Patient information: Postmenopausal hormone therapy and breast cancer

POSTMENOPAUSAL HORMONE THERAPY AND BREAST CANCER OVERVIEW

Postmenopausal hormone therapy refers to the use of hormones, including estrogen and progesterone, during and after the menopause. Estrogen levels fall at the time of menopause, producing well-known symptoms such as hot flashes and vaginal dryness. In addition, lower levels of estrogen are believed to increase a woman's risk for both bone thinning (osteoporosis) and heart disease after menopause. Many women use estrogen and progestin replacement to relieve bothersome symptoms of menopause.

This article provides information about the link between hormone therapy and breast cancer. Detailed discussions of the risks and benefits of postmenopausal hormone therapy are found elsewhere. (See "Patient information: Postmenopausal hormone therapy" and "Patient information: Postmenopausal hormone therapy alternatives".)

ESTROGEN AND BREAST CANCER

Estrogen is produced by the ovaries, although the amount of estrogen that is produced varies over a lifetime. Evidence from numerous studies indicate that exposure to naturally occurring estrogen can affect a woman's risk of breast cancer. The risk appears to increase with prolonged exposure (for women who have their first menstrual periods at an early age or menopause at a late age). The risk may also increase if she is exposed to high levels of estrogen. A full discussion of risk factors for breast cancer is available separately. (See "Patient information: Risk factors for breast cancer".)

HOW DO HORMONES AFFECT MY RISK OF BREAST CANCER?

Estrogen and progesterone can stimulate breast cells to proliferate (grow and multiply). Proliferating cells are more likely to develop the genetic damage that leads to breast cancer. Furthermore, estrogen and progesterone can stimulate the growth of breast cancers that have already developed. Therefore, one of the main concerns for women thinking about taking hormone therapy is the risk of developing breast cancer.

The best information about hormone therapy and the risk of breast cancer is from the Women's Health Initiative (WHI), a large clinical trial comparing the risk of breast cancer in women who took HRT versus women who took a placebo (sugar pill). The WHI also examined the risk of other conditions, such as heart disease, bone thinning, and colon cancer. Women who did not have a uterus (eg, after hysterectomy) were randomly assigned to take estrogen (Premarin) or placebo; women with a uterus took combined estrogen-progestin (Prempro) or placebo.

Estrogen plus progestin — Researchers expected to see a decreased risk of heart disease and a slightly increased risk of breast cancer in women who took hormones. Instead, they found that women who took combined estrogen-progestin had an increased risk of breast cancer and cardiovascular complications (heart attacks, strokes, blood clots). There were 38 cases of breast cancer per 10,000 women/year taking hormones versus 30 per 10,000 women taking placebo (sugar pills). This means that 8 additional women per year per 10,000 women developed breast cancer because of their use of estrogen-progestin. Similar findings have been noted in a number of other studies.

For these reasons, the estrogen plus progestin part of the trial was stopped in July 2002. Although there are other benefits of hormone therapy (lower risk of osteoporotic fracture and colon cancer), the overall risks outweigh the benefits for many women if hormone therapy is taken long-term. Hormone therapy is an effective short-term treatment for menopausal symptoms, but is no longer recommended as a long-term treatment (greater than five years).

One criticism of the WHI was that the average age of women who enrolled was 63 years. Thus, the results of the study may be different for peri- and newly postmenopausal women, who are typically 10 to 15 years younger. Therefore, the risks of hormone therapy may be less concerning for women in their 50's compared to women in their 60's, especially if hormone therapy is taken for less than five years.

Effects of progestins — There is good evidence that use of estrogen and a progestin increases the risk of breast cancer more than if estrogen is used alone. However, women who have a uterus should not take estrogen alone because of the increased risk of developing endometrial hyperplasia or uterine cancer; these conditions can develop after as little as six months of estrogen alone. Thus, women who have a uterus must take a progestin if estrogen is taken. For women who have had a hysterectomy, estrogen alone is preferred.

Estrogen alone — The results of the WHI trial of unopposed estrogen were different than those of combination estrogen and progestin: it showed an increased risk of stroke and blood clots, but no increase in breast cancer or heart attack risk. (See "Patient information: Postmenopausal hormone therapy".)

Duration of use — All of these studies suggest that the major increase in breast cancer risk occurs after a woman has used estrogen-progestin for four to five years. Again, in the WHI, there was no increased risk of breast cancer in the women who took only estrogen.

Effects of past use — The risk of breast cancer associated with hormone therapy decreases after a woman stops using hormone therapy, even if she has taken hormones for a long time. In one study, the risk of breast cancer in women who had stopped using hormone therapy more than five years ago was the same as the risk in women who had never been on hormone therapy. Ongoing studies will help clarify the long-term effects of past hormone therapy use on breast cancer risk.

Personal history of breast cancer — Women with breast cancer who take hormone therapy are at increased risk for a breast cancer recurrence. Therefore, we do not recommend using estrogen or estrogen plus progestin in women with a personal history of breast cancer. Instead, alternatives to hormone therapy may be helpful. (See "Patient information: Postmenopausal hormone therapy alternatives".)

It was previously thought that women who developed breast cancer while taking hormone therapy had a better chance of cure compared to women with breast cancer who were not taking hormone therapy. Based upon the results of the WHI, this does not appear to be true.

SCREENING FOR BREAST CANCER

Regular breast cancer screening is essential for all women, especially those who decide to use hormone therapy. Screening includes a combination of breast self-exams, annual breast exams with a healthcare provider, and an annual mammogram. (See "Patient information: Breast cancer screening".)

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two people are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

Some of the most pertinent include:

Patient Level Information:
Patient information: Postmenopausal hormone therapy
Patient information: Postmenopausal hormone therapy alternatives
Patient information: Risk factors for breast cancer
Patient information: Breast cancer screening

Professional Level Information:
Androgen production and therapy in women
Clinical manifestations and diagnosis of vaginal atrophy
Continuous postmenopausal hormone therapy
Estrogen and cognitive function
Menopausal hot flashes
Postmenopausal hormone therapy and cardiovascular risk
Postmenopausal hormone therapy and the risk of breast cancer
Postmenopausal hormone therapy in the prevention and treatment of osteoporosis
Postmenopausal hormone therapy: Benefits and risks
Preparations for postmenopausal hormone therapy
Treatment of menopausal symptoms with hormone therapy
Treatment of vaginal atrophy

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable.

• National Cancer Institute

       1-800-4-CANCER
       (www.nci.nih.gov)

• People Living With Cancer: The official patient information

      website of the American Society of Clinical Oncology
      (www.cancer.net/portal/site/patient)

• National Comprehensive Cancer Network

      (www.nccn.com)

• American Cancer Society

       1-800-ACS-2345
      (www.cancer.org)

• National Library of Medicine

      (www.nlm.nih.gov/medlineplus/healthtopics.html)

• Susan G. Komen Breast Cancer Foundation

       (www.komen.org)

• The Hormone Foundation

      (www.hormone.org/public/menopause.cfm, available in English and Spanish)

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