Behaviour of metastasis in relation to vascular index in patients with node-positive breast cancer treated with adjuvant tamoxifen

Some experimental studies suggested that one possible oestrogen-receptor-un related mechanism of action of tamoxifen involves inhibition of angiogenesi s. We evaluated the correlation of the degree of vascularisation of the pri mary tumour and we assessed it by using the panendothelial marker anti- CD3 1 and immunohistochemistry with microvessels count, performed at the vascul ar 'hot spot' of each single cancer, with the risk of recurrence in time. A cohort of 176 consecutive patients with node-positive invasive breast canc er treated with adjuvant tamoxifen (30 mg/daily for 3 years) and a median f ollow-up of 72 months was studied. Sixty-two patients developed metastasis (30 visceral, 18 skeletal and 14 in soft tissues) during the time of observ ation. The study of the hazard function for metastasis was performed by a g eneralized linear modelling approach with a binomial error according to Efr on. The risk of first recurrence was strictly associated with vascular inde x, having the patients with the highest microvessel counts the highest risk of metastasis during all the period of observation. We did not find an int eraction of vascularity with oestrogen receptor (ER) status. However, in th e subgroup of patients with ER-positive tumours the hazard of metastasis wa s almost constant in time, while in that with ER-negative tumours it increa sed rapidly up to 20 months and, thereafter, decreased sharply. The results of our study are an indirect evidence that the patients with highly vascul arized breast cancers may gain poor benefit of adjuvant tamoxifen and, ther efore, that this antioestrogen is unlikely to retain a clinically relevant antiangiogenic activity in human breast cancer. Our data need confirmation by a prospective randomized clinical trial.