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Pattern of Hormone Receptor Status of Secondary Contralateral Breast Cancers in Patients Receiving Adjuvant Tamoxifen

Departments of Surgery [T. B-H., B. P-G., M. G., S. T., D. K., E. J., P. D., S. R., E. S., R. J.] and Pathology [M. R.], University of Vienna, A-1090 Vienna, Austria

In breast cancer patients receiving adjuvant tamoxifen after unilateral treatment, contralateral breast cancer (CBC) is extremely rare. As a result, only limited data are available on the hormone receptor status of CBCs evolving in tamoxifen-treated patients. The aim of our investigation was to evaluate the pattern of hormone receptor status of CBCs in patients treated with adjuvant tamoxifen at our institution. Material was collected from 35 patients. We have found that 27 of the 35 patients included into our investigation developed an estrogen receptor (ER)-positive CBC despite adjuvant tamoxifen. Seven ER-positive CBCs occurred after tamoxifen had been discontinued, and 20 patients developed an ER-positive CBC while receiving tamoxifen. Notably, 80% of these CBCs displayed moderate-to-strong levels of ER. In our opinion, the selection of ER-negative CBCs, which has previously been implicated to be the pivotal mechanism of tumor escape of CBCs evolving in tamoxifen-treated patients, is only one mechanism of tumor escape in patients receiving antiestrogen treatment. The emergence of ER-positive CBCs in the majority of tamoxifen-treated patients suggests that alternative escape mechanisms may be equally relevant. These include the emergence of ER-positive CBCs that display tamoxifen-dependent growth properties, the selection of CBCs that are tamoxifen resistant because of ER mutations with altered ER function, and, finally, the selection of ER-positive CBCs that overexpress c-erbB2.

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