Endometrial Cancer Risk Among Germline <i>BRCA1</i>/<i>2</i> Pathogenic Variant Carriers: Review of Our Current Understanding and Next Steps.

Abstract

To review the literature exploring endometrial cancer (EC) risk among surgical candidates with germline <i>BRCA1/2</i> pathogenic variants (PVs) to guide decisions around risk-reducing (rr) hysterectomy in this population. A comprehensive review was conducted of the current literature that influences clinical practice and informs expert consensus. We present our understanding of EC risk among <i>BRCA1/2</i> PV carriers, the risk-modifying factors specific to this patient population, and the available research technology that may guide clinical practice in the future. Limitations of the existing literature are outlined. Patients with <i>BRCA1/2</i> PVs, those with a personal history of tamoxifen use, those who desire long-term hormone replacement therapy, and/or have an elevated BMI are at higher risk of EC, primarily endometrioid EC and/or uterine papillary serous carcinoma, and may benefit from rr-hysterectomy. Although prescriptive clinical guidelines specific to <i>BRCA1/2</i> PV carriers could inform decisions around rr-hysterectomy, limitations of the current literature prevent more definitive guidance at this time. A large population-based study of a contemporary cohort of <i>BRCA1/2</i> PV carriers with lifetime follow-up compared with cancer-gene negative controls would advance this topic and facilitate care decisions. This review validates a potential role for rr-hysterectomy to address EC risk among surgical candidates with <i>BRCA1/2</i> PVs. Evidence-based clinical guidelines for rr-hysterectomy in <i>BRCA1/2</i> PV carriers are essential to ensure equitable access to this preventive measure, supporting insurance coverage for patients with either <i>BRCA1</i> or <i>BRCA2</i> PVs to pursue rr-hysterectomy. Overall, this review highlights the complexity of EC risk in <i>BRCA1/2</i> PV carriers and offers a comprehensive framework to shared decision making to inform rr-hysterectomy for <i>BRCA1/2</i> PV carriers.