Male breast cancer: Specific biological characteristics and survival in a Portuguese cohort

Abstract

Male breast cancer (BC) represents an individual subtype of BC, with therapeutic procedures based on female BC therapy results. The present study evaluated the parameters currently used for the characterization and therapy of male BC, and their association with disease-free (DFS) and overall survival (OS), aiming to obtain a comprehensive basis to improve the personalized care of male BC. A total of 196 patients from March 1970 to March 2018 (mean follow-up, 84.9 months) were profiled, using clinicopathological review, molecular assessment [BRCA1/2, DNA repair associated (BRCA1/2) status, immunohistochemistry, fluorescence in situ hybridization and DNA flow cytometry] and Cox regression statistical analysis. The median age of patients was 66.5 years. At presentation, 39.2% of patients with invasive carcinomas were in anatomic stage (AS) I. Patients exhibited primarily invasive carcinomas of no special type, histological grade 2, estrogen receptor α-(ERα) and progesterone receptor (PR)-positive, receptor tyrosine kinase erbB-2-negative, high Ki-67, Luminal B-like and aneuploid tumors. A total of 13 of the 44 (29.5%) BRCA-evaluated patients exhibited BRCA2 mutations, significantly associated with family history (FH), bilaterality, high Ki-67 expression, absence of PR and Luminal B-like tumors. Bilaterality was associated with the occurrence of non-breast primary neoplasms (NBPN). The 5 and 10-year DFS rates, excluding patients with distant metastasis, NBPN and in situ carcinomas (n=145) were 65.9 and 58.2%, respectively, and the 5 and 10-year OS rates were 77.5 and 59.2%, respectively. In the univariate analysis, Luminal B-like subtype, BRCA2 mutations, high Ki-67 expression, and AS II and III were significantly associated with shorter DFS and OS. In addition, age >70 years was associated with low OS. In the multivariate analysis, FH, AS II and III, and Luminal B-like subtypes were associated with poorer OS. In conclusion, the data from the present study emphasize the high incidence of BRCA2 mutation in male BC, and its association with FH, bilaterality, high Ki-67 expression, negative PR expression and Luminal B-like subtypes, and with shorter DFS and OS in univariate analysis.

Male Breast Cancer—Immunohistochemical Patterns and Clinical Relevance of FASN, ATF3, and Collagen IV

“…Germinal mutational BRCA (g BRCA ) status had been formerly evaluated on 26 cases of male BC, as described in our previous study. 6 …”

“…In this series of previously evaluated estrogen receptor alpha (ERα) and progesterone receptor (PR) male BC, 6 we sought to complete the hormonal characterization by performing androgen receptor (AR) analysis, and make a comprehensive study of the eventual interactions between cell cycle regulation proteins, cell-surface proteins, fatty acid metabolism, and components of extracellular matrix. We chose these molecules, which have been little studied in male BC because of their functional interplay and potential relationship with cell proliferation.…”

Analysis of Epigenetic Alterations in Homologous Recombination DNA Repair Genes in Male Breast Cancer

“…Notwithstanding the biological peculiarities of male BC, the uselessness of mammographic screening due to low incidence rates, the high incidence of gynecomastia that may have overlapping clinical presentation, the particular anatomic characteristics of the male breast, the absence of publicly-available information about the disease, the prevalence in old age groups and the fact that males are less likely to report symptoms that would guide to an early diagnosis, contribute to the significant number of advanced stage disease at diagnosis and, consequently, the high mortality rates of male BC [25]. Indeed, in this cohort, 39.1% of the patients presented at stages III and IV and 31.3% died of disease, underlining the importance of early diagnosis.…”

“…Patient data, including age, family history, tumor bilaterality, presence of non-breast primary neoplasms, information about distant metastasis and follow-up were obtained from clinical records. Germline mutational BRCA2 status was evaluated in 37 cases of male BC and in one case of gynecomastia, as previously described [25]. This study was approved by the Ethics Committee of Portuguese Oncology Institute of Lisbon (UIC/859 in 12/11/2013).…”

Male breast cancer: clinicopathological, immunohistochemical and radiological study

“…Although male breast cancer occurs in all age groups, it is frequently observed between 60 and 70 years of age on average (2,3,10,(12)(13)(14). Genetic factors, BRCA2 mutations, family history, obesity, Klinefelter's syndrome, gynecomastia, liver disease, orchitis, undescended testicle, alcohol use, exogenous estrogen and testosterone use, and radiation are accused in the etiology (1,8,9,(15)(16)(17). Patients mostly present with a painless mass, nipple discharge, skin ulceration, or nipple retraction (2,4).…”