Association of Moderate-Risk Breast Cancer Genes with Contralateral Prophylactic Mastectomy and Bilateral Disease

The impact of ATM, CHEK2, and PALB2, the three most prevalent moderate-risk breast cancer genes, on surgical decision making is not well known.

Our retrospective study included patients with resectable non-metastatic breast cancer who underwent multigene panel testing between July 2014 and January 2020 with at least one genetic alteration (pathogenic or variant of uncertain significance [VUS] in ATM [n = 49], CHEK [n = 57], or PALB2 [n = 27]). Our objectives were to determine the rate of contralateral prophylactic mastectomy (CPM) and the rate of bilateral breast cancer. Univariable analyses (UVA) and multivariable analyses (MVA) were performed to identify factors associated with CPM and bilateral breast cancer.

The rate of CPM was 39% (n = 49/127), with 54% (n = 25/46) of patients with a pathogenic mutation and 30% (n = 24/81) of patients with a VUS choosing CPM. On MVA, premenopausal status (odds ratio [OR] 3.46) and a pathogenic alteration (OR 3.01) were associated with increased use of CPM. Bilateral disease was noted in 16% (n = 22/138). Patients with pathogenic mutations had a 22% (n = 11/51) incidence of bilateral breast cancer, while patients with VUS had a 13% (n = 11/87) incidence, although this was not statistically significant on UVA or MVA. On MVA, premenopausal status was associated with a decreased risk of bilateral disease (OR 0.33, p = 0.022). During follow-up, a breast cancer event occurred in 16% (n = 22/138).

Our study identified a high rate of CPM among those with ATM, CHEK2, and PALB2 alterations, including VUS. Further studies are needed to clarify reasons for CPM among patients with moderate-risk alterations.