Tamoxifen Reduces Risk of Breast Cancer in High-Risk Women
Reviewed study: "Tamoxifen Reduces Risk of Breast Cancer in High-Risk Women" by B. Fisher et al., Journal of the National Cancer Institute, November 16, 2005
Is this for me? If you are at high risk for breast cancer and are considering taking protective medication, you might want to read this article.
Background and importance of the study: In 1992, the National Surgical Adjuvant Breast and Bowel Project (NSABP) started the Breast Cancer Prevention Trial, known as P-1. It was designed to see if taking tamoxifen could reduce the risk of breast cancer in women who were at high risk for the disease.
Initial results from the study were released in 1998. The results showed that taking tamoxifen reduced the risk of developing both invasive and non-invasive breast cancers by nearly 50%. The first report of this study was revealed early, because the benefit of tamoxifen happened early on and was significant.
The study kept going and finished collecting data in March 2005. The review here offers the final results of the study.
Study design: Only women considered to be at high risk for breast cancer were eligible for this study. More than 13,000 women from across the United States participated.
In this study, high risk for breast cancer was defined in several ways:
- being at least 60 years old (getting older is one of the biggest risks for breast cancer),
- having been diagnosed with lobular carcinoma in situ (LCIS), or atypical hyperplasia (the breast cells are growing in an abnormal way), or
- being assessed as high risk for breast cancer using a special computer calculation that looks at a variety of risk factors together.
The women could not take any other form of hormone therapy—such as hormone-replacement therapy for menopause or birth control pills—during the study.
Half the women took 20 milligrams of tamoxifen in pill form, and the other half took a placebo (a sugar pill that looked just like the tamoxifen). They took either tamoxifen or the placebo for five years. The women were then followed for seven years.
After the initial results were released, information was released on who was taking tamoxifen and who was taking a placebo. Women who were taking the placebo were offered the chance to switch to tamoxifen. About one-third of these women made this switch.
Results: After seven years of follow-up, the final results were almost identical to the first results: tamoxifen reduced the risk of developing both invasive and non-invasive cancers by almost 50%.
More specifically, tamoxifen was able to reduce the risk of developing a hormone-receptor-positive breast cancer. But tamoxifen was unable to reduce the risk of getting a hormone-receptor-negative breast cancer. These results are statistically significant, meaning they are due to the tamoxifen and not just to chance.
The researchers also looked to see if tamoxifen offered benefits to specific subgroups of women in the study. These groups were selected by:
- age (the age groups were age 35 to 49, age 50 to 59, and age 60 and older),
- history of lobular carcinoma in situ (LCIS),
- history of atypical hyperplasia, or
- predicted risk of breast cancer based on the computer calculation.
Tamoxifen significantly reduced the risk of invasive breast cancer in all these subgroups.
Other benefits included:
- Fewer bone fractures (broken bones): women who took tamoxifen had significantly fewer bone fractures (80 women) than women who took the placebo (116 women). Most of the broken bones (89%) were in women age 50 and older. Tamoxifen reduced broken bones in women age 50 and older by 29%. In women age 49 and younger, tamoxifen reduced broken bones by 53%.
- Lower cholesterol: women who took tamoxifen had lower total cholesterol than women who took the placebo. But tamoxifen did not reduce the risk of heart disease.
Side effects of tamoxifen included:
- Uterine cancer: women age 50 or older who took tamoxifen had a significant increase in uterine cancer (41 women) compared to women who took the placebo (8 women). The risk of uterine cancer DID NOT increase for women who were age 49 or younger.
- Blood clots: women who took tamoxifen had significantly more dangerous blood clots (77 women) than women who took the placebo (47 women).
- Strokes: women who took tamoxifen had more strokes (71 women) than women who took the placebo (50 women). But this difference wasn't significant. (This means that the researchers weren't sure if the tamoxifen caused the strokes or if it just happened by chance.) Women age 49 or younger who took tamoxifen DID NOT have an increased risk of strokes. Women age 50 and older who took tamoxifen were more at risk for strokes, but again, not significantly.
- Cataracts: women who took tamoxifen were significantly more likely to develop cataracts.
Conclusions: The researchers concluded that tamoxifen significantly reduces the risk of breast cancer in women at high risk for the disease. The amount of benefit a woman gets from taking a protective dose of tamoxifen depends on how high her risk for breast cancer is. This benefit is then weighed against her risk of side effects.
The risk of blood clots and uterine cancer associated with taking tamoxifen depends on a woman's age and race. Women age 60 or older have a higher risk of blood clots and uterine cancer than younger women. And African-American women have a higher risk of blood clots and uterine cancer than white women.
These side effects need to be weighed against the benefits. Older women or African-American women might have more side effects. So tamoxifen is going to have to offer them enough benefit to override these side effects.
If a woman is younger than age 50 and has a high risk of breast cancer, the side effects of tamoxifen are unlikely to be serious. As a result, it's easier for the benefits of tamoxifen to outweigh the side effects.
An original video-on-demand educational initiative brought to you by Breastcancer.org and Comcast. Visit www.comcast.net/pinkribbon each week through the end of October for engaging, up-to-date videos and information about the fight to end breast cancer.
What breastcancer.org says about this article…
Tamoxifen Reduces Risk of Breast Cancer in High-Risk Women
This long, large study reconfirms the benefits of tamoxifen for women who are at high risk for breast cancer but who have not had breast cancer before. By taking a protective dose of tamoxifen for five years, women at high risk can:- reduce their risk of breast cancer by almost 50%—although tamoxifen only works to reduce the risk of hormone-receptor-positive breast cancers
- reduce their risk less aggressively than prophylactic (preventive) mastectomy
- get more time until something better comes along
But these benefits have to be weighed against tamoxifen's possible serious side effects. As you and your doctor look at the pros and cons of protective tamoxifen for YOU, keep in mind that more and more treatment options are being discovered all the time.
If you're at high risk for breast cancer and want to be aggressive about reducing your risk, talk to your doctor about tamoxifen. If you are postmenopausal, you may be able to participate in a clinical trial looking at the role of aromatase inhibitors. Balance the benefits and risks for your unique situation. It may take more than one discussion to come to a decision. Take as much time as you need and make decisions that you're comfortable with. You and your doctor also will reevaluate your treatment plan periodically. As new research results are published and new medicines are tested, you may want to change your medication to ensure you're getting the best protection for you.