Prophylactic Bilateral Mastectomy Among Women With Breast Cancer and Pathogenic Variants in High-Penetrance and Moderate-Penetrance Genes

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In a study reported in JAMA Oncology, Reid et al found that undergoing prophylactic bilateral mastectomy was as common in women with breast cancer with pathogenic/likely pathogenic variants in ATM and CHEK2 (moderate-penetrance genes) as in those with variants in BRCA1, BRCA2, or PALB2 (high-penetrance genes).

As stated by the investigators, “Risk-reducing mastectomy is a consideration in female BRCA1, BRCA2, and PALB2 heterozygotes, in contrast with ATM and CHEK2 heterozygotes, per current national practice guidelines. The objective of this study was to evaluate differences in surgical treatment across high- and moderate-penetrance breast cancer genes with differing clinical recommendations.”

Study Details

The study used data from the Inherited Cancer Registry (ICARE) on 684 women with breast cancer and confirmed pathogenic/likely pathogenic variants in BRCA1 (n = 235), BRCA2 (n = 217), PALB2 (n = 121), ATM (n = 50), or CHEK2 (n = 61). Mean age at diagnosis was 53 years (range = 23–83years); 91% of patients were White.

Key Findings

No significant differences in rates of bilateral mastectomy were observed among patients with variants in BRCA1 (42%), BRCA2 (44%), PALB2 (45%), ATM (55%), or CHEK2 (43%) (overall P = .73), and no significant difference was observed in comparison of the total groups of patients with high-penetrance vs moderate-penetrance genes (33% vs 36%, P = .47). On multivariate analysis, there was no association between receipt of bilateral mastectomy and the gene with the pathogenic/likely pathogenic variant.

Family history of breast cancer was similar across all five genes, with no significant association between receipt of bilateral mastectomy and family history being observed on multivariate analysis.

On multivariate analysis, factors associated with receipt of bilateral mastectomy were breast cancer diagnosis at age < 50 years vs ≥ 50 years (adjusted odds ratio [OR] = 2.21, 95% CI = 1.44–3.40) and receipt of genetic testing prior to vs after surgery (adjusted OR = 5.79, 95% CI = 3.83–8.76).

The investigators concluded, “Our findings indicated similar rates of bilateral mastectomy across high- and moderate-penetrance genes…. Similar rates of bilateral mastectomy across all five genes of varied penetrance are concerning, given that prophylactic contralateral mastectomy for risk reduction is considered only for high-penetrance genes, per national practice guidelines. These findings warrant further evaluation to explore possible overtreatment among patients with breast cancer who have ATM and CHEK2 pathogenic/likely pathogenic variants.”

Tuya Pal, MD, of Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, is the corresponding author for the JAMA Oncology article.

Disclosure: The study was supported by the National Cancer Institute, Susan G. Komen Foundation, and ASCO. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.