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 invol ved in breast cancer progression and metastasis, To investigate whethe r the determination of angiogenesis adds prognostic information to the estrogen receptor (ER) status, we studied a series of 178 node-positi ve breast cancer patients, with a median follow-up time exceeding 5 ye ars, treated with adjuvant tamoxifen (TAM), We assessed angiogenesis b y the quantification of the intratumoral microvessel density and the d etermination of the Chalkley score using light microscopy, Microvessel s were immunostained using the anti-CD31 antibody, The other features studied were ER status and the conventional clinicopathological progno stic indicators, Results were pooled from two collaborating Centers us ing Chalkley counts to convert intratumoral microvessel density to a c ommon quantification system, We found that Chalkley score was not asso ciated with any other feature studied, In univariate analysis, Chalkle y score was significantly predictive of both relapse-free survival (RF S) and overall survival (OS; P < 0.00001 and P = 0.00004, respectively ), Likewise, ER status, the number of metastatic axillary nodes, histo logical grading, and tumor size were significantly predictive for RFS and OS, Cox multivariate analysis showed that Chalkley score was the s trongest significant independent predictor of outcome, For RFS, ER sta tus, the number of metastatic nodes, and histological grading also ret ained significance, For OS, the number of metastatic nodes, tumor size , and histological grading were independent prognostic factors, The jo int assessment of the above variables had a satisfactory prognostic ca pability, as found using the Harrel statistics (c = 0.77). These resul ts suggest the validity of using Chalkley counts to assess and compare angiogenesis for prognostic purposes between different Centers, We fo und that angiogenesis adds significant prognostic information to ER st atus in predicting the outcome of breast cancer patients treated with adjuvant TAM, In fact, irrespective of the ER status, the patients wit h highly angiogenic tumors had a poor outcome, even if treated with TA M. For these patients, the inhibition of angiogenesis with specific an gioinhibitory drugs may be a promising new therapeutic strategy.