Survival analysis of cancer risk reduction strategies for BRCA1/2 mutation carriers

Abstract

Purpose: Women with BRCA1/2 mutations inherit high risks of breast and ovarian cancer; options to reduce cancer mortality include prophylactic surgery or breast screening, but their efficacy has never been empirically compared. We used decision analysis to simulate risk-reducing strategies in BRCA1/2 mutation carriers and to compare resulting survival probability and causes of death.

Methods: We developed a Monte Carlo model of breast screening with annual mammography plus magnetic resonance imaging (MRI) from ages 25 to 69 years, prophylactic mastectomy (PM) at various ages, and/or prophylactic oophorectomy (PO) at ages 40 or 50 years in 25-year-old BRCA1/2 mutation carriers.

Results: With no intervention, survival probability by age 70 is 53% for BRCA1 and 71% for BRCA2 mutation carriers. The most effective single intervention for BRCA1 mutation carriers is PO at age 40, yielding a 15% absolute survival gain; for BRCA2 mutation carriers, the most effective single intervention is PM, yielding a 7% survival gain if performed at age 40 years. The combination of PM and PO at age 40 improves survival more than any single intervention, yielding 24% survival gain for BRCA1 and 11% for BRCA2 mutation carriers. PM at age 25 instead of age 40 offers minimal incremental benefit (1% to 2%); substituting screening for PM yields a similarly minimal decrement in survival (2% to 3%).

Conclusion: Although PM at age 25 plus PO at age 40 years maximizes survival probability, substituting mammography plus MRI screening for PM seems to offer comparable survival. These results may guide women with BRCA1/2 mutations in their choices between prophylactic surgery and breast screening.

Fig 1.

Survival probability after different risk-reducing strategies, including no intervention, screening with mammography plus magnetic resonance imaging (screening), prophylactic mastectomy (PM), and prophylactic oophorectomy (PO) performed at various ages in 25-year-old women with mutations in (A) BRCA1 and (B) BRCA2, compared with women without BRCA1/2 mutations.

Fig 2.

Distribution of health status, comprising survival probability (Surviving) and probability of death by cause, including breast cancer death (BCD), ovarian cancer death (OCD), and other-cause death (OD), by age 70 years. Interventions include screening with mammography and magnetic resonance imaging (screening), prophylactic mastectomy (PM), and prophylactic oophorectomy (PO) in 25-year-old women with mutations in (A) BRCA1 and (B) BRCA2.