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Poster Display session 2

4301 - Immune infiltrate composition across intrinsic subtypes in hormone receptor (HR)+/HER2- early breast cancer (BC) enrolled in the prospective LETLOB trial

Date

29 Sep 2019

Session

Poster Display session 2

Presenters

Gaia Griguolo

Citation

Annals of Oncology (2019) 30 (suppl_5): v55-v98. 10.1093/annonc/mdz240

Authors

G. Griguolo1, M.V. Dieci2, L. Paré3, F. Miglietta2, D.G. Generali4, A. Frassoldati5, G. Bisagni6, F. Piacentini7, E. Tagliafico8, K. Cagossi9, G. Ficarra10, A. Prat3, P.F. Conte2, V. Guarneri2

Author affiliations

  • 1 Medical Oncology 2, Istituto Oncologico Veneto IRCCS, 35128 - Padova/IT
  • 2 Department Of Surgery, Oncology And Gastroenterology, University of Padova, 35128 - Padova/IT
  • 3 Medical Oncology, Hospital Clinic de Barcelona/IDIBAPS - SOLTI Breast Cancer Research Group, Barcelona/ES
  • 4 U.o. Multidisciplinare Di Patologia Mammaria, ASST O. Istituti Ospitalieri di Cremona, of Cremona/University of Trieste, Cremona/IT
  • 5 Clinical Oncology, Department Of Morphology, Surgery And Experimental Medicine, S Anna University Hospital, 44100 - Ferrara/IT
  • 6 Department Of Oncology And Advanced Technologies, Oncology Unit, Azienda USL-IRCCS di Reggio Emilia, 42100 - Reggio Emilia/IT
  • 7 Division Of Medical Oncology, Department Of Medical And Surgical Sciences For Children And Adults, University Hospital of Modena, 41125 - Modena/IT
  • 8 Center For Genome Research, University of Modena and Reggio Emilia, Modena/IT
  • 9 Breast Unit Ausl Modena, Ramazzini Hospital, Carpi/IT
  • 10 Department Of Pathology, Azienda Ospedaliero-Universitaria Policlinico di Modena, Modena/IT
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Resources

Abstract 4301

Background

In HR+/HER2- early BC, high tumour infiltrating lymphocytes (TIL) levels predict higher pathological complete response to neoadjuvant chemotherapy, but are associated with shorter overall survival (Denkert, Lancet Oncol 2018). HR+/HER2- BC is a biologically heterogeneous disease, encompassing all BC molecular intrinsic subtypes, with different clinical behaviour (Cejalvo, CTR 2018). Little is known concerning the distribution of TIL levels and immune infiltrate composition across intrinsic subtypes in HR+/HER2- BC.

Methods

Gene-expression data (Affymetrix platform) from pre-treatment frozen core-biopsies was available from 66 postmenopausal patients with HR+/HER2- early BC from the LETLOB trial (neoadjuvant letrozole+/-lapatinib) (Guarneri, JCO 2014). Intrinsic subtype was assigned using a research-based PAM50 subtype predictor. Relative leukocyte fractions were calculated using CIBERSORT (Newman, Nature Methods 2015), a deconvolution method based on RNA gene-expression signatures. Pre-treatment stromal TILs were assessed on centralized HES slides according to recommendations (Salgado, Ann Oncol 2015).

Results

Intrinsic subtype distribution was as follows: basal 18% (N = 12), HER2-enriched 8% (N = 5), Luminal A 39% (N = 25), Luminal B 36% (N = 24). Non-luminal subtypes (HER2-enriched and Basal) had significantly higher baseline TIL levels than luminal subtypes (median (range): 7 (0-100) and 2 (0-35), respectively; p = 0.038). Non-luminal subtypes also presented higher fractions of CD4 memory activated T-cells (p = 0.018), γδ T-cells (p = 0.010) and M1 macrophages (p = 0.001) and lower fractions of T-regulatory cells (p = 0.002) than luminal subtypes.

Conclusions

In HR+/HER2- early BC, non-luminal subtypes show higher TIL levels and a more pro-inflammatory anti-tumour immune infiltrate composition. This immune heterogeneity across intrinsic subtypes should be considered when analysing the complex prognostic role of TILs in HR+/HER2- early BC.

Clinical trial identification

NCT00422903.

Editorial acknowledgement

Legal entity responsible for the study

University of Padua.

Funding

GlaxoSmithKline funded the clinical trial (LETLOB) including gene-expression analysis; DOR grants 1721185/17 and 1830512/18 from the University of Padua.

Disclosure

M.V. Dieci: Advisory / Consultancy: EliLilly; Advisory / Consultancy: Genomic Health; Advisory / Consultancy: Celgene. A. Frassoldati: Advisory / Consultancy: Roche; Advisory / Consultancy: Novartis; Honoraria (self): Pfizer; Honoraria (self): Novartis; Honoraria (self): AstraZeneca; Honoraria (self): Roche; Honoraria (self): Eisai. A. Prat: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Amgen; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Research grant / Funding (institution): Daiichi Sankyo; Advisory / Consultancy: Puma; Advisory / Consultancy: Oncolytics Biotech; Honoraria (institution), Research grant / Funding (institution): Nanostring; Research grant / Funding (institution): Boehringer; Research grant / Funding (institution): Lilly. P.F. Conte: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy: EliLilly; Honoraria (self), Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Tesaro; Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self), Research grant / Funding (institution): BMS; Research grant / Funding (institution): Merck-KGa. V. Guarneri: Advisory / Consultancy, Speaker Bureau / Expert testimony: EliLilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Research grant / Funding (institution): Roche. All other authors have declared no conflicts of interest.

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