitsilonis OE, Bekris E, Voutsas IF, Baxevanis CN, Markopoulos C,
Papadopoulou SA, Kontzoglou K, Stoeva S, Gogas J, Voelter W,
Papamichail M.
Cancer Immunology and Immunotherapy Centre, St. Savas Cancer Hospital,
Abstract
The prognosis of breast cancer is of major clinical importance and several
histopathological, biochemical and immunological variables have been
reported to be useful prognostic factors. In the present study, we
investigated the clinical significance of the levels of alpha-thymosins in
relation to established prognostic factors, both in breast cancer and non-
malignant breast lesions, alpha-thymosin levels were measured in breast
tissue extracts by specific radioimmunoassays (RIAs) developed for human
prothymosin alpha (ProT alpha) and parathymosin alpha (ParaT alpha) and
were found to be significantly higher (up to 17.2-fold) in malignant but not in
benign breast lesions, as compared to the values of the neighbouring
tissues. When alpha-thymosin levels of the tumor samples were correlated
with various known prognostic parameters a statistically significant
correlation (p < 0.05) was observed between the levels of ProT alpha in
malignant tissues to the grade of cancer and the lymph node status of the
patient. An association between ProT alpha levels with increase in risk of
death from breast cancer was also noticed. These results suggest that the
expression of alpha-thymosins in human breast cancer a) depends on the
proliferation status of the tumor, b) associates with established prognostic
factors describing the metastatic potential of the tumor and c) is related to
the overall survival of the patient. The fact that such relationships hold only
for cancer tissues encourages the future use of alpha-thymosins as potent
prognostic factors in breast cancer.
Markopoulos C - PubMed - NCBI PMID: 9673361 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms, Substances
c Cytopathology. 1998 Apr;9(2):107-13.
85. Evaluation of cytological morphologic criteria and
AgNOR expression in male breast lesions.
Karakitsos P, Botsoli-Stergiou EM, Ioakim-Liossi A, Georgoulakis J,
Markopoulos C, Gogas J, Kyrkou K.
Department of Clinical Cytology and Cytogenetics, Laiko Hospital, Athens, Greece. Abstract
Fine needle aspiration (FNA) breast smears from 81 male patients have
been examined in our laboratory between 1988 and 1994. The cytological
criteria for diagnosing male breast lesions and the expression of nuclear
organizer regions were evaluated. Of the 81 cases examined cytologically,
50 cases were proven cytologically and histologically to be inactive
gynaecomastia, two cases showed florid gynaecomastia and there were 10
adenocarcinomas; in the 17 cases in which no cytological evidence of
gynaecomastia or malignancy was found, the histological diagnosis was
gynaecomastia in 13 and there was one case of mastopathy; in two cases
suspicious of malignancy on cytology the histological examination proved to
be florid gynaecomastia in one case and the other showed an
adenocarcinoma. The absolute specificity of FNA in this study was 74.28%,
the complete specificity 98.5%, the absolute sensitivity 90.9% and the
complete sensitivity 100%. The overall accuracy was 97.5%, the positive
predictive value 91.66% and the negative predictive value 98.5%. In all
cases of male breast carcinoma, AgNOR mean value was > or = 3; thus, it
appears that AgNOR mean value 3 could be used as a cut-off value
between benign and malignant male breast lesions. Our experience
suggests that FNA is an acceptable procedure for the investigation of male
breast lesions.
PMID: 9577737 [PubMed - indexed for MEDLINE] MeSH Terms
c Eur J Gynaecol Oncol. 1998;19(3):291-3.
86. Mucoepidermoid carcinoma of the breast.
Markopoulos C, Gogas H, Livaditou A, Floros D.
