BRCA1 and BRCA2 Carriers and Hormone Therapy
BRCA1 and BRCA2 Carriers and Hormone Therapy
Abstract & Commentary
By Leon Speroff, MD, Editor, Professor of Obstetrics and Gynecology, Oregon Health and Science University, Portland, is Editor for OB/GYN Clinical Alert.
Synopsis: Short-term HRT use does not negate the protective effect of bilateral prophylactic oophorectomy on subsequent breast cancer risk in BRCA1/2 mutation carriers.
Source: Rebbeck TR, et al. Effect of short-term hormone replacement therapy on breast cancer risk reduction after bilateral prophylactic oophorectomy in BRCA1 and BRCA2 mutation carriers: the PROSE study group. J Clin Oncol. 2005;23:7804-7810.
Rebbeck and colleagues identified a cohort of 462 women with BRCA1/2 mutations from 13 medical centers in North America and Europe.1 The incidence of breast cancer was compared in 155 of these women who had undergone bilateral prophylactic oophorectomy with 307 women who did not have the operation. The women who had oophorectomy had a 60% reduction in the risk of developing breast cancer: HR = 0.40 (CI = 0.18-0.92). Hormone therapy of any type did not alter the reduction in breast cancer experienced by the women undergoing oophorectomy. Rebbeck and colleagues concluded that short-term use (several years) of hormone therapy did not have an adverse effect on the beneficial reduction in breast cancer risk following prophylactic oophorectomy.
Commentary
Women with either BRCA1 or BRCA2 germline mutations are advised to undergo bilateral prophylactic oophorectomy after childbearing because approximately 90% will develop breast or ovarian cancer. This surgery reduces the risk of ovarian cancer by about 90% and the risk of breast cancer by about 50%. These relatively young women must consider the postoperative consequences of surgical menopause in their decision-making. This report is the first to provide data on the experience of women undergoing bilateral prophylactic oophorectomy who subsequently used hormone therapy. And the news is good.
Helzlsouer had previously reported that the use of hormone therapy did not adversely affect the reduction of breast cancer observed after prophylactic oophorectomy, but the conclusion was limited by very small numbers.1 In the current report, 93 (60%) of the women who underwent oophorectomy used hormone therapy. The average length of follow-up was 2.6 years (more than 5 years in 16%) in the surgically treated group and 4.1 years (more than 5 years in 33%) in the non-oophorectomized group. There was no hint of a difference in breast cancer reduction comparing hormone users and nonusers. The findings were similar in 34 women who used a combination of estrogen and progestin, but the power of this finding was limited by the small number.
In their discussion, Rebbeck et al review the reasons to add hysterectomy to bilateral oophorectomy, citing possible adverse effects of progestin treatment and increased risks of uterine, cervical, and fallopian tube cancer in BRCA mutation carriers. The accompanying editorial points out that the data on uterine and cervical cancers are limited by small numbers and not all reports agree. In addition, fallopian tube cancer has not been reported following bilateral prophylactic salpingo-oophorectomy. In those women not willing to undergo prophylactic mastectomy, tamoxifen treatment is offered as preventive therapy. Hysterectomy, of course, removes the possibility of tamoxifen-induced endometrial side effects.
Women who are BRCA carriers face difficult decisions. The experience reported in the PROSE study (Prevention and Observation of Surgical Endpoints) indicates that hormone therapy can be used safely for several years. Continuing follow-up of this cohort may extend this period of safety even longer. The PROSE study has provided new and important information to help BRCA women and their clinicians. It is appropriate for these women to consider hormone therapy as a means to avoid the consequences of surgical menopause.
Reference
- Helzlsouer KJ. Bad news/good news: information about breast cancer risk following prophylactic oophorectomy. J Natl Cancer Inst. 1999;91:1442-1443.
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