Hormonal therapy: Current and new directions

The well-established hormonal risk factors for breast cancer and laboratory models of estrogen-driven breast cancer cell growth have long provided a rationale for hormonal therapy. After the early use of therapeutic oophorectomy, antiestrogens, now known as selective estrogen response modulators (SERMs), became widely used. Large-scale trials have now shown that the SERM prototype, tamoxifen, is effective for palliation in advanced breast cancer, for improvements in recurrence and mortality risk in early stage disease, local recurrence in ductal carcinoma in situ (DCIS), and as prevention for early stage breast cancer. Questions still remain about the optimal selection of patients for early stage disease, DCIS, and prevention. New highly potent aromatase inhibitors (Als) have now been tested in advanced stage disease, where they have become the treatment of choice for postmenopausal patients. Early results from a large randomized trial (Anastrozole, Tamoxifen, Alone or in Combination [ATAC]) suggest that the Al anastrozole is superior to tamoxifen in lowering the risk of recurrence. Fewer vaginal symptoms and hot flashes were seen with anastrozole, but more bone fractures in this group have raised the concern of long-term bone mineral density and other hormonal effects in a population of patients who are less likely to die of breast cancer than of other causes. Als are also being tested for primary prevention, and a hint of this benefit was seen in the ATAC trial. Signs of hormonal deficiency are a common problem in women who have been treated for breast cancer, and this adversely affects their overall quality of life. The controversies concerning hormonal supplementation and the limited data in this regard are discussed.