Timing of Genetic Testing in BRCA1/2 and PALB2-Associated Breast Cancer: Preoperative Result Disclosure Increases Uptake of Risk-Reducing Mastectomy and Reduces Unnecessary Exposure to Radiotherapy

Abstract

The impact of timing of genetic testing on uptake of risk reducing mastectomy (RRM) in affected female BRCA1/2 or PALB2 carriers remains an area of evolving interest, particularly with the introduction of mainstream genetic testing initiatives. Women with stage I-III breast cancer and a confirmed germline pathogenic variant in BRCA1/2 or PALB2 between 2000 and 2023 were identified from an institutional genetics database. Uptake of RRM was evaluated according to disclosure of genetic testing results before or after index surgery for a first diagnosis of breast cancer. The cohort included 287 female BRCA1/2 or PALB2 carriers with a median age of 44 years (IQR, 36-52). Overall, 155 (54%) carriers received genetic testing results before and 132 (46%) after index breast surgery. Receipt of genetic testing results before surgery was associated with a higher rate of index bilateral mastectomy (58.7% vs. 7.6%, p<0.001) and a commensurate decrease in adjuvant radiation (41.9% vs. 74.2%, p<0.001). At a median follow up of 4.4 years after genetic testing, 219 (76.3%) affected carriers had undergone bilateral RRM, including 83.9% with preoperative knowledge and 67.4% of patients with postoperative knowledge of their germline pathogenic variant (log rank, p<0.001). On multivariate regression, disclosure of genetic testing results before index breast surgery was independently associated with long-term uptake of bilateral mastectomy (HR 1.69, 95% CI 1.21-2.38). Genetic testing results delivered prior to index breast surgery increase uptake of bilateral RRM in affected BRCA1/2 and PALB2 carriers. Efforts to mainstream genetic testing would help optimize surgical decision-making.