Assessment of intratumoral vascularization (angiogenesis) in breast cancer prognosis

Abstract

The search for prognostic markers is important both to identify those patients with occult metastases and also to spare chemotherapy in those patients whose tumors have not developed the capacity for distant spread. Angiogenesis, the formation of new blood vessels, is necessary for breast cancer growth and metastasis. Good correlation has been demonstrated between intratumoral vascularization and outcome in patients with breast cancer. Intratumoral vascularization in human breast cancer can be measured by using standard immunohistochemical methods. Strict guidelines for scoring need to be followed. Although attempts are being made to automate the reading, visual scoring remains superior. We studied a population of women with small node-negative breast cancer who received no adjuvant therapy and have a median follow-up of 15 years. We have found intratumoral vascularization, as measured by microvessel count, to be an independent prognostic factor for disease-free survival. Low microvessel count identifies a group of patients with a 20 year disease free survival of 93%. The proportion of women with low microvessel count decreases with increase in tumor size and increases with patient age. But even in mammographically detected nonpalpable breast cancer, that is, the smallest breast cancer we currently detect, the majority already have high microvessel count. Intratumoral vascularization appears to be an early event that is necessary but not sufficient for metastatic progression. Microvessel count seems to be an excellent marker to identify patients with good prognosis because those with low microvessel count have a 93% disease-free survival irrespective of size, grade, or estrogen receptor status, but is less good at predicting those at high risk since the 20-year disease-free survival is still 67-70% in those with high microvessel count. Thus, the higher risk group needs to be further stratified using additional prognostic factors.