Association Between Genetic Testing for Hereditary Breast Cancer and Contralateral Prophylactic Mastectomy Among Multiethnic Women Diagnosed With Early-Stage Breast Cancer

Abstract

Purpose: Increasing usage of multigene panel testing has identified more patients with pathogenic or likely pathogenic (P or LP) variants in low-moderate penetrance genes or variants of uncertain significance (VUS). Our study evaluates the association between genetic test results and contralateral prophylactic mastectomy (CPM) among patients with breast cancer.

Methods: We conducted a retrospective cohort study among women diagnosed with unilateral stage 0-III breast cancer between 2013 and 2020 who underwent genetic testing. We examined whether genetic test results were associated with CPM using multivariable logistic regression models.

Results: Among 707 racially or ethnically diverse women, most had benign or likely benign (B or LB) variants, whereas 12.5% had P or LP and 17.9% had VUS. Racial or ethnic minorities were twice as likely to receive VUS. Patients with P or LP variants had higher CPM rates than VUS or B or LB (64.8% v 25.8% v 25.9%), and highest among women with P or LP variants in high-penetrance genes (74.6%). On multivariable analysis, P or LP compared with B or LB variants were significantly associated with CPM (odds ratio = 4.24; 95% CI, 2.48 to 7.26).

Conclusion: Women with P or LP variants on genetic testing were over four times more likely to undergo CPM than B or LB. Those with VUS had similar CPM rates as B or LB. Our findings suggest appropriate genetic counseling and communication of cancer risk to multiethnic breast cancer survivors.

FIG 1.

Patients with pathogenic variants who underwent prophylactic mastectomy, stratified by gene penetrance. Total number of pathogenic variants shown is 89 because one patient had P or LP in two genes. P or LP, pathogenic or likely pathogenic.

FIG A1.

CONSORT diagram. GT, genetic testing.