Publication Year: 2000 Visited: 215

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HER2 Overexpression Predicts Adjuvant Tamoxifen (TAM) Failure for Early Breast Cancer (EBC): Complete Data at 20 Yr of the Naples GUN Randomized Trial. Angelo Raffaele Bianco, Michelino De Laurentiis, Chiara Carlomagno, Ciro Gallo, Luigi Panico, Sabino De Placido, Univ Fed II, Napoli, Italy.

We Studied factors potentially predictive of adjuvant TAM efficacy for EBC. From 1978 to 1983, 433 patients (pts) were enrolled in the GUN randomized trial: 206 were assigned to TAM versus 227 controls (no-TAM). Premenopausal pts with axillary lymph node involvement (60 TAM vs 65 no-TAM) also received nine CMF cycles. Preliminary data on the predictive role of HER2 on a subsets of pts have been reported (Carlomagno, JCO 1996; Bianco, Proc.ASCO 1998). In the present study, eight biological markers were retrospectively assayed for most pts in the trial: estrogen (ER), progesterone (PgR) and prolactin (PrlR) receptors, microvessel count (MVC), s-phase fraction (SPF), tumor ploidy, epidermal growth factor receptor (EGFR) and HER2. We performed a multivariate test (Cox model) of the TAM/covariate interactions to establish whether these variables predicted for TAM efficacy. Estimates of the TAM effect were expressed as hazard ratio of death (HR) of TAM over no-TAM pts with 95% confidence intervals (95%CI). At a median follow-up of 15 years, PrlR, MVC, SPF, ploidy and EGFR did not influence TAM efficacy. Differently, HER2 had an overall significant predictive effect: HR=0.59 (95%CI: 0.40-0.87) in HER2- pts versus HR=1.09 (95%CI: 0.63-1.87) in HER2+ pts (interaction test: p=0.04). At subgroup analysis, HER2 expression had no predictive effect in pts who received concurrent CMF. Conversely, a strong HER2/TAM interaction was observed in the CMF-free subgroup with an apparent detrimental effect of TAM in HER2+ pts (HR= 2.23; 95%CI: 0.95-5.23).{table}S-phase, ploidy, EGFR, prolactin receptor and MVC do not predict for TAM efficacy. The data indicate that tumours overexpressing HER2 are unresponsive to adjuvant TAM.