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Adjuvant Hormonal Therapy for Breast Cancer and Risk of Hormone Receptor–Specific Subtypes of Contralateral Breast Cancer

¹ Division of Public Health Sciences and ² Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA

Requests for reprints: Christopher I. Li, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M4-C308, P.O. Box 19024, Seattle, WA 98109-1024. Phone: 206-667-7444; Fax: 206-667-5948; E-mail: cili{at}fhcrc.org.

Key Words: breast cancer • tamoxifen • estrogen receptor • progesterone receptor • contralateral breast cancer

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. Adjuvant hormonal therapy reduces this risk, but preliminary data indicate that it may also increase risk of hormone receptor–negative contralateral tumors. We conducted a population-based nested case-control study including 367 women diagnosed with both first primary estrogen receptor (ER)–positive invasive breast cancer and second primary contralateral breast cancer and 728 matched control women diagnosed only with a first breast cancer. Data on adjuvant hormonal therapy, other treatments, and breast cancer risk factors were ascertained through telephone interviews and medical record abstractions. Two-sided statistical tests using conditional logistic regression were conducted to quantify associations between adjuvant hormonal therapy and risk of hormone receptor–specific subtypes of contralateral breast cancer (n = 303 ER+ and n = 52 ER– cases). Compared with women not treated with hormonal therapy, users of adjuvant tamoxifen for 5 years had a reduced risk of ER+ contralateral breast cancer [odds ratio, 0.4; 95% confidence interval (CI), 0.3–0.7], but a 4.4-fold (95% CI, 1.03–19.0) increased risk of ER– contralateral breast cancer. Tamoxifen use for <5 years was not associated with ER– contralateral breast cancer risk. Although adjuvant hormonal therapy has clear benefits, risk of the relatively uncommon outcome of ER– contralateral breast cancer may now need to be tallied among its risks. This is of clinical concern given the poorer prognosis of ER– compared with ER+ tumors. [Cancer Res 2009;69(17):6865–70]