Association of angiogenesis and disease outcome in node-positive breast cancer patients treated with adjuvant cyclophosphamide, doxorubicin, and fluorouracil: a Cancer and Leukemia Group B correlative science study from protocols 8541/8869.
OBJECTIVE
Increased microvessel density (MVD), a reflection of tumor angiogenesis, is associated with diminished relapse-free and overall survival (OS) in several subsets of breast cancer patients. However, the utility of this assay in node-positive patients treated with adjuvant cyclophosphamide, doxorubicin, and fluorouracil (CAF) has not been well studied.


METHODS
Immunostaining for factor VIII-related antigen was performed on tissue sections from a subset of node-positive patients who received one of three dose/schedule regimens of CAF during participation in Cancer and Leukemia Group B protocol 8541. Sections from 577 cancers exhibited acceptable tumor and immunostaining quality and were included in the study. Each section was examined quantitatively for MVD as well as non-quantitatively by scoring the presence or absence of a prominent vascular pattern.


RESULTS
MVD counts were not associated with relapse-free or OS in univariate analysis. The presence of a prominent plexiform vascular pattern was correlated with decreased OS (P =.0085) in univariate analysis, but this pattern was not an independent prognostic indicator of survival in multivariate analysis. No apparent clinically important interactions between measures of angiogenesis, other prognostic factors, administration of tamoxifen, and chemotherapy dose were observed.


CONCLUSIONS
Assessment of angiogenesis does not provide useful information regarding prognosis in node-positive breast cancer patients treated with adjuvant CAF, nor do these measures predict which patients will benefit from dose intensification or addition of tamoxifen.
Guidi
Anthony J
AJ
North Shore Medical Center, Salem, MA, USA.
Berry
Donald A
DA
Broadwater
Gloria
G
Helmchen
Birgit
B
Bleiweiss
Ira J
IJ
Budman
Daniel R
DR
Henderson
I Craig
IC
Norton
Larry
L
Hayes
Daniel F
DF
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000627:therapeutic use*; D004317:Doxorubicin / Q000627:therapeutic use*; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000473:pathology*; D015588:Observer Variation; D016896:Treatment Outcome; D014841:von Willebrand Factor / Q000032:analysis
D014841:von Willebrand Factor; D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil