Tamoxifen Significantly Lowers Risk of Contralateral Breast Cancer in BRCA-Positive Patients

Patients with mutations of BRCA1 or BRCA2 who received tamoxifen after their initial diagnosis of breast cancer reduced their chances of developing contralateral or secondary breast cancer by more than half.

A pooled analysis of three large cohort studies found that patients with mutations of BRCA1 or BRCA2 who received tamoxifen after their initial diagnosis of breast cancer reduced their chances of developing contralateral or secondary breast cancer by more than half.

The results of the analysis were published in the Journal of Clinical Oncology.

Previous randomized clinical trials have shown that women who received adjuvant treatment with tamoxifen after their first breast cancer diagnosis reduces the risk of contralateral breast cancer by half. However, this reduction of risk has not been studied in patients with BRCA1 or BRCA2 mutations, a patient population that is five times more likely to develop breast cancer over the course of a lifetime, according to the National Cancer Institute.

"In the past, the only way of reducing breast cancer risk for these high-risk women was to do invasive surgery to remove their breasts and/or ovaries," said Kelly-Anne Phillips, MBBS, MD, a consultant medical oncologist at the Peter MacCallum Cancer Centre in East Melbourne, Australia, and lead author of the study, in a statement. "For women who choose not to undergo such surgery, or who would prefer to delay surgery until they are older, tamoxifen could now be a viable alternative."

In this analysis, researchers reviewed data on patients enrolled in three international cohorts: the International BRCA1 and BRCA2 Carrier Cohort Study (IBCCS), the Kathleen Cunningham Foundation Consortium for Research into Familial Breast Cancer (kConFab), and the Breast Cancer Family Registry (BCFR). Patients were enrolled in these cohorts between September 1, 1993, and December 2, 2009.

A total of 2464 women were included in this analysis, with 1583 having mutations of BRCA1 and 881 with mutations of BRCA2. According to participant characteristics, the median time since diagnosis of first breast cancer was 6.6 years. The study combined retrospective and prospective data.

When the data from all three cohorts were pooled together, patients who had the BRCA1 mutation had a 62% lower chance of developing contralateral breast cancer if they received tamoxifen for their first breast cancer (hazard ratio [HR] = 0.38; 95% CI, 0.27-0.55; P < .001). The risk of developing this secondary breast cancer was 67% lower in patients with the BRCA2 mutation who received tamoxifen (HR = 0.33; 95% CI, 0.22 — 0.50; P < .001).

Among the 1083 women for whom prospective data were available — including 657 patients with the BRCA1 mutation and 426 patients with the BRCA2 mutation — the risks were not lowered as much, with a 42% reduction in BRCA1-mutated patients (HR = 0.58; 95% CI, 0.29 — 1.13; P = .1) and a 52% reduction in the BRCA2-mutated patients (HR = 0.48; 95% CI, 0.22 — 1.05; P = .07). However, the researchers noted that there was not enough power to appropriately make a comparison.

“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 wrote.

Though only incomplete data on whether patients were estrogen receptor (ER)-positive patients were available, this positivity did not seem to impact the effect tamoxifen had on the reduction of risk for the development of contralateral breast cancer.

The authors suggest that this study provides evidence that prescribing tamoxifen for first breast cancer may reduce the chances of developing contralateral breast cancer, and further follow-up from these cohorts will provide more definitive information.

Phillips K-A, Milne RL, Rookus MA, et al. Tamoxifen and risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers [published online ahead of print August 5, 2013]. J Clin Oncol. doi:10.1200/JCO.2012.47.8313.