B' Propedeutic Department of Surgery, Medical School, University of Athens, Abstract
Mucoepidermoid carcinomas are very rare breast tumors. The morphology
Markopoulos C - PubMed - NCBI of this breast tumour is similar to its counterpart in the salivary gland. The first two cases reported were low-grade and neither patient had metastatic disease. Furthermore, none of the five patients with low-grade mucoepidermoid carcinoma reported by Fisher had axillary lymph node involvement and were alive with no evidence of disease 4 to 10 years after diagnosis and were considered of probable favourable prognosis. A high grade form of mucoepidermoid cancer might occur in the breast as it does in the salivary gland. All high-grade variant cases published had demonstrable lymph node or distant metastases and rapidly fatal outcomes. This report describes a case of high-grade mucoepidermoid carcinoma of the breast with a disease-free interval of 5 years, despite of unfavourable histologic features at the time of diagnosis. PMID: 9641234 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms
c Eur J Gynaecol Oncol. 1998;19(3):246-8.
87. Cavernous haemangioma of the breast. A case
Markopoulos C, Sampalis F, Gogas H, Despotidis P, Kyriakou V.
B' Propedeutic Department of Surgery, Medical School, University of Athens, PMID: 9641223 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms
c Eur J Gynaecol Oncol. 1998;19(2):163-6.
88. 99mTc Tetrofosmin imaging in breast tumours.
Markopoulos C, Sampalis F, Zerva C, Kiriaki D, Kitsou E, Alevizou-Terzaki
V, Gogas J.
B'Propedeutic Department of Surgery, Medical School-University of Athens,
Abstract
Eighty-five women, 18 to 80 years of age, with palpable breast lumps were
studied 1-4 days before surgery in order to evaluate 99mTc Tetrofosmin
imaging for the detection of malignant breast tumours. Intravenous injection
of 99mTc Tetrofosmin was followed by 3 min planar images at 5-60 min
postinjection. In the latter 57 patients, planar imaging was preceded by a
dynamic study of 20x5 sec images. The myocardium was always included in
the field of the left breast. Count rates in suspicious areas were compared
with normal tissue areas in the same and the opposite breast and with
myocardial counts. Data analysis showed that 77 of the 85 scan results
were in agreement with the histological findings; six scans were false
negative and two false positive for malignancy. The sensitivity of the method
was 90.32% and the specificity 91.30%, with a positive predictive value of
96.55%. We conclude that breast scanning with 99mTc Tetrofosmin may
Markopoulos C - PubMed - NCBI play an important role in the detection of breast malignancies. PMID: 9611058 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms, Substances
c Eur J Gynaecol Oncol. 1998;19(2):150-4.
89. Thyroid function in postmenopausal women with
breast cancer on tamoxifen.
Kostoglou-Athanassiou I, Ntalles K, Markopoulos C, Athanassiou P, Gogas
J, Proukakis C.
Department of Medical Physics, Medical School, University of Athens, Greece.
Abstract
In 42 postmenopausal women with breast cancer, aged 48-85 years (mean
age 62.4 years) serum thyroid hormone concentrations were measured
before and after 6 months of tamoxifen therapy (20 mg daily). In particular
triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free
thyroxine (FT4), thyroxine-binding globulin (TBG) and thyroid-stimulating
hormone (TSH) concentrations before and 30 minutes after thyrotrophin-
releasing hormone (TRH) administration (200 microg i.v.) were measured
before and 6 months after tamoxifen therapy. T3 and T4 concentrations
increased significantly (p<0.001 and p<0.05, respectively) whereas FT3 and
FT4 remained unchanged (p>0.05), TBG increased significantly (p<0.001)
and basal TSH concentrations as well as TSH response to TRH injection
increased significantly (p<0.05) after tamoxifen therapy. It is concluded that
tamoxifen administration changes thyroid hormone concentrations. However
free thyroid hormone levels remain unchanged and the patients remain
euthyroid after long-term tamoxifen therapy.
PMID: 9611055 [PubMed - indexed for MEDLINE] MeSH Terms, Substances
c Anal Quant Cytol Histol. 1997 Oct;19(5):453-60.
