Breast cancer ER, PR, and HER2 expression variance by germline cancer predisposition genes.

person Grace Wei USF Health Morsani College of Medicine, Tampa, FL info_outline Grace Wei, Marilin Rosa, Maxine Chang, Brian J. Czerniecki, Xia Wang

Authors person Grace Wei USF Health Morsani College of Medicine, Tampa, FL info_outline Grace Wei, Marilin Rosa, Maxine Chang, Brian J. Czerniecki, Xia Wang Organizations USF Health Morsani College of Medicine, Tampa, FL, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, GeneHome, H. Lee Moffitt Cancer Center, Tampa, FL, Hosp of the Univ of Pennsylvania, Philadelphia, PA, Moffitt Cancer Center, Tampa, FL Abstract Disclosures Research Funding No funding received None Background: The association between breast cancer characteristics and survival with estrogen receptor (ER) and progesterone receptor (PR) expression has been primarily studied via binomial categories, ER-positive and ER-negative. In order to better characterize germline genetic influences on these markers, we investigated their IHC expression semi-quantitatively in cancer predisposition germline pathogenic variant (PV) carriers of the following genes: BRCA1, BRCA2, PALB2 , TP53 , PTEN , CDH1 , ATM , CHEK2 , and Lynch syndrome genes. The HER2 expression was also analyzed. Methods: We conducted a retrospective chart review of patients with germline panel genetic testing for cancer predisposition genes at Moffitt Cancer Center’s GeneHome clinic. Inclusion criteria included 1) women ≥18 years old, 2) breast cancer diagnosis, 3) cancer predisposition germline panel genetic test results, 4) available ER and PR expression levels, and 5) available HER expression and/or amplification status. ER, PR, and HER2 status were compared between PV carriers and non-PV carriers via Mann-Whitney U at p>0.05. Results: A total of 847 cases were reviewed for the study. Among 658 patients with a breast cancer diagnosis and complete ER PR data, 365 cases (55.5%) were non-PV carriers and 293 cases (44.5%) carried a PV in at least one of the genes listed above. Among 635 cases with available HER2 expression/amplification status, 355 (55.9%) cases were non-PV carriers and 288 (45.4%) cases were PV-carriers. When compared with non-PV carrier controls, BRCA1 PV carriers’ breast tumors had significantly lower ER and/or PR expression. Further, BRCA2 and TP53 PV tumors also displayed moderately lower ER expression. Contrarily, CHEK2 tumors displayed higher ER and PR expression compared to controls. Further, BRCA1 and BRCA2 PV carriers were more likely to have HER2- breast cancers. Conclusions: Differences in ER, PR, HER2 expression levels were observed in germline PV carrier breast cancers, signaling differential impacts by germline PVs on the tumor evolution process. It is likely that tumor differences in PV carriers influence responses to therapies, including hormone therapy, anti-HER2 therapy, and subsequent survival. ER, PR and HER2 expressions based on germline pathogenic variants. ER% mean (SD) P-Value PR% mean (SD) P-Value HER2- Case No. % HER2+ Case No. % P-Value BRCA1 14.3 (32.7) 0 6.41 (20.2) 0 58 (98.3%) 1 (1.7%) 0 BRCA2 69.0 (38.0) 0.001 45.3 (37.7) 0.19 63 (95.5%) 3 (4.5%) 0 TP53 52.1 (46.7) 0.011 38.6 (44.7) 0.306 13 (61.9%) 8 (38.1%) 0.084 PALB2 68.2 (39.5) 0.114 39.5 (34.4) 0.163 20 (90.9%) 2 (9.1%) 0.112 ATM 80.1 (34.0) 0.609 51.0 (40.0) 0.631 21 (80.8%) 5 (19.2%) 0.471 CHEK2 93.3 (17.4) 0.003 72.0 (34.6) 0.001 32 (80.0%) 8 (20.0%) 0.462 MMRs 60.9 (47.8) 0.285 40.4 (42.5) 0.454 11 (61.1%) 7 (38.9%) 0.093 PTEN 96.8 (3.82) 0.305 83.8 (17.9) 0.066 4 (100%) 0 (0.0%) 0.368 Control/ Reference 78.0 (34.5) - 48.8 (41.1) - 276 (77.7%) 79 (22.3%) -