A new analysis of Women's Health Initiative data presented at the annual San Antonio Breast Cancer Symposium has reported that estrogen-only hormone replacement therapy (HRT) may be safe for the majority of postmenopausal women and may, in fact, protect against breast cancer. The analysis was designed to examine the difference between exogenous estrogen (estrogen-only HRT) and endogenous estrogen (estrogen produced by the ovaries and other tissues in the body) in their influence on risk of breast cancer. The Women's Health Initiative is a long-term U.S. national health study that examines strategies for preventing heart disease, breast and colorectal cancer, and fracture in postmenopausal women. In 2002, it was reported that breast cancer incidence was increased by HRT in the Women's Health Initiative trial of combined HRT (estrogen plus progestin). However, the authors' recent reviews of data from the Women’s Health Initiative hormone replacement therapy trials (which included both combined HRT and estrogen-only HRT) suggested that estrogen alone can be protective while combined HRT based on estrogen plus progestin can be carcinogenic. Endogenous estrogen is thought to promote breast cancer. Evidence for this is that reducing estrogen levels by removing the ovaries or using anti-estrogens such as tamoxifen or aromatase inhibitors is protective against breast cancer in high risk women, as well as being effective treatment at all stages of estrogen receptor positive (ER+) breast cancer. However, exogenous estrogen may be protective. To help examine this proposition, the authors present results of the Women's Health Initiative HRT trial 2 (which included 10,739 women who had had a hysterectomy, randomized to receive estrogen-alone HRT or placebo) with analyses according to prior history of benign breast disease, a first degree relative with breast cancer, or prior HRT use.

Overall, women in the trial who received estrogen-only HRT had a 20% lower risk of breast cancer than women receiving the placebo. When considering women without certain factors known to increase breast cancer risk, estrogen-only HRT appeared to be even more protective. Women using estrogen only HRT compared to placebo had a 43% lower risk of breast cancer if they had no prior history of benign breast disease, a 32% lower risk if they had no first degree relative with breast cancer, and a 35% lower risk if they had no prior history of HRT use. The protective effect of treatment with estrogen alone is comparable in magnitude to that reported with tamoxifen use in high risk women. Based on the data, the authors propose that (1) in selected women, the use of HRT based on estrogen alone may be appropriate to manage menopausal symptoms, since it is associated with a significant reduction of breast cancer rates; and (2) the use of exogenous estrogen in chemoprevention merits validation, including determination of the optimum estrogen regimen (type of estrogen, dose, mode of delivery). In a separate interview, lead researcher Joseph Ragaz suggested that “while the use of HRT with estrogen alone may reduce the risk of breast cancer and may also be appropriate to manage menopausal symptoms, further research is warranted to elaborate on the optimum treatment regimen, to refine the selection of ideal candidates for estrogen therapy, and to understand the estrogen mechanisms that support the prevention of human breast cancer.”