By Kathleen Fergus, MS, CGC

Reviewed by Andrea Fishbach, MS, MPH
Last updated December 7, 2000

In the past few years, women at high risk for breast cancer have received some good news; two medications appear to substantially decrease their chances of developing breast cancer. Although these two drugs—tamoxifen and raloxifene — share similar chemical properties and function, each has different associated risks and side effects, and only one (tamoxifen) has been approved by the FDA for use in preventing breast cancer. Several studies that are currently underway to test the relative effectiveness of these drugs should help high-risk women make their decision about what prevention is right for them.

More on Assessing Your Risk for Breast and Ovarian Cancer

How the Drugs Work

Tamoxifen may reduce the risk of breast cancer in high-risk women by almost 50 percent.

When estrogen binds to some breast cancer cells, it instructs those cells to continue growing and dividing. SERMs such as tamoxifen and raloxifene block this message by preventing estrogen from binding to those cells. If estrogen can't bind to the cancer cell, it can't deliver its message, and the cell consequently will not know to grow and divide. Hence the growth of cancerous cells is halted.

The interesting thing about SERMs, however, is that although they block the effect of estrogen in some tissues, they mimic the hormone's effect in others. So while tamoxifen blocks the effect of estrogen on breast tissue, it acts like estrogen in the bones, heart, and uterus — a good thing for the bones and heart, but a bad thing for the uterus, where its growth-stimulating effect increases the risk of endometrial cancer (cancer of the lining of the uterus). Raloxifene is similar to tamoxifen in its effect on the breasts, bones, and heart. However, it has the opposite effect on the uterus — that is, raloxifene blocks estrogen's effect there, which means that unlike tamoxifen it does not increase a woman's risk of endometrial cancer.

Although tamoxifen and raloxifene are similar both chemically and in the way they function, there are a number of differences in their associated side effects and risks. The following table provides an at-a-glance summary of each. Keep in mind, however, that these findings are based on early studies that examined women at risk for different disorders and that took place over varying lengths of time — tamoxifen for many years and raloxifene for about three years. As scientists continue to study these drugs, they may discover additional risks and/or side effects, and these preliminary findings may change.

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Tamoxifen

While the FDA only recently approved the use of tamoxifen for preventing breast cancer, doctors have used the drug for decades to treat existing breast cancers. In fact, it was during these years of therapeutic use that scientists and doctors began to suspect that the drug could be employed to prevent breast cancer as well. For starters, they were able to prove that tamoxifen reduced the recurrence of breast cancer in women who had already been diagnosed with the disease. They also found that women who used the drug were more likely to survive their cancer and were less likely to develop cancer in the other breast (that is, the opposite breast from the one in which the initial diagnosis was made).

Based on these findings, scientists designed a study — the Breast Cancer Prevention Trial (BCPT) — to look at the preventive effects of tamoxifen. Their findings were dramatic: In a comparison of 13,388 women at high risk for breast cancer, researchers found that the women who took 20 mg of tamoxifen per day were 49 percent less likely to develop breast cancer than those who received a daily placebo.

However, the news was not all good. As is the case with many drugs, tamoxifen — besides offering real hope to many — also poses some serious risks. In the BCPT, tamoxifen increased the risk of endometrial cancer by about 2.5 times. In addition, tamoxifen also appears to be linked with blood-clotting problems. The most serious side effect of tamoxifen is that it increases the risk for pulmonary embolism (a blood clot in the lungs), which can be life-threatening. Although pulmonary embolism is rare, in the BCPT the rate was three times as high in the tamoxifen group compared with the placebo groups.

Women taking tamoxifen are also more likely to develop cataracts (clouding of the cornea), a condition that, although not life threatening, can require surgery to correct. And, because tamoxifen can mimic estrogen in some tissues, women taking this medication are likely to experience some of the side effects associated with hormone replacement therapy such as hot flashes, night sweats, and vaginal dryness. For some women, these side effects are a minor and tolerable annoyance. For others, they are significant enough to dissuade them from taking the medication. (For recent news about Tamoxifen's side effects, see Related News below.)

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Raloxifene (Evista)

Raloxifene can reduce a woman’s risk of breast cancer by 50 to 70 percent.

The less serious side effects associated with raloxifene are similar to those reported by women taking tamoxifen or undergoing hormone replacement therapy. In the case of raloxifene, the most common of these are hot flashes and leg cramps.

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Long-Term Effects

Although studies have shown that both tamoxifen and raloxifene appear to decrease the risk of breast cancer, much remains to be learned about their effectiveness in different groups of women. Although we have many years experience using tamoxifen to treat breast cancer, we have only limited experience using either tamoxifen or raloxifene as a preventative agent. We don't yet have good data on the long-term effects of this type of use.

