Women with mutations in the BRCA1 or BRCA2 genes can reduce their risk for breast and ovarian cancer by having their ovaries removed, but then must decide whether to use hormone replacement therapy (HRT) for menopause symptoms triggered by that surgery. Fears that using HRT could compromise their reduced risk of breast cancer may now be diminished, because of results published early online in the Journal of Clinical Oncology.

Researchers at 13 cancer centers in North America and Europe identified a prospective cohort of 462 women with BRCA1 or BRCA2 gene mutations, 155 of whom had bilateral prophylactic oophorectomy (BPO). Compared with 307 mutation carriers who kept one or both ovaries, the BPO patients' breast cancer risk was reduced by 60 percent.

This reduced risk reflects what other studies have found, and explains why women with the mutations - as many as 90 percent of whom may develop breast or ovarian cancer if not treated - are advised by clinicians to undergo some form of BPO after completing childbearing.

But the researchers found that, among the women who had BPO, those who did receive short-term HRT had the same breast cancer risk reduction as those who did not.

Though recent findings suggest an increased risk of breast and endometrial cancer from HRT - especially estrogen and progesterone used together - no such effect appeared after short-term use in this study, with one-third of the controls and 16 percent of BPO patients followed thus far for at least 5 years. "Questions still remain, however, about longer-term use," said Dr. Sheila Prindiville, of NCI's Center for Cancer Research.

Dr. Timothy R. Rebbeck of the University of Pennsylvania School of Medicine and colleagues wrote that "adoption of effective cancer risk reduction interventions is critical" for this population. They have formed the Prevention and Observation of Surgical Endpoints (PROSE) Study Group to develop and test clinical interventions for women with BRCA1 or BRCA2 mutations.

During more than a decade of genetic testing, many thousands of women have been identified as BRCA1 or BRCA2 mutation carriers. An earlier PROSE study found bilateral oophorectomy combined with mastectomy to be an effective preventive treatment, but also raised quality-of-life issues over whether women were prepared to accept such a drastic strategy.

Therefore, clinicians are trying to discover alternative ways to reduce cancer risk in this population. They know from previous studies that surgery to remove both ovaries reduces the risk of ovarian cancer by about 90 percent and breast cancer by about half, and in this study by 60 percent.

Yet some premenopausal women decline BPO, fearing the prospect of surgically induced menopause without HRT to mitigate symptoms. Thus, both patient perceptions and clinical findings about the impact of HRT on breast cancer risk are important.

This study demonstrates that short-term HRT does not adversely affect the breast cancer risk reduction from BPO in premenopausal women. There were not enough women on HRT to produce definitive findings on the question of opposing estrogen with progesterone, and Dr. Prindiville noted that "it is important to try to quantify that risk."

By Addison Greenwood