Breast Cancer Prevention Studies 

Key Points 

• Breast cancer prevention studies are clinical trials involving women who 

have not had cancer but are at high risk of developing the disease (see 

Question 1). 

• In the Breast Cancer Prevention Trial (BCPT), women who received 

tamoxifen had a lower incidence of breast cancer than women who did not 

receive the drug. Initial results of this study were published in 1998 (see 

Question 2). 

• Another trial, the Study of Tamoxifen and Raloxifene (STAR), found that 

tamoxifen and another drug called raloxifene are equally effective in 

reducing breast cancer risk in postmenopausal women who are at 

increased risk of the disease (see Question 3). 

• Other breast cancer prevention studies are in progress (see Question 4). 

1. What are breast cancer prevention studies? 

Breast cancer prevention studies are clinical trials (research studies) that explore ways of 

reducing the risk, or chance, of developing breast cancer. These studies usually involve 

women who have not had breast cancer but are at high risk of developing the disease. 

For example, it is clear that breast cancer occurs more often in women over the age of 60 

years; so, these women have a higher risk of developing breast cancer than younger 

women. Other factors associated with increased risk include a personal or family history 

of breast cancer and changes in certain genes, such as BRCA1 and BRCA2. 

Most breast cancer prevention research is based on evidence linking the development of 

this disease, in many cases, with exposure to the hormone estrogen. The focus of several 

breast cancer prevention studies has been on testing the effectiveness of drugs called 

selective estrogen receptor modulators (SERMs). SERMs are drugs that have some 

antiestrogen properties and some estrogen-like properties. Their antiestrogen activity 

may help reduce the risk of breast cancer by blocking the effects of estrogen on breast 

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tissue. Their estrogen-like properties may help prevent the loss of bone density in 

postmenopausal women; however, some SERMs may cause bone loss in premenopausal 

women. 

2. What is the Breast Cancer Prevention Trial (BCPT)? 

The Breast Cancer Prevention Trial (BCPT) was funded by the National Cancer Institute 

(NCI), a part of the National Institutes of Health, and conducted by the National Surgical 

Adjuvant Breast and Bowel Project (NSABP). The BCPT was designed to see whether 

tamoxifen (Nolvadex®), a SERM, could prevent breast cancer in women who are at an 

increased risk of developing this disease. The study began recruiting participants in April 

1992 and closed to enrollment in September 1997. In the study, 13,388 premenopausal 

and postmenopausal women were enrolled at more than 300 centers across the United 

States and Canada and randomly assigned to receive tamoxifen or a placebo orally each 

day for 5 years. 

Initial results of the BCPT were published in September 1998 (1). Among the women 

randomly assigned to take tamoxifen, there were 49 percent fewer diagnoses of invasive 

breast cancer than among the women randomly assigned to take the placebo. Women on 

tamoxifen also had 49 percent fewer diagnoses of noninvasive breast tumors, such as 

ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS). 

Most of the side effects associated with tamoxifen in the study were temporary. 

However, long-term increased risks were found for several serious health problems: 

endometrial cancer (cancer of the lining of the uterus), uterine sarcoma (cancer of the 

muscular wall of the uterus), pulmonary embolism (blood clot in the lung), deep vein 

thrombosis (blood clot in a large vein), and stroke. These increased risks for serious 

health problems were generally greater among postmenopausal women than among 

premenopausal women. The increased risk for endometrial cancer was found only 

among postmenopausal women. 

In November 2005, updated results of the BCPT were published (2). The updated results 

confirmed tamoxifen’s ability to reduce the risk of breast cancer in women at increased 

risk of developing the disease. Through 7 years of follow-up (that is, at least 2 years past 

the maximum time that women assigned to take tamoxifen received the drug), there were 

43 percent fewer cases of invasive breast cancer diagnosed among the women assigned to 

tamoxifen than among the women assigned to the placebo. The reduction in risk of 

developing noninvasive breast tumors also persisted at 7 years, with 27 percent fewer 

diagnoses of noninvasive breast tumors among the women who took tamoxifen than 

among the women who took the placebo. In addition, the previously observed increased 

risks of stroke, pulmonary embolism, and deep vein thrombosis were somewhat reduced 

at 7 years of follow-up. 

In October 1998, based on the initial results of the BCPT, the U.S. Food and Drug 

Administration (FDA) approved the use of tamoxifen for the prevention of breast cancer 

in women at high risk of developing the disease. 
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More information about the BCPT is available on NCI’s Web site at 

http://www.cancer.gov/clinicaltrials/digestpage/BCPT on the Internet. 

