Application of a newly developed ELISA for BCAR1 protein for prediction of clinical benefit of tamoxifen therapy in patients with advanced breast cancer.

Abstract

Advanced breast cancer is frequently treated with the antiestrogen tamoxifen. Response is observed in approximately one half of estrogen receptor (ER)-positive patients but ultimately fails because the cancer becomes resistant. The mechanisms for resistance of breast cancer to tamoxifen treatment are not yet understood (1). The breast cancer anti-estrogen resistance protein 1 ( BCAR1 ) gene was identified in a search for genes that cause proliferation of estrogen-dependent breast cancer cells in the presence of an antiestrogen drug (2). To assess the role of the BCAR1 protein in breast cancer progression, we developed a specific and sensitive ELISA. Here we report the use of this BCAR1 ELISA to measure BCAR1 protein concentrations in human breast cancer cytosols to predict success of tamoxifen treatment for advanced disease. Primary invasive breast tumors were collected between 1978 and June 1995. Our study design was approved by the medical ethics committee of the Erasmus MC Rotterdam. Selection of samples for analysis of response to tamoxifen in recurrent breast cancer was based on the availability of stored cytosol extracts (in liquid nitrogen), which remained after routine ER and progesterone receptor analyses (3). Tissue specimens that were sampled after neoadjuvant treatment or obtained from a biopsy were not included. In addition, the samples selected were only from ER-positive (>10 fmol/mg of protein) tumors of patients who developed recurrent disease and were treated with tamoxifen as first-line therapy. Of these 592 patients, 133 had received adjuvant chemotherapy (89 receiving cyclophosphamide–methotrexate–5-fluorouracil and 44 receiving 5-fluorouracil–epirubicin–cyclophosphamide), and none had received adjuvant hormonal therapy. The median age at the start of tamoxifen treatment for recurrent disease was 61 years (range, 28–91 years); 144 patients were premenopausal and 448 were postmenopausal. During the follow-up period, 527 of 592 patients (89%) showed tumor progression, and 433 patients (73%) died. …