Il Carcinoma Metastatico Della Mammella: Quali Obiettivi?

Abstract

The medical approach to the treatment of metastatic breast cancer has changed in the last decade since the introduction of new drugs that demonstrate high activity and better tolerability profiles. The hormonal treatment, usually considered the first choice therapy for ER-positive metastatic breast cancer patients, has seen several improvements with the discovery of new selective aromatase-inhibitor agents and pure antiestrogens. New aromatase-inhibitors have shown higher activity and fewer side effects compared to megestrol acetate in second line treatment. The first line treatment has unchanged so far, but in the next future is possible that different agents, with lower toxicity, will replace tamoxifen since studies comparing this agent with pure antiestrogens or selective aromatase-inhibitors are ongoing. These new drugs would provide a better palliation of metastatic breast cancer in terms of higher clinical benefit, tolerability and quality of life. Chemotherapy is often used in ER-negative patients or in aggresive hormone refractory disease. Randomized trials have demonstrated that anthracyclin-containing regimens were more effective than combinations without anthracyclines. New cytotoxic drugs with high activity, such as taxanes (paclitaxel and docetaxel), vinorelbine, gemcitabine and capecitabine, have been intoduced. Compared with older therapies, improved objective response rates and/or improved duration of response have been reported with these newer agents alone or in combination with other drugs. However, no clear improvement of overall survival has been shown so far. Taxanes alone or in combination are today considered the second line treatment of choice and studies are assessing the value of a taxane-anthracycline containing regimen in first line treatment. Some new agents (vinorelbine) showed, alone or in combination, an interesting cost-effectiveness ratio with similar or higher “quality adjusted progression free survival'’ if compared to taxanes. Promising are also the results of agents that own low toxicity with comparable efficacy such as liposomal anthracycline.

Attempts to improve overall survival with increased dose intensity or with high dose chemotherapy are disappointing.

Conclusions

Since the goal of treatment of metastatic breast cancer is disease control rather than disease kill i.e palliation of patients with complications of progressive cancer, the new agents have brought significant improvements (higher response rates, median time to progression, cost benefit and better tolerability). Future progresses for this disease, hopefully even in overall survival, will depend on the introduction of new therapies such as immunotherapy, inhibition of intracellular signaling, interference with tumor angiogenesis, gene-therapy and the developement of vaccines.