Hormone Replacement Therapy And Breast Cancer Risk: Results Of Women's Health Initiative Studies

In the 1990s, Hormone Replacement Therapy (HRT) medications were among the most frequently prescribed medications in the United States. Almost 35% of postmenopausal women were taking HRT. Based on results of research available at the time, HRT was expected to lower a woman’s risk of heart disease and osteoporosis, along with easing symptoms of menopause including hot flashes, night sweats, and vaginal dryness. Imagine the shock to millions of women when, in 2002, a large multi-center randomized clinical trial known as the Women’s Health Initiative (WHI) revealed that HRT use was associated with increased risk of heart disease, breast cancer, stroke, and pulmonary embolism. The news headlines caused panic, and subsequent reports did little to calm the panic or explain the study results. However, research evidence is far from black and white, and hopefully this brief review will help explain results of the WHI clinical trials of HRT. The WHI was the first large (16,608 women), well done experimental study on the effects of HRT on long term health benefits and risks, including risk of invasive breast cancer. In high quality clinical trial experiments funded by the federal government, researchers are required to set criteria for monitoring unexpected disease. The study is then observed by reviewers not associated with the study, and if cases of disease exceed the set number, reviewers can call for an end to the study for safety and ethical reasons. That is what happened in the WHI study, which was supposed to continue through 2005, but was stopped in 2002 based on health risks that exceeded health benefits. Results of the study were presented in terms of “person years” which is one way to describe the risk of disease for a group based on available information. For every 1000 women taking HRT and followed for 10 years (10,000 person years), women experienced 7 more cases of coronary heart disease, 8 more strokes, 8 more pulmonary embolisms, and 8 more invasive breast cancers than the comparable group of women who were not taking HRT. The study also showed that the HRT group experienced 6 fewer colorectal cancers and 5 fewer hip fractures. A second report from the WHI that looked specifically at breast cancer reported 199 cases of invasive breast cancer among women taking HRT compared to 150 cases among women not taking HRT. Tumors diagnosed in the HRT group were larger and were more likely to have spread compared to tumors diagnosed in women not taking HRT. These results suggested that HRT stimulates breast cancer growth and makes diagnosis more difficult. A third WHI study looked at the effects of estrogen alone (ERT, not combined with progesterone) in postmenopausal women with hysterectomies. ERT is not given to women who still have their uterus, because it has been shown to increase risk of uterine cancer. The study found that the use of ERT increased the risk for stroke, decreased the risk of hip fracture, does not affect the risk of coronary heart disease, and possibly lowered the risk of breast cancer.  Based on these WHI studies, as well as many other studies, the prolonged use of HRT/ERT for chronic disease prevention is not recommended. Short term use of lower dose HRT may be appropriate for management of menopause symptoms, but each woman needs to discuss her individual risk profile with her physician. And if you are a woman who took HRT for many years, don’t panic. Researchers still do not know what causes breast cancer – most women who took HRT did not develop breast cancer, and women not taking HRT developed breast cancer. All that is known is that HRT increases risk of breast cancer in large populations of women. It may be that HRT works with some other factor in promoting the growth of breast cancer. Because the specific cause of breast cancer is not known, the importance of early detection cannot be stressed enough. The American Cancer Society, along with most other medical groups, recommends regular mammography (once each year beginning at age 40 years) for women at average risk, along with an annual clinical breast exam by a physician and monthly self breast exams. If a woman’s doctor believes the woman is at high risk for developing breast cancer based on family history, reproductive history or lifestyle factors, she may begin regular mammography at an earlier age, and/or have additional screening with ultrasound or MRI.