90. Application of the learning vector quantizer to the
classification of breast lesions.
Markopoulos C, Karakitsos P, Botsoli-Stergiou E, Pouliakis A, Ioakim-
Liossi A, Kyrkou K, Gogas J.
2nd Propedeutic Surgical Clinic, Athens University Medical School, Greece.
Abstract
OBJECTIVE:
To investigate the potential of the learning vector quantization
(LVQ) neural network for the discrimination of benign from malignant breast
lesions.
STUDY DESIGN: Using a custom image analysis system on Giemsa-
stained smears, 25 parameters describing the size, shape and texture of the
cell nucleus were measured. Three thousand nuclei from a total of 9,356
Markopoulos C - PubMed - NCBI were selected as a training set for the neural network, and the whole data set was used for testing. An additional 238 cells from 16 cases without final cytologic diagnoses were evaluated by the system. The total number of cells (9,594) was collected from 100 patients (68 carcinomas and 32 benign lesions). Cytologic examination RESULTS:
of the cases gave two false positive and two false negative results. However, in eight cases of ductal breast carcinoma and in eight cases of benign lesions, histologic confirmation was necessary in order to confirm the cytologic diagnosis. Application of the LVQ permitted correct classification of 87.41% of the cells. Classification at the patient level by using a hypothesis test for proportion with a hypothesis value equal to 50% permitted the correct diagnosis in 98% of patients. CONCLUSION: These results indicate that the use of neural networks
combined with image morphometry and statistical techniques may offer
useful information about the potential for malignancy, improving the
diagnostic accuracy of fine needle aspiration of breast lesions.
PMID: 9349906 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms
c Cytopathology. 1997 Oct;8(5):322-7.
91. DNA content and p53 protein expression in ductal
breast cancer.
Ioakim-Liossi A, Karakitsos P, Markopoulos C, Aroni K, Delivelioti K,
Gogas J, Kyrkou K.
Department of Pathology, Medical School, University of Athens, Greece.
Abstract
The DNA content of 85 ductal breast cancers of different histological grades
was evaluated using static cytometry and correlated with
immunocytochemical expression of p53 protein in tumour cells in cytological
material. A statistically significant difference was observed between p53
protein expression and grade of malignancy (P < 0.001). The percentage of
euploid tumours significantly decreased from grade I through grade II to
grade III tumours (P < 0.001). Clonal DNA heterogeneity was observed in
26.6% of cases analysed and was correlated with p53 protein expression (P
< 0.001). These changes probably reflect genomic alterations which may
affect potential malignancy of breast cancer.
PMID: 9313984 [PubMed - indexed for MEDLINE] MeSH Terms, Substances
c Cytopathology. 1997 Jun;8(3):171-6.
92. DNA ploidy and pS2 protein expression in breast
Markopoulos C - PubMed - NCBI Ioakim-Liossi A, Karakitsos P, Aroni K, Markopoulos C, Delivelioti K,
Gogas J, Kyrkou K.
Department of Clinical Cytology and Cytogenetics, Medical School, Athens
University, Greece. Abstract
The DNA content of ductal breast carcinomas of varying histological grade
was measured using static image cytometry and correlated with pS2
expression in the tumour cells. Our study was performed on imprint of
surgical biopsies of 60 women with ductal breast cancer. A statistically
significant difference was observed between pS2+ expression and grade of
malignancy (P < 0.001). The percentage of euploid tumours significantly
decreased from grade I to grade II to grade III (P = 0.01). The percentage of
aneuploid tumours increased from pS2+ to pS2- breast tumours (P < 0.001).
These findings may be indicative of pS2 and DNA ploidy alterations and
tumour aggressiveness.
PMID: 9202892 [PubMed - indexed for MEDLINE] MeSH Terms, Substances
c Acta Cytol. 1997 May-Jun;41(3):713-6.
93. Expression of pS2 protein and estrogen and
progesterone receptor status in breast cancer.
