ErbB2 status and the benefit from two or five years of adjuvant tamoxifen in postmenopausal early stage breast cancer

Aim: We aimed to study the importance of erbB2 status in early stage postme nopausal breast cancer for patients who participated in a trial of five vs. two years of adjuvant tamoxifen. Patients and methods: We analysed the erbB2 status of the tumours from 577 patients participating in the trial, either by a DNA amplification assay (n = 181) or by measurement of the protein level with flow cytometry (n = 396 ). Results: ErbB2 was overexpressed or gene amplified in 102 of the patients ( 18%). Overall, erbB2-positive patients had a significantly lower recurrence -free probability than others, 62% at five years as compared to 83%, and sh owed a significantly decreased breast cancer survival rate (P = 0.0007). Er bB2 status was significantly associated with recurrence and death in Cox mu ltivariate analysis, adjusting for nodal status, tumour size and estrogen r eceptor status. The relative risk of recurrence (RR) for five vs. two years of tamoxifen was analysed in relation to erbB2 status for patients still d isease-free two years after surgery. Whereas erbB2-negative patients showed significant benefit from prolonged treatment (RR = 0.62, 95% confidence in terval (95% CI): 0.42-0.93), no benefit was evident for erbB2-positive pati ents (RR = 1.1, 95% CI: 0.41-3.2). When the same analysis was restricted to ER-positive patients a similar difference in relative hazard was obtained but the difference was not strictly significant (P = 0.065). Conclusions: For early stage breast cancer patients treated with adjuvant t amoxifen, overexpression of erbB2 is an independent marker of poor prognosi s. The results suggest that overexpression decreases the benefit from prolo nged tamoxifen treatment.