ADJUVANT CHEMOENDOCRINE THERAPY FOR EARLY BREAST-CANCER - IS IT WORTHWHILE - (REVIEW)

The overview published in 1999 by the Early Breast Cancer Trialist' Co operative Group demonstrated that systemic therapy after surgical remo val of primary breast tumors prolongs both disease-free and overall su rvival of patients when compared with no systemic therapy, Specificall y, both chemotherapy and ovarian ablation in patients aged less than 5 0 and tamoxifen in those aged 50 or more achieve a reduction of one-fi fth to one-fourth in the annual odds of recurrence or death from any c ause. The relative effect of different therapies is independent of the stage of the disease, while the absolute benefit depends not only upo n the relative effect of treatment but also upon the baseline prognosi s of patients. The overview did not report a direct estimation of the effect of combined chemoendocrine adjuvant therapy. Among the effects that may confound the evaluation of chemoendocrine adjuvant therapy ar e: (a) the possibility of biological interactions between drugs; (b) t he presence on tumor cells of steroid hormone receptors; (c) the suppr ession of ovarian activity induced by chemotherapy in most premenopaus al patients; (d) the scheduling of chemotherapy and endocrine therapy. Based on data of the overview, relevant questions are: (i) does the a ddition of endocrine therapy (tamoxifen dr ovarian ablation) to chemot herapy improve the outcome of premenopausal patients? (ii) does the ad dition of chemotherapy to tamoxifen improve the outcome of postmenopau sal patients? We have reviewed single randomised trials in an attempt to answer these questions. In premenopausal patients, the addition of tamoxifen to chemotherapy probably induces only small advantages. The addition of ovarian ablation to chemotherapy could improve survival. T he relationship between oophorectomy and receptor status has not been extensively studied; however, the addition of oophorectomy, like the a ddition of tamoxifen, to chemotherapy could be cost effective in cases of estrogen receptor-positive tumors. The effect of tamoxifen in asso ciation with ovarian ablation, after chemotherapy, has not yet been st udied. In postmenopausal patients the addition of chemotherapy to tamo xifen is debated. The role of receptor status seems to be important in these patients. Most studies found that chemotherapy does not signifi cantly increase the effect of tamoxifen in the subgroup of patients wi th receptor-positive tumors, while it does increase toxicity. On the c ontrary, the addition of chemotherapy to tamoxifen, in patients with r eceptor-negative tumors could significantly improve results.