Menopause Hormone Therapy and Breast Cancer

Estrogen/progestin combination hormone therapy causes breast cancer

On July 9, 2002, officials from the National Institutes of Health announced that one form of hormone therapy (HT), Prempro, had been found to cause breast cancer in previously healthy women. These women were volunteer participants in the Women's Health Initiative, the largest and longest ever trial of estrogen therapy (ET) and HT. Volunteers had knowingly accepted a possible increased risk of breast cancer in an effort to finally determine, more than fifty years after ET was first approved by the FDA, whether long-term use was beneficial. Just over 16,000 women participated in this section of the trial; half were given an estrogen/progestin combination in the form of Prempro, and the other half was given a look-alike placebo with no active ingredients.

By the time the trial was stopped, women had been taking their pills for an average of 5.2 years each. During that time, 166 women taking the hormone combination developed invasive breast cancer, compared to 124 women on placebo, an overall increase of 26 percent.[1] Another way of expressing the increased risk caused by Prempro is that each year, among 10,000 postmenopausal women taking estrogen/progestin, eight more will have invasive breast cancer. This increased risk of breast cancer does not appear until the hormones have been taken for at least two years. It also appears that the risk continues to increase with longer use.

Since 2002, the results of the trial have been updated several times, most recently in October 2010, when it was determined that HT use increased the risk of dying from breast cancer. [4]  After 11 years of follow-up, the risk of dying of breast cancer increased from 1.3 deaths per 10,000 women per year to 2.6 deaths per 10,000 women per year in women who used combined estrogen/progestin HT.

What about estrogen alone?

Another group of more than 10,000 women took part in a related trial within the Women's Health Initiative. These women all had hysterectomies and took estrogen alone in the form of Premarin. This trial found no increased risk of breast cancer over nearly seven years.[2] In fact, it found a decreased risk of breast cancer but these results were a surprise because there is suggestive evidence that estrogen used alone also increases the risk of breast cancer, although not as quickly or dramatically as does the estrogen/progestin combination.

Observational studies that have included women who used estrogen alone for more than five years have found a 20 to 30 percent increased risk of breast cancer.[3] Observational studies can be wrong, but observational studies correctly predicted increased breast cancer risk among women using combined HT.

Are other forms of hormone therapy safe?

Although there are many other versions of hormone therapy, none have been put to the test of a long-term randomized trial. While it is possible that some form of hormones or hormone combinations may not increase the risk of breast cancer, the existing evidence suggests otherwise. Until proven otherwise, we believe that women should assume that long-term use of hormone therapy increases breast cancer risk.

Newer forms of therapy, called selective estrogen receptor modifiers (SERMs), have become available during the last several years. These drugs mimic some, but not all, of estrogen's effects. Pharmaceutical companies hope to someday create a SERM that will help relieve hot flashes and vaginal dryness and prevent osteoporosis, heart disease and Alzheimer's without increasing risk of cancer or blood clots. So far, companies have successfully created a SERM that reduces the risk of fracture without increasing the risk of breast cancer in the short term.

•  Raloxifene (Evista) is approved to prevent and treat osteoporosis. In one study, it reduced the number of breast cancer cases in low risk women, and the government is studying it to see if it will reduce risk for women at higher risk of breast cancer as well. (However, raloxifene increases blood clots as well as hot flashes.)
• Tamoxifen was the very first SERM and has been used by breast cancer survivors for decades. It can decrease the risk of breast cancer while being used, but it significantly increases risks of blood clots, stroke and uterine cancer. It is too risky for most healthy women to use.

Resources

To join with thousands of individuals to advocate for better treatments and access to care, contact the National Breast Cancer Coalition, http://www.stopbreastcancer.org. To find out more about the activities of groups working on a national level to address the causes of breast cancer, including environmental connections, contact Breast Cancer Action, http://www.bcaction.org and the Breast Cancer Fund, http://www.breastcancerfund.org.

References

1. Writing group for the Women's Health Initiative investigators. "Risks and benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women. Principal Results from the Women's Health Initiative Randomized Controlled Trial." JAMA, July 17, 2002; 288: 321-333.
2. Collaborative group on hormonal factors in breast cancer. "Breast cancer and Hormone Replacement Therapy: Collaborative Reanalysis of Data from 51 Epidemiological Studies of 52,705 Women with Breast Cancer and 108,411 Women Without Breast Cancer." Lancet, 1997: 350:1047-1059.
3. The Women's Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy. The Women's Health Initiative randomized controlled trial. JAMA, April 14, 2004; 291: 1701-1712.
4. Chlebowski, RT, et al.  Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women.  JAMA, October 20, 2010; 304:  1684-1692.
 

Updated: 10/10