Ioakim-Liossi A, Karakitsos P, Markopoulos C, Aroni K, Delivelioti K,
Gogas J, Kyrkou K.
Department of Clinical Cytology and Cytogenetics, University of Athens Medical
Abstract
OBJECTIVE:
To investigate pS2 protein expression and estrogen (ER) and
progesterone receptor (PR) status of imprints from surgical biopsies of
breast cancer cases in relation to the histologic grade of malignancy.
STUDY DESIGN: The study group consisted of 50 cases of primary breast
carcinomas. For the demonstration of pS2 protein expression an
immunocyto-chemical avidin-biotin complex technique was applied.
Monoclonal antibody pS2 was used as the primary antibody,
diaminobenzidine as the chromogene and hematoxylin as the counterstain.
For the evaluation of ERs and PRs, a biochemical method was applied.
Sixty-two percent of RESULTS:
breast cancer cases showed positive expression of pS2. Of the 31 pS2+ cases, 74% had positive ERs and PRs. A statistically significant difference was observed between pS2 protein expression, ER+, PR+ and histologic grade of malignancy (P < .001). CONCLUSION: Two groups of breast cancer cases can be distinguished:
one group that is ER+, PR+ and pS2+, with low malignancy potential, and
another group that is ER-, PR- and pS2-, with high malignancy potential.
PMID: 9167689 [PubMed - indexed for MEDLINE] Markopoulos C - PubMed - NCBI MeSH Terms, Substances
c Eur J Gynaecol Oncol. 1997;18(6):495-6.
94. Bilateral Paget's disease of the breast.
Markopoulos C, Gogas H, Sampalis F, Kyriakou B.
B'Propedeutic Department of Surgery, Medical School, University of Athens, Abstract
A rare case of metachronous bilateral Paget's disease of the nipple is
presented. The occasional failure of routine follow-up to detect certain
tumours until biologically advanced and the value of patient observations
are mentioned.
PMID: 9443019 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms
c Horm Res. 1997;47(3):116-20.
95. Sex hormones in postmenopausal women with
breast cancer on tamoxifen.
Kostoglou-Athanassiou I, Ntalles K, Gogas J, Markopoulos C, Alevizou-
Terzaki V, Athanassiou P, Georgiou E, Proukakis C.
Department of Medical Physics, Medical School, University of Athens, Greece.
Abstract
In 42 postmenopausal women with breast cancer aged 48-85 (mean age
62.4) years, the blood sex hormone levels were measured before and after
6 months of tamoxifen administration (20 mg daily). Follicle-stimulating
hormone and luteinizing hormone levels decreased after tamoxifen
administration (p < 0.001), but remained in the postmenopausal range,
oestradiol levels increased (p < 0.05), sex hormone binding globulin levels
increased (p < 0.001), testosterone levels remained stable (p > 0.1), free
testosterone levels decreased (p < 0.001), delta4-androstenedione, 17-
hydroxyprogesterone, and dehydroepiandrosterone sulfate levels remained
unchanged (p > 0.1), and basal prolactin levels and their response to
thyrotrophin-releasing hormone injection decreased significantly (p < 0.001)
after tamoxifen therapy. It is concluded that tamoxifen has many and
diverse effects on sex hormone levels, and its adverse effects do not affect
the biological status of the patient, except perhaps for oestradiol, that
increases in some cases, whose possible effect must be studied.
PMID: 9050950 [PubMed - indexed for MEDLINE] MeSH Terms, Substances
c Langenbecks Arch Chir. 1997;382(1):15-8. Markopoulos C - PubMed - NCBI 96. Fournier's gangrene: still highly lethal.
