Abstract P6-08-11: Association between genetic testing for hereditary breast cancer and contralateral prophylactic mastectomy among young women diagnosed with early-stage breast cancer
Authors: McGuinness Julia E , Guo Boya , Trivedi Meghna S , Jones Tarsha , Chung Wendy K , Rao Roshni , Levinson Elana , Koval Carrie , Russo Donna , Chilton Ilana 
Published: March 2020

Background: Contralateral prophylactic mastectomy (CPM) is a risk-reducing surgery offered to women with unilateral breast cancer intended to reduce the risk of contralateral breast cancer. The rate of CPM among women with unilateral early-stage breast cancer has risen in the United States over the past two decades, despite limited evidence for a survival benefit in the majority of patients. We evaluated sociodemographic and clinical factors, including receipt and results of BRCA1/2 genetic testing or multigene panel testing, associated with CPM among young women with unilateral early-stage breast cancer.

Methods: We conducted a retrospective cohort study of women diagnosed with unilateral stage 0-III breast cancer at age ≤ 50 years between January 2007 and December 2017 at Columbia University Irving Medical Center (CUIMC) in New York, NY. Patients with bilateral breast cancer, male breast cancer, metastatic disease, or missing breast surgery information were excluded from the analysis. Demographics (age, race/ethnicity, marital status, primary health insurance) and clinical information (stage and year of diagnosis, family history of breast cancer) were collected from the electronic health record (EHR) and New York Presbyterian Hospital (NYPH) Tumor Registry. We also determined receipt of genetic testing (yes/no) and results (pathogenic/likely pathogenic [P/LP], variant of uncertain significance [VUS], negative). The primary outcome of interest was receipt of CPM. Multivariable logistic regression models were used to assess the association between demographic and clinical factors, including receipt and results of genetic testing, and CPM.

Results: Among the 1207 women who met inclusion criteria, median age was 42.9 years (standard deviation [SD], 5.7 years), and 43% identified as non-Hispanic white, 27% Hispanic, 13% non-Hispanic black, 10% Asian, and 7% other. Nearly half (49.5%, N=597) underwent germline genetic testing for cancer susceptibility genes, and of those tested, 12.6% had P/LP variants (of which 69.3% were in BRCA1/2), 14.2% had VUSs, and 73.2% had negative results. Over one-quarter (27.7%, N = 334) underwent CPM, 29.8% had a unilateral mastectomy and 42.5% had lumpectomy. In multivariable analysis, women with a younger age at diagnosis, more advanced stage disease, and a family history of breast cancer were more likely to undergo CPM. There were no differences in CPM rates by primary health insurance. Asian women were less likely to undergo CPM compared to non-Hispanic white women (odds ratio [OR]=0.56, 95% confidence interval [CI]=0.34-0.95). Compared to women who did not undergo genetic testing, CPM rates were higher among those who had a P/LP variant (OR=5.12, 95% CI=2.94-8.89), those who had a VUS (OR=1.94, 95% CI=1.23-3.36) or negative results (OR=1.51, 95% CI=1.09-2.09). From 2007 to 2017, rates of genetic testing uptake in the study population increased from 17.9% to 67.1%, and CPM rates increased from 15.2% to 30.0%.

Conclusions: Among young women with unilateral early-stage breast cancer, CPM rates were relatively high and increased over time. Women with P/LP variants were over 5 times more likely to undergo CPM compared to those who did not undergo genetic testing, however, even those with VUS or negative results were over 50% more likely to undergo CPM. The American Society of Breast Surgeons now recommends genetic testing for hereditary breast cancer among all women diagnosed with breast cancer. As multigene panel testing is increasingly utilized among women with breast cancer, further evaluation of its role in decisions regarding risk-reducing surgery such as CPM is warranted, particularly given the unclear implications of moderate-risk pathogenic variants and VUS results on contralateral breast cancer risk.

Citation Format: Julia E McGuinness, Boya Guo, Meghna S Trivedi, Tarsha Jones, Wendy K Chung, Roshni Rao, Elana Levinson, Carrie Koval, Donna Russo, Ilana Chilton. Association between genetic testing for hereditary breast cancer and contralateral prophylactic mastectomy among young women diagnosed with early-stage breast cancer [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 P6-08-11.