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Risk-Lowering Drugs

Chemoprevention is the use of drugs to lower the risk of breast cancer in women at higher risk. Tamoxifen and raloxifene are the only two drugs FDA-approved for breast cancer chemoprevention.  

 

For a summary of research studies on tamoxifen and raloxifene and breast cancer chemoprevention, visit the Breast Cancer Research section.

Tamoxifen and raloxifene

 

Tamoxifen
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Both tamoxifen and the osteoporosis drug raloxifene can [47]:

  • Lower the risk of breast cancer (tamoxifen by about 50 percent and raloxifene by about 38 percent)
  • Lower the risk of non-invasive breast cancers, such as ductal carcinoma in situ (DCIS) (tamoxifen by about 50 percent and raloxifene by about 39 percent)

Tamoxifen and raloxifene only reduce the risk of estrogen receptor-positive breast cancers. Neither drug reduces the risk of estrogen receptor-negative cancers [47].

Although raloxifene is slightly less effective than tamoxifen in reducing breast cancer risk, it has fewer harmful health effects [47]. This makes raloxifene a better choice for some women. For example, tamoxifen increases the risk of cancer of the uterus and cataracts, while raloxifene does not. Tamoxifen also increases the risk of blood clots in the lungs and large veins more than raloxifene [47].

A summary of the differences between tamoxifen and raloxifene are listed in the table below. 

 

Tamoxifen 

Raloxifene 

Who can take the drug? 

Premenopausal and postmenopausal women

Postmenopausal women only

How is high-risk defined? 

Women at least 35 years of age with a 5-year risk of breast cancer of 1.7% or more according to the Breast Cancer Risk Assessment Tool (Gail model)  

Women with any one of the following:

 

What are the breast cancer risk reduction benefits? 

Lowers the risk of:

 

Lowers the risk of:

 

What are the health risks? 

Modestly increases the risk of:

  • Cancer of the uterus
  • Stroke
  • Blood clots in the large veins (deep venous thrombosis)
  • Blood clots in the lungs (pulmonary emboli)
  • Cataracts

Side effects occur mainly in older postmenopausal women.

Modestly increases the risk of:

  • Stroke

Slightly increases the risk of:

  • Blood clots in the large veins (deep venous thrombosis)
  • Blood clots in the lungs (pulmonary emboli)

Side effects occur mainly in older postmenopausal women.

What are the short-term side effects? 

  • Hot flashes
  • Vaginal discharge

Other side effects are rare.

  • Hot flashes
  • Leg cramps
  • Swelling in the legs, hands or feet
 

What about use in treatment? 

Effective in the treatment of hormone receptor-positive breast cancer.

Has not been shown to be effective for the treatment of breast cancer.

Adapted from selected sources [47,246-253].

Tamoxifen and raloxifene also have some long-term side effects (see table above) and may not be suitable for all women at higher risk. Talk to your health care provider about the potential harms and benefits of these drugs.  

Learn more about talking to your health care provider.

Tamoxifen and anti-depressants

Certain types of anti-depressants called selective serotonin reuptake inhibitors (SSRIs) can interfere with the metabolism of tamoxifen (how tamoxifen works in the body) [254]. If you are taking SSRIs to treat depression or menopausal symptoms, talk to your health care provider about possible drug interactions and other options for treating symptoms.  

BRCA1/2 gene mutations and tamoxifen

Researchers are assessing whether tamoxifen lowers the risk of breast cancer in women who have a BRCA1 or BRCA2 mutation [228,255-256]. Some studies have suggested that tamoxifen may be more effective in preventing breast cancer in BRCA2 carriers than BRCA1 carriers [256-257]. BRCA2-related tumors are more likely to be estrogen receptor-positive. Tamoxifen works by attaching to estrogen receptors and only reduces the risk of estrogen receptor-positive cancers. Although one study suggested tamoxifen could lower breast cancer risk in healthy BRCA2 carriers, the study was too small to be conclusive [256].

Some findings have shown tamoxifen might offer benefit to BRCA1 and BRCA2 carriers who have been diagnosed with breast cancer in the past [255,258-259]. The risk of breast cancer in the unaffected breast may be reduced by as much as 75 percent with two to four years of tamoxifen use [255].

Ethnicity and tamoxifen

Although we know much about the potential benefits and harms of tamoxifen for white women, at this time, there are few data for African American women and women of other ethnicities. However, African American women may get less benefit and more harm from tamoxifen than white women. African American women have a lower rate of breast cancer than white women and are more likely to suffer some of the harmful side effects of tamoxifen [260-261].

Aromatase inhibitors

The hormone drugs aromatase inhibitors are part of standard treatment for estrogen receptor-positive breast cancer in postmenopausal women (learn more). There are three aromatase inhibitors that are FDA-approved for use in the United States: anastrozole (Arimidex), letrozole (Femara), and exemestane (Aromasin). They appear to be equally effective in treating breast cancer.

Findings from a recent randomized controlled trial of 4,560 cancer-free postmenopausal women at high risk showed the aromatase inhibitor exemestane lowered the risk of breast cancer. After three years, women taking exemestane had a 65 percent lower risk of developing invasive breast cancer than women taking a placebo [262].

Unlike tamoxifen and raloxifene, exemestane did not appear to increase the risk of blood clots. However, similar to tamoxifen and raloxifene, menopausal symptoms were more common among women taking exemestane compared to placebo [262]. Other studies have shown aromatase inhibitors can cause a loss of bone density [263-266].

Although exemestane is FDA-approved for use in breast cancer treatment, it does not yet have FDA-approval for use in the chemoprevention setting.

Learn about exemestane and other aromatase inhibitors and breast cancer treatment.

Other risk-lowering drugs

Other drugs currently used to treat breast cancer are under study for use in prevention and new risk-lowering drugs are being developed.

If you are at higher risk of breast cancer and would like to consider joining a clinical trial of risk-lowering drugs, discuss the potential risks and benefits with your health care provider.

Learn more about emerging areas in chemoprevention.

Learn more about clinical trials.

Prescription drug assistance

Medicare and many insurance providers offer prescription drug plans. One may already be included in your policy or you may be able to buy an extra plan for prescriptions. And, you may qualify for assistance from programs that help with drug costs or offer low-cost or free prescriptions.

Tamoxifen is available in a generic form (cheaper than the name brand).

Learn more about insurance plans and prescription drug assistance programs.

Updated 01/23/12

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