Key Points
	The risk of breast cancer increases as women get older. No one knows why some women develop breast cancer and others do not. Risk factors include personal history of breast abnormalities, current age, age at first menstrual period, age at first live birth, breast cancer history of close relatives, whether a woman has had a breast biopsy, and race Tamoxifen is a drug that is used to treat patients with breast cancer. This drug works against breast cancer, in part, by interfering with the activity of estrogen. The Breast Cancer Risk Assessment Tool estimates a woman's risk of developing breast cancer for two time periods: over the next five years and for her lifetime An estimated 213,000 American women will be diagnosed with breast cancer in 2006.

This fact sheet provides information on the Breast Cancer Risk Assessment Tool and about breast cancer risk and the drug tamoxifen. Study results from the Breast Cancer Prevention Trial show that tamoxifen can reduce the likelihood of developing breast cancer in women at increased risk for the disease.

1. Who gets breast cancer?
Breast cancer is the most frequently diagnosed non-skin cancer in American women. An estimated 213,000 American women will be diagnosed with breast cancer in 2006. The risk of breast cancer increases as women get older. No one knows why some women develop breast cancer and others do not. Over the years, researchers have identified certain characteristics, usually called "risk factors," that influence a woman's chance of getting the disease. Still, many women who develop breast cancer have no known risk factors other than growing older, and many women with known risk factors do not get breast cancer.

2. What is the Breast Cancer Risk Assessment Tool?
The Breast Cancer Risk Assessment Tool is a computer program that was developed by scientists at the National Cancer Institute and the National Surgical Adjuvant Breast and Bowel Project (NSABP) to assist health care providers in discussing breast cancer risk and tamoxifen with their female patients. The tool allows one to project a woman's individual estimate of breast cancer risk over a 5-year period of time and over her lifetime and compares the woman's risk calculation with the average risk for a woman of the same age. Information about the risks and benefits of taking tamoxifen are also included. The Breast Cancer Risk Assesment Tool can be found at the following link: http://bcra.nci.nih.gov/brc/

3. What does the Breast Cancer Risk Assessment Tool do?
The Breast Cancer Risk Assessment Tool estimates a woman's risk of developing breast cancer for two time periods: over the next five years and for her lifetime. The tool compares these risks (given as a percentage) to those of a woman of the same age with NO risk factors other than her age, and with the risk of women who were eligible to participate in the Breast Cancer Prevention Trial.

4. What are the risk factors used to estimate breast cancer risk in the Breast Cancer Risk Assessment Tool?
The risk factors included in the tool are: personal history of breast abnormalities, current age, age at first menstrual period, age at first live birth, breast cancer history of close relatives, whether a woman has had a breast biopsy, and race.

Personal history of breast abnormalities. Two breast tissue abnormalities - ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS) - are associated with increased risk for developing an invasive breast cancer.

Age. The risk of developing breast cancer increases with age. The majority of breast cancer cases occur in women older than age 50.

Age at menarche (first menstrual period). Women who had their first menstrual period before age 12 have a slightly increased risk of breast cancer.

Age at first live birth. Women who had their first full-term pregnancy after age 30 and women who have never borne a child have a greater risk of developing breast cancer.

Breast cancer among first-degree relatives (sisters, mother, daughters). Having one or more first-degree blood relatives who have been diagnosed with breast cancer increases a woman's chances of developing this disease.

Breast biopsies. Women who have had breast biopsies have an increased risk of breast cancer, especially if the biopsy showed a change in breast tissue known as atypical hyperplasia. These women are at increased risk because of whatever prompted the biopsies, NOT because of the biopsies themselves.

Race. White women have greater risk of developing breast cancer than Black women (although Black women diagnosed with breast cancer are more likely to die of the disease).

5. Why are some other risk factors left out?
Other risk factors for breast cancer have been identified or proposed, but are not included in the Breast Cancer Risk Assessment Tool for two reasons: either evidence that these factors contribute to breast cancer risk is not conclusive, or researchers cannot determine how much these factors contribute to breast cancer risk as precisely as with the factors listed above. Such risk factors include: age at menopause, dense breast tissue, use of birth control pills or hormone replacement therapy, a high-fat diet, alcohol, radiation exposure, and environmental pollutants.

6. Is the Breast Cancer Risk Assessment Tool useful for all women?
The Breast Cancer Risk Assessment Tool gives an estimated risk. It is not accurate for women who are younger than age 20, who have already had a diagnosis of breast cancer or who are known to have specific alterations in breast cancer susceptibility genes (BRCA1 or BRCA2). There is also some doubt about whether women from other countries will have accurate results because the tool is based on U.S. women.

7. What was the Breast Cancer Prevention Trial (BCPT)?
The Breast Cancer Prevention Trial (BCPT) was designed to see whether taking the drug tamoxifen (Nolvadex®) can prevent breast cancer in women who are at an increased risk of developing the disease. The BCPT was also looking at whether taking tamoxifen decreases the number of heart attacks and reduces the number of bone fractures in these women The study enrolled over 13,000 women ages 35 and older. Researchers with the National Surgical Adjuvant Breast and Bowel Project (NSABP) conducted the study in more than 300 centers across the United States and Canada.