3. What is the Study of Tamoxifen and Raloxifene (STAR)?

The Study of Tamoxifen and Raloxifene, known as STAR, was a follow-up study to the 

BCPT. In STAR, another SERM called raloxifene (Evista®) was compared with 

tamoxifen in preventing breast cancer in postmenopausal women at increased risk of 

developing the disease. The study, which was funded by NCI and conducted by the 

NSABP, involved more than 19,000 postmenopausal women who were at least 35 years 

of age and were at increased risk of developing breast cancer. The women were 

randomly assigned to receive tamoxifen or raloxifene orally each day for 5 years. STAR 

began recruiting participants in July 1999 and completed enrollment in November 2004. 

More than 200 centers across the United States, Canada, and Puerto Rico participated in 

the study. 

Initial results from STAR were published in June 2006 (3). The results showed that 

raloxifene and tamoxifen are equally effective in reducing breast cancer risk in 

postmenopausal women who are at increased risk of the disease. Both drugs reduced the 

risk of developing invasive breast cancer by about 50 percent. However, raloxifene, 

unlike tamoxifen, did not reduce the risk of noninvasive breast tumors, such as DCIS and 

LCIS. 

Information collected from STAR participants about their physical and mental health 

revealed no significant differences between the women who took raloxifene and those 

who took tamoxifen; however, women in the tamoxifen group reported better sexual 

functioning. Although symptom severity in the study was generally low, women in the 

tamoxifen group also reported more vasomotor problems (e.g., hot flashes, cold sweats), 

gynecologic problems (e.g., bleeding or spotting, vaginal discharge), bladder problems 

(e.g., difficulty with bladder control when laughing or crying), and leg cramps; women in 

the raloxifene group reported more musculoskeletal problems (e.g., joint pain, muscle 

stiffness), pain during sexual intercourse, and weight gain (4). 

With regard to risks for serious health problems, there were fewer cases of endometrial 

cancer, pulmonary embolism, and deep vein thrombosis among the women who took 

raloxifene. There was no difference in the incidence of stroke between the raloxifene 

group and the tamoxifen group. 

More information about STAR is available on NCI’s Web site at 

http://www.cancer.gov/clinicaltrials/digestpage/STAR on the Internet. 

In September 2007, the FDA approved raloxifene to reduce the risk of invasive breast 

cancer in postmenopausal women with osteoporosis and in postmenopausal women at 

high risk for invasive breast cancer. Raloxifene was approved by the FDA as a treatment 

for osteoporosis in 1999. 
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4. What other breast cancer prevention studies are being funded by NCI?

NCI is supporting additional clinical studies to determine whether other drugs or natural 

products are able to help prevent breast cancer in women who are at increased risk of 

developing the disease. Drugs called aromatase inhibitors (AIs) are being tested by NCI 

in a few small studies. 

AIs block the activity of an enzyme called aromatase, which the body uses to make 

estrogen. Although the ovary is the main site of aromatase and estrogen production in a 

woman’s body, other tissues, including adipose (fat), bone, and brain tissue, make these 

substances as well. 

Using AIs to block estrogen production in premenopausal women is not very effective, in 

part because the ovary is stimulated to make more aromatase (and, therefore, estrogen) 

when the blood level of estrogen falls below normal. This does not happen in 

postmenopausal women, whose ovaries have stopped making aromatase and estrogen. 

Therefore, AIs are being studied primarily in postmenopausal women. 

AIs have already been approved by the FDA for the treatment of hormone-sensitive 

breast cancer in postmenopausal women. All three FDA-approved AIs are being tested in 

breast cancer prevention studies. These drugs are anastrozole (Arimidex®), exemestane 

(Aromasin®), and letrozole (Femara®). 

In addition, scientists are continuing to study the basic biology and genetics of breast 

cancer. This research may lead to other, better ways to prevent breast cancer. 

For information about ongoing clinical studies of breast cancer prevention, visit NCI’s 

Web site at http://www.cancer.gov or contact NCI’s Cancer Information Service (CIS) 

(see below). 

5. What additional options are available for women at increased risk of breast cancer? 

Doctors generally suggest that high-risk women be closely monitored and have regular 

medical checkups, so that if breast cancer develops, it is likely to be detected at an early 

stage, when it is most treatable (5). These women may also consider participating in 

breast cancer prevention studies, taking tamoxifen or raloxifene, or undergoing 

preventive surgery to reduce breast cancer risk. 

Preventive mastectomy is surgery to remove one or both breasts in an effort to prevent or 

reduce the risk of breast cancer (6). Existing data suggest that preventive mastectomy 

may significantly reduce (by about 90 percent) the chance of developing breast cancer in 

women at high risk of developing the disease due to BRCA1 or BRCA2 gene mutations 

(7). Other data suggest that preventive oophorectomy (surgery to remove the ovaries) in 

women at high risk of ovarian cancer because of BRCA1 or BRCA2 gene mutations may 

also reduce the risk of breast cancer by about 50 percent (8). 
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More information about preventive mastectomy can be found in the NCI fact sheet 

Preventive Mastectomy: Questions and Answers, which is available at 

http://www.cancer.gov/cancertopics/factsheet/Therapy/preventive-mastectomy on the 

Internet. 