Papachristodoulou AJ, Zografos GN, Papastratis G, Papavassiliou V, Markopoulos CJ, Mandrekas D, Gogas JG. Second Propedeutic Surgical Department, Laikon Hospital, Athens University, Abstract
Five patients with necrotizing soft tissue infections of the perineum and
scrotum are presented. There were one female and four male patients,
aged from 35 to 70 years. Portals of entry were perirectal abscesses in four
cases and a scrotal abscess in one case. All patients required extensive
surgical debridement and intravenous broad-spectrum antibiotics. Operative
debridement involved the scrotum, the perineal and inguinal area, the upper
thighs and the anterior abdominal wall. One patient required transverse loop
colostomy and one loop sigmoidostomy. One patient was reoperated on
after inadequate drainage of a perirectal abscess. Three patients were
referred to our unit after some delay, while one patient did not seek medical
care until after being febrile for 2 weeks. Despite aggressive debridement,
this last patient died of fulminant sepsis. Fournier's gangrene, which is not
so rare as in generally considered, is still associated with a high mortality,
which can be reduced only by improving medical awareness and early
treatment both of the primary cause and of necrotizing fasciitis.
PMID: 9049954 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms, Substances
c Zentralbl Chir. 1997;122(5):339-43.
97. [Experiences with surgical therapy of hepatic
echinococcosis].
[Article in German]
Gogas J, Papachristodoulou A, Zografos G, Papastratis G, Gardikis S,
Markopoulos C, Skalkeas G.
Second Propedeutic Surgical Department, Athens University, Laikon Hospital, Abstract
Between January 1984 and December 1990, 56 patients with hydatid liver
disease were treated surgically at our Department. Diagnosis was made by
using clinical criteria, serology and imaging techniques. Most frequent
clinical symptom was abdominal pain or local discomfort (38 patients, 68%).
Plain X-ray of the abdomen was helpful in 20 patients (36%), liver
ultrasound in 53 (93%) and computerised tumorgraphy in 56 patients,
(100%). The immunoelectrophoresis test of "arc 5" was sensitive in 51
patients (91%). Thirty patients (53%) underwent partial resection and
omentoplasty, 17 patients (30%) underwent external drainage, two cystic
resection (3%), one left lateral lobectomy (2%) and six (11%) underwent
omentoplasty and T-tube insertion. Fatal complications did not occur. Four
patients developed hepatic abscess (7%), three wound infection (5%), one
Markopoulos C - PubMed - NCBI bowel obstruction (2%) and in five instances (8%) drainage was maintained for more than three months. Of the 49 patients available for follow-up (87%), three (6%) developed recurrent disease. PMID: 9334094 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms
c Eur J Gynaecol Oncol. 1996;17(6):520-1.
98. Endometrioid carcinoma arising in a scar of
caesarean section. Case report.
Markopoulos C, Gogas H, Eleftheriou G, Floros D.
2nd Department of Surgery, Medical School, Athens University, Greece. Abstract
Endometriosis of a surgical scar is rare and occurs mainly when a
hysterectomy has been performed in the past. Development of malignancy
in such a lesion is very unusual. A rare case of primary endometrioid
carcinoma in the endometriosis of a caesarean scar is described.
PMID: 8971533 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms
c Cytopathology. 1995 Oct;6(5):325-30.
99. DNA ploidy and vimentin expression in primary
breast cancer.
Ioakim-Liossi A, Karakitsos P, Markopoulos C, Aroni K, Gogas J, Kyrkou K.
Department of Clinical Cytology and Cytogenetics, Athens University, Greece.
Abstract
The DNA content of 50 breast cancers of varying tumour type, grade and
stage was measured using static image cytometry, and correlated with
vimentin expression in the tumour cells. A tendency to increased vimentin
expression and aneuploidy was observed in high grade and late stage
tumours. A statistically significant difference was observed in DNA index
and ploidy balance between grade 1 and grades 2 and 3 carcinomas (P <
0.05) and between grade I and stage II carcinomas (P < 0.05). There was a
significant difference in the expression of vimentin between grades 1, 2, 3
(P < 0.001), and stages I, II, and III ductal carcinomas (P < 0.05). No
significant difference was observed in the proliferation index and the degree
of hyperploidy (P > 0.05) Clonal heterogeneity was observed in 25% of
breast carcinomas, and was associated with increased vimentin expression.
