Increased number of TILs at baseline is associated with pathological complete response (pCR) and improved outcomes in HER2+ early breast cancer (BC) treated with anti-HER2-based chemotherapy. The associations in the neoadjuvant setting in the absence of chemotherapy and the effect of on-treatment TILs changes on pCR in the breast (pCRB) are unknown.
PAMELA is a prospective study in HER2+ BC designed to evaluate the ability of the PAM50 intrinsic subtypes (IS) to predict pCRB following neoadjuvant lapatinib and trastuzumab (with hormonal therapy if hormone receptor-positive[HR+]). Levels of TILs as continuous and categorical (TILs-low = 50%) variables and their changes were correlated with pCRB.
TILs evaluation was available for 148 baseline (BS) and 134 Day-15 (D15) samples of 151 recruited patients. At BS, the median (interquartile range) levels of TILs were 10% (5-20). Median TILs distribution according to IS was: HER2-E (10%), Luminal (Lum) A (7.5%), LumB (5%), Basal-like (5%) (p = 0.02). Levels of TILs were higher in HR- (10%, 1-20) vs HR + (5%, 1-20) tumors, although not statistically significant (p = 0.07). pCRB rates were 58.3% (7/12) for TILs-high and 27.2% (37/136) for TILs-low (p = 0.03). At baseline, TILs were significantly associated with pCR in univariate analysis. At D15, median levels of TILs were 15% (5-30) with an increase across all the different IS (p
The presence of TILs at D15 is an independent predictive marker of pCRB in HER2+ early BC treated with neoadjuvant anti-HER2 agents without chemotherapy.
Clinical trial identification
Legal entity responsible for the study
SOLTI Breast Cancer Research Group
GlaxoSmithKline (now Novartis)
All authors have declared no conflicts of interest.