Background: Tamoxifen reduces the risk for contralateral breast cancer by approximately 30%-50%, with benefits probably limited to women with estrogen receptor (ER)-positive primary disease. In a retrospective analysis of data from National Surgical and Adjuvant Breast and Bowel Project trials B-18, B-22, and B-25, we determined whether the ER status of primary breast cancer predicts the ER status of a subsequent contralateral breast cancer and whether tamoxifen treatment affects this relationship. In these trials, tamoxifen at 20 mg/day had been administered only to women aged 50 years or older, rather than to those determined by the ER status of their primary tumor, allowing an assessment of the treatment's effects in ER-negative disease.
Methods: Among the 5513 eligible patients, 176 patients developed a contralateral breast cancer. The ER status of the primary and contralateral tumor was determined and cross-classified for women who did not receive tamoxifen (i.e., those aged 49 years or younger) and for women who did (i.e., those aged 50 years or older). ER data were available for 110 evaluable invasive contralateral breast cancers.
Results: Among patients who did not receive tamoxifen (n = 62), 89% with an ER-positive primary cancer had an ER-positive contralateral breast cancer and 70% with an ER-negative primary breast cancer had an ER-negative contralateral breast cancer (odds ratio for the association between primary and contralateral ER status = 14.8, 95% confidence interval = 3.8 to 74.3; P<.001). Among patients who received tamoxifen (n = 48), 56% with an ER-positive primary cancer had an ER-positive contralateral breast cancer and 78% with an ER-negative primary cancer had an ER-negative contralateral breast cancer (odds ratio = 3.4, 95% confidence interval = 0.53 to 39.2; P =.25).
Conclusion: The ER status of the primary breast cancer was associated with that of the contralateral breast for patients not receiving tamoxifen. Patients with an ER-positive primary cancer who received tamoxifen had a lower concordance rate with fewer ER-positive contralateral breast cancers, which may be a result of tamoxifen treatment.