These changes may be indicative of genomic alteration and tumour
aggressiveness.
PMID: 8785370 [PubMed - indexed for MEDLINE] Markopoulos C - PubMed - NCBI MeSH Terms, Substances
c Cytopathology. 1995 Feb;6(1):14-21.
100. Relationship of epidermal growth factor receptor
(EGFR), proliferating cell nuclear antigen (PCNA)
and vimentin expression and various prognostic
factors in breast cancer patients.
Koutselini H, Markopoulos C, Lambropoulou S, Gogas H, Kandaraki C,
Gogas J.
Department of Cytopathology, Evangelismos Hospital, Athens, Greece.
Abstract
Cytologic specimens (FNA) from 42 primary invasive ductal breast
carcinomas and 22 matched specimens of cancer tissue were tested for
EGFR status, PCNA index and vimentin expression by
immunocytochemical staining, using an Extravidin-Biotin method, and their
relationship with various prognostic factors was investigated. EGFR
positivity, high PC10 score and vimentin positivity were significantly
correlated with high histologic grade. The coordinate expression of EGFR,
PCNA and vimentin was significantly associated with ER-negative breast
carcinomas. A positive trend was observed between high proliferating
tumours and EGFR expression. EGFR status and PCNA index were not
correlated with axillary lymph node involvement, tumour size, age and
menopausal status. Vimentin was preferentially expressed in tumours, with
lymph node metastases. Co-expression of EGFR, PCNA and vimentin was
determined in most cases. These data suggest that EGFR status, PCNA
index and vimentin expression may be important for the prediction of
biologically aggressive tumours.
PMID: 7734697 [PubMed - indexed for MEDLINE] MeSH Terms, Substances
c Am Surg. 1994 Jun;60(6):447-50.
101. Hamartomas of the breast.
Gogas J, Markopoulos C, Gogas H, Skandalakis P, Kontzoglou K,
Stavridou A.
Second Propaedeutic Department of Surgery, University of Athens, Greece.
Abstract
Hamartomas of the breast are rare tumor-like lesions composed of ducts,
lobules, fat, and fibrous tissue. The clinical and pathologic findings of six
cases of patients ranging in age from 19 to 63 years are reported.
Diagnosis is difficult, and we emphasize that fine needle aspiration and
cytology of the smears is not diagnostic for hamartomas.
PMID: 8198338 [PubMed - indexed for MEDLINE] Markopoulos C - PubMed - NCBI Publication Types, MeSH Terms
c Am Surg. 1993 Nov;59(11):733-5.
102. Bilateral breast cancer.
Gogas J, Markopoulos C, Skandalakis P, Gogas H.
Second Propedeutic Department of Surgery, University of Athens, Greece.
Abstract
Seventy-eight confirmed cases of second primary breast cancer in the
contralateral breast were encountered over a 22-year period in 1332
women with invasive breast cancer treated in our department. Tumors
were grouped into those simultaneously detected in both breasts or within
6 months of each other (synchronous, 1.6%) and those detected within
more than 6 months (metachronous, 4.2%). The mean interval between
metachronous cancers was 117 months. Patients with bilateral tumors
were more likely to have a family history of breast cancer than those with
unilateral disease. Women with metachronous tumors tended to be
younger when diagnosed with the first carcinoma as compared with those
having unilateral or synchronous bilateral cancers. No differences were
noticed in size and lymph node status between the first or second tumor of
bilateral cases in comparison to patients with unilateral disease.
Significantly more (P < 0.05) first metachronous tumors were found to be
lobular invasive cancers. Histopathologic type of the first tumor was the
same as the second in 62.8 per cent of all cases. Concordance of estrogen
receptor status between bilateral tumors was 71.4 per cent. Our results
indicate that the risk of developing, a contralateral breast cancer is related
to the patient's age, family history of breast cancer, and lobular histology of
the tumor.
