Patient education: Medications for the prevention of breast cancer (Beyond the Basics)
- Wendy Y Chen, MD, MPH
Wendy Y Chen, MD, MPH
- Assistant Professor of Medicine
- Harvard Medical School
- Graham A Colditz, MD, DrPH
Graham A Colditz, MD, DrPH
- Neiss-Gain Professor in Medicine
- Washington University School of Medicine
Approximately 250,000 women in the United States are newly diagnosed with breast cancer each year. Certain risk factors may increase the likelihood that a woman will develop breast cancer, including advancing age, a strong family history of breast cancer, and having a precancerous breast condition, such as lobular carcinoma in situ (LCIS) or atypical hyperplasia.
Based upon a careful risk assessment, healthcare providers sometimes recommend therapy with medications to reduce the chance of developing breast cancer for women at increased risk. These medications include selective estrogen receptor modulators (SERMs), of which there are two: tamoxifen and raloxifene. Another group of medications, called the aromatase inhibitors (AIs; eg, exemestane), has also been shown to be effective for breast cancer prevention, though none are US Food and Drug Administration (FDA)-approved for this indication.
These medications only work to prevent tumors that are known to be responsive to female hormones, which can be identified by the presence of hormone receptors. Tumors that have hormone receptors are called either ER-positive (short for estrogen receptor-positive) or PR-positive (short for progesterone receptor-positive).
The following is a discussion of studies evaluating the effectiveness of both SERMs and AIs for breast cancer prevention in women without a history of breast cancer, possible side effects, and information about which women should consider taking one of these agents. The role of SERMs and AIs in women with a history of breast cancer is covered separately. (See "Patient education: Early-stage breast cancer treatment in postmenopausal women (Beyond the Basics)" and "Patient education: Early stage breast cancer treatment in premenopausal women (Beyond the Basics)".)
HOW DO PREVENTIVE AGENTS WORK?
The preventive agents all work by interfering with the effects of the female hormone estrogen. Selective estrogen receptor modulators (SERMs) work by blocking the effects of estrogen on breast tissue. Aromatase inhibitors (AIs) work by blocking an enzyme (aromatase) that is responsible for producing estrogen within the body in postmenopausal women (or women after menopause).
Selective estrogen receptor modulators
Tamoxifen — Multiple studies have examined the effectiveness of tamoxifen for the prevention of breast cancer. Overall, these studies suggest that tamoxifen can prevent hormone-positive breast cancers from developing in women at risk for the disease. In general, tamoxifen, given daily for five years, reduces the risk of developing breast cancer by at least one-third. Tamoxifen can be used in women before and after menopause.
Despite the evidence that it reduces the risk of developing breast cancer in high-risk women, tamoxifen has not been widely used for breast cancer prevention. That is largely because tamoxifen does not improve survival when given as a preventive treatment and the small risk of serious adverse events, including uterine cancer and blood clots in the legs or lungs.
Raloxifene — Raloxifene is used for the prevention and treatment of osteoporosis (low bone density) in postmenopausal women. Several studies suggest that in postmenopausal women at high risk of developing breast cancer, raloxifene can reduce the risk of developing an invasive hormone-positive (estrogen receptor-positive) breast cancer.
In the STAR Breast Cancer Prevention Trial that directly compared tamoxifen and raloxifene, raloxifene was slightly less effective than tamoxifen at preventing breast cancer. On the other hand, raloxifene was associated with fewer of the most serious side effects associated with tamoxifen, including a lower risk of uterine cancer. Raloxifene has been tested only in postmenopausal women; its benefit in premenopausal women is unknown.
Precautions — Tamoxifen and raloxifene are not recommended for some women, including those who:
●Have a history of blood clots in the legs or lungs (known as "deep vein thrombosis" or "pulmonary embolism")
●Require anticoagulant or blood-thinning medications
●Are pregnant, planning on becoming pregnant, or breastfeeding (tamoxifen may cause birth defects if taken during pregnancy)
Women who use tamoxifen prior to menopause should use a non-hormonal method of birth control (such as condoms and a diaphragm), since hormonal methods of birth control, such as oral contraceptives, may alter the effectiveness of tamoxifen. A woman should immediately notify her doctor if she becomes pregnant while on tamoxifen. (See "Patient education: Birth control; which method is right for me? (Beyond the Basics)".)
Women who use tamoxifen or raloxifene should be closely monitored by their healthcare provider. In particular, women should:
●Immediately report any abnormal gynecologic symptoms, such as menstrual irregularities, abnormal vaginal bleeding or spotting, staining, or pelvic pressure or pain. (See "Patient education: Abnormal uterine bleeding (Beyond the Basics)".)
●Seek immediate medical care if they develop signs or symptoms of a blood clot, such as calf tenderness, swelling, pain, or severe, unexplained breathlessness or a fast heart rate.
Aromatase inhibitors — Both anastrozole and exemestane have been tested in randomized trials for breast cancer prevention, which showed that compared with placebo, either drug reduces the risk of breast cancer (both in situ and invasive disease) by at least 50 percent [1,2]. For the trial that randomly assigned women to anastrozole or placebo , five-year follow-up showed no difference in mortality, although there were too few deaths to allow for a meaningful estimate on survival. These data suggest that aromatase inhibitors (AIs) are reasonable alternatives to a selective estrogen receptor modulator (SERM), although none are US Food and Drug Administration (FDA)-approved for this indication in the United States at this time. Questions remain as to long-term effects of these drugs on bone loss and cardiovascular risk. Furthermore, joint and muscle symptoms associated with AIs may limit patient acceptance of this medication for preventive purposes.
