Hormones And Risk - Risk Factors: Breast Cancer

Content provided by the Faculty of the Harvard Medical School

Hormones and risk

Another factor in breast cancer risk is long-term exposure to ovarian hormones, particularly the female hormones estrogen and progesterone, which are produced during the menstrual cycle. Scientists suggest that it may be abnormal, biologically speaking, for a woman's body to be exposed to the high hormone levels of the menstrual cycle for many years.

Before the mid-1900s, most women didn't start having periods until their late teens, frequently because of poor nutrition. Then, before birth control became readily available, women often spent much of their reproductive lives either pregnant or breast-feeding, both of which change breast tissue in ways that prevent breast cells from turning cancerous. Longer and more frequent periods of breast feeding (lactation) may be associated with some protective effect of developing breast cancer.

Today, most girls in developed countries begin puberty around age 10-12, have their first child at a later age than previous generations, have fewer children or no children, and may not experience menopause until their 50s. That means that today, a woman's breast cells might be subject to the hormonal stimulation for more than 40 years - a far greater lifetime exposure than most women of past centuries experienced.

Although the precise roles these hormones play in a woman's breast cancer risk are not yet known, the number of menstrual cycles she has during her lifetime appears to influence her risk of cancer. For that reason, a woman's age at menarche (when she starts menstruating) and her age at menopause (when menstruation stops) are important in determining her risk.

If menarche was early (age 12 or before) and menopause was late (after age 55), she has a slightly greater chance of developing breast cancer. This risk also exists if a woman has had no children (nulliparous) or had her first child after age 35. It has been estimated that there is a 30 to 50% higher risk of developing breast cancer for a nulliparous woman and approximately a 25 % higher risk if the first full time pregnancy occurs after age 35.

On the other hand, if a woman's ovaries are removed early and she doesn't use hormone therapy, the risk declines.

Because a woman's long-term exposure to estrogen can influence her risk of breast cancer, researchers have studied medications that contain estrogen, including birth control pills and postmenopausal hormone therapy, for their effects on breast cancer risk. The role of estrogen and progesterone in the development of breast cancer underlies the increased breast cancer risk associated with postmenopausal hormone therapy.

Contraceptives

Research shows that over all, oral contraceptives do not significantly increase the risk of breast cancer. A major study published in the New England Journal of Medicine in 2002 compared a group of 4,575 women who had breast cancer with 4,682 women who didn't. Among women ages 35-64, past use of oral contraceptives didn't significantly increase the odds of developing breast cancer. However, the risk was higher among women who were currently using oral contraceptives than among women who had stopped using them or who never used them.

Another major study, called the Collaborative Group on Hormonal Factors in Breast Cancer Study, found that women who were using oral contraceptives or who had used them within the previous 10 years had a slightly higher risk of breast cancer than women who had never used them. For most women, after 10 years, the risk dropped to the same level as that of women who had never used the pill. There was one exception: Women who started using oral contraceptives before age 20 continued to have an elevated risk of breast cancer even 10 years after they stopped using them. Specifically, they were at increased risk of breast cancer diagnosed before they turned 40.

If you take birth control pills or are considering taking them, it's important to consider this small increase in risk as you evaluate your overall breast cancer risk and your choice of contraceptive method. It is also important to appreciate that some (but not all) studies have reported that oral contraceptive use may be associated with a slightly increased risk of breast cancer in women with a strong family history of breast cancer or those who have a mutation in the BRCA gene.

Postmenopausal hormone therapy

Postmenopausal hormone therapy has long been known to increase the risk of breast cancer, but experts used to think that the risk was relatively small and that it was outweighed by other benefits of the medication, particularly protection against hip fractures and heart attacks. That changed in 2002 with the announcement of findings from the most definitive study on the effects of hormone therapy, a clinical trial called the Women's Health Initiative. This study found not only that the breast cancer risk for women taking the most common form of hormone therapy - a combination of estrogen and progestin known as Prempro - was greater than previously thought, but also that the therapy actually increased the risk of heart attack and stroke.

The Women's Health Initiative researchers found that after just one year, more of the Prempro users had abnormal mammograms than did a control group of women who were not taking any hormone therapy: About 9% of women taking Prempro had abnormal mammograms, compared with about 5% in the control group.

Women taking hormone therapy for five years faced a 26% higher risk of invasive breast cancer. This meant that eight additional women would discover they had breast cancer each year for every 10,000 women taking the hormone therapy. Researchers also found that the cancers in women taking hormone therapy were more likely to be larger and in an advanced stage, such as a higher rate of cancerous lymph nodes in the armpit. Larger and more advanced cancers require more intensive treatment and have a lower cure rate.

Because of these findings, researchers halted the portion of the trial involving Prempro. Research continued on the use of estrogen alone, without progestin. New findings suggest that low dose estrogen alone does not carry the same breast cancer risks. It's important to note that unopposed estrogen (estrogen without progestin) is linked with an increase in cancer of the uterus, so this therapy is not recommended for women who have not had a hysterectomy.

Other forms of hormone therapy also increase the risk of breast cancer, but the combination of estrogen and progestin seems to carry the highest risk. A British study of one million women published in the journal Lancet in 2003 - the largest to date on hormone therapy and breast cancer - found that taking the combined preparation doubled women's risk of developing breast cancer, while taking estrogen therapy alone increased the risk by a third. The study found that the longer women used hormone therapy, the greater their risk. Stopping the therapy gradually reduced the risk. Five years after stopping, women had no greater risk of breast cancer than women who had never used hormone therapy.

If you are at high risk for breast cancer, avoid hormone therapy. Otherwise, talk with your doctor about the risks and benefits for you of hormone therapy (estrogen alone or estrogen with progestin), as well as alternatives to hormone therapy. The benefits of hormone therapy are a decreased risk of hip fractures and colorectal cancer and highly effective relief from hot flashes and other symptoms of menopause.

Long term use of estrogen is not recommended for prevention of chronic diseases, such as osteoporosis. Supplemental calcium with vitamin D and doing regular weight-bearing exercise, such as walking, can help maintain bone density and protect you from osteoporosis later in life. If needed, medications such as raloxifene or a bisphosphonate (Actonel, Boniva, Fosamax) can be prescribed to impede bone loss.

Raloxifene may help prevent breast cancer in certain postmenopausal women at high risk of breast cancer. Bisphosphonates have no role in breast cancer prevention. But for some women already diagnosed with breast cancer, one of these drugs can be used to prevent bone complications and decrease bone pain if cancer has spread to the bone, and possibly delay breast cancer from spreading to bones.

Last updated:	April 23, 2007