Metastatic breast cancer: Tailored endocrine therapy for premenopausal women

One-quarter of breast cancer patients are premenopausal at the time of diagnosis [1], and 60% are steroid hormone-receptor-positive (HR+) [2]. Fortunately, only 5% of patients present with disseminated disease, but more than 20% will ultimately become metastatic [3]. Steroid hormone-receptor expression strongly predicts efficacy of endocrine manipulation, producing responses in approximately 60% of women with estrogen receptor (ER)- and progesterone receptor (PR)-positive (ER+/PR+) breast cancer, 30% with either ER+ or PR+ alone, and fewer than 10% with ERnegative (ER-)/PR-negative (PR-) tumors [4, 5]. In addition, higher levels of ER and/or PR correlate with a greater likelihood of response to hormonal therapies [4]. Endocrine therapy is generally the first-line approach to HR+ metastatic disease, except in women with visceral or central nervous system involvement or rapidly progressing disease, because of its efficacy and favorable toxicity profile. Options for endocrine therapy in premenopausal women with metastatic breast cancer include ovarian ablation via oophorectomy or ovarian irradiation, ovarian suppression via administration of luteinizing hormone-releasing hormone (LHRH) analogs, monotherapy with the selective ER modulator (SERM) tamoxifen, or the combination of these modalities. In addition, aromatase inhibitors, which inhibit peripheral conversion of androgens to estrogens, may be used in conjunction with ovarian ablation or suppression. Finally, progestins such as megestrol acetate are available for third-line endocrine therapy. The challenge is to determine for an individual patient whether these therapies are best combined or given as sequential monotherapy, and if given as monotherapy, the best order in which to give them.