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 < 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 (chi(2) 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.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.

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 / Dieci, M. V; Prat, A; Tagliafico, Enrico; Paré, L; Ficarra, G; Bisagni, G; Piacentini, Federico; Generali, D. G; Conte, P; Guarneri, V.. - In: ANNALS OF ONCOLOGY. - ISSN 0923-7534. - 27:10(2016), pp. 1867-1873. [10.1093/annonc/mdw262]

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

TAGLIAFICO, Enrico;PIACENTINI, Federico;
2016

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 < 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 (chi(2) 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.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.
2016
2-ago-2016
27
10
1867
1873
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 / Dieci, M. V; Prat, A; Tagliafico, Enrico; Paré, L; Ficarra, G; Bisagni, G; Piacentini, Federico; Generali, D. G; Conte, P; Guarneri, V.. - In: ANNALS OF ONCOLOGY. - ISSN 0923-7534. - 27:10(2016), pp. 1867-1873. [10.1093/annonc/mdw262]
Dieci, M. V; Prat, A; Tagliafico, Enrico; Paré, L; Ficarra, G; Bisagni, G; Piacentini, Federico; Generali, D. G; Conte, P; Guarneri, V.
File in questo prodotto:
File Dimensione Formato  
PAM50 in CherLOB trial.pdf

Accesso riservato

Descrizione: Articolo principale
Tipologia: Versione pubblicata dall'editore
Dimensione 218.31 kB
Formato Adobe PDF
218.31 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
VOR_Integrated evaluation of PAM50 subtypes.pdf

Open access

Tipologia: Versione pubblicata dall'editore
Dimensione 197.09 kB
Formato Adobe PDF
197.09 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1118122
Citazioni
  • ???jsp.display-item.citation.pmc??? 51
  • Scopus 96
  • ???jsp.display-item.citation.isi??? 88
social impact