In situ immune response after neoadjuvant chemotherapy for breast cancer predicts survival
- 25 March 2011
- journal article
- research article
- Published by Wiley in The Journal of Pathology
- Vol. 224 (3) , 389-400
- https://doi.org/10.1002/path.2866
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. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.Keywords
Funding Information
- Fondation de France
- Ligue Contre le Cancer
- Association pour la Recherche sur le Cancer
- Inserm
- Inca
This publication has 37 references indexed in Scilit:
- Neoadjuvant Treatment With Trastuzumab in HER2-Positive Breast Cancer: Results From the GeparQuattro StudyJournal of Clinical Oncology, 2010
- Understanding the Mechanisms Behind Trastuzumab Therapy for Human Epidermal Growth Factor Receptor 2–Positive Breast CancerJournal of Clinical Oncology, 2009
- Immunoglobulin G Fragment C Receptor Polymorphisms and Clinical Efficacy of Trastuzumab-Based Therapy in Patients With HER-2/neu–Positive Metastatic Breast CancerJournal of Clinical Oncology, 2008
- Trastuzumab plus Adjuvant Chemotherapy for Operable HER2-Positive Breast CancerNew England Journal of Medicine, 2005
- Trastuzumab after Adjuvant Chemotherapy in HER2-Positive Breast CancerNew England Journal of Medicine, 2005
- Significantly Higher Pathologic Complete Remission Rate After Neoadjuvant Therapy With Trastuzumab, Paclitaxel, and Epirubicin Chemotherapy: Results of a Randomized Trial in Human Epidermal Growth Factor Receptor 2–Positive Operable Breast CancerJournal of Clinical Oncology, 2005
- Increased Populations of Regulatory T Cells in Peripheral Blood of Patients with Hepatocellular CarcinomaCancer Research, 2005
- Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survivalNature Medicine, 2004
- Foxp3 programs the development and function of CD4+CD25+ regulatory T cellsNature Immunology, 2003
- Clinical Course of Breast Cancer Patients With Complete Pathologic Primary Tumor and Axillary Lymph Node Response to Doxorubicin-Based Neoadjuvant ChemotherapyJournal of Clinical Oncology, 1999