These authors share co-authorship.
In situ immune response after neoadjuvant chemotherapy for breast cancer predicts survival†
Article first published online: 25 MAR 2011
Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 224, Issue 3, pages 389–400, July 2011
How to Cite
Ladoire, S., Mignot, G., Dabakuyo, S., Arnould, L., Apetoh, L., Rébé, C., Coudert, B., Martin, F., Bizollon, M. H., Vanoli, A., Coutant, C., Fumoleau, P., Bonnetain, F. and Ghiringhelli, F. (2011), In situ immune response after neoadjuvant chemotherapy for breast cancer predicts survival. J. Pathol., 224: 389–400. doi: 10.1002/path.2866
No conflicts of interest were declared.
- Issue published online: 6 JUN 2011
- Article first published online: 25 MAR 2011
- Accepted manuscript online: 3 FEB 2011 09:11AM EST
- Manuscript Accepted: 30 JAN 2011
- Manuscript Revised: 24 JAN 2011
- Manuscript Received: 8 NOV 2010
- Fondation de France
- Ligue Contre le Cancer
- Association pour la Recherche sur le Cancer
- immune response;
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.