Was Angelina Jolie Right? Optimizing Cancer Prevention Strategies Among BRCA Mutation Carriers

Abstract

Female carriers of a BRCA1 or BRCA2 genetic mutation face significantly elevated risks of cancer, with 45%–65% of women developing breast cancer and 15%–39% developing ovarian cancer in their lifetimes. Prophylactic surgery options to reduce cancer risk include a bilateral mastectomy (BM), bilateral salpingo-oophorectomy (BSO), or both surgeries. No comprehensive model providing recommendations at which age to perform the surgeries to optimize quality-adjusted life years (QALYs) exists. Using available clinical data, we develop a Markov decision process model of a mutation carrier’s health states and corresponding transitions, including age-dependent breast and ovarian cancer risk, distribution of each cancer subtype and stage, and mortality. We convert the problem to a linear program to solve for the optimal surgery sequence that maximizes the carrier’s expected lifetime QALYs under varying assumptions about individual patient preferences on postsurgery quality of life, fertility considerations, advances in cancer screening or treatment, and others. Baseline results demonstrate that a QALY-maximizing sequence recommends BM between ages 30 and 60 and BSO after age 40. Surgeries are recommended later for BRCA2 mutation carriers, given their lower risk for both cancers compared to BRCA1 mutation carriers. We derive structural properties from the model and show that when a carrier has already undergone one surgery, there exists an optimal control limit beyond which performing the other surgery is always QALY maximizing.