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.
Resources from the same session
2686 - Clinicopathological characteristics, survival and prognostic factors of breast cancer-related microangiopathic haemolytic anemia: a multicenter study
Presenter: Marion Alhenc Gelas
Session: Poster Display session 2
Resources:
Abstract
1565 - Metabolic tumor volume by 18F-FDG PET/CT is an independent prognostic factor in metastatic breast cancer
Presenter: Heekyung Ahn
Session: Poster Display session 2
Resources:
Abstract
4498 - Patient Preferences for breast cancer treatments: A Discrete Choice Experiment from four European countries
Presenter: Thomais Konstantopoulou
Session: Poster Display session 2
Resources:
Abstract
1423 - Palbociclib plus fulvestrant as second- or later-line therapy for patients with locally advanced, inoperable or metastatic HR+/HER2- breast cancer in Germany: Interim results of the INGE-B phase 2 study
Presenter: Diana Lüftner
Session: Poster Display session 2
Resources:
Abstract
2284 - Ventriculoperitoneal Shunt for CNS Metastasis in Breast Cancer: Clinical Outcomes Based on Intrinsic Subtype
Presenter: Hee Kyung Kim
Session: Poster Display session 2
Resources:
Abstract
4598 - Administration of chemotherapy for metastatic breast cancer near the end of life: a population registry study
Presenter: Luisa Edman Kessler
Session: Poster Display session 2
Resources:
Abstract
5706 - Prognostic value of histological growth pattern in patients operated for breast cancer liver metastases
Presenter: Ali Bohlok
Session: Poster Display session 2
Resources:
Abstract
1697 - Illness perceptions, quality of life and mood in metastatic breast cancer patients
Presenter: Isabel Domingues
Session: Poster Display session 2
Resources:
Abstract
1935 - Multidisciplinary Treatments Increases Overall Survival in Patients with Newly Diagnosed Stage IV Breast Cancer:An Analysis of 2010–2014 SEER Data
Presenter: Jian Zhang
Session: Poster Display session 2
Resources:
Abstract
3875 - Correlation of radiotherapy with the prognosis of elderly patients with hormone receptor-positive breast cancer according to immunohistochemical subtyping
Presenter: Jin Zhang
Session: Poster Display session 2
Resources:
Abstract