Determination of angiogenesis adds information to estrogen receptor status in predicting the efficacy of adjuvant tamoxifen in node-positive breast cancer patients

There is experimental and clinical evidence that angiogenesis is involved in breast cancer progression and metastasis. To investigate whether the determination of angiogenesis adds prognostic information to the estrogen receptor (ER) status, we studied a series of 178 node-positive breast cancer patients, with a median follow-up time exceeding 5 years, treated with adjuvant tamoxifen (TAM). We assessed angiogenesis by the quantification of the intratumoral microvessel density and the determination of the Chalkley score using light microscopy. Microvessels were immunostained using the anti-CD31 antibody. The other features studied were ER status and the conventional clinicopathological prognostic indicators. Results were pooled from two collaborating Centers using Chalkley counts to convert intratumoral microvessel density to a common quantification system. We found that Chalkley score was not associated with any other feature studied. In univariate analysis, Chalkley score was significantly predictive of both relapse-free survival (RFS) and overall survival (OS; P < 0. 00001 and P = 0.00004, respectively). Likewise, ER status, the number of metastatic axillary nodes, histological grading, and tumor size were significantly predictive for RFS and OS. Cox multivariate analysis showed that Chalkley score was the strongest significant independent predictor of outcome. For RFS, ER status, the number of metastatic nodes, and histological grading also retained significance. For OS, the number of metastatic nodes, tumor size, and histological grading were independent prognostic factors. The joint assessment of the above variables had a satisfactory prognostic capability, as found using the Harrel statistics (c = 0. 77). These results suggest the validity of using Chalkley counts to assess and compare angiogenesis for prognostic purposes between different Centers. We found that angiogenesis adds significant prognostic information to ER status in predicting the outcome of breast cancer patients treated with adjuvant TAM. In fact, irrespective of the ER status, the patients with highly angiogenic tumors had a poor outcome, even if treated with TAM. For these patients, the inhibition of angiogenesis with specific angioinhibitory drugs may be a promising new therapeutic strategy.