The decision to join a clinical study, take medication, or undergo preventive surgery is an 

individual one. With any medical procedure or intervention, both the benefits and the 

risks of the treatment must be considered. The balance of these factors will vary 

depending on a woman’s personal and family health history and how she weighs the 

benefits and risks. Women who are considering surgery or other steps to reduce the risk 

of breast cancer should discuss their personal risk factors with their doctor. 

6. Where can women learn more about estimating their risk for breast cancer? 

NCI’s Cancer Risk: Understanding the Puzzle Web site is an interactive site with 

information to help women make informed decisions about lowering their risk of cancer. 

It includes a section on breast cancer where women can find out the basics about breast 

cancer risk, determine which risk factors apply to them, and identify ways to reduce their 

risk. It includes questions women can ask their doctors about their risk for breast cancer. 

The site also includes links to NCI’s Breast Cancer Risk Assessment Tool and tips on 

how to analyze stories in the news about cancer. This site is available at 

http://understandingrisk.cancer.gov on the Internet. 

Additional information can be found in the PDQ® Breast Cancer Prevention summary 

for patients. This summary of information from PDQ, NCI’s comprehensive cancer 

information database, provides information about breast cancer and how often it occurs, 

describes breast cancer prevention methods, and gives current facts about which people 

or groups of people would most likely be helped by following breast cancer prevention 

methods. This resource is available at 

http://www.cancer.gov/cancertopics/pdq/prevention/breast/patient on the Internet. 

People who are concerned about their cancer risk are encouraged to talk with their doctor. 

Selected References 

1. Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast 

cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P–1 study. 

Journal of the National Cancer Institute 1998; 90(18):1371–1388. 

2. Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for the prevention of breast 

cancer: Current status of the National Surgical Adjuvant Breast and Bowel Project P–1 

study. Journal of the National Cancer Institute 2005; 97(22):1652–1662. 
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3. Vogel VG, Costantino JP, Wickerham DL, et al. Effects of tamoxifen vs raloxifene on 

the risk of developing invasive breast cancer and other disease outcomes: The NSABP 

Study of Tamoxifen and Raloxifene (STAR) P–2 trial. Journal of the American Medical 

Association 2006; 295(23):2727–2741. 

4. Land SR, Wickerham DL, Costantino JP, et al. Patient-reported symptoms and quality of 

life during treatment with tamoxifen or raloxifene for breast cancer prevention: The 

NSABP Study of Tamoxifen and Raloxifene (STAR) P–2 trial. Journal of the American 

Medical Association 2006; 295(23):2742–2751. 

5. Thull DL, Vogel VG. Recognition and management of hereditary breast cancer 

syndromes. The Oncologist 2004; 9(1):13–24. 

6. Stefanek M, Hartmann L, Nelson W. Risk-reduction mastectomy: Clinical issues and 

research needs. Journal of the National Cancer Institute 2001; 93(17):1297–1306. 

7. Rebbeck TR, Friebel T, Lynch HT, et al. Bilateral prophylactic mastectomy reduces 

breast cancer risk in BRCA1 and BRCA2 mutation carriers: The PROSE Study Group. 

Journal of Clinical Oncology 2004; 22(6):1055–1062. 

8. Rebbeck TR, Lynch HT, Neuhausen SL, et al. Prophylactic oophorectomy in carriers of 

BRCA1 or BRCA2 mutations. New England Journal of Medicine 2002; 346(21):1616–

1622. 

# # # 

Related NCI materials and Web pages: 

• National Cancer Institute Fact Sheet 7.5, Preventive Mastectomy: Questions and 

Answers (http://www.cancer.gov/cancertopics/factsheet/Therapy/preventivemastectomy)

• National Cancer Institute Fact Sheet 7.16, Tamoxifen: Questions and Answers

(http://www.cancer.gov/cancertopics/factsheet/Therapy/tamoxifen)

• Breast Cancer Home Page (http://www.cancer.gov/cancertopics/types/breast) 

• If You Want To Find Ways To Prevent Cancer...Learn About Prevention Clinical 

Trials (http://www.cancer.gov/clinicaltrials/learning/about-prevention-trials)

• What You Need To Know AboutTM Breast Cancer

(http://www.cancer.gov/cancertopics/wyntk/breast) 
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For more help, contact: 

NCI’s Cancer Information Service 

Telephone (toll-free): 1–800–4–CANCER (1–800–422–6237) 

TTY (toll-free): 1–800–332–8615

LiveHelp® online chat: https://cissecure.nci.nih.gov/livehelp/welcome.asp

This fact sheet was reviewed on 7/23/08