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Ymittos Athens, Greece

Skarlos P.,Agios Savvas Cancer Hospital | Christodoulou C.,Metropolitan Hospital | Kalogeras K.T.,Translational Research Section | Kalogeras K.T.,Aristotle University of Thessaloniki | And 22 more authors.
Cancer Chemotherapy and Pharmacology | Year: 2012

Purpose: It is well recognized that breast cancer is a heterogeneous disease. The purpose of the current study was to classify patients according to the immunohistochemical phenotype of their tumors in an effort to evaluate the outcome of the respective groups of patients and specifically of those with triple-negative breast cancer (TNBC) following dose-dense sequential adjuvant chemotherapy. Methods: A total of 595 patients with high-risk breast cancer were treated with adjuvant anthracycline-based dose-dense sequential chemotherapy with or without paclitaxel in the context of a randomized study. ER, PgR, HER2, Ki67, EGFR, and CK5 protein expression were evaluated in 298 formalin-fixed paraffin-embedded tumor samples by immunohistochemistry (IHC). HER2 was also evaluated by chromogen in situ hybridization (CISH). HER2 status and Ki67 protein expression differentiated luminal IHC subtypes (luminal B tumors being HER2 and/or Ki67-positive). Results: Among the 298 tumors, the immunohistochemical panel classified 37 (12%) as luminal A, 198 (66%) as luminal B, 27 (9%) as HER2 enriched, and 36 (12%) as TNBC. The median follow-up time was 97 months. Patients with luminal A tumors had the best prognosis, with improved disease-free survival (log-rank, P = 0.033) and overall survival (P = 0.006) compared with the other three tumor subtypes. The three subtypes had an increased risk for relapse and death compared with luminal A in multivariate analysis, as well. No benefit from paclitaxel treatment was detected in any of the four subtypes or the total cohort. Hierarchical clustering based on mRNA expression of ER, PgR, and HER2 by quantitative RT-PCR identified patient groups that were comparable to the subtypes identified by IHC. Conclusions: The results of this study confirm that triple negative, luminal B and HER2-enriched phenotypes identified by IHC are of adverse prognostic value in high-risk breast cancer patients treated with dose-dense sequential adjuvant chemotherapy. © 2011 Springer-Verlag. Source


Fostira F.,National Diagnostics | Tsitlaidou M.,National Diagnostics | Papadimitriou C.,National and Kapodistrian University of Athens | Pertesi M.,National Diagnostics | And 17 more authors.
Breast Cancer Research and Treatment | Year: 2012

In spite the close association of the triple-negative breast cancer immunophenotype with hereditary breast cancers and the BRCA1 pathway, there is a lack of population studies that determine the frequency of BRCA1 mutations among triple-negative breast cancer patients. To address this, we have screened a large sample of 403 women diagnosed with triple-negative invasive breast cancer, independently of their age or family history, for germline BRCA1 mutations. Median age at diagnosis was 50 years (range 20-83). The overall prevalence of triple-negative cases among the initial patient group with invasive breast cancer was 8 %. BRCA1 was screened by direct DNA sequencing in all patients, including all exons where a mutation was previously found in the Greek population (exons 5, 11, 12, 16, 20, 21, 22, 23, 24-77 % of the BRCA1 coding region), including diagnostic PCRs to detect the three Greek founder large genomic rearrangements. Sixty-five deleterious BRCA1 mutations were identified among the 403 triple-negative breast cancer patients (16 %). Median age of onset for mutation carriers was 39 years. Among a total of 106 women with early-onset triple-negative breast cancer (<40 years), 38 (36 %) had a BRCA1 mutation, while 27 % of women with triple-negative breast cancer diagnosed before 50 years (56/208) had a BRCA1 mutation. A mutation was found in 48 % (50/105) of the triple-negative breast cancer patients with family history of breast or ovarian cancer. It is noteworthy, however, that of the 65 carriers, 15 (23 %) had no reported family history of related cancers. All but one of the carriers had grade III tumors (98 %). These results indicate that women with early-onset triple-negative breast cancer, and ideally all triple-negative breast cancer patients, are candidates for BRCA1 genetic testing even in the absence of a family history of breast or ovarian cancer. © 2012 Springer Science+Business Media, LLC. Source


