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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

From the North Shore Medical Center, Salem, MA; University of Texas, M.D. Anderson Cancer Center, Houston, TX; Cancer and Leukemia Group B Statistical Center, Durham, NC; Mt Sinai Medical Center, and Memorial Sloan Kettering Cancer Center, New York; North Shore University Hospital, Manhasset, NY; University of California at San Francisco, San Francisco, CA; and University of Michigan Comprehensive Cancer Center, Ann Arbor, MI.

Address reprint requests to Daniel F. Hayes, MD, University of Michigan Comprehensive Cancer Center, CCGC 6312, 1500 E Medical Center Dr, Ann Arbor, MI 48109-0942; email: hayesdf@ umich.edu.

PURPOSE: 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.

PATIENTS AND 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 nonquantitatively 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.

CONCLUSION: 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.

The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.

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