Adjuvant Hormonal Therapy for Breast Cancer May Affect Contralateral Breast Cancer Risk

From Medscape Medical News
Laurie Barclay, MD

September 1, 2009 — Long-term adjuvant hormonal therapy for breast cancer may affect the risk for contralateral estrogen receptor (ER)–positive or ER-negative tumors, according to the results of a population-based, nested case-control study reported in the August 25 online issue of Cancer Research.

"Compared with the breast cancer risk women in the general population have, breast cancer survivors have a substantially higher risk of developing a second primary contralateral breast cancer," write Christopher I. Li, MD, PhD, from the Fred Hutchinson Cancer Research Center in Seattle, Washington, and colleagues. "Adjuvant hormonal therapy reduces this risk, but preliminary data indicate that it may also increase risk of hormone receptor–negative contralateral tumors."

The study sample consisted of 367 women diagnosed with both first primary ER-positive invasive breast cancer and second primary contralateral breast cancer (case patients) and 728 matched women diagnosed only with a first breast cancer (control subjects). Telephone interviews and medical record review allowed collection of data on adjuvant hormonal therapy, other treatments, and breast cancer risk factors. Associations between adjuvant hormonal therapy and the risk for hormone receptor–specific subtypes of contralateral breast cancer were measured with two-sided statistical tests with use of conditional logistic regression.

Among case patients, 303 had ER-positive breast cancer and 52 had ER-negative breast cancer. Women who used adjuvant tamoxifen for at least 5 years had a lower risk for ER-positive contralateral breast cancer (odds ratio [OR], 0.4; 95% confidence interval [CI], 0.3 - 0.7) but a 4.4-fold (95% CI, 1.03 - 19.0) increased risk for ER-negative contralateral breast cancer vs women not treated with hormonal therapy. Tamoxifen use for less than 5 years did not appear to affect the risk for contralateral ER-negative breast cancer.

"Although adjuvant hormonal therapy has clear benefits, risk of the relatively uncommon outcome of ER-negative contralateral breast cancer may now need to be tallied among its risks," the study authors write. "This is of clinical concern given the poorer prognosis of ER– compared with ER+ tumors."

Limitations of the study include recall bias, possibly insufficient statistical power to determine a dose-response relationship for the relatively rare outcome of an ER-negative second primary contralateral tumor, relatively small sample size, and lack of generalizability to users of other types of hormonal therapy.

"The considerable benefits of adjuvant hormonal therapy for women with hormone receptor–positive breast cancer are clear as they confer substantially reduced risks of breast cancer recurrence, contralateral breast cancer, and mortality," the study authors conclude. "Nevertheless, risk of a hormone receptor–negative contralateral breast cancer may now need to be tallied among the risks of treatment with tamoxifen, and further studies are needed to determine if other hormonal therapies and the increasingly used aromatase inhibitors in particular, also carry this risk."

The National Cancer Institute supported this study. The study authors have disclosed no relevant financial relationships.

Cancer Res. Published online August 25, 2009. Abstract