TAMOXIFEN BENEFITS BRCA CARRIERS

A new study confirms that tamoxifen reduces the risk for breast cancer recurrences in women who carry the BRCA1 andBRCA2 mutations. It offers an option for women who do not want surgery, the researchers comment.

"Our findings are consistent with those of other smaller observational studies that used retrospective data and strengthen those findings," write the authors, led by Kelly-Anne Phillips, MD, Division of Cancer Medicine, Peter MacCallum Cancer Centre, Victoria, Australia.

The study is published online ahead of print in the Journal of Clinical Oncology.

Among women in the general population, extensive data have shown that adjuvant tamoxifen treatment following a first diagnosis of breast cancer can cut the risk for contralateral breast cancer in half. However, the authors note, it is not yet certain whether tamoxifen has a similar effect for women carrying mutations in BRCA1 or BRCA2. Thus, it is not commonly prescribed to this population for the purpose of preventing breast cancer.

Surgery is the usual option in this population. BRCA carriers face a heightened risk for both breast and ovarian cancer, and undergoing bilateral mastectomy and premenopausal bilataleral salpingo-oophorectomy are associated with a more than 90% reduction in the risk of developing breast cancer, the authors note. However, these are not acceptable interventions for some women, they add.

Role for Tamoxifen

A second breast cancer is very common in this population, commented Steven Narod, MD, who holds the Canada Research Chair in breast cancer at the University of Toronto and Women's College Research Institute, in Ontario, Canada. "For a BRCA carrier, the chance of getting a second breast cancer could be as high as 50%."

"This study shows that tamoxifen is effective and cuts it in half," said Dr. Narod, who was approached by Medscape Medical News for an independent comment. "It's not as good as we'd like. Surgery cuts the risk by 100%, and my recommendation for women with breast cancer who are BRCA carriers is bilateral mastectomy and oophorectomy."

There is a role for tamoxifen for women who decide not to have surgery, he continued. "Most women will opt for surgery, and that brings the risk to zero. About 60% of the BRCA carriers at our institution will have surgery."

But the question is, Dr. Narod pointed out, whether there is a larger role for tamoxifen in preventing in the first place. Drawing from these results, does it make sense to give tamoxifen to BRCA carriers prior to developing breast cancer in the first place?

"I think the answer is yes," he said. "Is it worth doing? I think the answer to that is yes also."

Dr. Narod added that he would have no hesitation recommending tamoxifen to BRCA carriers who decide not to undergo prophylactic surgery.

Although the data in this article are not new, "there is value to this paper because it corroborates what has already been shown," he said.

Study Details

Dr. Phillips and colleagues evaluated whether adjuvant tamoxifen treatment for BRCA1 and/or BRCA2mutation carriers with a first diagnosis of breast cancer would reduce the risk for contralateral recurrence. They also examined whether the strength of any association differs according to the estrogen receptor (ER) status.

Their analysis used pooled observational cohort data from several studies: the International BRCA1, and BRCA2 Carrier Cohort Study, the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, and the Breast Cancer Family Registry.

Of 1583 BRCA1 and 881 BRCA2 mutation carriers who were identified, 383 (24%) and 454 (52%), respectively, took tamoxifen after being diagnosed with breast cancer. Overall, there was a total of 520 contralateral breast cancer cases during 20,104 person-years of observation.

Contralateral breast cancer developed in 520 women (24% of BRCA1 and 17% of BRCA2 mutation carriers), and 100 of these cases occurred after the patients' entry into the cohort. An analysis that included both retrospective and prospective data found a hazard ratio (HR) of 0.38 (P < .001) forBRCA1 carriers and an HR of 0.33 (P < .001) for BRCA2 carriers.

However, when the analysis was limited to prospective data, the effect was reduced, with an HR forBRCA1 carriers of 0.58 (P = .1); for BRCA2 mutation carriers, the HR was 0.48 (P = .07).

Prospective Analysis Limited

The authors note that when the analyses were restricted to prospective data only, there was only weak evidence that tamoxifen use is associated with reduced risk for contralateral breast cancer, with "statistically nonsignificant HR estimates that were less than 1." Thus, the post hoc power for analyzing prospective data was limited, in that for each of BRCA1 andBRCA2 mutation carriers, there was 80% power at P < .05 to detect HRs of 0.35 or less.

"Therefore, our statistically nonsignificant findings from analysis of the prospective data only should not necessarily be interpreted as a lack of confirmation of the highly significant results from the analysis of the pooled retrospective and prospective data, especially given the consistency in the HR estimates from the two analyses," the authors point out.

They add that additional follow-up of these cohorts will provide "increased statistical power for prospective analyses and thus a more definitive answer to this important question in the future."

The authors have disclosed no relevant financial relationships.

J Clin Oncol. Published online August 5, 2013. Abstract