Tamoxifen and Raloxifene for Breast Cancer Prevention

Tamoxifen and raloxifene have been shown to reduce the risk breast cancer, but they can have their own risks and side effects. Tamoxifen and raloxifene are the only drugs that are approved in the US to help lower the risk of breast cancer. 

What kind of drugs are tamoxifen and raloxifene?

Both of these drugs are selective estrogen receptor modulators (or SERMs). This means that they act against (or block) estrogen (a female hormone) in some tissues of the body, but act like estrogen in others. Estrogen can fuel the growth of breast cancer cells. Both of these drugs block estrogen in breast cells, which is why they can be useful in lowering breast cancer risk.

These drugs are used more often for other things.

  • Tamoxifen mainly is used to treat hormone receptor-positive breast cancer (breast cancer with cells that have estrogen and/or progesterone receptors on them).
  • Raloxifene is used mostly to prevent and treat osteoporosis (very weak bones) in post-menopausal women.

Both drugs are pills taken once a day. Tamoxifen also comes in a liquid form. Tamoxifen can be used by women whether or not they have gone through menopause, but raloxifene is only approved to be used by post-menopausal women. To lower the risk of breast cancer, these drugs are taken for 5 years.

How much do these drugs lower the risk of breast cancer?

The effect of these drugs on breast cancer risk has varied in different studies. Tamoxifen has been shown to lower risk by 13% to 48%, while raloxifene has lowered risk by 18% to 58%. When the results of all the studies are taken together, the overall reduction in risk for these drugs was about 38% (more than a third). These drugs lower the risk of both invasive breast cancer and ductal carcinoma in situ.

What would this mean for me?

Although a medicine that cuts your risk by more than a third (or 38%) sounds like it must be a good thing, what it would really mean for you depends on how high your risk is in the first place (your baseline risk).

For example, if you had an 8% risk of getting breast cancer in the next 5 years, you would be considered to be at increased risk. An 8% risk would mean that over the next 5 years, 8 of 100 people with your risk would be expected to get breast cancer. A 38% relative risk reduction means that the risk would go from 8% to 5%. So now only 5 of the 100 people would get breast cancer over the next 5 years. So for you, a change in the relative risk of 38% actually means a 3% change in your absolute risk (from 8% to 5%).

Since the change in absolute risk depends on your baseline risk, you would benefit less if you had a lower baseline risk, and you would benefit more if your risk was higher. If you had a baseline risk of only 1.7% (which is what was needed to be in some of the studies of these drugs), the 38% change in relative risk would mean that your risk would go down to 1.05%. This means a 0.65% change in absolute risk.

Your doctor can estimate your breast cancer risk based on factors like your age, medical history, and family history. This can help you see how much benefit you might get from taking one of these drugs.

Are there other benefits to taking these drugs?

Both tamoxifen and raloxifene can help prevent osteoporosis, a severe weakening of the bones that is more common after menopause.

What are the risks and side effects of taking these drugs?

The most common side effects of these drugs are symptoms of menopause. These include hot flashes and night sweats. Tamoxifen can also cause vaginal dryness and vaginal discharge. Pre-menopausal women taking tamoxifen can experience menstrual changes. Menstrual periods can become irregular or even stop. Although periods often start again after the drug is stopped, they don’t always, and some women go into menopause. This is more likely in women who were close to menopause when they started taking the drug.

Other more serious side effects are rare. These include serious blood clots and cancer of the uterus.

Blood clots

Both tamoxifen and raloxifene increase your risk of developing blood clots in a vein in your leg (deep venous thrombosis) or in your lungs (pulmonary embolism). These clots can sometimes cause serious problems, and even death. In the breast cancer prevention studies, the overall risk of these blood clots over 5 years of treatment was less than 1%. This risk could be higher if you had a serious blood clot in the past, so these drugs are not recommended to lower breast cancer risk in anyone with a history of blood clots.

If you are taking tamoxifen or raloxifene, tell your doctor if you develop leg swelling, chest pain, or shortness of breath, as these can be symptoms of blood clots.

Because these drugs increase your risk of developing serious blood clots, there is also concern that they also increase your risk of heart attack or stroke. So far, though, this hasn’t been seen in studies.

Cancer of the uterus

Because tamoxifen acts like estrogen in the uterus, it can increase your risk of endometrial cancer and uterine sarcoma (cancers of the uterus). It also is linked to a higher risk of endometrial pre-cancers. Raloxifene does not act like estrogen in the uterus and is not linked to an increased risk of uterine cancer.

Although tamoxifen does increase the risk of uterine cancer, the overall increase in risk is low. In one large study of women taking the drug for up to 5 years to lower breast cancer risk, less than 1% of women taking the drug were diagnosed with uterine cancer. Most of these cancers were found at a very early stage. Some women were diagnosed with endometrial pre-cancer. Risk of uterine cancer goes back to normal within a few years of stopping the drug.

The increased risk seems to affect the women over 50 and not the younger women.

If you are taking tamoxifen, tell your doctor if you have any abnormal vaginal bleeding or spotting, especially after menopause, as these are possible symptoms of uterine cancer. If you have been diagnosed with uterine cancer or pre-cancer you should not take tamoxifen.

If you have had a hysterectomy (surgery to remove the uterus), you are not at risk for endometrial cancer or uterine sarcoma and do not have to worry about these cancers.

The American Cancer Society medical and editorial content team
Our team is made up of doctors and master’s-prepared nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Cuzick J, Sestak I, Bonanni B, et al; for the SERM Chemoprevention of Breast Cancer Overview Group. Selective oestrogen receptor modulators in prevention of breast cancer: an updated meta-analysis of individual participant data. Lancet. 2013 Apr 29.

King MC, Wieand S, Hale K, et al. Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial. JAMA. 2001;286(18):2251-6.

USPSTF summary http://www.uspreventiveservicestaskforce.org/uspstf13/breastcanmeds/breastcanmedsrs.htm

Last Medical Review: June 1, 2016 Last Revised: August 18, 2016

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