PMID: 8239195 [PubMed - indexed for MEDLINE] MeSH Terms, Substances
c Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9504-7.
103. Expression of alpha-thymosins in human tissues in
normal and abnormal growth.
Tsitsiloni OE, Stiakakis J, Koutselinis A, Gogas J, Markopoulos C,
Yialouris P, Bekris S, Panoussopoulos D, Kiortsis V, Voelter W, et al.
Zoological Laboratory, Faculty of Science, University of Athens, Greece.
Abstract
Radioimmunoassays specific for the N and C termini of human
prothymosin alpha and the N terminus of human parathymosin alpha were
employed for the measurement of the levels of alpha-thymosins in human
thymus, spleen, and liver during normal growth and intestine and breast in
malignant growth. A differential expression of the two alpha-thymosins was
observed in thymus (prothymosin alpha-rich) and liver (parathymosin
Markopoulos C - PubMed - NCBI alpha-rich). A decline in the levels of both alpha-thymosins was found with age, with prothymosin alpha in thymus showing the sharpest change (15- to 30-fold). The levels of both alpha-thymosins were higher in malignant tissues as compared with healthy ones. In breast cancer, in particular, the mean increase for prothymosin alpha and parathymosin alpha was 17.9- and 11.5-fold, respectively. The major crossreactive material was characterized in all cases as intact prothymosin alpha and parathymosin alpha. These results suggest an in vivo relationship of the expression of alpha-thymosins with the human tissue cell proliferation activity. PMID: 8415730 [PubMed - indexed for MEDLINE] PMCID: PMC47597
Free PMC Article
Publication Types, MeSH Terms, Substances
c J R Coll Surg Edinb. 1993 Oct;38(5):296-8.
104. Obstructive colonic cancer.
Papachristodoulou A, Zografos G, Markopoulos C, Fotiadis C, Gogas J,
Sechas M, Skalkeas G.
2nd Propedeutic Surgical Department, Athens University School of Medicine,
Abstract
The records of 121 patients with obstructing cancer of the colon were
reviewed. About one-third of the patients had metastatic disease at the
time of operation. Primary resection and anastomosis of the intestine was
performed for most cancers of the ascending or transverse colon.
Hartmann's procedure was performed in most patients with cancer of the
sigmoid colon and rectum. Wound infection occurred in 20 patients
(16.5%) and anastomotic leakage in six (4.9%). The operative mortality
rate was 14.9%. The 5-year survival rate was 13.5%. Acute colonic
obstruction is associated with high morbidity and mortality. The high
incidence of advanced disease, advanced age, delay in tumour excision
and unprepared bowel are some of the factors resulting in the poor
prognosis of these patients.
PMID: 7506782 [PubMed - indexed for MEDLINE] MeSH Terms
c Lancet. 1988 May 28;1(8596):1218.
105. Tamoxifen and breast cancer in the elderly.
Gazet JC, Markopoulos C, Ford HT, Coombes RC, Bland JM, Dixon RC.
PMID: 2897020 [PubMed - indexed for MEDLINE] Markopoulos C - PubMed - NCBI Publication Types, MeSH Terms, Substances
c Br Med J (Clin Res Ed). 1988 May 14;296(6633):1349-51.
106. Oestrogen receptor content of normal breast cells
and breast carcinomas throughout the menstrual
cycle.

Markopoulos C, Berger U, Wilson P, Gazet JC, Coombes RC.
