Abstract
BackgroundThe presence of tumour-infiltrating lymphocytes (TILs) is associated with response to neoadjuvant chemotherapy among patients with triple-negative and HER2-positive breast cancer. However, the significance of TILs is less clear in luminal breast cancer. Here, we in postmenopausal patients with primary oestrogen receptor-positive (ER+), HER2 normal, operable breast cancer assessed the importance of inducing TILs during 4 months of letrozole on response in a neoadjuvant phase II study.MethodsParticipants were postmenopausal women with ER+, HER2 normal operable breast cancer assigned to 4 months of neoadjuvant letrozole. Pretreatment core biopsies and surgical specimens were assessed centrally for the percentage of TILs on haematoxylin and eosin-stained slides according to the International Immuno-Oncology Biomarker Working Group on Breast Cancer guidelines. Pathological response was assessed by the Residual Cancer Burden (RCB) index and a modified Miller-Payne grading system and was analysed according to change in TILs.ResultsTumour specimens were available from 106 of the 112 patients treated per protocol. TIL concentration increased with mean 6.8 percentage point (p < 0.0001) during treatment (range − 39 to 60). An increase in TILs was significantly associated with pathological response with OR = 0.71 (95% CI 0.53–0.96; p = 0.02) per 10% absolute increase for pathological response and correspondingly OR = 0.56 (95% CI 0.40–0.78; p = 0.0007) for lower RCB index per 10% increase.ConclusionIncreasing TILs during letrozole was significantly associated with a poor treatment response. An increase in TILs during endocrine therapy might imply immunogenicity, and these patients could be targetable by immunotherapy.Trial registrationClinicalTrials.govNCT00908531, registered 27 May 2009.
Highlights
The presence of tumour-infiltrating lymphocytes (TILs) is associated with response to neoadjuvant chemotherapy among patients with triple-negative and Human epidermal growth factor receptor 2 (HER2)-positive breast cancer
Study population Patients were treated with neoadjuvant letrozole for 4 months prior to curative intended surgery as part of a clinical phase II study conducted by the Danish Breast Cancer Group (DBCG) between 2009 and 2012
We found that an increase in TILs during neoadjuvant letrozole was associated with a poor treatment response, regardless of the pathological assessment method
Summary
The presence of tumour-infiltrating lymphocytes (TILs) is associated with response to neoadjuvant chemotherapy among patients with triple-negative and HER2-positive breast cancer. Tumour-infiltrating lymphocytes (TILs) have been established as a predictive biomarker for response to neoadjuvant chemotherapy irrespective of molecular subtype [1]. The presence of TILs has in oestrogen receptor-positive (ER+) breast cancer been suggested to be an adverse prognostic factor and associated with poor response to aromatase inhibitors [1, 4, 5]. Neoadjuvant studies have a major strength that by comparing sequential specimens from patients before and after treatment it is possible to obtain predictive and prognostic information using tumour response, linking biology with clinical response. The Preoperative Endocrine Therapy Prognostic Index (PEPI) score has been applied in some occasions [11]. The PEPI score is not routinely used mainly due to the lack of standardisation and validity of Ki67 scoring [12]
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