Predictors of pathologic complete response following neoadjuvant TCHP in HER2-positive breast cancer.

Abstract

e12519 Background: In HER2+ breast cancer (BC), pathologic complete response (pCR) following HER2-directed neoadjuvant therapy is an established surrogate marker for long-term survival. In a HERMET trial, the addition of metformin to standard docetaxel, carboplatin, trastuzumab and pertuzumab (TCHP) did not result in a significant improvement in pCR rates. We performed a post hoc analysis of all participants enrolled in the HERMET trial to identify pathologic predictors of pCR. Methods: This single-center study enrolled 61 patients with operable HER2+ BC (tumor ≥2 cm and/or node-positive) who were randomized 1:1 to neoadjuvant TCHP for 6 cycles + placebo (n = 30) or metformin (n = 31). The primary endpoint was pCR, defined as the absence of residual invasive disease in the breast and axillary lymph nodes at the time of surgery. Logistic regression was performed using a prespecified multivariable model that included estrogen receptor (ER) status (0–9% vs ≥10%), HER2 category (IHC 3+ vs 2+), and Ki-67. Results: 61 patients were enrolled between August 17, 2017, and March 21, 2023; median age was 51 years. Overall, pCR was achieved in 30 of 61 (49.2%). HER2 IHC 3+ disease was present in 53 (86.9%), while 8 (13.1%) had HER2 IHC 2+ FISH positive disease. pCR occurred in 29 of 53 (54.7%) with HER2 IHC 3+ tumors compared with 1 of 8 (12.5%) with HER2 IHC 2+ tumors (Fisher’s exact p = 0.053). Ki-67 was available for 51 patients. Median Ki-67 was higher among patients who achieved pCR compared with those who did not (40% vs 32%). On univariate analysis, higher Ki-67 was associated with increased odds of pCR (odds ratio [OR] 1.03 per 1% increase; p = 0.028). In the prespecified multivariable model including ER status and HER2 category (N = 61), ER 0–9% was independently associated with higher odds of pCR compared with ER ≥10% (adjusted OR 2.7; 95% CI, 1.0–7.6; p = 0.049). HER2 IHC 3+ disease demonstrated a large but statistically borderline association with pCR compared with HER2 IHC 2+ disease (adjusted OR 7.8; 95% CI, 0.9–70; p = 0.061). Conclusions: Although patients with HER2+ BC defined as IHC 2+ with FISH amplification are treated similarly to those with IHC 3+ disease, their pCR rates were comparable to those observed in hormone receptor–positive, HER2-negative BC. Clinical trial information: NCT03238495 . pCR by ER status and HER2 category. Variable Group N pCR N (%) ER 0-9% 23 15 (65.2) ≥10% 38 15 (39.5) HER2 2+ 8 1 (12.5) 3+ 53 29 (54.7)