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

M. V. Dieci, Annik Prat, Enrico Tagliafico, Laia Paré, G. Ficarra, G. Bisagni, Federico Piacentini, D G Generali, P. Conte, V. Guarneri

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The aim of this work was to evaluate the impact of (and relative contribution of) tumor-related and immunerelated diversity of HER2-positive disease on the response to neoadjuvant chemotherapy plus anti-HER2 agents. Patients and methods: 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&slides. Intrinsic subtyping was carried out using the researchbased 50-gene prediction analysis of a microarray (PAM50) subtype predictor. Immune-related gene signatures were also evaluated. Results: Continuous Str-TILs and It-TILs were significantly associated with pCR [OR 1.03, 95% CI 1.02-1.05 (P < 0.001) and OR 1.09, 95% CI 1.04-1.15 (P < 0.001) for Str-TILs and It-TILs, respectively]. According to PAM50, the subtype distribution was as follows: HER2-enriched 26.7%, Luminal A 25.6%, Luminal B 16.3%, Basal-like 14% and Normal-like 17.4%. The highest rate of pCR was observed for the HER2-enriched subtype (50%), followed by Basal-like, Luminal B and Luminal A (x2 test, P = 0.026). Immune gene signatures significantly associated with pCR in univariate analyses were identified: most of them maintained a significant association with pCR in multivariate analyses corrected for PAM50 subtypes, whereas TILs did not. Conclusions: In this study, both tumor-related and immune-related features contribute to the modulation of pCR after neoadjuvant chemotherapy plus anti-HER2 agents. Immune signatures rather than TILs added significant prediction of pCR beyond PAM50 intrinsic subtypes.

Original languageEnglish
Pages (from-to)1867-1873
Number of pages7
JournalAnnals of Oncology
Volume27
Issue number10
DOIs
Publication statusPublished - Oct 1 2016

Keywords

  • Breast cancer
  • HER2
  • Immune signatures
  • Neoadjuvant
  • PAM50
  • Tumor-infiltrating lymphocytes

ASJC Scopus subject areas

  • Hematology
  • Oncology

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