Selection of optimal adjuvant endocrine therapy for early-stage breast cancer.

Oophorectomy was found to cause regression of advanced breast cancer toward the end of the 19th century. Decades later, the discovery that estrogen plays a central role in this process eventually led to two important consequences: first, different modalities were developed to suppress or antagonize estrogen; and second, the ability to detect estrogen receptor in breast cancer tissue became a predictor of response to treatment--probably the best marker for response among all solid tumors. Tamoxifen, which works by competitively antagonizing hormonal receptors in breast cancer cells, has been for the past three decades the standard of care for adjuvant therapy for any woman with hormone receptor-positive early breast cancer, regardless of nodal status or menopausal setting. But as we strive to improve the utility of antagonizing or suppressing estrogen, new modalities are being developed. In the premenopausal setting, the advent of gonadotropin hormone-releasing hormone (also known as luteinizing hormone-releasing hormone) analogues has allowed for medical and reversible suppression of ovarian function. This method has already been proven as effective as chemotherapy in preventing recurrence, and ongoing trials are aiming to better define its role in the adjuvant setting. In the postmenopausal setting, aromatase inhibitors (AIs) have revolutionized the adjuvant treatment of hormone-responsive cancers of all stages. The current standard of care has come to include AIs, as an alternative, in sequence, of after 5 years of tamoxifen. Ongoing research continues to develop agents to overcome hormonal therapy resistance.