Purpose: Experimental studies suggest that angiogenesis is necessary for breast cancer progression and metastasis and that it may play a role in responsiveness to some chemotherapeutic agents and to tamoxifen. To investigate whether angiogenesis predicts the clinical outcome of patients with node-positive breast cancer, we determined intratumoral microvessel density in a series of patients treated with either adjuvant hormone therapy (n=84) or chemotherapy (n= 107).
Patients and methods: We monitored 191 patients for a median of 62 months. Intratumoral microvessel density was measured using light microscopy, and microvessels were immunostained using the anti-CD31 antibody. Microvessels were carefully counted (per 200x field) in the most vascularized area of each tumor. The results of intratumoral microvessel density were analyzed by both univariate and multivariate statistical analysis and were correlated with clinical outcome.
Results: In univariate analysis, intratumoral microvessel density was significantly associated with relapse-free survival and overall survival, both in patients who received adjuvant hormone therapy and those who received chemotherapy. In the group treated with adjuvant hormone therapy, estrogen receptor status was also predictive for both relapse-free and overall survival. The number of involved nodes was predictive for overall survival. In patients treated with adjuvant chemotherapy, the number of involved nodes, tumor size, and progesterone receptor status were significantly predictive for relapse-free and overall survival. Multivariate analysis showed that intratumoral microvessel density was the strongest independent predictor of outcome in both treatment groups.
Conclusions: Intratumoral microvessel density is an independent predictive indicator in node-positive breast cancer patients treated with either adjuvant chemotherapy or adjuvant hormone therapy. Assessment of tumor angiogenesis may therefore be useful in selection of those patients who are more likely to benefit from conventional adjuvant therapies (i.e., those with minimally vascularized tumors) from those with highly vascularized and more aggressive tumors, for whom novel forms of systemic therapy are advocated.