Comparative genomic hybridization analysis on male breast cancer

Abstract

The spectrum of genetic alterations in primary male breast cancer is not well established. We analyzed chromosomal imbalances in 39 tumor samples from primary male breast cancer by comparative genomic hybridization (CGH) and correlated CGH findings with clinicopathological factors. Chromosomal gains were most frequent at 1q (46%), 8q (46%), 16p (36%), 17q (36%), Xq (28%), 20q (26%) and Xp (18%). Losses were most commonly observed at 8p (36%), 16q (28%), 13q (28%), 6q (18%), 11q (18%) and 22q (18%). Gains at 16p, 20q and Xq and losses at 13q correlated significantly with higher degree of cytogenetic complexity. Significant associations with clinicopathological factors were observed for 18q and 216q with larger tumor size and 216q with lower proliferative activity and lower grade of malignancy. A comparison with reported CGH data from female breast cancer showed a similar pattern of chromosomal imbalances, including 11q, 28p, 18q, 213q, 116p, 216q, 117q and 120q. Our results indicate that male breast cancer shares a common pattern of imbalances with female breast cancer, suggesting that similar genetic events may underlie the development and progression of male and female breast cancer. ' 2005 Wiley-Liss, Inc.Key words: male breast cancer; comparative genomic hybridization; genomic aberrations Male breast cancer is an uncommon disease, accounting for 1% of all breast cancer cases. 1 The phenotypic characteristics are not well studied, and are mainly inferred from female breast cancer. Although both diseases share similarities, there are notable differences in risk factors, prognosis and survival. 2 Most male breast cancers are estrogen receptor (ER) and progesterone receptor (PR) positive 1 and expression levels of the HER-2/neu receptor are typically low. 3 The vast majority are ductal tumors and lobular tumors are rare. 4 The comparably unfavorable outcome in male breast cancer has been attributed to more advanced local tumor stages and high incidence of lymph node invasion. It has been postulated that close proximity to skin and nipple facilitates early invasion of lymph vessels, leading to earlier regional and distant metastasis. 5 Germline BRCA2 mutations account for a significant part of male breast cancer, but the majority of patients lack a known inherited predisposition. 6 As in women, axillary lymph node status, tumor size, histological grade and hormone receptor status have been proposed to be the prognostic factors in men with breast cancer. 1 Data regarding more recent molecular markers and their prognostic significance in male breast cancer are limited. The identification of genetic changes and new molecular markers in male breast cancer may provide insights into the biologic differences between male and female breast cancer patients and could aid in clinical management. 7 So far, data on the presence of specific genetic alterations in male breast cancer are limited. Most of these studies are focused on the analysis of germline mutations.No comprehensive molecular cytogenetic study on male breast ca...

Gene copy number variation in male breast cancer by aCGH

“…MBC alterations targeted chromosomes 1, 2, 4, 7, 11, 14 and X in more than 50% of the cases, while chromosomes 1, 2, 3, 7, 11, 15, 16, 17 and 20 were altered in more than 50% of the female series. Our data strengthens the reports of Rudlowski et al [21], who found similar imbalances between male and female BC with a less sensitive CGH. CNAs have been demonstrated to determine cancer predisposition in most high risk cancer syndromes.…”

High-resolution genomic profiling of male breast cancer reveals differences hidden behind the similarities with female breast cancer

“…We show here that male and female breast cancers share many similarities and that the main genomic aberrations are indeed the same [41][42][43], despite substantial differences in, e.g., hormonal levels [44] and HER2 status [8]. These results are in line with earlier findings using lower resolution metaphase CGH [43,45], and also imply that the key genes/genomic regions involved in the evolution and progression of MBC might indeed be fairly similar to FBC. Overall, the frequency of genomic aberrations was similar in male and female breast cancers, but when gains and losses were analyzed separately significant differences became apparent, with MBCs harboring more gains and fewer losses than FBCs.…”

Analysis of copy number changes on chromosome 16q in male breast cancer by multiplex ligation-dependent probe amplification

“…Previous studies in male breast cancer used the comparative genomic hybridization method to analyze genetic alterations. 7,8 Largely in line with these two studies, we found similarities but also differences in cytogenetic aberrations between female breast cancer and male breast cancer. In the study conducted by Rudlowski et al, 8 gain on 16p and loss of 16q was reported in a lower percentage of cases compared with our results; 36% and 42% vs 31% and 53%, respectively.…”

“…High-grade ductal cancer often has complex changes, typically small regions of gain together with larger regions of loss. [2][3][4][5][6] Genetic alterations on chromosome 16 in male breast cancer are poorly characterized compared with female breast cancer, and only a few studies have been performed 1,7,8 of which the first analyzes only one gene on 16q and the latter studies analyze small series of male breast cancer. These studies report frequent chromosomal imbalances on both the short and long arm of chromosome 16.…”