Tamoxifen therapy for primary breast cancer and risk of contralateral breast cancer

Background: Women diagnosed with breast cancer have a twofold to sixfold gr eater risk of developing contralateral breast cancer than women in the gene ral population have of developing a first breast cancer. Tamoxifen therapy reduces this risk, but it is unclear if this benefit exists for both estrog en receptor (ER)-positive and ER-negative contralateral tumors. Methods: Us ing data from a population-based tumor registry that collects information o n the ER status of breast tumors, we followed 8981 women residing in wester n Washington State who were diagnosed with a primary unilateral invasive br east cancer during the period from 1990 through 1998 to identify cases of c ontralateral breast cancer. We restricted our analyses to women who were at least 50 years old and whose first breast cancer had a localized or region al stage; women who received adjuvant hormonal therapy but not chemotherapy (n = 4654) were classified as tamoxifen users, while those who received ne ither adjuvant hormonal therapy nor chemotherapy (n = 4327) were classified as nonusers of tamoxifen, By reviewing selected patient abstracts, we esti mated that 94% of the subjects were classified correctly with respect to ta moxifen use. The risk of contralateral breast cancer associated with tamoxi fen use was estimated with the use of Cox regression. All statistical tests were two-sided. Results: Of the 89 tamoxifen users and 100 nonusers of tam oxifen diagnosed with contralateral breast Cancer, 112 had ER-positive tumo rs, 20 had ER-negative tumors, and 57 had tumors with an ER status that was unknown or had not been determined by an immunohistochemical assay. The ri sk of developing an ER-positive and an ER-negative contralateral tumor amon g tamoxifen users was 0.8 (95% confidence interval [CI] = 0.5 to 1.1) and 4 .9 (95% CI = 1.4 to 17.4), respectively, times that of nonusers of tamoxife n, This difference in risk by ER status was statistically significant (P < .0001). Conclusions: Tamoxifen use appears to decrease the risk of ER-posit ive contralateral breast tumors, but it appears to increase the risk of ER- negative contralateral tumors.