Who should consider medication for breast cancer prevention? — Guidelines from expert groups recommend that the risks and benefits of breast cancer prevention be discussed with premenopausal and postmenopausal women who are at high risk for the disease [3,4]. Appropriate candidates for breast cancer prevention include the following groups of women ≥35 years:
●Women with a history of lobular carcinoma in situ (LCIS) or atypical hyperplasia.
●Women who have a calculated five-year risk of developing breast cancer of 1.66 percent or higher, according to a system called the Gail model. The Gail model uses a woman's current age, age at first menstrual period, age at first live birth, the number of first-degree relatives with breast cancer, and the number and pathologic findings of any breast biopsies to estimate the probability of breast cancer over time.
A program called the Breast Cancer Risk Assessment Tool is available to calculate an individual woman's risk according to the Gail model . Risk assessment tools such as these were developed for health professionals; patients who use them on their own should speak with their clinician for help interpreting the results. In addition, the presence of breast cancer risk factors does not mean that cancer is inevitable. Many women with risk factors never develop breast cancer.
An important issue is that the Gail model does not consider the risk of cancer associated with inherited breast cancer-predisposing genes such as BRCA1 and BRCA2. Limited data suggest that tamoxifen may reduce the risk of breast cancer in women with BRCA mutations, though further study is needed before it is routinely recommended for women with BRCA mutations. (See "Patient education: Genetic testing for breast and ovarian cancer (Beyond the Basics)".)
Choice of agent: Tamoxifen, raloxifene, or an aromatase inhibitor?
For women who choose to pursue breast cancer prevention, the choice of agent depends on a number of factors, including her menopausal status and the side effects expected with each agent.
Postmenopausal women have the choice between a selective estrogen receptor modulator (SERM) or an aromatase inhibitor (AI). However, there are no studies comparing these two strategies with each other. In addition, while the use of AIs for prevention is supported by some professional organizations (including the American Society of Clinical Oncology and the National Comprehensive Cancer Network), they are not approved for primary prevention in the United States. Questions remain as to long-term effects of an AI on bone loss and cardiovascular risk.
If a SERM is chosen, tamoxifen appears to be more effective than raloxifene in preventing breast cancer. However, raloxifene has fewer serious side effects. Models to assess benefit and risk of tamoxifen versus raloxifene in individual women are available. (See "Selective estrogen receptor modulators and aromatase inhibitors for breast cancer prevention".)
Tamoxifen is the only option for premenopausal women who choose to pursue breast cancer prevention. At present, raloxifene is not used for breast cancer prevention in premenopausal women because of the lack of data regarding safety in this population. In addition, AIs are generally not used in premenopausal women for cancer prevention because they can actually increase estrogen production in women whose ovaries are still producing the hormone.
WHERE TO GET MORE INFORMATION
Your healthcare provider is the best source of information for questions and concerns related to your medical problem.
This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.
Patient level information — UpToDate offers two types of patient education materials.
The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.
Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.
Patient education: Factors that modify breast cancer risk in women (Beyond the Basics)
Patient education: Bone density testing (Beyond the Basics)
Patient education: Osteoporosis prevention and treatment (Beyond the Basics)
Patient education: Deep vein thrombosis (DVT) (Beyond the Basics)
Patient education: Birth control; which method is right for me? (Beyond the Basics)
Patient education: Abnormal uterine bleeding (Beyond the Basics)
Patient education: Genetic testing for breast and ovarian cancer (Beyond the Basics)
Professional level information — Professional-level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional-level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.
Factors that modify breast cancer risk in women
Genetic counseling and testing for hereditary breast and ovarian cancer
Managing the side effects of tamoxifen
Management of patients at high risk for breast and ovarian cancer
Menopausal hormone therapy and the risk of breast cancer
Overview of hereditary breast and ovarian cancer syndromes
Screening for breast cancer: Strategies and recommendations
Selective estrogen receptor modulators and aromatase inhibitors for breast cancer prevention
The following organizations also provide reliable health information.
●National Comprehensive Cancer Network
●Website of the American Society of Clinical Oncology
●National Cancer Institute
●American Cancer Society
- Goss PE, Ingle JN, Alés-Martínez JE, et al. Exemestane for breast-cancer prevention in postmenopausal women. N Engl J Med 2011; 364:2381.
- Cuzick J, Sestak I, Forbes JF, et al. Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial. Lancet 2014; 383:1041.
- Visvanathan K, Chlebowski RT, Hurley P, et al. American society of clinical oncology clinical practice guideline update on the use of pharmacologic interventions including tamoxifen, raloxifene, and aromatase inhibition for breast cancer risk reduction. J Clin Oncol 2009; 27:3235.
- Medications for Risk Reduction of Primary Breast Cancer in Women. http://www.uspreventiveservicestaskforce.org/uspstf/uspsbrpv.htm (Accessed on January 28, 2014).
- Breast cancer risk asssessment tool. www.cancer.gov/bcrisktool/ (Accessed on March 20, 2012).
All topics are updated as new information becomes available. Our peer review process typically takes one to six weeks depending on the issue.