Predictive markers of treatment response to neoadjuvant systemic therapy with dual HER2-blockade

Abstract

Abstract Background In patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, achievement of pathologic complete response (pCR) is a known prognostic indicator after neoadjuvant systemic therapy (NAST). We investigated the clinicopathological factors associated with pCR in patients with HER2-positive breast cancer treated with dual HER2-blockade. Methods In this retrospective study, 348 patients with HER2-positive breast cancer were included, who received NAST with docetaxel and carboplatin, combined with trastuzumab and pertuzumab (TCHP). We assessed the effects of HER2 protein expression (3 + vs. 2 + on immunohistochemistry [IHC]) and tumor-infiltrating lymphocyte (TIL) levels (< 30%, low; ≥ 30%, or high) on pCR (ypT0/is and ypN0). Results Of the 348 patients with HER2 protein expression data, 278 (79.9%) had HER2 IHC 3+. Among the 305 patients with available TIL data, 121 (39.7%) had high TIL levels. A higher pCR rate was observed in patients with HER2 IHC grade 3+ (71.6% vs. 34.3%, p < 0.001) and high TILs levels (71.9% vs. 57.6%, p = 0.011). After adjusting other clinicopathologic factors, the HER2 IHC 3+ (Odds ratio [OR], 3.66; 95% confidence interval [CI], 1.92–6.96; p < 0.001), high TIL (OR, 1.94; 95% CI, 1.09–3.45; p = 0.024), and hormone-receptor (HR)-negative (OR, 3.33; 95% CI, 1.88–5.91; p < 0.001) were found to be independently associated with pCR. In HR-positive cases, HER2 IHC 3 + and high TILs levels remained independent predictors of pCR but not in HR-negative breast cancer. Conclusions Our results suggest that high HER2 protein expression and TIL predict treatment response to neoadjuvant TCHP, especially in HR-positive breast cancer.