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Decision Analysis of Prophylactic Surgery or Screening for BRCA1 Mutation Carriers: A More Prominent Role For Oophorectomy

From the Joint Center for Radiation Oncology Arnhem-Nijmegen (RADIAN) and Department of Human Genetics and Hereditary Cancer Clinic, University Medical Center Nijmegen; Nijmegen Institute for Cognition and Information, University of Nijmegen; and Department of Medical Psychology, Academic Medical Center, Amsterdam, the Netherlands.

Address reprint requests to Mariëlle van Roosmalen, MSc, Joint Center for Radiation Oncology Arnhem-Nijmegen (RADIAN), University Medical Center Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands; email: m.vanroosmalen{at}rther.azn.nl

PURPOSE: BRCA1 mutation carriers have a high risk of developing breast and ovarian cancer. Carriers may opt for prophylactic surgery and screening. Recent data suggesting that prophylactic oophorectomy reduces breast cancer risk have been incorporated in a decision analysis.

METHODS: A Markov model was developed to compare LE and QALE following four strategies: (1) prophylactic mastectomy and prophylactic oophorectomy (PMPO), (2) screening for breast cancer and prophylactic oophorectomy (BSPO), (3) prophylactic mastectomy and screening for ovarian cancer (PMOS), and (4) screening for breast and ovarian cancer (BSOS). The analysis was performed for a high (85% breast cancer, 63% ovarian cancer) and medium (56% breast cancer, 16% ovarian cancer) risk level. Utilities for the health states after prophylactic surgery were obtained from mutation carriers. Other model parameter values were obtained from the literature. Sensitivity analyses were performed.

RESULTS: When compared with BSOS, the average gain in LE for 30-year-old carriers in the high (medium) risk group was 11.7 (6.6) years for PMPO, 9.5 (5.3) years for BSPO, and 4.9 (4.4) years for PMOS. For 30-year-old carriers, BSPO had a QALE advantage when PO was performed before age 40. In the medium-risk group, there was a stronger advantage for BSPO when QALE was considered.

CONCLUSION: PMPO is the most effective strategy to prolong life. However, if patient preferences were taken into account, BSPO tends to be a better strategy in most women at medium risk or in young women at high risk when PO was performed before age 40.

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