Abstract LB-123: High-resolution genomic profiling of male breast cancer

Abstract

Abstract Male breast cancer (MBC) is a rare disease, accounting for only 1% of all breast cancer cases. Although it is similar to female breast cancer in many ways, distinct differences in incidence, age distribution, levels of hormone receptors, prognosis and survival have been reported. Due to the rarity of the disease, no large comprehensive studies of the etiology of the disease or randomized trials for optimizing patient management have been conducted. Thus, the recommendations for treating MBC are extrapolated from prior knowledge of female breast cancer. The aim of this study was to characterize MBC by genomic imbalances using high-resolution genomic data, and further to investigate whether this holds any prognostic information. Fifty-six fresh frozen MBC tumors were analyzed using tiling BAC arrays comprising ∼32,000 clones, making this the first study on a large series of MBC using array comparative genomic hybridization (aCGH) to date. Our data revealed that MBC in general has fewer aberrant regions than female breast cancer; many aberrations are large, involving whole chromosome arms. The most common aberrations (present in more than 25% of the cases) were: +8q, +1q, +16p, +17q, +20, +19, −8p, −11q, −13, −16q, −22q and −6q. Furthermore, chromosome 18 was completely gained or lost in 40% of the cases. These results are similar to genetic aberrations documented in female breast cancer. Recurrent high-level amplifications were defined as occurring in >1% of the samples with a log2ratio>0.9 and we identified 6 of these: 8p12 (9%), 11q13.3 (5%), 8q24.21 (4%), 12q15 (4%), 13q34 (4%), 14q21.3 (4%). These regions include known oncogenes like MYC, MDM2 and FGF4. Using Genomic Identification of Significant Targets in Cancer (GISTIC), 39 significant genomic aberrations were found, 25 gains and 14 losses. Hierarchical clustering was performed on all GISTIC regions using Pearson correlation and complete linkage of log2ratios, revealing different genomic subgroups. Two HER2 amplified cases were included, and they clustered together in a small group where 17q12 was gained in all samples. Fifteen patients were diagnosed before the age of 61 and 12 of them clustered together; 29% within this group developed metastases. A cluster containing the majority of tumors with high-level amplifications had worse survival compared to all other cases (HR=3.1; p=0.14). Most tumors in this group displayed low levels of Ki67. The majority of patients who developed metastases in the whole cohort also had Ki67 low tumors. A Kaplan-Meier analysis of metastasis free survival among ER+ patients by mode of Ki67 was performed, whereupon no difference in survival was observed between the groups. In summary, there are many similarities between male and female breast cancer with respect to genomic imbalances, but there are also distinct differences as revealed by high-resolution genomic profiling. MBC can be divided into comprehensive genomic subgroups, which may be of prognostic value. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-123.