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Elsevier, Annals of Oncology, 10(27), p. 1867-1873, 2016

DOI: 10.1093/annonc/mdw262

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Integrated evaluation of PAM50 subtypes and immune modulation of pCR in HER2-positive breast cancer patients treated with chemotherapy and HER2-targeted agents in the CherLOB trial

Journal article published in 2016 by M. V. Dieci, A. Prat, E. Tagliafico, L. Paré, G. Ficarra, G. Bisagni, D. G. Generali, F. Piacentini ORCID, P. Conte ORCID, V. Guarneri
This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

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Abstract

In the CherLOB study, intrinsic subtypes, TILs and immune signatures all contribute to the chance of pCR after neoadjuvant chemotherapy plus anti-HER2 agents for HER2-positive breast cancer. However, immune gene signatures rather than TILs provide significant independent prediction of pCR beyond intrinsic subtypes.The aim of this work was to evaluate the impact of (and relative contribution of) tumor-related and immune-related diversity of HER2-positive disease on the response to neoadjuvant chemotherapy plus anti-HER2 agents.The CherLOB phase II study randomized 121 HER2-positive breast cancer patients to neoadjuvant chemotherapy plus trastuzumab, lapatinib or both. Tumor samples from diagnostic core biopsy were centralized. Tumor-infiltrating lymphocytes (TILs) were evaluated on H&E slides. Intrinsic subtyping was carried out using the research-based 50-gene prediction analysis of a microarray (PAM50) subtype predictor. Immune-related gene signatures were also evaluated.Continuous Str-TILs and It-TILs were significantly associated with pCR [OR 1.03, 95% CI 1.02-1.05 (P