Earlier genetic testing predicts bilateral mastectomy in young BRCA carriers

1. Across two decades, utilization of bilateral mastectomy increased among BRCA carriers 40 years old or younger with early breast cancer, while breast conservation became less common.

2. Learning one’s BRCA result before or at diagnosis was the strongest predictor of opting for bilateral surgery.

Evidence Rating Level: 2 (Good)

Study Rundown: Women who develop breast cancer at younger ages carry inherited BRCA1 or BRCA2 changes more often than older patients, and these underlying genomic changes increase the chances that a new, separate cancer will occur in the opposite breast. At diagnosis, a genetic carrier and her surgeon must weigh options including breast conservation, removal of the affected breast only, or removal of both breasts. However, the forces shaping that choice worldwide have been poorly understood. This international study tracked thousands of young BRCA carriers treated across two decades and found that double mastectomy grew steadily more common while breast conservation faded. The strongest influence toward removing both breasts was whether a woman knew she carried a BRCA mutation before or at the time of her diagnosis, since early knowledge permits a single planned operation rather than a later return to surgery. Patient locale mattered too, with patients electing for double mastectomy more frequently in North America than in Asia or Africa. Carriers with larger or more advanced tumors were somewhat less likely to opt for bilateral mastectomy. Because medical records were reviewed retrospectively, the study was unable to capture the more nuanced considerations behind patient decisions, including those such as insurance coverage barriers or fertility plans. Even so, the findings argue for earlier testing of potential carriers to preserve the full degree of surgical options.

Click to read the study in JAMA Network Open

Relevant Reading: Comparison of Outcomes Between BRCA Pathogenic Variant Carriers Undergoing Breast-Conserving Surgery Versus Mastectomy

In-Depth [retrospective cohort]: This multinational study spanned 109 institutions across five continents. The study examined 4,715 women aged 40 or younger with germline BRCA1/2 pathogenic or likely pathogenic variants who had surgery for stage I to III invasive disease diagnosed from 2000 through 2020. Surgery was classified as breast conservation (n = 1,805, 38.3%), unilateral mastectomy (n = 1,752, 37.2%), or bilateral mastectomy (n = 1,158, 24.6%), the last combining therapeutic and contralateral risk-reducing procedures. Conservation fell from roughly 56% of surgical elections in 2000 to 27% in 2020, whereas bilateral mastectomy rose from 8% to 44% (P < .001). Multivariable logistic regression identified pre-diagnosis testing as the dominant correlate of bilateral surgery compared with post-diagnosis testing (AOR 20.72, 95% CI 15.27-28.13), with testing at diagnosis also influential (AOR 6.83, 95% CI 5.39-8.66). North America had the highest regional odds of undergoing bilateral mastectomy compared to Southern Europe (AOR 4.79, 95% CI 3.69-6.21), while Asia and Africa were the least likely (AOR 0.65, 95% CI 0.51-0.84). Bulkier tumors (T3-T4: AOR 0.55, 95% CI 0.41-0.73) and greater nodal involvement (N2-N3: AOR 0.68, 95% CI 0.51-0.91) reduced the odds of undergoing bilateral mastectomy, as did upfront surgery instead of neoadjuvant therapy (AOR 0.27, 95% CI 0.22-0.33). Among 2,327 women who knew their genetic status within six months of their breast cancer diagnosis, 42.0% chose bilateral mastectomy, ranging from 26.1% in Asia and Africa to 66.4% in North America. Reconstruction after mastectomy reached 78.4% by 2020. These findings, spanning the largest global cohort of its kind, indicated that earlier genetic testing is the strongest actionable factor for informing local therapy choices in young BRCA1/2 carriers.

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