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Medline ® Abstract for Reference 25

of 'HER2 and predicting response to therapy in breast cancer'

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.
Yamauchi H, O'Neill A, Gelman R, Carney W, Tenney DY, Hösch S, Hayes DF
J Clin Oncol. 1997;15(7):2518.
PURPOSE: Overexpression 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 METHODS: Circulating 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.
RESULTS: NRP 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 response toDRO (odds ratio of response, 22.4; P = .0001). Elevated pretreatment NRP levels were also associated with a shorter time to progression (TTP) and survival duration.
CONCLUSION: Pretreatment circulating NRP levels predict a low likelihood of benefit from HT, specifically DRO, in patients with estrogen receptor (ER)-positive and/or progesterone receptor (PgR)-positive or receptor-unknown metastatic breast cancer, even when adjusted for other known predictive factors, such as ER and/or PgR levels, site of disease, disease-free interval from primary treatment to recurrence, and prior adjuvant chemotherapy. These data suggest that pretreatment NRP levels may be useful in deciding whether to treat a patient who otherwise appears to be likely to respond to HT.
Lombardi Cancer Center, Department of Medicine, Georgetown University Medical Center, Washington, DC, USA.