Tumor infiltrating lymphocytes is prognostic and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial
Menée à partir des échantillons tumoraux prélevés sur 1 010 patientes atteintes d'un cancer du sein de stade précoce et incluses dans un essai de phase III évaluant l'ajout du trastuzumab à une chimiothérapie, cette étude met en évidence une association entre le nombre de lymphocytes infiltrant la tumeur et le bénéfice, en termes de survie sans maladie distante, du trastuzumab
Background : We have previously shown the prognostic importance of tumor infiltrating lymphocytes (TILs) in newly-diagnosed triple-negative breast cancer (TNBC) using tumor samples from a large clinical trial cohort. In this study, we aimed to validate these findings and also investigate associations with trastuzumab benefit in HER2-overexpressing disease (HER2+).
Patients and Methods : A prospective-retrospective study was conducted using samples from the FinHER adjuvant, phase III trial that enrolled 1010 early-stage BC patients, 778 of whom were HER2-non-amplified. Those with HER2+ disease (n=232) were randomized to 9 weeks of trastuzumab or no trastuzumab in addition to chemotherapy. Two pathologists independently quantified stromal TILs in 935 (92·6%) available slides. The primary endpoint of distant disease-free survival (DDFS) and interactions with trastuzumab were studied in Cox regression models.
Results : Confirming our previous findings in TNBC (n=134), each 10% increase in TILs located in the stroma was significantly associated with decreased distant recurrence in TNBC; for DDFS hazard-ratio adjusted for clinic-pathological factors: 0·77; 95%CI 0·61-0·98,P=0·02. In HER2+ BC (n=209), each 10% increase in lymphocytic infiltration was significantly associated with decreased distant recurrence in patients randomized to the trastuzumab arm (DDFS Pinteraction=0·025).
Conclusions : Higher levels of TILs present at diagnosis were significantly associated with decreased distant recurrence rates in primary TNBC. This data confirms our previous data and further support that TILs should be considered a robust prognostic factor in this BC subtype. We also report for the first time an association between higher levels of TILs and increased trastuzumab benefit in HER2+ disease. Further research into why some TN and HER2+ BCs can or cannot generate a host anti-tumor immune response and how trastuzumab can favorably alter the immune microenvironment is warranted.
Annals of Oncology , résumé, 2014