Tamoxifen Linked to Reduced Contralateral Breast Cancer Risk

Use of tamoxifen and aromatase inhibitors during and after breast cancer treatment were found to reduce the risk of contralateral breast cancer in a community healthcare setting, according to a study published in JAMA Oncology.

The authors of the real-world retrospective study found that among estrogen receptor (ER)-positive breast cancer patients who survived at least 5 years, tamoxifen use for 4 years or more prevented an estimated three contralateral breast cancer cases for every 100 women by year 10. This absolute risk reduction is consistent with prior results from tamoxifen clinical trials, according to study authors led by Gretchen L. Gierach, PhD, MPH, of the division of cancer epidemiology and genetics at the National Cancer Institute.

Clinical trials with tamoxifen have previously shown that the adjuvant therapy can also reduce primary cancer recurrences and improve survival.

“If adjuvant endocrine therapy is indicated for breast cancer treatment, these findings along with the findings from clinical trials suggest that women should be encouraged to complete the full [tamoxifen] treatment course,” Gierach told Cancer Network.

Gierach and colleagues analyzed 7,541 women diagnosed with a first primary unilateral invasive breast cancer at one of two Kaiser Permanente centers between 1990 and 2008. The women were followed for a median of 6.3 years (range, 1-20.9 years), were predominantly white (92.9%), and had a median age of 60.6 years at diagnosis.

Fifty-two percent of the participants (3,900 of 7,541) used tamoxifen (median, 3.3 years).

A total of 248 women (3%) developed contralateral breast cancer after an initial breast cancer diagnosis (45 in situ and 203 invasive cases). Current tamoxifen users had a 24% relative risk reduction of contralateral breast cancer for every year of tamoxifen use. There was a relative risk reduction of 66% for patients with 4 years of tamoxifen use compared with those who did not use tamoxifen.

Even women who discontinued tamoxifen use had a relative risk reduction of contralateral breast cancer, but to a lesser extent-about 15% per year of tamoxifen use for at least 5 years after treatment cessation.

Use of aromatase inhibitors in patients not treated with tamoxifen was also associated with reduced contralateral breast cancer risk (relative risk, 0.48 [95% CI, 0.22–0.97]) compared with nonusers. Risk reductions were most apparent among ER-positive patients.

“The report … is reassuring because all the rules derived, until now, from randomized clinical trial overview analyses hold true,” wrote Balkees Abderrahman, MD, and V. Craig Jordan, OBE, PhD, of the department of breast medical oncology at the University of Texas MD Anderson Cancer Center, Houston, in an accompanying editorial.

The hurdle, the editorial authors point out, is the ability of women to adhere to their tamoxifen regimen long-term. Citing previously published work, “low adherence results in early recurrence, increased medical costs, and a much worse quality of life,” they wrote.