By 2005, after seven years of follow-up, investigators found that healthy women assigned to take tamoxifen developed 145 cases of invasive breast cancer compared to 250 cases in the women assigned to take placebo. This final analysis confirms that tamoxifen reduces the risk of invasive breast cancer in both pre- and post-menopausal women at increased risk for the disease. Additionally, risk of pulmonary embolism was 11 percent lower than initially reported and risk of endometrial cancer was about 29 percent higher, but neither of these differences was statistically significant.

8. Did the Breast Cancer Prevention Trial show that tamoxifen can prevent breast cancer?
In the BCPT, breast cancer was diagnosed half as often in the women who were assigned to take tamoxifen compared with women who were assigned to take the placebo. Tamoxifen offered this benefit along with no apparent increased risk of serious side effects for women ages 35 to 49, but the benefit for women ages 50 and older came with an increased risk of serious side effects.

9. What is tamoxifen?
Tamoxifen is a drug that has been used for more than 25 years to treat patients with breast cancer. This drug works against breast cancer, in part, by interfering with the activity of estrogen, a female hormone that promotes the growth of breast cancer cells. For this reason, tamoxifen is often called an "anti-estrogen."

10. What are the adverse effects of tamoxifen?
In the BCPT, tamoxifen caused mild, non-life-threatening side effects in some women. These mild side effects included hot flashes and vaginal discharge.

In addition, women over age 50 who took tamoxifen had an increased chance of developing three rare but serious health problems: endometrial cancer (cancer of the lining of the uterus), pulmonary embolism (a blood clot in the lung), and deep vein thrombosis (blood clots in major veins).

11. How great is the risk of endometrial cancer for women who take tamoxifen?
In the BCPT, tamoxifen more than doubled a woman's chances of developing endometrial cancer compared with women of the same age who did not take tamoxifen. The risk of endometrial cancer from tamoxifen was similar to that for postmenopausal women who take estrogen replacement therapy.

The increased risk for endometrial cancer was seen mainly in women ages 50 and older who were taking tamoxifen: they had four times the chances of developing endometrial cancer as women of the same age who were not taking tamoxifen. The risk of developing endometrial cancer in women ages 50 and older on the BCPT was equivalent to 30 cases of endometrial cancer per 10,000 women per year in the women assigned to take tamoxifen compared to eight cases per 10,000 women per year in the women assigned to take placebo.

Women taking tamoxifen should be closely monitored by their health care provider for possible signs or symptoms of endometrial cancer, especially abnormal vaginal bleeding. Women who have had a hysterectomy have no known risk of developing endometrial cancer.

12. How great is the risk of serious blood clots (deep vein thrombosis and pulmonary embolism) for women who take tamoxifen?
Deep vein thrombosis occurs when blood clots form in a major vein. Sometimes the clot can break off and travel to the lung, becoming a pulmonary embolism. In the BCPT, tamoxifen nearly tripled a woman's chances of developing a deep vein thrombosis or pulmonary embolism. This increased risk due to tamoxifen is about the same as that for a woman taking birth control pills or estrogen replacement therapy.

13. Should all women at increased risk of breast cancer take tamoxifen?
Tamoxifen may not be right for every woman. Women should discuss with their health care provider their individual risks and the potential benefits of taking tamoxifen. However, women at increased risk for blood clots and those who are pregnant or who plan to become pregnant should not take tamoxifen. Animal studies have suggested that the use of tamoxifen during pregnancy might harm the fetus. Women taking any birth control pills or hormone replacements must stop those medications before beginning tamoxifen. Premenopausal women who take tamoxifen should use some method of birth control other than birth control pills.

14. Are there other ways to decrease the chance of developing breast cancer?
Postmenopausal women ages 35 or older at increased risk for breast cancer participated in the Study of Tamoxifen and Raloxifene (STAR). The study compared tamoxifen with raloxifene, an osteoporosis drug. STAR began enrolling participants in 1999, and reached its goal of enrolling 19,000 women in June, 2004. Results of the trial were announced on April 17, 2006 (see http://www.cancer.gov/newscenter/pressreleases/STARresultsApr172006) and showed that the drug raloxifene works as well as tamoxifen in reducing breast cancer risk for postmenopausal women at increased risk of the disease. In STAR, both drugs reduced the risk of developing invasive breast cancer by about 50 percent. In addition, within the study, women who were prospectively and randomly assigned to take raloxifene daily, and who were followed for an average of about four years, had 36 percent fewer uterine cancers and 29 percent fewer blood clots than the women who were assigned to take tamoxifen. Uterine cancers, especially endometrial cancers, are a rare but serious side effect of tamoxifen. Both tamoxifen and raloxifene are known to increase a woman's risk of blood clots.

15. What else can a woman do about breast cancer?
Women can take an active part in the early detection of breast cancer by having regular clinical breast exams (breast exams performed by health professionals). NCI recommends that women in their 40s or older get screening mammograms on a regular basis, every one to two years. Many women also perform breast self-exams, although this is not a substitute for clinical breast exams or mammography.

Information Resources from the National Cancer Institute
For more information and free publications on the prevention, early detection, diagnosis and treatment of breast cancer, call the National Cancer Institute's Cancer Information Service at 1-800-4-CANCER. Specially trained staff provide the latest scientific information in understandable language. CIS staff answer questions in English and Spanish. People with TTY equipment, dial 1-800-332-8615. For easy access to clinical trials information from NCI, go to http://cancertrials.nci.nih.gov on the World Wide Web.