Hormone replacement therapy and life expectancy after prophylactic oophorectomy in women with BRCA1/2 mutations: a decision analysis.
OBJECTIVE
The decision about prophylactic oophorectomy is difficult for many premenopausal women with BRCA1/2 mutations because of concerns and controversy about the use of hormone replacement therapy (HRT) after oophorectomy.


METHODS
A Markov decision analytic model used the most current epidemiologic data to assess the expected outcomes of prophylactic oophorectomy with or without HRT (to age 50 years or for life) in cohorts of women with BRCA1/2 mutations. Sensitivity analyses were conducted to assess the impact of alternative assumptions about effects of HRT, effects of prophylactic oophorectomy, and risks of cancer associated with BRCA1/2 mutations.


RESULTS
In our model, prophylactic oophorectomy lengthened life expectancy in women with BRCA1/2 mutations, irrespective of whether HRT was used after oophorectomy. This gain ranged from 3.34 to 4.65 years, depending on age at oophorectomy. Use of HRT after oophorectomy was associated with relatively small changes in life expectancy (+0.17 to -0.34 years) when HRT was stopped at age 50, but larger decrements in life expectancy if HRT was continued for life (-0.79 to -1.09 years). HRT was associated with a gain in life expectancy of between 0.39 and 0.79 years for mutation carriers undergoing both prophylactic mastectomy and oophorectomy.


CONCLUSIONS
On the basis of the results of this decision analysis, we recommend that women with BRCA1/2 mutations undergo prophylactic oophorectomy after completion of childbearing, decide about short-term HRT after oophorectomy based largely on quality-of-life issues rather than life expectancy, and, if using HRT, consider discontinuing treatment at the time of expected natural menopause, approximately age 50 years.
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6021, USA. karmstro@mail.med.upenn.edu
Katrina
K
Armstrong
J Sanford
JS
Schwartz
Thomas
T
Randall
Stephen C
SC
Rubin
Barbara
B
Weber
D000328:Adult; D000367:Age Factors; D015331:Cohort Studies; D003661:Decision Support Techniques; D015914:Estrogen Replacement Therapy / Q000009:adverse effects; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006801:Humans; D008017:Life Expectancy; D008390:Markov Chains; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics / Q000517:prevention & control*; D010052:Ovariectomy; D011182:Postoperative Care; D012306:Risk; D016896:Treatment Outcome