How does menopausal hormone use affect breast cancer risk and survival?

In 2002, the estrogen plus progestin component of the WHI concluded that combined estrogen and progestin increases the risk of invasive breast cancer. After an average of 5.2 years of followup, the study found a 26-percent increase in breast cancer risk among women taking the hormones as compared with women taking the placebo. The increase amounted to an additional 8 cases of breast cancer for every 10,000 women treated for 1 year compared to 10,000 nonusers (2). 

After an average followup of 5.6 years, a more detailed analysis of the WHI results showed that, among women taking estrogen plus progestin, the breast cancers were slightly larger (1.7 versus 1.5 centimeters) and at more advanced stages compared with cancers in women taking the placebo. Among the women taking hormones, 25.4 percent of the cancers had spread outside the breast to nearby organs or lymph nodes compared with 16.0 percent among nonusers (11). The component of the WHI study that includes 11,000 trial participants taking estrogen alone is expected to end in 2005, and will provide evidence on the effects of this hormone on breast cancer risk. 

Observational studies also indicate an increase in breast cancer risk among hormone users. A 1997 analysis of over 90 percent of breast cancer studies throughout the world showed an increased risk of breast cancer for women who used menopausal hormones for 5 or more years. Most of the women included in these studies used estrogen alone; however, the women who used estrogen plus progestin appeared have a somewhat higher risk than those using estrogen alone (12). The increase in risk was seen not only in current users, but also in women who had stopped therapy some time in the previous 4 years. No increased risk was seen in women who had stopped therapy more than 4 years earlier. 

Additional observational studies support the conclusion that hormone use is associated with an increased risk of breast cancer, with the greatest risk among women using estrogen plus progestin (13, 14, 15). In the Million Women Study, British researchers found that current use of estrogen, estrogen plus progestin, or other hormone preparations (including varied delivery mechanisms) significantly increased the risk of developing breast cancer in women ages 50 to 64. Women using estrogen plus progestin were at greater risk than those using other hormone preparations. Current hormone users were also more likely to die from breast cancer than women who did not use them. Within about 5 years of stopping use, increased risk largely disappeared (13).

Questions and Answers About Menopausal Hormone Use

• What is menopause?

• What are menopausal hormones and why are they used?

• How do scientists determine the health outcomes associated with hormone use?

• Do the benefits of hormone use after menopause outweigh the risks?

• What are the effects of hormone use on the uterus?

• How does menopausal hormone use affect breast cancer risk and survival?

• How does menopausal hormone use affect the risk of ovarian cancer?

• What are the effects of menopausal hormones on heart disease?

• What are the effects of menopausal hormones on bone health?

• What are the effects of postmenopausal hormone use on quality of life and cognitive functions, specifically memory and learning?

• Are there other benefits or risks associated with menopausal hormone use?

• What are the risks of menopausal hormones for women who have a history of cancer?

• Does the route of administration of hormones make a difference?

• Are there any alternatives for women who choose not to take menopausal hormones?

• What research still needs to be done?