Hormonal approaches to breast cancer treatment and prevention: an overview.

Hormonal agents play a critical role in the palliation of advanced breast cancer, as well as adjuvant therapy to surgery and radiation in patients with primary breast cancer. Tamoxifen appears to be the therapy of choice for the initial treatment of metastatic breast cancer in both premenopausal and postmenopausal women, although some clinicians prefer oophorectomy or the use of luteinizing hormone releasing hormone analogues in premenopausal patients. Historically, second-line hormonal therapy for metastatic disease has been with a progestin; however, due to the troubling side effects of weight gain and dyspnea, progestins may soon be replaced by aromatase inhibitors. The development of new antiestrogens lacking estrogen-agonist activity for metastatic disease is in its earliest clinical developmental phases. For adjuvant therapy in postmenopausal women, there is conflicting evidence as to whether the combination of a hormonal agent (ie, tamoxifen) plus chemotherapy provides an advantage over hormonal therapy alone. In premenopausal women areas of active investigation include combination hormonal therapy (eg, tamoxifen plus luteinizing hormone releasing hormone analogues or oophorectomy) and combination chemohormonal therapy (concomitant v sequential). Tamoxifen had been associated with rare cases of thromboembolic events and secondary endometrial cancers. The etiology of these secondary cancers is unclear and controversial; however, the benefits of tamoxifen far outweigh the risks for both palliative and surgical adjuvant therapy. The success of tamoxifen in preventing cancer recurrence in the contralateral breast has led to clinical investigation of the drug for the chemoprevention of breast cancer in women at high risk for development of the disease. The role of tamoxifen for this indication remains to be determined following completion of the National Surgical Adjuvant Breast and Bowel Project trial in North America and additional trials in the United Kingdom and Italy.