St George's Hospital, London. Abstract
To examine the presence and distribution of oestrogen receptors in the
normal breast during the menstrual cycle cytological samples obtained by
fine needle aspiration from 69 premenopausal women with normal breasts
were analysed immunocytochemically with a monoclonal antibody to
oestrogen receptor; samples from 15 postmenopausal women were also
analysed. The receptor content of breast cancers from 83 premenopausal
women was also determined in relation to when during the menstrual cycle
excision was performed. In the normal premenopausal women oestrogen
receptors were detected in the nuclei of epithelial cells in 21 out 68 (31%)
assessable samples. All 21 of these samples were obtained from the 35
women who were studied during the first half of their menstrual cycle (days
28 to 14). None of the 33 samples obtained during the second half of the
cycle contained oestrogen receptors. Samples were assessable in eight of
the postmenopausal women, six giving a positive result for oestrogen
receptor. Fifty one of the 83 carcinomas were positive for oestrogen
receptor, 24 having been excised during the first half of the cycle and 27
during the second half. Production of oestrogen receptor protein is
suppressed at the time of ovulation in the normal breast epithelium of
premenopausal women. In contrast, breast carcinoma cells either
synthesise this protein continuously throughout the cycle or fail to express
it despite fluctuations of serum hormone concentrations.
PMID: 3134982 [PubMed - indexed for MEDLINE] PMCID: PMC2545825
Free PMC Article
MeSH Terms, Substances
c Lancet. 1988 Mar 26;1(8587):679-81.
107. Prospective randomised trial of tamoxifen versus
surgery in elderly patients with breast cancer.
Gazet JC, Markopoulos C, Ford HT, Coombes RC, Bland JM, Dixon RC.
Breast Unit, St George's Hospital, London.
Markopoulos C - PubMed - NCBI Abstract
116 patients aged 70 or over who were judged to have surgically
resectable cancer of the breast were prospectively randomised to
tamoxifen 20 mg daily or surgical resection. At a median follow-up of three
years, local relapse or progression was seen in 15 (25%) of 60 patients in
the tamoxifen group and 21 (37.5%) of 56 in the surgical arm. Distant
metastases occurred in 8 (13%) in the tamoxifen group and in 10 (18%) in
the surgical arm. There were 13 deaths in the tamoxifen group and 11 in
the surgical arm, of which 8 and 9, respectively, were attributable to breast
cancer. Disease-free survival did not differ between the groups.
PMID: 2895214 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms, Substances
c Eur J Surg Oncol. 1988 Feb;14(1):77-8.
108. Paget's disease of the nipple occurring after
conservative management of early breast cancer.
Markopoulos C, Gazet JC.
Combined Breast Clinic, St. George's Hospital, Tooting, London, UK. Abstract
A patient with Paget's disease of the nipple is reported. The case is of
interest in that Paget's disease occurred 21 months after presentation of an
infiltrating cancer in the same breast which was treated by conservative
surgery reserving the nipple and thus the opportunity for Paget's disease to
occur.
PMID: 2831103 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms
c Am Surg. 1987 Jun;53(6):347-9.
109. Medullary carcinoma of the thyroid gland.
Gogas J, Markopoulos C, Skandalakis P, Sechas M.
Abstract
Nine cases of medullary carcinoma of the thyroid gland (MTC) are
reported. Four of the carcinomas were of the familial type. Five of the
patients were men and four were women. Patient age ranged from 23 to 66
years, with a mean age of 40 years. The median age of the four patients
with the familial MTC was 32 years. A total or a subtotal thyroidectomy was
performed in four and five patients, respectively, associated with a
modified neck dissection in six patients with involved cervical lymph
nodules. An underlying pheochromocytoma of the left adrenal was excised
in one patient prior to thyroidectomy. In all cases the parathyroid glands
were identified, and in two cases of familial MTC, in which they were
Markopoulos C - PubMed - NCBI grossly enlarged, the parathyroid glands were removed. Four patients died as a result of their disease within 3 years, whereas patients are well 4 to 12 years after surgery. The best chance of cure lies in early diagnosis and an aggressive surgical removal of the primary tumor and any cervical metastases. PMID: 3579051 [PubMed - indexed for MEDLINE] MeSH Terms

Source: http://www.markopoulos.gr/uploaded/publications/Markopoulos_abstracts_pubmed.pdf

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