Prediction of response to antiestrogen therapy in advanced breast cancer patients by pretreatment circulating levels of extracellular domain of the HER-2/c-neu protein.

PURPOSEOverexpression of the HER-2/c-neu/c-erbB2 proto-oncogene is associated with a worse prognosis in patients with breast cancer, perhaps due to an association of the HER-2 proto-oncogene protein with resistance to hormone and/or chemotherapy. Circulating levels of the extracellular domain (ECD) of the HER-2/c-neu-related protein (NRP) are elevated in 20% to 40% of patients with metastatic breast cancer. We investigated whether pretreatment levels of NRP predict response to hormone therapy (HT).MATERIALS AND METHODSCirculating NRP levels were determined in 94 patients who participated in a randomized trial of three different doses of the antiestrogen, droloxifene (DRO), as first-line HT for metastatic breast cancer.RESULTSNRP levels were elevated (> or = 5,000 U/mL) in 32 of 94 patients (34%). Only three of 32 patients (9%) with elevated NRP levels responded to DRO, compared with 35 of 62 (56%) with nonelevated NRP levels (P = .00001). Low pretreatment NRP level was the most powerful predictor of respo...