title: In situ immune response after neoadjuvant chemotherapy for breast cancer predicts survival.
abstract: Accumulating preclinical evidence suggests that anticancer immune responses contribute to the success of chemotherapy. However, the predictive value of tumour-infiltrating lymphocytes after neoadjuvant chemotherapy for breast cancer remains unknown. We hypothesized that the nature of the immune infiltrate following neoadjuvant chemotherapy would predict patient survival. In a series of 111 consecutive HER2- and a series of 51 non-HER2-overexpressing breast cancer patients treated by neoadjuvant chemotherapy, we studied by immunohistochemistry tumour infiltration by FOXP3 and CD8 T lymphocytes before and after chemotherapy. Kaplan-Meier analysis and Cox modelling were used to assess relapse-free survival (RFS) and overall survival (OS). A predictive scoring system using American Joint Committee on Cancer (AJCC) pathological staging and immunological markers was created. Association of high CD8 and low FOXP3 cell infiltrates after chemotherapy was significantly associated with improved RFS (p = 0.02) and OS (p = 0.002), and outperformed classical predictive factors in multivariate analysis. A combined score associating CD8/FOXP3 ratio and pathological AJCC staging isolated a subgroup of patients with a long-term overall survival of 100%. Importantly, this score also identified patients with a favourable prognosis in an independent cohort of HER2-negative breast cancer patients. These results suggest that immunological CD8 and FOXP3 cell infiltrate after treatment is an independent predictive factor of survival in breast cancer patients treated with neoadjuvant chemotherapy and provides new insights into the role of the immune milieu and cancer.
authors: Department of Medical Oncology, Georges François Leclerc Center, Dijon, France; Institut National de la Santé et de la Recherche Médicale, Avenir Team INSERM, CRI-866 University of Burgundy, Dijon, France.
authors: Sylvain
authors: S
authors: Ladoire
authors: Grégoire
authors: G
authors: Mignot
authors: Sandrine
authors: S
authors: Dabakuyo
authors: Laurent
authors: L
authors: Arnould
authors: Lionel
authors: L
authors: Apetoh
authors: Cedric
authors: C
authors: Rébé
authors: Bruno
authors: B
authors: Coudert
authors: Francois
authors: F
authors: Martin
authors: Marie Hélène
authors: MH
authors: Bizollon
authors: André
authors: A
authors: Vanoli
authors: Charles
authors: C
authors: Coutant
authors: Pierre
authors: P
authors: Fumoleau
authors: Franck
authors: F
authors: Bonnetain
authors: François
authors: F
authors: Ghiringhelli
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D017024:Chemotherapy, Adjuvant; D004812:Epidemiologic Methods; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects* / Q000276:immunology; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D051858:Forkhead Transcription Factors; D018719:Erb-b2 Receptor Tyrosine Kinases; C418974:FOXP3 protein, human; C508053:ERBB2 protein, human