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), the 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 tissue. Their estrogen-like properties may help prevent the loss of bone density in postmenopausal women; however, 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.

   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.

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).

   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.
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.

# # #

• National Cancer Institute Fact Sheet 7.5, Preventive Mastectomy: Questions and Answers ¹
  (http://www.cancer.gov/cancertopics/factsheet/Therapy/preventive-mastectomy)
• National Cancer Institute Fact Sheet 7.16, Tamoxifen: Questions and Answers ²
  (http://www.cancer.gov/cancertopics/factsheet/Therapy/tamoxifen)
• Breast Cancer Home Page ³(http://www.cancer.gov/cancertopics/types/breast)
• If You Want To Find Ways To Prevent Cancer...Learn About Prevention Clinical Trials ⁴ (http://www.cancer.gov/clinicaltrials/learning/about-prevention-trials)
• What You Need To Know About™ Breast Cancer ⁵ (http://www.cancer.gov/cancertopics/wyntk/breast)

For more help, contact:

NCI's Cancer Information Service
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LiveHelp^® online chat: https://cissecure.nci.nih.gov/livehelp/welcome.asp

Glossary Terms

An anticancer drug that is used to decrease estrogen production and suppress the growth of tumors that need estrogen to grow. It belongs to the family of drugs called nonsteroidal aromatase inhibitors.

A substance that prevents cells from making or using estrogen (a hormone that plays a role in the formation of female sex characteristics, the menstrual cycle, and pregnancy). Antiestrogens may stop some cancer cells from growing and are used to prevent and treat breast cancer. They are also being studied in the treatment of other types of cancer. An antiestrogen is a type of hormone antagonist.

In healthcare, a process used to learn about a patient’s condition. This may include a complete medical history, medical tests, a physical exam, a test of learning skills, tests to find out if the patient is able to carry out the tasks of daily living, a mental health evaluation, and a review of social support and community resources available to the patient.

The organ that stores urine.

A tissue with red blood cells, white blood cells, platelets, and other substances suspended in fluid called plasma. Blood takes oxygen and nutrients to the tissues, and carries away wastes.

A gene on chromosome 17 that normally helps to suppress cell growth. A person who inherits a mutated (changed) BRCA1 gene has a higher risk of getting breast, ovarian, or prostate cancer.

A gene on chromosome 13 that normally helps to suppress cell growth. A person who inherits a mutated (changed) BRCA2 gene has a higher risk of getting breast, ovarian, or prostate cancer.

A term for diseases in which abnormal cells divide without control. Cancer cells can invade nearby tissues and can spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord.

CIS. The Cancer Information Service is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER (1-800-422-6237), or by using the LiveHelp instant-messaging service at https://cissecure.nci.nih.gov/livehelp/welcome.asp. Also called CIS.

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called a clinical trial.

The process of identifying a disease, such as cancer, from its signs and symptoms.

DCIS. A noninvasive condition in which abnormal cells are found in the lining of a breast duct. The abnormal cells have not spread outside the duct to other tissues in the breast. In some cases, ductal carcinoma in situ may become invasive cancer and spread to other tissues, although it is not known at this time how to predict which lesions will become invasive. Also called DCIS and intraductal carcinoma.

A block in an artery caused by blood clots or other substances, such as fat globules, infected tissue, or cancer cells.

Cancer that forms in the tissue lining the uterus (the small, hollow, pear-shaped organ in a woman's pelvis in which a baby grows). Most endometrial cancers are adenocarcinomas (cancers that begin in cells that make and release mucus and other fluids).

A protein that speeds up chemical reactions in the body.

A drug used to treat advanced breast cancer and to prevent recurrent breast cancer in postmenopausal women who have already been treated with tamoxifen. It is also being studied in the treatment of other types of cancer. Exemestane causes a decrease in the amount of estrogen made by the body. It is a type of aromatase inhibitor. Also called Aromasin.

A record of a person's current and past illnesses, and those of his or her parents, brothers, sisters, children, and other family members. A family history shows the pattern of certain diseases in a family, and helps to determine risk factors for those and other diseases.

Monitoring a person's health over time after treatment. This includes keeping track of the health of people who participate in a clinical study or clinical trial for a period of time, both during the study and after the study ends.

The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein.

Inherited; having to do with information that is passed from parents to offspring through genes in sperm and egg cells.

Having to do with the female reproductive tract (including the cervix, endometrium, fallopian tubes, ovaries, uterus, and vagina).

A sudden, temporary onset of body warmth, flushing, and sweating (often associated with menopause).

Cancer that has spread beyond the layer of tissue in which it developed and is growing into surrounding, healthy tissues. Also called infiltrating cancer.

A drug used to treat advanced breast cancer in postmenopausal women. Letrozole causes a decrease in the amount of estrogen made by the body. It is a type of aromatase inhibitor. Also called Femara.

One of a pair of organs in the chest that supplies the body with oxygen, and removes carbon dioxide from the body.

