Weighing the Risks and Benefits of Tamoxifen to Reduce Risk of Breast Cancer

National Cancer Institute
Tuesday, 2 November 1999

Overview

Additional information to help women decide whether they should take the drug tamoxifen to reduce their risk of getting breast cancer has been published as a Special Article in the Journal of the National Cancer Institute 1. Investigators from the National Cancer Institute (NCI) and the National Surgical Adjuvant Breast and Bowel Project (NSABP) and their co-authors conclude that tamoxifen is most beneficial for younger women with an elevated risk of breast cancer, but emphasize that a decision to take the drug depends on many factors, not just breast cancer risk.

Despite the individual nature of a woman's decision to use tamoxifen and the effect that her health will have on the risks and benefits of the drug, some generalizations are made by the investigators:

- younger women at high risk of breast cancer are most likely to benefit from tamoxifen because their breast cancer risk substantially outweighs the potential for adverse effects;

- women of any age without a uterus are not at risk of endometrial cancer, which removes that particular concern;

- older women have a higher risk of bone fractures, which may be reduced by tamoxifen, but are generally at higher risk for stroke and pulmonary embolism, which may be increased by tamoxifen;

- black women, as a population, have higher rates for stroke and pulmonary embolism and lower rates of endometrial cancer, all of which may be increased by tamoxifen, and lower rates for hip fractures, which tamoxifen helps prevent.

The authors point out that there is considerable uncertainty in weighing the risks and benefits of tamoxifen in minority populations, a point re-emphasized in the accompanying editorial.

Background

In 1998, NCI and NSABP investigators announced that women at increased risk for breast cancer who had been taking tamoxifen for up to five years (an average of four years) as part of the Breast Cancer Prevention Trial (BCPT) had 49 percent fewer diagnoses of breast cancer than their counterparts who had been taking a placebo. Participants taking tamoxifen also had fewer fractures of the hip, wrist, and spine than women taking the placebo. However, the drug increased the women's chances of developing four potentially life-threatening health problems: endometrial cancer (cancer of the lining of the uterus), deep vein thrombosis (blood clots in large veins), pulmonary embolism (blood clot in the lung), and stroke. Most of these problems occurred in women age 50 and older.

Following release of the BCPT results, NCI produced and distributed the Breast Cancer Risk Assessment Tool, software to help physicians estimate a woman's risk of developing the disease. The calculations in this "Risk Disk," as it is known, were adapted to estimate a potential BCPT participant's risk of developing invasive breast cancer and were used to estimate breast cancer risk in the article published today. NCI also sponsored a workshop to develop information to assist in the counseling of women at increased risk of the disease who are considering taking tamoxifen outside of a clinical trial. The Special Article is a result of that workshop, but also includes analyses and data not presented there.

The article published today provides physicians and counselors with methods for projecting a woman's breast cancer risk and with tables presenting the various risks and benefits of tamoxifen. Physicians and counselors can use the information to discuss tamoxifen with women at increased risk of breast cancer.

The method used to estimate breast cancer risk has been validated in several ways 2 and is based on individual risk factors, such as the number of close relatives with breast cancer. The data used to estimate the adverse effects of tamoxifen are less specific to individual women and are associated with more uncertainties. Estimates of risk for endometrial cancer, stroke, and blood clots are based on how often these events occur in women in specific age and racial/ethnic groups. The estimates do not take into account underlying health conditions, such as obesity, uncontrolled high blood pressure or diabetes, or a history of blood clots or stroke, known to increase risk of cardiovascular events.

Tables that calculate a risk/benefit ratio of taking tamoxifen for prevention of breast cancer at various ages and with various levels of increased risk are given in different ways: two tables use population-based data for women with or without a uterus and one uses estimates of adverse effects based on the rate that they occurred in women who participated in the BCPT (who tended to be healthier than the general population and predominantly white). Working with her physician, a woman can discuss which estimate may be most appropriate for her, given her personal and medical history.

In addition, a table nearly identical to the one being used during the informed consent process of the follow-up study to the BCPT (the Study of Tamoxifen and Raloxifene or STAR) is provided as a counseling tool. This table gives the risks of various medical problems that might occur in a woman of a specific age and breast cancer risk over five years, and how those risks might change if she took tamoxifen.

In response to the publication of this article, NCI will revise the Breast Cancer Risk Assessment Tool to include more specific language on the adverse effects of tamoxifen in specific groups of people.

Postmenopausal women at increased risk of breast cancer who are considering taking tamoxifen should also consider participating in the Study of Tamoxifen and Raloxifene. STAR is designed to extend our understanding of both tamoxifen and raloxifene, an osteoporosis prevention drug that may also reduce risk for developing breast cancer.

For further information on STAR or the Breast Cancer Risk Assessment Tool, contact the NCI's Cancer Information Service at 1-800-4-CANCER or visit the CancerTrials web site at http://cancertrials.nci.nih.gov.

1 The Special Article is titled "Weighing the Risks and Benefits of Tamoxifen Treatment for Preventing Breast Cancer." The authors are Mitchell H. Gail, Joseph P. Costantino, John Bryant, Robert Croyle, Laurence Freedman, Kathy Helzlsouer, and Victor Vogel. Journal of the National Cancer Institute, Vol. 91, No. 21, Nov. 3, 1999.

2 See the article titled, "Validation Studies for Models Projecting the Risk of Invasive and Total Breast Cancer Incidence." The authors are Joseph P. Costantino, Mitchell H. Gail, David Pee, Stewart Anderson, Carol K. Redmond, Jacques Benichou, and H. Samuel Wieand. Journal of the National Cancer Institute, Vol. 91, No.18, Sept. 15, 1999.

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