Additive endocrine therapy for advanced breast cancer - back to the future.

While novel endocrine treatment options have been implemented in the advanced - as well as adjuvant setting, recent results suggest a place for "old-fashioned" additive treatment with estrogens in advanced breast cancer. This paper reviews the biological rationale for endocrine therapy in general and additive treatment with estrogens in particular. The finding that patients becoming resistant to treatment with aromatase inhibitors may subsequently respond to estrogen therapy adds important information to our understanding of therapy resistance in general. Moreover, the return of a therapeutic option abandoned more than 20 years ago, now to be used in a different sequential setting, suggests a critical examination whether there may be other conventional treatment options still earning a place as treatment in advanced disease as well. While ablative therapies including surgical oophorectomy, hypophysectomy and adrenalectomy are not candidate treatment options due to morbidity, there are additive treatment options apart from estrogen therapy that may be considered. Androgens administered at therapeutic doses are not feasible for toxicity reasons; yet, the potential of adding androgens in small doses as adjuvant to aromatase inhibitors should be further explored. Whether patients become resistant to other treatment options may still benefit from megestrol acetate, remains to be explored.