Hormone therapy and the risks of breast and endometrial cancers

Breast cancer

Your risk of developing breast cancer increases slowly as you age, especially after age 50. Of American women who live to age 80, about 1 in every 8 will have been diagnosed with breast cancer at some point in her life.¹ Taking estrogen with progestin (hormone replacement therapy, HRT) further increases that risk.² Taking estrogen alone may slightly increase breast cancer risk. Large studies have shown either a slight risk increase or none at all.^{3, 4}

These average increased breast cancer risks are relatively low for the general population of postmenopausal women. However, your personal risk that hormone therapy will stimulate cancerous cell growth may be significantly lower or higher, depending on your risk factors. For more information about breast cancer risk factors, see the topic Breast Cancer.

Endometrial cancer

In the United States, endometrial (uterine) cancer is the most common cancer of the lower female genital tract. About 1 woman in 50 (2%) will develop endometrial cancer in her lifetime.⁵ Women with an intact uterus who take estrogen therapy without progestin increase their risk of endometrial cancer. Adding progestin protects the uterus from this risk.

Weighing cancer risks for women who still have a uterus

• Taking only estrogen (estrogen replacement therapy, ERT) after menopause increases your risk of endometrial cancer.
• Taking progestin along with estrogen (HRT) eliminates endometrial cancer risk. (Estrogen-only therapy stimulates overgrowth of the uterine lining, which can become cancerous. Progestin regulates that growth.)
• Although adding progestin protects your uterus, it increases breast cancer risk. The British Million Women Study researchers have found that, among women ages 50 to 64, long-term (10-year) HRT after menopause causes more breast cancers than long-term estrogen replacement therapy (19 per 1,000 versus 5 per 1,000).³ American Women's Health Initiative researchers have similarly found that after 5.2 years of use, HRT causes 4 per 1,000 breast cancers. Their ERT data do not show breast cancer from ERT use. However, experts still take the ERT cancer risk seriously.^{6, 4}
• Some experts have recently asserted that there may be no advantage to taking progestin with estrogen (to prevent endometrial cancer), because the addition of progestin increases breast cancer risk.

Unanswered questions about short-term and low-dose hormone therapy

Using hormone therapy for a short time just after menopause is hoped to be low-risk. Some studies have suggested that short-term use of hormone therapy (up to 4 years) may not increase breast cancer risk.^{5, 6} Ongoing study is needed to see how much lower-dose and shorter-term HRT and ERT reduce the risks of using long-term hormone replacement, including risks of breast and gynecological cancers, cardiovascular disease, and Alzheimer's disease.

Other treatments that do not appear to increase breast cancer risk are available for hot flashes, osteoporosis, and heart disease.

Citations

1. National Cancer Institute (2006). Probability of breast cancer in American women. National Cancer Institute Fact Sheet. Available online: http://www.cancer.gov/cancertopics/factsheet/Detection/probability-breast-cancer.

2. American College of Obstetricians and Gynecologists Women's Health Care Physicians (2004). Breast cancer. Obstetrics and Gynecology, 104(4, Suppl): 11S–16S.

3. Million Women Study Collaborators (2003). Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet, 362(9382): 419–427.

4. Women's Health Initiative Steering Committee (2004). Effects of conjugated equine estrogen in postmenopausal women with hysterectomy. JAMA, 291(14): 1701–1712.

5. Mishell DR (2001). Menopause. In MA Stenchever et al., eds., Comprehensive Gynecology, 4th ed., pp. 1217–1258. St. Louis: Mosby.

6. Rossouw JE, et al. (2002). Risks and benefits of estrogen plus progestin in healthy postmenopausal women. Principal results from the Women's Health Initiative randomized controlled trial. JAMA, 288(3): 321–333.