Abstract PS4-31: Characteristics of HER2/<i>neu</i> positive breast cancer among patients with and without germline <i>BRCA</i>mutations
Authors: Mihir A Shukla, Angelica Gutierrez Barrera, Stephen Karl Gruschkus, Rachel M Layman, Rashmi K Murthy, Banu K Arun
Journal: Cancer Research (2021)

Abstract Introduction: Breast cancer in BRCA 1/2 carriers is a well-characterized disease process, and its association with triple negative breast cancer has been extensively studied. In contrast, there is limited data on BRCA carriers and HER2/neu positive breast cancer, which identifies this topic as an area for further investigation. The BRCA protein plays an important role in DNA replication, whereas HER2/neu is a proto-oncogene that, when overexpressed, correlates with aggressive cancers. The relationship between these two mutations is poorly understood. There have been major strides with anti-HER2/neu therapies for HER2/neu positive disease and PARP inhibitors for BRCA germline positive patients, however there is a clinical knowledge gap in BRCA carriers who also have HER2/neu positive breast cancer. Further research into the characteristics of this population, treatment strategies, and outcomes is needed. More specifically, determining the utility of anti-HER2/neu therapies, PARP inhibitors, or the combination in this population could prove to have clinical utility. We aim to characterize the clinical characteristics, treatment strategies, and outcomes within this population. Methods: Using a prospective research patient database at the UT MD Anderson Cancer Center 1038 patients were identified to have HER2/neu associated breast cancer who had undergone genetic counseling and testing for hereditary breast cancer syndromes between 1996 and 2019. This population was descriptively characterized to evaluate the prevalence of BRCA 1/2 positivity. Clinical and pathological characteristics as well as treatment, and recurrence were collected. Chi-square was used for statistical analysis. The Kaplan-Meier method was used to compare overall survival based on BRCA status. Results: Amongst 1038 patients, germline BRCA mutation was detected in 49 (4.7%) of the patients. The median age at diagnosis for patients with BRCA mutations was significantly younger, 41.7 years (27-76), compared to 44.9 years (21-83) in the BRCA negative group (p= 0.0147). More patients were premenopausal in the BRCA positive group (p=0.027). Further characteristics are shown in Table 1. Overall survival was 71.6 months for the BRCA1 population, 81.3 months for the BRCA2 population, and 70.7 months for the BRCA negative population (p = 0.63). Recurrence free survival was 71 months for the BRCA1, 51.2 months for the BRCA2, and 59.6 months for the BRCA negative cohort (p = 0.4). Conclusion: HER2/neu positive breast cancer patients with and without germline BRCA mutations have different clinical presentations. While we did not detect a survival difference due to small number of patients, this presents an opportunity to evaluate whether new treatment strategies, such as combining anti-HER2/neu therapies with PARP inhibitors can further improve outcomes for these patients. Table 1:BRCA negativeBRCA positivep valuen%n%RaceASIAN666.724.10.0122BLACK979.8510.2HISPANIC16716.936.1NATIVE AMERICAN50.500.0OTHER111.148.2WHITE64365.03571.4Menopause Status at DxN/A40.400.00.0268POST17818.036.1PRE53454.03265.3Unknown27327.61428.6Age at Dxavg (range)44.9 (21-83)41.7 (27-76)0.0147Histology Typeductal93694.64591.80.3741lobular181.812.0mixed262.636.1other90.900.0StageI23523.81632.70.3293II46747.22040.8III28228.51224.5Unknown50.512.0Hormone Receptor StatusER and/or PR positive62663.33061.20.7271ER/PR negative35736.11938.8Unknown60.600.0Nuclear GradeI90.912.00.3474II22222.4714.3III69370.13673.5Unknown656.6510.2Ki67avg (range)40.5 (0-99)46 (10-90)0.1858Chemotypeadj32733.11632.70.2932neoadj56757.32551.0no chemo959.6816.3Herceptin Trxadj27027.31428.60.4093neoadj50651.22142.9none21121.31428.6unknown20.200.0Adj HormoneN44244.72449.00.5558Y54755.32551.0XRTN38038.42244.90.3637Y60961.62755.1989100.049100.0 Citation Format: Mihir A Shukla, Angelica Gutierrez Barrera, Stephen Karl Gruschkus, Rachel M Layman, Rashmi K Murthy, Banu K Arun. Characteristics of HER2/neu positive breast cancer among patients with and without germline BRCAmutations [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-31.