Researchers from the United Kingdom, Europe, Australia, and New Zealand report in the September 14, 2002 issue of the Lancet that women who took tamoxifen were able to reduce their risk of developing breast cancer by 32% compared to those who were given a placebo (inactive) pill. Researchers also found, however, that those taking the drug were 2.5 times more likely to develop blood-clotting problems, especially after surgery. Additionally (though the numbers were not great enough to reach statistical significance) there were more cases of endometrial cancer in women taking tamoxifen. This issue, coupled with the increase in some side effects, raises questions about the use of tamoxifen to reduce the risk of breast cancer in women at high risk for the disease.

Tamoxifen, often called an “anti-estrogen,” counteracts the growth promoting effects of estrogen on breast cancer cells. As a treatment for breast cancer, the drug slows or stops the growth of cancer cells that are present in the body. Previous studies have also shown that using tamoxifen in the early stages of breast cancer can reduce the recurrence of the original cancer, and may also reduce the risk of developing new cancers in the other breast. Based on these findings, many researchers are studying the usefulness of tamoxifen in preventing breast cancer in women who have an increased risk of developing the disease. (For instance, those with a family history of the disease or benign lesions associated with an increased risk of breast cancer.)

About the Study

The International Breast Cancer Intervention Study (IBIS) was designed to compare tamoxifen to placebo in the prevention of breast cancer. The researchers also looked at other cancers, thromboembolic events (blood clots), cardiovascular events (heart attack and stroke), and the rate and cause of death. Specifically, researchers across Europe, the UK, Australia, and New Zealand randomized 7152 women over age 35 to receive either 20mg per day of tamoxifen or a placebo for 5 years. Only women classified as high risk for getting breast cancer were allowed to participate, including women who had at least one of the following risk factors for breast cancer:

  • First-degree relative who developed breast cancer at or before age 50
  • First-degree relative with breast cancer involving both breasts
  • Two or more first-degree or second-degree relatives with breast cancer
  • Lobular carcinoma in situ (a precursor to breast cancer)
  • No children and a first-degree relative who developed breast cancer
  • Benign breast biopsy and a first-degree relative who developed breast cancer
  • Judged by the study chairman to be at high risk for some other reason

Women were excluded if they had any previous cancer other than skin cancer, a previous deep-vein thrombosis or pulmonary embolism, currently used anticoagulants, or had a life expectancy of less than 10 years. Pregnant women, or those planning to become pregnant, were also excluded.

All of the women had a mammogram at the start of the study, and every 12 to 18 months thereafter. Blood samples were collected at the beginning and again at the 1-year and 5-year visits. Every 6 months, while subjects were taking the drug or placebo, the women were asked about side effects, symptoms, diagnoses, and procedures. Yearly questionnaires were then sent out for up to 5 additional years thereafter.

The researchers compared the rates of breast cancer and other diseases and conditions in those who took the tamoxifen with those who took a placebo for five years.

The Findings

Women taking tamoxifen were 32% less likely to develop breast cancer than their counterparts taking placebo. Based upon these findings, 90 high-risk women out of every 10,000 would be expected to avoid breast cancer if they took tamoxifen. Women taking tamoxifen suffered 21% more gynecological or vasomotor problems (such as vaginal discharge/dryness and abnormal bleeding), and over two times more blood-clotting problems than women not taking the drug. Those in the tamoxifen group were also more than twice as likely to develop endometrial cancer, though this was not statistically significant. Though the death rate for all causes was higher in the tamoxifen group than in the placebo group, only the deaths from the increase in blood-clotting problems seemed to be directly attributable to the drug therapy.

Age and use of hormone replacement therapy did not seem to affect the reduction of breast cancer risk among those taking tamoxifen.

Although these results suggest that tamoxifen could be useful in preventing breast cancer in high-risk women, there are a number of limitations to the study. First, it is not apparent whether the researchers looked at other factors (such as exercise, diet, and supplement use) that could influence the development of breast cancer. There was also no mention of adjusting the data for race, education, or other environmental factors that may play a role in breast cancer. Data was also not examined for meaningful differences among women from the different countries. Having a larger sample size and a randomized study such as this often means that these factors will be balanced between the intervention and control groups, but we cannot assume that this is the case without looking at the data. Finally, because primary cause of death (rather than underlying cause) was used (e.g., deaths from pulmonary embolism after breast cancer surgery were recorded as death from pulmonary embolism) some breast cancer-related deaths may have been misclassified as unrelated to breast cancer.

How Does This Affect You?

The jury is still out on whether women with an increased risk of developing breast cancer should consider taking tamoxifen to reduce their chances of developing this disease. Because of the potential side effects and risks associated with tamoxifen, any decision to take this drug should be carefully assessed by a woman and her physician. Because most of the serious risks in the tamoxifen group occurred after surgery, it may be wise to discontinue its use before any surgery.

Keep in mind that there is currently no evidence that tamoxifen is beneficial for women who do not have an increased risk of developing breast cancer. More research is needed to shed light on whether tamoxifen is a safe option for preventing breast cancer.