Clinical benefit of sequential use of endocrine therapies for metastatic breast cancer.

Sequential use of endocrine agents is common in estrogen receptor (ER)-positive metastatic breast cancer (MBC). In premenopausal women with MBC, tamoxifen and/or a luteinizing hormone-releasing hormone (LH-RH) agonist are options for endocrine treatment. Meta-analysis showed that the combination of the two agents is superior to either monotherapy. Under ovarian ablation or function-suppression, an agent used to treat postmenopausal women, such as the aromatase inhibitor (AI), fulvestrant, becomes possible as a subsequent therapy. In postmenopausal women, endocrine treatment options are widely available and an optimal sequence has not yet to be determined. Options for first-line therapy of metastatic disease include an AI for women who have received adjuvant tamoxifen, or tamoxifen for patients who have received adjuvant AI. In addition, data suggest that fulvestrant is a promising therapeutic option that has proven efficacy in the treatment of postmenopausal women with MBC. Other agents that may be used in the sequence include a steroidal AI or a progestin. Furthermore, estrogen additive therapy by with diethylstilbestrol or ethinylestradiol has recently been revived and showed a high response rate as a salvage endocrine therapy, although its mechanism of action is still unclear. Thus, sequential use of endocrine therapies, especially the use of a subsequent therapy with a different mechanism of action to the prior therapy, has a beneficial effect in maintaining a good quality of life and extending survival for MBC with hormone responsiveness.