286P Prognostic Role of HER2 Expression in Patients with ER-positive/HER2-negative Breast Cancer: Results from a Population-Based Cancer Registry Study

Estrogen Receptor (ER)-positive (+)/Human Epidermal Growth Factor Receptor 2 (HER2)-negative (-) breast cancers (BCs) express variable protein levels of HER2, which can influence prognosis. This cohort study was conducted using data on all consecutive patients (pts) diagnosed with BC between 2005 and 2017, which were systematically and prospectively collected by the Emilia-Romagna Cancer Registry (Provinces of Piacenza, Parma, Modena, and Ferrara), Italy. The study included 13527 pts with ER+/HER2- BC. Tumors were classified by HER2 IHC score (0 [n=7155], 1+ [n=5186], or 2+ with negative FISH [n=1186]). Comparisons of clinicopathologic characteristics and disease outcome were performed. BCs with late-stage diagnosis, high histological grade, or high proliferative rate were more likely to be HER2 1+ or 2+/FISH- in comparison with earlier stage, low-grade, or low-proliferative tumors (lower bounds of 95% confidence intervals [CIs] for odds ratios [ORs] > 1). BCs with high expression of ER (≥ 80% [n=12383]) were more enriched with HER2 1+ (OR 1.39; 95%CI, 1.2-1.6) or 2+/FISH- tumors (OR 1.26; 95%CI, 1.0-1.6) than ER-low/moderate (1-79% [n=1144]) ones. The 5-year overall survival (OS) for HER2 1+ BCs was lower than that for HER2 0 or 2+/FISH- tumors (P = 0.0018). This finding was confirmed also after stratification by ER status (low/moderate and high expression; P = 0.07 and 0.007, respectively). The worse prognostic impact of HER2 expression in pts with ER-positive/HER2-negative BCs seems to be restricted to HER2 1+ tumors. The better outcome observed in pts with HER2 2+/FISH- BCs may be related to the known FISH-negative (HER2-non-amplified) status of this subgroup. These findings may help identify optimal patient inclusion criteria for clinical trials with novel anti-HER2 therapies in ER-positive/HER2-negative disease.