Evaluation of pathologic and genomic characteristics in male breast cancer (MBC) patients.

Abstract

1098 Background: MBC is a rare entity comprising less than 1% of breast cancers [Siegel RL 2017]. Due to the low incidence of MBC, information about the genomic landscape of MBC is lacking. Here we describe detailed pathologic and genomic characteristics of MBC patients. Methods: IRB approval was obtained for a retrospective analysis of archived pathology on patients treated at Cancer Treatment Centers of America. Comprehensive genomic profiling of tumors was derived from Foundation One next generation sequencing. Clinical information was derived from retrospective chart review. Inclusions: adult males with breast cancer with stage IV metastatic disease. Exclusions: Females, stage 0-IIIC disease, missing genomic and pathology information. Results of clinical, pathology and genomic data were summarized. Results: 10 patients met study criteria. Median age: 56 yrs., range 39-61 yrs. Race: 5/10 (50%) Caucasian, 5/10 (50%) African American. Number of prior treatment regimens: mean = 2.6 (range 0-6). Intrinsic subgroup: hormone receptor (HR)+/ HER2- 7/10 (70%), HR+/ HER2+ 2/10 (20%), HR-/ HER2+ 1/10 (10%), triple negative breast cancer (TNBC) 0/10 (0%). Tumor histology: invasive ductal carcinoma 10/10 (100%). Histology grade: poorly differentiated (diff.) 4/10 (40%), moderate diff. 4/10 (40%), well diff. 1/10 (10%), unknown 1/10 (10%). Biopsy site: primary tumor 4/10 (40%), metastatic site 4/10 (40%), liquid biopsy 1/10 (10%). Most frequent genomic alterations: PIK3CA 5/9 (56%), CCND1 4/9 (44%), ZNF703 3/9 (33%), FGF4 3/10 (33%), GATA3 3/9 (33%) FGF 19 3/9 (33%), FGF3 3/9 (33%) Alterations in FGF seen 14/38 (36.8%) of total genomic alterations. Most frequent alterations by primary tumor: ZNF703 3/4 (75%), FGF3 2/4 (50%), FGFR1 2/4 (50%), CCND1 2/4 (50%), FGF19 2/4 (50%), FGF4 2/4 (50%); by metastatic site: PIK3CA 4/5 (80%), GATA 3 2/5 (40%), CCND1 2/5 (40%), FGF3 1/5 (20%), FGF19 1/5 (20%), FGF4 1/5 (20%). Genomic alteration by histologic subgroup; HR+ HER2- PIK3CA 3/6 (50%), CCND1 3/6 (50%), FGF4 3/6 (50%), ZNF703 3/6 (50%), FGF19 3/6 (50%), FGF3 3/6 (50%); HR+/ HER2+: PIK3CA 2/2 (100%), CCND1 1/2 (50%), GATA3 1/2 (50%), MLL3 1/2 (50%); TNBC: BRCA2 1/1 (100%), BARD1 1/1 (100%). Microsatellite status was stable in 6/6 (100%) of patients. Conclusions: MBC patients display a heterogeneous variety of complex genomic alterations. Mutations in FGF genes were most commonly observed. Other common alterations seen in this series include PIK3CA, CCND1, ZNF703, and GATA3. Furthermore, the genomic profile of primary tumor site differed from the genomic profile of the metastatic site.