Evolution and prognostic significance of HER-2 changes from primary to residual disease in patients with HER-2–negative breast cancer receiving neoadjuvant chemotherapy.

Abstract

583 Background: HER-2 changes during the neoadjuvant chemotherapy has not been thoroughly evaluated. The current study aimed to analyze the HER-2 status changes from primary to residual disease in HER-2 negative patients after neoadjuvant chemotherapy and evaluate its impact in survival outcomes. Methods: HER-2 negative breast cancer patients with residual disease after NACT who had paired pre- and post-therapeutic HER2 testing results were retrospectively analyzed. Data on clinical and pathological characteristics, treatment information, and survival outcomes were collected for all eligible patients. HER2 changes from the primary to residual disease were described and logistic regression were performed to identify factors associated with HER2 changes. The Kaplan–Meier method and multivariate Cox regression were used for survival analysis. Results: 571 HER-2 negative breast cancer patients with residual disease after NACT were enrolled, including HER2-zero (35.2%, n=201) and HER2-low (64.8%, n=370) patients before NAC. The overall rate of HER-2 changes rate was 32.4% (negative to positive 1.1%, low to zero 15.4%, zero to low 15.9%). Among the patients with HER-2-zero before NAC, patients with HER-2 changes (zero to low) were likely to be hormone receptor positive (68.1% vs 36.7%, P<0.0001) and had a higher proportion of patients with Ki-67≤20 (Ki-67≤20 27.5% vs 15.6%, P=0.035). Among the patients with HER2-low before NAC, a higher proportion of hormone receptor negative were observed in HER2 changes patients (low to zero) (31.8% vs 18.4%, P=0.008) and the Ki-67 is relatively high in HER-2 changes patients (Ki-76 > 20 73.9% vs 65.0% P=0.030). Multivariable logistic regression analyses showed patients with hormone receptor positive before NAC were related to underwent HER2-zero transferring to HER2-low (OR, 3.436, P<0.0001). The median follow-up time was 50.0 months. In the HER-2 zero group, HER2 changes (zero to low) was significantly associated with better DFS comparing with constant HER2-zero (HR0.49, P=0.01) after adjustment, with 4-year DFS rate was 80.1%,55.7% (Log-rank P =0.033). Subgroup analysis showed that in the hormone receptor positive subgroup, patients with HER2 zero to low has a significant better DFS than patients with constant HER2-zero (Log-rank P=0.037). In the HER2-low group, no significant differences in survival outcomes between constant HER2-low and HER2 low to zero (HR1.07, P=0.778). Conclusions: HER2 status showed instability from primary tumor to residual disease after neoadjuvant treatment. HER2 changes (zero to low) was associated with better DFS in HER-2 zero patients.