A person’s overall psychological and emotional condition. Good mental health is a state of well-being in which a person is able to cope with everyday events, think clearly, be responsible, meet challenges, and have good relationships with others.

Having to do with muscles, bones, tendons, ligaments, joints, and cartilage.

Any change in the DNA of a cell. Mutations may be caused by mistakes during cell division, or they may be caused by exposure to DNA-damaging agents in the environment. Mutations can be harmful, beneficial, or have no effect. If they occur in cells that make eggs or sperm, they can be inherited; if mutations occur in other types of cells, they are not inherited. Certain mutations may lead to cancer or other diseases.

The National Cancer Institute, part of the National Institutes of Health of the United States Department of Health and Human Services, is the Federal Government's principal agency for cancer research. The National Cancer Institute conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the National Cancer Institute Web site at http://www.cancer.gov. Also called NCI.

NIH. A federal agency in the U.S. that conducts biomedical research in its own laboratories; supports the research of non-Federal scientists in universities, medical schools, hospitals, and research institutions throughout the country and abroad; helps in the training of research investigators; and fosters communication of medical information. Access the National Institutes of Health Web site at http://www.nih.gov. Also called NIH.

Surgery to remove one or both ovaries.

By or having to do with the mouth.

A condition that is marked by a decrease in bone mass and density, causing bones to become fragile.

Cancer that forms in tissues of the ovary (one of a pair of female reproductive glands in which the ova, or eggs, are formed). Most ovarian cancers are either ovarian epithelial carcinomas (cancer that begins in the cells on the surface of the ovary) or malignant germ cell tumors (cancer that begins in egg cells).

One of a pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus.

PDQ is an online database developed and maintained by the National Cancer Institute. Designed to make the most current, credible, and accurate cancer information available to health professionals and the public, PDQ contains peer-reviewed summaries on cancer treatment, screening, prevention, genetics, complementary and alternative medicine, and supportive care; a registry of cancer clinical trials from around the world; and directories of physicians, professionals who provide genetics services, and organizations that provide cancer care. Most of this information, and more specific information about PDQ, can be found on the NCI's Web site at http://www.cancer.gov/cancertopics/pdq. Also called Physician Data Query.

An inactive substance or treatment that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.

Having to do with the time after menopause. Menopause (“change of life”) is the time in a woman's life when menstrual periods stop permanently.

Having to do with the time before menopause. Menopause ("change of life") is the time of life when a woman's menstrual periods stop permanently.

In medicine, action taken to decrease the chance of getting a disease or condition. For example, cancer prevention includes avoiding risk factors (such as smoking, obesity, lack of exercise, and radiation exposure) and increasing protective factors (such as getting regular physical activity, staying at a healthy weight, and having a healthy diet).

Used to prevent disease.

Surgery to reduce the risk of developing breast cancer by removing one or both breasts before disease develops. Also called prophylactic mastectomy.

Having to do with the lungs.

Something that may increase the chance of developing a disease. Some examples of risk factors for cancer include age, a family history of certain cancers, use of tobacco products, certain eating habits, obesity, lack of exercise, exposure to radiation or other cancer-causing agents, and certain genetic changes.

A problem that occurs when treatment affects healthy tissues or organs. Some common side effects of cancer treatment are fatigue, pain, nausea, vomiting, decreased blood cell counts, hair loss, and mouth sores.

In statistics, describes a mathematical measure of difference between groups. The difference is said to be significant if it is greater than what might be expected to happen by chance alone. Also called statistically significant.

The extent of a cancer in the body. Staging is usually based on the size of the tumor, whether lymph nodes contain cancer, and whether the cancer has spread from the original site to other parts of the body.

In medicine, a loss of blood flow to part of the brain, which damages brain tissue. Strokes are caused by blood clots and broken blood vessels in the brain. Symptoms include dizziness, numbness, weakness on one side of the body, and problems with talking, writing, or understanding language. The risk of stroke is increased by high blood pressure, older age, smoking, diabetes, high cholesterol, heart disease, atherosclerosis (a build-up of fatty material and plaque inside the coronary arteries), and a family history of stroke.

A procedure to remove or repair a part of the body or to find out whether disease is present. An operation.

An indication that a person has a condition or disease. Some examples of symptoms are headache, fever, fatigue, nausea, vomiting, and pain.

The formation or presence of a thrombus (blood clot) inside a blood vessel.

An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumors may be benign (not cancerous), or malignant (cancerous). Also called neoplasm.

A rare type of uterine cancer that forms in muscle or other tissues of the uterus (the small, hollow, pear-shaped organ in a woman's pelvis in which a baby grows). It usually occurs after menopause. The two main types are leiomyosarcoma (cancer that begins in smooth muscle cells) and endometrial stromal sarcoma (cancer that begins in connective tissue cells).

The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a baby grows. Also called the womb.

Having to do with the vagina (the birth canal).

Affecting the narrowing and widening of the blood vessels.