Medications for the prevention of breast cancer

Patient information: Medications for the prevention of breast cancer

Authors
Wendy Y Chen, MD, MPH
Graham A Colditz, MD, DrPh
Section Editor
Daniel F Hayes, MD
Deputy Editor

Don S Dizon, MD, FACP
Disclosures

INTRODUCTION — Approximately 210,000 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).

Based upon a careful risk assessment, healthcare providers sometimes recommend therapy with one of several medications to reduce the chance of developing breast cancer for women at increased risk. These medications fall into two general groups:

Medications called selective estrogen receptor modulator (SERM), of which there are two: tamoxifen and raloxifene.
Medications called the aromatase inhibitors (AIs); these include exemestane and anastrozole.
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 progestin-receptor positive).

The following is a discussion of studies evaluating the effectiveness of both SERMs and AIs for breast cancer prevention, possible adverse effects, and information about which women should consider taking one of these agents.

HOW DO PREVENTIVE AGENTS WORK? — The preventive agents all work by interfering with the effects of the female hormone estrogen. SERMs work by blocking the effects of estrogen on breast tissue. AIs work by blocking an enzyme, aromatase, that is responsible for producing estrogen within the body.

EFFECTIVENESS

SERMs

Tamoxifen — One American and three European research studies have examined the effectiveness of tamoxifen for the prevention of breast cancer. Overall, the evidence from these studies suggests that tamoxifen can prevent hormonally responsive 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 about one-half.

Despite the evidence that it reduces the risk of developing breast cancer in high-risk women, tamoxifen has not been widely accepted for breast cancer prevention. That is largely because there is no evidence that tamoxifen improves survival when given as a preventive treatment, and because the medication has a small risk of serious adverse events, including uterine cancer and blood clots in the legs or lungs.

Raloxifene — Raloxifene is currently used for the prevention and treatment of the bone-thinning disorder osteoporosis 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 hormonally responsive (ER 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. 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
Smoke
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 information: Birth control; which method is right for me?”.)

Women who use tamoxifen or raloxifene should be closely monitored by their healthcare provider. In particular, women should:

Have an annual gynecologic examination, including a breast examination and, if recommended, a yearly mammogram and Pap smear (screening of the cervix for cancerous or precancerous cells). Any woman who finds a new breast lump should speak with her healthcare provider about the need for diagnostic testing (mammogram, ultrasound, biopsy).
Immediately report any abnormal gynecologic symptoms, such as menstrual irregularities, abnormal vaginal bleeding or spotting, staining, or pelvic pressure or pain. (See “Patient information: Abnormal uterine bleeding”.)
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 — A single trial examined the effectiveness of the AI exemestane for preventing breast cancer in high-risk women. In this trial, exemestane reduced the risk of breast cancer by approximately 65 percent. Menopausal symptoms such as hot flashes, fatigue, sweating, insomnia, muscle, bone, and joint pain were common among all women in the study but were more common in women taking exemestane than among those taking placebo. Still, the differences were modest. Overall health-related quality of life was similar in both groups.

AIs are an option for breast cancer prevention in high-risk postmenopausal women. Although they are associated with fewer serious side effects, they are not necessarily preferred over SERMs. Questions remain as to long-term effects of an AI on bone loss and cardiovascular risk. Furthermore, joint and muscle symptoms associated with AIs may limit patient acceptance of this medication for preventive purposes.

SUMMARY

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 [1-3]. Appropriate candidates for breast cancer prevention include the following groups:

Women over the age of 60
Women with certain high-risk conditions found on breast biopsy, such as lobular carcinoma in situ (LCIS) or atypical ductal or lobular hyperplasia.
Women between the ages of 35 and 59 years 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 [4]. 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. Preliminary data suggest that tamoxifen helps reduce the risk of breast cancer in women with BRCA mutations, but benefit may be limited to certain women who inherit these mutations. (See “Patient information: Genetic testing for breast and ovarian cancer”.)
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, the side effects expected with each agent, and cost.

Postmenopausal women have the choice of tamoxifen, raloxifene, or an AI. Although the risk of a life-threatening side effect is lower with an AI compared with a SERM, and AIs are as effective as SERMs for prevention of breast cancer, questions remain as to long-term effects of an AI on bone loss and cardiovascular risk. Furthermore, AIs are associated with more joint and muscle pain.

Additionally, exemestane is more costly than tamoxifen or raloxifene, although an alternative AI is available (anastrozole) as a less expensive generic medication. There are no published prevention trials with this agent, but it has similar activity to exemestane when used for breast cancer treatment.

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”, section on ‘Models to assess benefit/risk for chemoprevention with SERMs’.)

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 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.

 

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

Patient information: Risk factors for breast cancer
Patient information: Bone density testing
Patient information: Osteoporosis prevention and treatment
Patient information: Deep vein thrombosis (DVT)
Patient information: Birth control; which method is right for me?
Patient information: Abnormal uterine bleeding
Patient information: Genetic testing for breast and ovarian cancer

Professional-level information

Epidemiology and risk factors for breast cancer
Genetic testing for hereditary breast and ovarian cancer syndrome
Managing the side effects of tamoxifen
Management of hereditary breast and ovarian cancer syndrome and patients with BRCA mutations
Postmenopausal hormone therapy and the risk of breast cancer
Characteristics of hereditary breast and ovarian cancer syndromes
Screening for breast cancer
Selective estrogen receptor modulators and aromatase inhibitors for breast cancer prevention

The following organizations also provide reliable health information.

People Living With Cancer: The official patient information
Web site of the American Society of Clinical Oncology
(www.cancer.net/portal/site/patient)

National Comprehensive Cancer Network
(www.nccn.com/default.asp)

National Cancer Institute
1-800-4-CANCER
(www.nci.nih.gov)

American Cancer Society
1-800-ACS-2345
(www.cancer.org)

Susan G. Komen Breast Cancer Foundation
(www.komen.org)

REFERENCES
U.S. Preventive Services Task Force. Chemoprevention of breast cancer: recommendations and rationale. Ann Intern Med 2002; 137:56.
Guidelines for cancer prevention from the National Comprehensive Cancer Network (NCCN) available online at www.nccn.org (Accessed on June 10, 2011).
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.
Breast cancer risk asssessment tool available online at www.cancer.gov/bcrisktool/ (Accessed July 7, 2009).