Scientists are also uncertain about how well tamoxifen and raloxifene work in women who have inherited a mutation in one of the two genes (BRCA1 or BRCA2) known to be associated with breast cancer. For example, even though the Breast Cancer Prevention Trial studied the use of tamoxifen in women at increased risk for breast cancer, that risk was based on previous biopsy findings and family histories. The study did not test participants for BRCA1 or BRCA2 mutations, and so we can't use these data to determine whether women with mutations are more or less likely to benefit from tamoxifen than other women.

However, one recent study has found that women with mutations in BRCA1 or BRCA2 have a reduced risk of developing cancer in the opposite breast when they take tamoxifen to treat an existing cancer. (See Related News below for more information about this study). This study gives preliminary evidence that tamoxifen may be useful for preventing cancers in this group of women.

More on the Genetics of Breast and  Ovarian Cancer More on Tamoxifen in Women With BRCA1 or BRCA2 Mutations

Is Chemoprevention Right for You?

The American Cancer Society estimates that 182,800 women will develop breast cancer in the year 2000, while only 36,100 women will develop endometrial cancer.

Although raloxifene is likely to be approved for the prevention of breast cancer, tamoxifen is the only chemoprevention option available today for this type of cancer — and then only for high-risk women between the ages of 35 and 59 as well as for all women over the age of 60. Because the use of tamoxifen involves a complex mix of potential benefits and risks, any woman considering this option will need to weigh a number of factors.

• Increased risk of endometrial cancer. Obviously, taking a drug to prevent one kind of cancer that increases the risk of another is not optimal. However, for some people the trade-off may be worthwhile. In the case of tamoxifen, a woman must weigh her chances of developing breast cancer against her odds of developing endometrial cancer. Women in the general population are far more likely to get breast cancer than endometrial cancer — and in women at high risk for breast cancer, that gap is wider still. For many, the danger of endometrial cancer pales in comparison to the decrease in breast cancer risk promised by tamoxifen. Add to this the fact that endometrial cancer is easier to detect in its earliest stages (especially for women who receive regular medical care and report symptoms such as irregular vaginal bleeding), and one begins to understand why some women are willing to consider this trade-off. For a woman who's had a hysterectomy, the decision is less complex: With no uterus, the risk for endometrial cancer is eliminated. As researchers learn more about the link between tamoxifen and endometrial cancer, it will likely become easier for women to weigh the benefits and risks of this type of cancer chemoprevention.
  
  
• Other associated risks. In deciding whether or not to use tamoxifen, women must also consider some additional complications that have been associated with the drug, such as blood-clotting and eye problems. For example, women with a history of blood clots requiring medical treatment and women who need to take blood thinning medication should not take tamoxifen.
  
  
• Hormone replacement therapy/pregnancy. Because tamoxifen is a hormone, women who are undergoing hormone replacement therapy or taking raloxifene should not use tamoxifen. In addition, women should not become pregnant and should use reliable birth control (something other than oral contraceptives) while taking tamoxifen.
  
  

Chemoprevention of breast cancer is an exciting new field, but it's also a complex one. Thus, any woman considering taking this route to reduce her risk of breast cancer must talk to her doctor and analyze the benefits and risks in the context of her personal and family medical history.

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Related News

In order to view these articles you will need to have a MyGeneticHealth account. If you are not already a member, selecting the article will automatically take you to a page where you can sign up. Tamoxifen may protect heart Device may prevent tamoxifen side effect Tamoxifen use tied to poor endometrial cancer prognosis Tamoxifen reduces risk of contralateral breast cancer in BRCA carriers

Burger, H. G. (2000). Selective Oestrogen Receptor Modulators. Horm Res 53 Suppl S3: 25-29.

Chlebowski, R. T., D. E. Collyar, et al. (1999). American Society of Clinical Oncology technology assessment on breast cancer risk reduction strategies: tamoxifen and raloxifene. J Clin Oncol 17(6): 1939-55.

Cuzick, J. (2000). A brief review of the current breast cancer prevention trials and proposals for future trials. Eur J Cancer 36(10): 1298-302.

Dhingra, K. (1999). Antiestrogens--tamoxifen, SERMs and beyond. Invest New Drugs 17(3): 285-311.

Kardinal, C. G. and R. Veith (1999). Prevention of breast cancer in high-risk women. J La State Med Soc 151(4): 198-201.

Yao, K. and V. C. Jordan (1998). Questions about Tamoxifen and the Future Use of Antiestrogens. Oncologist 3(2): 104-110.

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