Clinical outcomes of early-stage triple-negative breast cancer after neoadjuvant chemotherapy according to HER2-low status☆

Abstract

Background: The impact of human epidermal growth factor receptor 2 (HER2) expression determined by immunohistochemistry (IHC) on outcomes in early-stage triple-negative breast cancer (eTNBC) is unclear. Using a large, multi-institutional cohort, we evaluated outcomes by HER2 IHC status in patients with eTNBC who received neoadjuvant therapy (NAT).

Patients and methods: Patients with stage I-III TNBC who received NAT and underwent surgery from January 2016 to June 2019 were identified from three databases. HER2 expression was defined as low (IHC1+ or 2+/FISH not amplified) or HER2 IHC score 0 by local testing at diagnosis. Pathological complete response (pCR) rates were compared using logistic regression adjusted for multiple factors. Survival outcomes were estimated using Kaplan-Meier and Cox proportional hazards models.

Results: Among 977 consecutive patients, 388 (39.7%) had HER2-low and 589 (60.3%) had HER2 IHC score 0 tumors. Median age at eTNBC diagnosis was 50.3 years (range 21.0-83.4 years). At baseline, clinical nodal positivity rate was significantly higher in HER2-low (55.0%) versus HER2 IHC score 0 tumors (46.6%) (P = 0.011); pCR rates were similar (32.0% versus 32.6%; adjusted P = 0.924). At a median follow-up of 3.5 years, recurrence-free survival (RFS) did not vary significantly between HER2-low versus HER2 IHC score 0 among patients with pCR (adjusted P = 0.368) or residual disease (RD) after NAT (adjusted P = 0.573). Distant RFS and overall survival (OS) did not differ by HER2 category for patients with pCR [distant RFS (DRFS), adjusted P = 0.509; OS, adjusted P = 0.514] or RD (DRFS, adjusted P = 0.812; OS, P = 0.285). Discordance of tumor HER2 status was seen in 31.1% of HER2 IHC score 0 cases, with HER2 expression observed post-treatment; 34.8% of HER2-low cases showed discordance, with absent HER2 expression in RD.

Conclusions: In this large cohort of patients with eTNBC treated with NAT, HER2-low status was not associated with pCR or survival after adjusting for clinical factors. The discordance in HER2 IHC pre- and post-NAT likely reflects challenges in HER2 quantification and heterogeneity.

Keywords: HER2 low; TNBC; breast cancer; early stage; pCR; survival.

Figure 1

Kaplan–Meier plots of (A) RFS, (B) DRFS, and (C) OS according to HER2-low versus HER2 IHC score 0 in patients with pCR or RD after NAT. DRFS, distant RFS; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; NAT, neoadjuvant therapy; OS, overall survival; pCR, pathological complete response; RD, residual disease; RFS, recurrence-free survival.

Figure 2

Change in HER2 score from TNBC diagnosis to surgery post-NAT. (A) Change in HER2-low versus HER2 IHC score 0.^a (B) Change in HER2 IHC (0 versus 1+ versus 2+).^b (C) Change in HER2-low IHC (1+ versus 2+).^c HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; ISH, in situ hybridization; NAT, neoadjuvant therapy; RD, residual disease; TNBC, triple-negative breast cancer. ^aAmong patients with RD after NAT who had HER2 status available from both diagnostic biopsy and surgical samples (n = 363). ^bAmong patients with RD after NAT who had HER2 status available from both diagnostic biopsy and surgical samples (n = 363). ^cAmong patients with HER2-low tumors at both diagnosis and surgery post-NAT (n = 89).