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High circulating HER2 extracellular domain levels correlate with reduced efficacy of an aromatase inhibitor in hormone receptor‐positive metastatic breast cancer: A confirmatory prospective study
Author(s) -
Colomer Ramon,
LlombartCussac Antonio,
Lloveras Belen,
Ramos Manuel,
Mayordomo Jose I.,
Fernández Roberto,
Tusquets Ignasi,
Gil Miguel,
Barnadas Agustí,
Constenla Manuel,
Gilabert Montserrat,
Alba Emilio
Publication year - 2007
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.23043
Subject(s) - medicine , letrozole , metastatic breast cancer , breast cancer , aromatase inhibitor , aromatase , oncology , hormone receptor , prospective cohort study , cancer , gynecology , gastroenterology
BACKGROUND. In this specifically designed, prospective study, the authors addressed the predictive value of circulating levels of the extracellular domain (ECD) of HER2 in patients with metastatic breast cancer who were treated with letrozole. METHODS. Two hundred twenty‐six patients with hormone receptor‐positive, metastatic breast cancer received letrozole (2.5 mg daily) until they developed either disease progression or unacceptable toxicity. Efficacy was measured primarily as the time to progression (TTP) and, secondarily, as the objective response rate (ORR) and overall survival. HER2 ECD levels were determined by using a sandwich enzyme HER2/ neu immunoassay before letrozole treatment was initiated. Positive HER2 ECD status was correlated with treatment efficacy. RESULTS. Forty‐two patients (19%) had elevated HER2 ECD levels, which were associated with primary tumor HER2 expression ( P < .001) but not with age, performance status, location, or number of metastatic sites. The median TTP was significantly shorter among patients who had elevated HER2 ECD compared with the median TTP among patients who had normal levels (4 months vs 14 months; P = .0004), and the ORR was lower in the group with elevated HER2 ECD levels (14% vs 30%; P < .036). Overall survival was significantly shorter among patients with elevated serum HER‐2 ECD ( P < .0005). CONCLUSIONS. Elevated HER2 ECD concentrations predicted poorer outcomes in postmenopausal women with metastatic hormone receptor‐positive breast cancer who were treated with aromatase inhibitors like letrozole. © 2007 American Cancer Society.