Prospective evaluation of estrogen receptor-β in predicting response to neoadjuvant antiestrogen therapy in elderly breast cancer patients

Abstract

It has been proposed that knowledge of estrogen receptor β (ER-β) expression may refine estrogen receptor α (ER-α) predictivity of response to endocrine therapy. We challenged this hypothesis in ERα-positive breast cancers subjected to preoperative antiestrogen treatment. Forty-seven elderly (≥65 years old) women with nonmetastatic, ER-α-positive (by immunohistochemistry) primary breast cancers (> 2 cm in diameter) entered a neoadjuvant hormone therapy protocol (60 mg/day toremifene for 3 months). ER-α and ER-β (ERs) mRNA was determined by semiquantitative RT-PCR, before (on core needle biopsy) and after (on surgical specimens) neoadjuvant treatment. Study end points included: (1) relation between treatment response and ER mRNA expression; and (2) changes in ER expression after treatment. The response was clinically assessed as tumor size change at the end of the preoperative treatment. ER mRNA expression was assessable before and after treatment in 38 and 20 cases respectively. ER-β was co-expressed with ER-α at variable levels and significantly correlated only with progesterone receptor (P = 0.0285). Objective clinical response, including patients with minor change (≥25–<50% tumor shrinkage after treatment), was documented in 68.4% of cases and was independent of ER-β levels or changes. ER-α levels were higher in tumors from patients in complete remission than in those from women achieving partial response or minor change compared with non-responsive patients (median expression values: 801 versus 516 versus 320 arbitrary units) and were consistently down-regulated by preoperative treatment. We conclude that in this elderly patient population with ER-α-positive tumors, ER-β mRNA was neither predictive of response to preoperative toremifene nor provided additional information to the knowledge of ER-α mRNA levels, which, conversely, were directly correlated with likelihood of response.