Baseline levels of tumour infiltrating lymphocytes (TIL) in pre–treatment biopsies from patients with HER2–positive breast cancer are significantly associated with pathological complete response (pCR) rates following neoadjuvant chemotherapy plus anti–HER2 agents (trastuzumab, lapatinib or their combination). These data, based on a meta–analysis of published data from five large clinical trials, was reported at the IMPAKT Breast Cancer Conference.

Cinzia Solinas of the Institut Jules Bordet, Bruxelles, Belgium and colleagues performed a systematic search of the PubMed, Embase and Cochrane library databases for randomised controlled trials (RCT) investigating neoadjuvant chemotherapy plus trastuzumab, lapatinib or their combination in HER2–positive breast cancer up until 31 October, 2016. These investigators analyzed the relationship between the frequency of pCR and pre–treatment levels of TIL by comparing subgroups of patients with high baseline TIL or ‘other’ levels of TIL (non–high TIL).

This analysis included 1,256 patients participating in the CherLOB, GeparQuattro, GeparQuinto, GeparSixto and NeoALTTO neoadjuvant trials. Patients were stratified into TIL subgroups using the cut–off for high TIL defined in each study. The cut–off value for high TIL was 60% in the first four trials using trastuzumab, lapatinib or their combination plus anthracycline– and taxane–based neoadjuvant chemotherapy; whereas, in NeoALTTO the cut–off was 30% and the treatment regime was trastuzumab, lapatinib or their combination plus taxane only–based neoadjuvant chemotherapy. Evaluation of the data from all five trials using random and fixed effects models demonstrated a significant association between pCR rates and high pre–treatment levels of TIL with an odds ratio (OR) 2.46; 95% confidence interval (CI) 1.36, 4.43 (p = 0.003).

No interaction was observed between high versus non–high TIL subgroups in terms of response to anti–HER2 agents, trastuzumab versus lapatinib versus trastuzumab/lapatinib (p = 0.747) or between regimes containing anthracyclines plus taxanes versus taxanes alone (p = 0.201).

The association between pCR and high TIL was higher in the 869 patients participating in the CherLOB, GeparQuattro, GeparQuinto, GeparSixto trials of neoadjuvant anthracycline– and taxane–based chemotherapy, which employed a 60% cut–off to define high TIL, OR 2.88; 95% CI 2.03, 4.08 (p < 0.001).

The authors noted that in HER2–positive breast cancer, high baseline TIL are associated with increased pCR probability, irrespective of anti–HER2 agent(s) and neoadjuvant chemotherapy regimes used. The subgroup of patients with >60% TIL prior to treatment demonstrated a stronger benefit from neoadjuvant chemotherapy combined with anti–HER2 therapy.