Extended neoadjuvant chemotherapy in locally advanced breast cancer combined with GM-CSF: effect on tumour-draining lymph node dendritic cells.
The effect of long-term administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) on dendritic cell (DC) activation and survival in patients with locally advanced breast cancer (LABC) was studied. To this end, the number of activated DC (i.e. positive for the marker S100) in tumour-draining lymph nodes (TDLN) was determined and compared between LABC patients receiving neoadjuvant chemotherapy with GM-CSF (n=52) or without GM-CSF (n=11), and a control group of chemonaïve breast cancer patients (n=10). A significantly higher mean percentage of S100+ DC in the TDLN of the GM-CSF-treated patients (9.9%) was found compared with each of the respective control groups (5.3 and 5.1%, P=0.002). Moreover, intrapatient comparison before and after treatment showed that the percentage of S100+ DC significantly increased over the course of the GM-CSF treatment (P=0.018). In a univariate survival analysis with a median follow-up of 64 months, relatively high percentages of S100+ DC (> or =8%) were associated with a longer disease-free survival (DFS) (P=0.078). In patients with a high tumour load, where immunosuppressed conditions generally prevail, long-term administration of GM-CSF may thus contribute to survival through enhanced DC activation and consequently improved chances of effective antitumour immunity.
Department of Medical Oncology, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands. hm.pinedo@vumc.nl
H M
HM
Pinedo
J
J
Buter
S A
SA
Luykx-de Bakker
P R
PR
Pohlmann
Y
Y
van Hensbergen
D A M
DA
Heideman
P J
PJ
van Diest
T D
TD
de Gruijl
E
E
van der Wall
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001365:Axilla; D001943:Breast Neoplasms / Q000188:drug therapy*; D002470:Cell Survival; D017024:Chemotherapy, Adjuvant; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D018572:Disease-Free Survival; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009418:S100 Proteins / Q000032:analysis; D016896:Treatment Outcome
D009418:S100 Proteins; C110294:S100A1 protein; D016178:Granulocyte-Macrophage Colony-Stimulating Factor