Primarily tamoxifen-unresponsive, steroid receptor-positive breast cancer may respond to an aromatase inhibition: a pilot study.

PURPOSE: Breast carcinomas becoming tamoxifen-resistant after objective clinical response to antiestrogen therapy may remain responsive to other endocrine agents due to different mechanisms of action. The aim of our study was to analyze whether primarily tamoxifen-unresponsive/steroid receptor (SR) - positive breast carcinomas can respond to an aromatase inhibition.

PATIENTS AND

METHODS

Thirteen postmenopausal, SR-positive, metastatic breast cancer (MBC) patients were included: they had previously failed to respond to tamoxifen, either as primary systemic therapy for advanced disease, or as adjuvant treatment (5 and 8 patients, respectively). Patients were treated with 2.5 mg letrozole daily, from 2-25 months, mostly until disease progression.

RESULTS

Partial response (PR) was obtained in one third of the patients (4/13); additionally, 3 patients showed disease stabilization (SD) longer than 6 months. The observed response duration lasted from 7 to 36+ months (median 9). Overall survival from the beginning of letrozole treatment was better in letrozole responders compared with nonresponders. It appeared as if there were two different subgroups of patients: one completely endocrine-unresponsive, and the other unresponsive to tamoxifen but responsive to letrozole (supposed to be primarily tamoxifen-resistant, but otherwise endocrine-responsive). HER-2 overexpression (immunohistochemically determined as 2+ and 3+) was found in 3 patients, which could not account for the different endocrine responsiveness.

CONCLUSION

Our study confirmed that some SR-positive breast carcinomas, primarily tamoxifen-unresponsive, may respond to letrozole, thus being endocrine-responsive, while others did not respond, probably due to complete endocrine unresponsiveness. It is not likely that HER-2 was the biomarker that made the difference between these two subgroups.