Prognostic role of HER2 expression in patients with ER-positive/HER2-negative breast cancer: Results from a population-based cancer registry study.

Abstract

547 Background: Estrogen Receptor (ER)-positive (+)/Human Epidermal Growth Factor Receptor 2 (HER2)-negative (-) breast cancers (BCs) express variable protein levels of both ER and HER2, which can influence prognosis. Methods: We evaluated all invasive ER+/HER2- BCs (n = 3633) that were diagnosed and systematically collected by the Parma Province Cancer Registry, Italy, from 2004 to 2018. Tumors were classified by HER2 (IHC score of 0, 1+ or 2+ with negative FISH) and ER status (ER-low [1-9%], ER-moderate [10-79%] or ER-high [80-100%]). Comparisons of clinicopathologic characteristics and disease outcome were performed. Results: BCs with late-stage diagnosis ( P = 0.04), high histologic grade ( P < 0.0001), or high proliferative rate ( P < 0.0001) were more likely HER2 2+/FISH-. The rate of ER-high BCs did not change from 2675 of 2938 (91%) HER2 0 tumors to 508 of 560 (90.7%) HER2 1+, and 124 of 135 (91.9%) HER2 2+/FISH- tumors. Correspondingly, ER-low BCs were not enriched among HER2 0 tumors compared to the other tumors with different HER2 expression ( P = 0.6). The 5-year overall survival (OS) for HER2 2+/FISH- BCs was lower than that for HER2 0 or 1+ tumors ( P = 0.03). ER-low/moderate tumors were associated with poorer OS in comparison with ER-high BCs ( P < 0.0001). HER2 2+/FISH- status was detrimental to OS among patients (pts) with ER-high tumors ( P = 0.04), while this finding was not observed among ER-low/moderate BCs ( P = 0.21). An interaction between HER2 2+/FISH- expression and ER-high status was found for poorer OS after adjusting for prognostic variables (HR = 1.7; 95% CI: 1.1-2.9). Conclusions: The prognostic role of HER2 expression in pts with ER-positive/HER2-negative BCs seems to be restricted to ER-high tumors, while the worse prognosis of tumors with lower ER expression is not associated with HER2 status. These findings may help identify optimal patient inclusion criteria for clinical trials with novel anti-HER2 therapies in ER-positive/HER2-negative disease.

Hormone Receptor-Positive/HER2-Positive Breast Cancer: Hormone Therapy and Anti-HER2 Treatment: An Update on Treatment Strategies

“…ER-low/moderate tumors were associated with poorer OS in comparison with ER-high BCs (p < 0.0001). ER-high tumors with HER2 2+/FISH-status had a worse OS (p = 0.04), while this association was not found among ER-low/moderate BCs (p = 0.21) [103,104].…”

“…In an Italian cohort, 5-year overall survival (OS) for HER2 2+/FISH-BCs was lower than that for HER2 IHC 0 or 1+ tumors (p = 0.03). In addition, HER2 2+/ISH-negative BCs have more likely late-stage diagnosis (p = 0.04), high grade (p < 0.0001), or high Ki67 (p < 0.0001) [103].…”