Surgical Decision Making and Management of CHEK2 and PALB2 Breast Cancer Mutation Carriers

Background: Next-generation genetic sequencing has increasingly identified carriers of breast cancer susceptibility genes CHEK2 and PALB2. Despite the growing population of non-BRCA mutation carriers, literature on surgical decision-making in this cohort remains limited. Methods: A retrospective cross-sectional study was conducted on patients diagnosed with CHEK2 or PALB2 genetic mutations between 2016 and 2024 at a breast clinic at a tertiary-care hospital. Demographics, surgical interventions, and complications were analyzed. Results: Of over 4000 patients who were tested for a full breast cancer genetic panel, 132 CHEK2 and/or PALB2 positive patients were included. 74.2% had a personal history of breast cancer and 25.8% were tested as part of screening. Genetic diagnosis awareness significantly impacted surgical choices, with 36.7% of patients aware of their diagnosis choosing a mastectomy over breast-conserving therapy, compared to 15.7% of patients unaware of their diagnosis. There was a 23.0% conversion rate from BCT to mastectomy. 12 patients had autologous breast reconstruction and 28 had implant-based reconstruction. The major complication rate was 7.5%, and the minor complication rate was 12.5%. Conclusion: Patients with CHEK2 or PALB2 genetic diagnoses have a lifetime breast cancer risk of up to 40%; high rates of cancer recurrence; and are six-times more likely to convert to a mastectomy after BCT compared to the general population. It is imperative that CHEK2/PALB2 carriers are informed about all surgical options—including contralateral prophylactic mastectomy, bilateral risk-reducing mastectomy, and breast reconstruction. Breast reconstruction is safe in this patient population, and early consultations are important for optimizing reconstructive outcomes.