Surgical Choice among Women with a First Breast Cancer and Pathogenic Variants in Breast Cancer Genes

Patient choice regarding risk-reducing mastectomy in the setting of a new breast cancer diagnosis is not well documented. The objective of this study was to evaluate patterns in surgical treatment choices among women with a first breast cancer diagnosis and a breast cancer susceptibility gene mutation.

We conducted a single-center, retrospective analysis of women with unilateral, stage 0-III breast cancer and a high (BRCA1/2, PALB2, PTEN, STK11, TP53) or moderate (ATM, BARD1, CHEK2, RAD51C/D) penetrance gene mutation. Multivariable logistic regression was used to identify factors associated with contralateral risk-reducing mastectomy (CRRM).

Of the 132 patients included, 52% had BRCA1/2 mutations, 8% had other high penetrance mutations, and 40% had moderate penetrance mutations. Most underwent bilateral mastectomy (80%), followed by lumpectomy (15%). Women who underwent CRRM were younger and more likely to be non-smokers (p < 0.001). CRRM rates differed significantly across genes: BRCA1 (90%), ATM (89%), BRCA2 (84%), CHEK2 (67%), PALB2 (63%) [p = 0.048]. Women with moderate penetrance mutations were significantly less likely to undergo CRRM than BRCA1/2 carriers (odds ratio 0.24, 95% confidence interval 0.07-0.69; p = 0.011) CONCLUSIONS: In this cohort of women with a first breast cancer and pathogenic or likely pathogenic gene variants, we identified differing rates of CRRM across high and moderate penetrance gene mutations. While the odds of CRRM receipt were significantly lower for those with moderate penetrance mutations compared with those with BRCA1/2 mutations, the high uptake of CRRM in CHEK2 and ATM carriers is noteworthy given the lack of consensus regarding surgical management options for women with non-BRCA mutations.