Hormone breast cancer risk normalizes after stopping pills

Researchers confirmed that a daily, combined dose of estrogen and progestin increases breast cancer risk in post menopausal women, but added that this risk begins to return to normal about six months after women stop taking the hormones.

The analysis was part of the National Institute of Child Health and Human Development (NICHD) Women’s Contraceptive and Reproductive Experiences Study and appears in the December, 2002 Obstetrics & Gynecology. The majority of the study’s funding was provided by the NICHD. The Centers for Disease Control and Prevention in Atlanta contributed additional staff and computer support for the study. The National Cancer Institute also provided additional funding.

“It is reassuring that breast cancer risk begins to return to normal six months after women stop combined dose estrogen-progestin therapy,” said Duane Alexander, M.D., Director of the NICHD. “Women, in consultation with their physicians, need to make the most informed decision possible. The study authors have provided them with one more piece of important information.”

The NIH Women’s Health Initiative (WHI) trial was the first large clinical trial to assess the risks and benefits of continuous combined hormone therapy. (The release describing the trial is available at http://www.nhlbi.nih.gov/new/press/02-07-09.htm.) Last July, researchers stopped the WHI trial because the risk of breast cancer and heart disease from combined hormone replacement therapy outweighed its potential benefits.

In this form of therapy, women take a combination of the hormones estrogen and progestin. Essentially, the hormone estrogen relieves such symptoms of menopause as hot flashes, night sweats, sleeplessness, and vaginal dryness. When taken alone, however, estrogen also increases a woman’s risk for cancer of the uterine lining, or endometrium. Combining estrogen with progestin virtually eliminates the risk of endometrial cancer.

“In planning the NICHD study, we sought to learn as much as we could about the risks associated with the various kinds of hormone therapy,” said Robert Spirtas, DrPH, Chief of NICHD’s Contraception and Reproductive Health Branch and senior author of the study. “At the time, little information existed on whether combined hormone therapy posed the same risks as estrogen therapy alone.”

In the WHI trial, women used continuous combined hormone therapy and researchers monitored their health during the course of the study. When it became clear that the women were developing breast cancer at higher than normal rates, the researchers stopped the trial. Because the study was stopped only recently, the WHI researchers cannot tell yet whether the women in the study face any increased risk of breast cancer now that they stop taking the hormones.

In contrast, researchers for the NICHD study began by questioning women who had been diagnosed with breast cancer about their hormone use and other potential risk factors for breast cancer. These women were then compared to a similar group of women who had not developed breast cancer.

“Our data suggest a positive association between continuous combined HRT and breast cancer risk among current, longer term users,” the study authors concluded. “Progestin administered in an uninterrupted regimen may be a contributing factor.”

The current study enrolled women who had been diagnosed with breast cancer between July 1, 1994 and April 30, 1998 at treatment centers in Atlanta, Detroit, Los Angeles, Philadelphia, and Seattle. A total of 3823 postmenopausal white and black women were analyzed for the study. In all, the medical histories of 1870 women who had developed breast cancer were compared to the histories of 1953 women who did not have breast cancer.

The researchers found that women on continuous combined therapy for 5 years or more were 1.54 times more likely to developing breast cancer than other women their age not on this form of therapy. The risk of breast cancer increased the longer the women used this form of therapy. However, six months after the women discontinued the combined therapy, their risk of breast cancer began to return to normal. This held true for women who took the hormones for 5 years or longer before stopping, as well as for women who took the hormones for only about 6 months.

“The NICHD study also included former users, and our data indicate that the increased risk associated with use of continuous combined hormone therapy began returning to normal about 6 months after the women stopped using them,” Dr. Spirtas said.

The analysis also found that an alternate form of hormone therapy, which involves taking the hormones separately, on different days of the month, may not increase breast cancer risk in this group of women. The alternate form of therapy, sequential estrogen-progestin therapy, includes a number of regimens in which patients take the hormone progestin only for 5 to 14 days per month. Earlier studies have indicated, however, that sequential estrogen-progestin therapy may increase the risk for cancer of the uterine lining, or endometrium. The increase in endometrial cancer from sequential estrogen-progestin therapy is thought to be less than the risk from taking estrogen alone.

Estrogen alone may be prescribed to women whose uterus has been surgically removed, as these women no longer have a risk of endometrial cancer. The NICHD study did not find any additional risk of breast cancer in women who took estrogen alone. A recent study by the NCI found, however, that women taking estrogen alone may be at increased risk for cancer of the ovary. (The NCI’s release on this study is available at http://newscenter.cancer.gov/pressreleases/Laceyovarian.html.)

A separate WHI study of estrogen alone in women who had a hysterectomy before joining the WHI hormone program continues unchanged because, at this point, researchers are uncertain of the balance of risks and benefits of estrogen.