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Hormone Replacement Therapy and Life Expectancy After Prophylactic Oophorectomy in Women With BRCA1/2 Mutations: a Decision Analysis

Posted on: Friday, 22 October 2004, 03:00 CDT

Objective:

To assess the potential of a decision analysis model in determining the impact of alternative assumptions about effects of hormone replacement therapy (HRT), effects of prophylactic oophorectomy and risks of cancer associated with BRCA1/2 mutations.

Introduction:

The approximate lifetime risk of developing ovarian cancer in women with a mutation in the BRCA1 or BRCA2 genes is 40% and 25%, respectively. Prophylactic oophorectomy reduces the risk of ovarian cancer in women with BRCA1/2 mutations by greater than 95% and greatly reduces the risk of breast cancer in this same population. Yet there is a reluctance to undergo a prophylactic oophorectomy in these women due to the controversial use of HRT, as well as the recent data from the Women's Health Initiative (WHI) trial. It is also unclear as to whether the duration of use of HRT following an oophorectomy in these women affects their balance of risks and benefits.

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 analyzes were conducted to assess the impact of prophylactic oophorectomy and HRT on five major diseases: breast cancer, ovarian cancer, coronary heart disease, osteoporosis and venous thrombosis.

Results:

* Prophylactic oophorectomy lengthened life expectancy in women aged 30-40 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. The decreased risk of ovarian and breast cancer from oophorectomy more than offset the increased risk of coronary heart disease and osteoporosis following an oophorectomy.

* Use of HRT after oophorectomy was associated with a relatively small change in life expectancy (0.17 to 0.34 years) when HRT was stopped at the age of 50 years, but there were 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 oophorectomy and mastectomy.

Conclusions:

The authors conclude that based on this particular decision analysis, women with BRCA1/2 mutations should undergo prophylactic oophorectomy after completion of childbearing. In addition, they should decide about short-term HRT after oophorectomy, based on quality of life issues rather than life expectancy. If they use HRT, they should consider discontinuing treatment at the time of expected natural menopause, approximately 50 years of age.

Selected references:

Rebbeck TR, Lynch H, Thomason D, et al. Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med 2002;346:1616- 22

Newman L. Prophylactic oophorectomy in the genome age: balancing new data against uncertainties. J Natl Cancer Inst 2001;93:173-5

Commentary:

Prophylactic oophorectomy reduces the risk of ovarian and breast cancer in women with BRCA1/2 mutations. However, there is a reluctance to undergo a prophylactic oophorectomy due to the controversial use of HRT in these women as well as the recent data from the WHI trial. Prophylactic oophorectomy was associated with a substantial increased life expectancy, irrespective of subsequent use of HRT.

The limitations of this analysis arise from inevitable uncertainty about many of the probability estimates and the need to restrict the number of options included in the model. The use of hysterectomy at the time of oophorectomy was not examined, however, there is insufficient evidence at this time to determine whether estrogen alone will have fewer side effects when compared to the use of both estrogen and progesterone.

The authors are commended on their insight in developing a decision analysis to help women and physicians with these difficult decisions.

Armstrong K, Schwartz JS, Randall T, Rubin SC, Weber B. J Clin Oncol 2004;6:1045-54

Further reading:

Grann V, Jacohson J, Thomason 15, et al. Effect of prevention strategies on survival and quality-adjusted survival of women with BRCA1/2 mutations: an updated decision analysis. J Clin Oncol 2002;20:2520-9

Commentary by: Sharmila Makhija, MD, Division of Gynecologic Oncology, University of Alabama at Birmingham, Birmingham, Alabama

Copyright CRC Press Jun 2004

Source: Women's Oncology Review

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