Ernestos B.,Metropolitan Hospital | Nikolaos P.,Agios Savvas Cancer Hospital | Koulis G.,Greek National Center For Scientific Research | Eleni R.,Metropolitan Hospital | And 3 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2010

Purpose: Several in vitro studies suggest that BRCA1 and BRCA2 mutation carriers present increased sensitivity to ionizing radiation. Different assays for the assessment of deoxyribonucleic acid double-strand break repair capacity have been used, but results are rather inconsistent. Given the concerns about the possible risks of breast screening with mammography in mutation carrier women and the potentially damaging effects of radiotherapy, the purpose of this study was to further investigate the radiosensitivity of this population. Methods and Materials: The G2 chromosomal radiosensitivity assay was used to assess chromosomal breaks in lymphocyte cultures after exposure to 1 Gy. A group of familiar breast cancer patients carrying a mutation in the BRCA1 or BRCA2 gene (n = 15) and a group of healthy mutation carriers (n = 5) were investigated and compared with a reference group of healthy women carrying no mutation (n = 21). Results: BRCA1 and BRCA2 mutation carriers had a significantly higher number of mean chromatid breaks per cell (p = 0.006) and a higher maximum number of breaks (p = 0.0001) as compared with their matched controls. Both healthy carriers and carriers with a cancer history were more radiosensitive than controls (p = 0.002 and p = 0.025, respectively). Age was not associated with increased radiosensitivity (p = 0.868). Conclusions: Our results indicate that BRCA1 and BRCA2 mutation carriers show enhanced radiosensitivity, presumably because of the involvement of the BRCA genes in deoxyribonucleic acid repair and cell cycle control mechanisms. © 2010 Elsevier Inc. All rights reserved. Source


Lekakis L.,Agios Savvas Cancer Hospital | Tryfonopoulos D.,Agios Savvas Cancer Hospital | Pistamatzian N.,Agios Savvas Cancer Hospital | Panopoulos C.,Agios Savvas Cancer Hospital | And 3 more authors.
Anticancer Research | Year: 2012

Background: The prognosis of patients with metastatic breast cancer who have failed to respond to at least two different chemotherapy regimens is poor. Such patients with metastatic disease to the liver have even worse prognosis. Cisplatin and 5-fluorouracil (5-FU) can be given in patients with impaired hepatic function but their combination has not been extensively studied in this setting. Patients and Methods: We retrospectively collected data from our registry on patients with advanced metastatic breast cancer who received combination of cisplatin/5-FU. We sought to determine the toxicity, the response rate, the disease control rate and the survival of this combination. Results: We identified 25 heavily pre-treated patients, out of which 19 (76%) had liver metastases. They had been treated before with a median of three lines of cytotoxic chemotherapy. The majority of patients had also received hormonal manipulation or trastuzumab. The median number of cisplatin/5-FU administered cycles, without toxic deaths or unexpected toxicities was four. The partial response (PR) rate was 32% and the disease control rate (DCR) was 68%. The time to progression was five months and the median survival after starting on cisplatin/5-FU was six months. Conclusion: The combination of cisplatin/5-FU is active and safe in heavily pre-treated patients with metastatic breast cancer even in the presence of liver metastases and jaundice. Source


Lekakis L.,Agios Savvas Cancer Hospital | Tryfonopoulos D.,Agios Savvas Cancer Hospital | Fakinos G.,Agios Savvas Cancer Hospital | Panopoulos C.,Agios Savvas Cancer Hospital | And 4 more authors.
Anticancer Research | Year: 2012

Breast cancer (BC), the most common type of cancer in women of the Western world, is often associated with paraneoplastic syndromes (PNS). Autoimmune pancreatitis is a recently recognized entity belonging to the spectrum of IgG4-related systemic diseases, which are characterized by target-organ plasmacytic infiltration and fibrosis. In this report we review PNS associated with BC and we present the first case of BC-associated autoimmune pancreatitis as well as its successful management with steroids and immunosuppressive BC-tailored chemotherapy. Source

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