Abstract 299P
Background
Neoadjuvant therapy (NAT) remains the standard of care for most early-stage breast cancer (BC) patients, especially in HER2+ and triple-negative (TNBC) subtypes. Patients who do not achieve pathological complete response (pCR) present an increased risk of disease recurrence. Here, we applied single cell RNA sequencing (SCS) to investigate tumor and immune landscape for the identification of predictive biomarkers of response to NAT.
Methods
Twenty-one BC patients treated with NAT were included in the study. Pre-treatment biopsies, matched residual disease and adjacent normal tissue samples were prospectively collected for all patients. After tissue dissociation, single cell RNA profiles were investigated using the Chromium Next GEM Single Cell 5' kit (10X Genomics). After removing batch effect using Seurat integration, cell clusters were annotated based on the expression of specific marker genes. Epithelial luminal cells (KRT18+/KRT19+) were classified as malignant or non-malignant using copy number profiles computed by inferCNV. Wilcoxon rank sum test was used to compare cell proportions between pCR and non-pCR groups.
Results
pCR rates were 61.5% (8/13), 100% (4/4) and 25% (1/4) in TNBC, HER2+ and Luminal B patients respectively. A total of 21 TNBC, 6 HER2+ and 6 Luminal B samples were profiled with SCS. Malignant luminal epithelial cells were classified in luminal progenitor (LP) (KIT+/SLPI+/KRT5low), luminal mature (LM) (KIT-/SLPI-/KRT5-) and luminal cycling cells (LC) (MKI67+/TOP2A+). Patients achieving pCR had a higher fraction of LC cells at baseline, considering all BC subtypes (p<0.05). Enrichment of LP cells at baseline was observed in TNBC patients achieving pCR (p<0.05). T cells reclustering further identified four CD4+ subtypes. Of note, lower proportions of FOXP3+ regulatory T cells and RORC+/CCR6+ Th17 cells at baseline were associated with a better response to NAT both in TNBC and HER2+ patients (p<0.05).
Conclusions
Our study showed substantial heterogeneity at the single cell level with specific cell types being associated with response to neoadjuvant chemotherapy, towards an improved BC care.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Institut Jules Bordet, Hôpital Universitaire de Bruxelles (H.U.B).
Funding
Fond de la Recherche Scientifique (FNRS), Télévie, Association Jules Bordet, Breast Cancer Research Foundation (BCRF), Fondation contre le Cancer, Fondation de l’Université Libre de Bruxelles.
Disclosure
C. Sotiriou: Financial Interests, Institutional, Advisory Board: Astellas, Vertex, Seattle Genetics, Amgen, INC, Merck & Co; Financial Interests, Personal, Advisory Board: Cepheid, Puma; Financial Interests, Personal, Invited Speaker: Eisai, Prime oncology, Teva; Financial Interests, Institutional, Other, Travel: Roche; Financial Interests, Institutional, Other, Internal speaker: Genentech; Financial Interests, Personal, Other, Regional speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: Exact Sciences. All other authors have declared no conflicts of interest.
Resources from the same session
263P - Efficacy and safety of neoadjuvant chemotherapy combination with pembrolizumab in triple-negative breast cancer: Real-world data
Presenter: Layal Rached
Session: Poster session 02
264P - Tumor-infiltrating lymphocytes (TILs) for prediction of response to platinum-based neoadjuvant chemotherapy (NACT) in triple-negative breast cancer (TNBC): Final analysis
Presenter: Sheyda Abdullaeva
Session: Poster session 02
265P - Effect of HER2-low-positive status on neoadjuvant chemotherapy and survival outcome of breast cancer: A 10-year dual-center retrospective study
Presenter: Yijun Li
Session: Poster session 02
266P - Discontinuation rate and serious adverse events of chemoimmunotherapy as neoadjuvant treatment for triple-negative breast cancer: A systematic review and meta-analysis
Presenter: Francesca Schipilliti
Session: Poster session 02
267P - Pathological complete response after neoadjuvant chemotherapy plus pertuzumab and trastuzumab for HER2+ early breast cancer: Real-world data from NeoPowER study
Presenter: Fabio Canino
Session: Poster session 02
268P - Evaluating the efficacy of adjuvant capecitabine in triple-negative breast cancer patients with residual disease: A real-world evidence study
Presenter: Min Jeong Kim
Session: Poster session 02
269P - Achieving treatment goals in elderly breast cancer patients with neoadjuvant chemotherapy: A remarkable insight
Presenter: Eda Caliskan Yildirim
Session: Poster session 02
270P - Influence of neoadjuvant chemotherapy-induced short-term amenorrhea on pathologic response and treatment outcome in ER+HER2- breast cancer
Presenter: Seung Eun Lee
Session: Poster session 02
271P - First clinical demonstration of the predictive value of tissue nanomechanical signature in breast cancer patients in neoadjuvant therapy setting
Presenter: Sara Nizzero
Session: Poster session 02