Analogues de la LHRH : leur utilisation dans le traitement du cancer du sein en situation métastatique et adjuvante☆

Abstract

Breast cancer is often an estrogen-dependent disease. The primary goals of the treatment of breast carcinomas are multiple, depending on the situation in which the patients are treated. In adjuvant setting, the aims are to delete the time of relapse, to increase the overall survival, and to offer to the patients the best quality of life they may expect. Tamoxifen is the standard hormonal agent for premenopausal women with receptor-positive breast cancer. Recent data show an increasing role for aromatase inhibitors in postmenopausal women. In metastatic setting, the primary goals are improved quality of life and prolonged survival; effective therapies with minimal toxicity, such as endocrine therapy, are highly desirable and should be considered a primary option over chemotherapy for selected estrogen-receptor positive patients. Ovarian ablation has been worldwide used. Methods of irreversible ovarian ablation include surgical oophorectomy and ovarian irradiation. Potentially reversible castration can be medically accomplished using luteinizing hormone releasing hormone analogues (LHRH agonists). In the metastatic setting, ovarian ablation (induced by the use of LHRH agonists or by surgical ovarian ablation) and tamoxifen monotherapies produce comparable outcomes, and may be more effective when used together (combined estrogen blockade). In advanced breast cancer, the combination prolongs the progression-free survival and increases response rates and duration of response rate relative to the use of LHRH agonist alone. In the adjuvant setting, data suggest that ovarian ablation followed by tamoxifen produces similar results to those obtained with adjuvant chemotherapy in hormone-receptor positive breast cancer women. The value of combining these modalities remains unclear, but the addition of the LHRH analogue goserelin to standard treatment results in a significant benefit in terms of relapse-free and overall survival, especially for estrogen-receptor positive patients. Finally, considering the efficacy of the new aromatase inhibitors, the interest of combining these drugs with the LHRH analogues has yet to be defined, both for pre- and post-menopausal patients.