Presence of Foxp3 expression in tumor cells predicts better survival in HER2-overexpressing breast cancer patients treated with neoadjuvant chemotherapy.
The Forkhead Box Protein 3 is highly expressed not only in regulatory T cells, but also in tumor cells, acting as a transcriptional repressor of breast oncogenes including HER2. We investigated the prognostic significance of Foxp3 expression in cancer cells in a large cohort of patients with HER2-overexpressing breast carcinoma treated with neoadjuvant chemotherapy. Foxp3-positive tumor cells were detected by immunohistochemistry in 103 patients with primary invasive HER2-overexpressing breast carcinoma, and treated with neoadjuvant chemotherapy, with or without trastuzumab. Kaplan-Meier analysis and Cox regression model were used to assess relapse-free and overall survival, respectively, and according to the presence or the absence of Foxp3 expression in tumor cells. Breast cancer cells were Foxp3+ in 57% of tumors. Foxp3 expression in breast cancer cells was associated with better relapse-free (P = 0.005) and overall survival (P = 0.03). By multivariate analysis, the presence of Foxp3+ tumor cells produced an independent prognostic factor for both better relapse-free (P = 0.006) and overall survival (P = 0.03). These findings indicate that the presence of Foxp3+ tumor cells represents a new independent prognostic factor of improved outcome in HER2-overexpressing breast carcinoma, which could help identify high-risk patients for additional therapies after neoadjuvant chemotherapy.
Department of Medical Oncology, Centre Regional de Lutte Contre Cancer Georges François Leclerc, Dijon, France.
Sylvain
S
Ladoire
Laurent
L
Arnould
Grégoire
G
Mignot
Bruno
B
Coudert
Cédric
C
Rébé
Fanny
F
Chalmin
Julie
J
Vincent
Mélanie
M
Bruchard
Bruno
B
Chauffert
François
F
Martin
Pierre
P
Fumoleau
François
F
Ghiringhelli
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002277:Carcinoma / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis*; D005602:France; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000037:antagonists & inhibitors; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D000068878:Trastuzumab; D016896:Treatment Outcome; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D051858:Forkhead Transcription Factors; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C418974:FOXP3 protein, human; C508053:ERBB2 protein, human