Abstract P6-08-21: Prevalence of HER2 positivity in germline BRCA 1/2-associated breast cancers (gBRCA1/2-BC)
Authors: Whitaker Kristen , Obeid Elias , Goldstein Lori , Daly Mary 
Published: March 2020

Abstract
Purpose: To define the prevalence of HER2 positive breast cancer (HER2+ BC) in women with gBRCA1/2-BC and to determine whether there are significant differences in the prevalence of HER2 positivity in BRCA1 mutation carriers compared to BRCA2 mutation carriers.
Background: It is estimated that 5-10% of patients with breast cancer have a BRCA1 or BRCA2 mutation. Two poly ADP ribose polymerase inhibitors (PARPi) have been approved for metastatic HER2-negative gBRCA1/2-BC, as trials excluded those with HER2+ BC and gBRCA1/2 mutations. Most often, breast tumors in BRCA1 carriers lack the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 receptor or gene amplification (HER2). BRCA2 tumors have similar rates of ER positivity as sporadic controls, but are less likely to be HER2+. The prevalence of HER2 positivity among BRCA1 and BRCA2 mutation carriers has been variably reported in the literature. The prevalence of HER2 positivity has generally been reported as lower among BRCA1 carriers than BRCA2 carriers. The prevalence of HER2 positivity in BRCA1 carriers and BRCA2 carriers has ranged from 0-10% and 0-13% respectively. The true prevalence of HER2+ breast cancer in gBRCA1/2-BC remains poorly defined.
Methods: In this study, we assessed the prevalence of HER2 positivity among a cohort of 137 BRCA1 and BRCA2 mutation carriers who consented for participation in a single institution risk assessment program registry between 2009 and 2019. To be eligible for this study, participants had to have a documented diagnosis of invasive breast cancer and be a confirmed BRCA1 or BRCA2 mutation carrier. Participants with all stages of invasive breast cancer were included. Fisher’s exact tests and univariate logistic regression were used to analyze differences between BRCA1 and BRCA2 mutation carriers.
Results: 69 BRCA1 mutation carriers and 68 BRCA2 carriers were included in the study. Only 38 BRCA1 mutation carriers and 41 BRCA2 mutation carriers had complete HER2 data and were included in this analysis for prevalence. 12.6 % (10/79) of the study participants had HER2+ invasive breast cancer; 3 of these participants were BRCA1 carriers and 7 were BRCA2 carriers. The prevalence of HER2 positivity in BRCA1 carriers was 7.9%. The prevalence of HER2 positivity among BRCA2 carriers was 17.0% (7/41). In this small sample, the prevalence of HER2 positivity in BRCA 2 mutation carriers was numerically higher than that in BRCA1 mutation carriers, although this difference was not statistically significant (p= 0.3145).
Conclusion: In this analysis, the rates of HER2 positivity among BRCA1 mutation carriers are consistent with the range of rates previously reported (0-10%). However, the rates of HER2 positivity in BRCA2 mutation carriers (17.0%) are higher than those previously reported (0-13%). This study included participants who received breast cancer treatment at our institution where their HER2 status was verified with a pathology report, but also participants who received their breast cancer treatment at outside institutions. In the latter, HER2 status most often was obtained by verbal self-reporting. It is possible that this led to over-reporting of positive HER2 status in either BRCA1 or BRCA2 mutation carriers. Thus, estimates of HER2 positivity might be slightly overestimated. Despite some variation in HER2 positivity rates among BRCA1 and BRCA2 mutation carriers, this study demonstrates that HER2 positive breast cancers may not be as rare in gBRCA1/2-BC as previously reported in initial studies (0-3% in either BRCA1 or BRCA2 carriers). Given that BRCA1/2 mutation carriers could potentially derive therapeutic benefit from drugs, such as PARPi, it is important that future studies include gBRCA1/2-BC with HER2 positive breast cancer.
Citation Format: Kristen Whitaker, Elias Obeid, Lori Goldstein, Mary Daly. Prevalence of HER2 positivity in germline BRCA 1/2-associated breast cancers (gBRCA1/2-BC) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-08-21.