Preventing Breast Cancer with Hormonal Therapy

Caroline Halsted and Danielle Shapiro, MD, MPH, Cancer Prevention and Treatment Fund

About 12% of women in the United States will be diagnosed with breast cancer at some point in their lifetimes.  Although most women survive breast cancer, many women are very afraid of the disease and consider undergoing medical treatments to prevent breast cancer from ever developing.  Hormonal therapy is a popular strategy among women who are afraid of breast cancer and want to reduce the chances of ever developing it.  What are the risks and benefits?

What is Hormonal Therapy?

Hormonal therapy prevents breast cancer by blocking or reducing the level of female hormones that can help breast cancer cells to grow. Approximately 80% of all breast cancers are “estrogen-receptor positive” which means that they need estrogen to grow.[1] Tamoxifen and raloxifene are two hormonal treatments that block estrogen in the breast but not in other parts of the body.  They are called selective estrogen receptor modulators (SERMs), and they are sometimes prescribed for pre-menopausal and post-menopausal women who have an above-average risk of developing breast cancer.

How Effective Are Tamoxifen and Raloxifine?

A study compared tamoxifen and raloxifene as prevention strategies for post-menopausal women who were at an increased risk of breast cancer.[2]  The study was called the STAR trial, which is the acronym for “The Study of Tamoxifen and Raloxifene.” Women were defined as increased risk in this study if they had a higher risk than the average 60-64 year old, which is estimated at 1.67% in the next 5 years.[3] Factors that determine a woman’s risk include:

  • age
  • number of first-degree relatives diagnosed with breast cancer
  • number of children
  • age at first delivery
  • number of breast biopsies undergone
  • whether there is presence of atypical hyperplasia
  • age at first menstrual period
  • age at menopause

There are other risk factors you can control, like smoking cigarettes and drinking alcohol. (Click here to read our article on alcohol and cancer). A United Kingdom study involving over 100, 000 women found a significant link between smoking and breast cancer. Over a 7-year period, about 2% of women who ever smoked developed cancer compared to about 1.6% of women who never smoked. This means that smoking causes about 4 in 1000 breast cancers. Even though that number seems small (less than half a percent), it is statistically significant. Starting smoking at a younger age, smoking 15 or more daily cigarettes, and smoking for at least 10 years increase the chances of developing breast cancer. If you smoke, you should talk to your doctor about ways to quit. Quitting decreases the chances of developing breast cancer, but it may take about 20 years to see the full benefits. To read more, click here.[4]

A tool determining your own risk of breast cancer can be found here.

The initial results of the STAR study found that tamoxifen and raloxifene were equally effective in preventing breast cancer after four years of treatment. However, after 5 years of treatment and 2 years of follow-up after the treatment ended, women taking tamoxifen were 1.1% less likely to develop breast cancer while women taking raloxifene were less than half a percent less likely to develop breast cancer (0.4%).[5] So, for example, if your 7-year risk of getting breast cancer was 4% (considered an increased risk), taking tamoxifen may decrease your risk to just under 3% and raloxifene to about 3.6%. This decrease in risk for women taking tamoxifen is very similar to the results of studies conducted more than 5 years earlier, which when combined found a 1.2% decreased risk of breast cancer for pre- and post-menopausal women at average or high risk of breast cancer.[6]

Hormonal therapy is even less beneficial to prevent breast cancer in pre-menopausal women, so it is only recommended for women who have mutations in the “breast cancer genes” (BRCA1 or BRCA2) or if they are older than 35 and have a very high risk of breast cancer.[7]

Although about 12% of U.S. women will be diagnosed with breast cancer at some point in their lifetime, 88% won’t.  Most women at “higher than average risk” will never develop breast cancer, and there are many things women can do to reduce their risks. Here are 5 ways you can reduce your risk of getting breast cancer. When considering whether to take hormonal therapy to reduce your chances of developing breast cancer, don’t focus on what is called “relative risk” –  make sure you understand the absolute risk.  For example, a woman with a 2% risk of developing breast cancer in the next 5 years can possibly reduce that risk by 50% by taking Tamoxifen, but that is only a reduction from 2% to 1%.  To decide whether that is worth it to you, it is important to consider the side effects and risks of these treatments, and not just the benefits.

Side Effects

Tamoxifen and raloxifene can be harmful. Because estrogen plays an important role in maintaining strong bones and healthy cholesterol, blocking estrogen can put healthy women at greater risk for heart disease and osteoporosis.

Here are the known side effects of tamoxifen:

  • endometrial (uterine) cancer- for every 1,000 women, 2 more will develop uterine cancer
  • blood clots- for every 1,000 women, 3 more will develop potentially dangerous blood clots
  • strokes- for every 100 women, 1 will develop a stroke
  • cataracts
  • hot flashes
  • vaginal discharge
  • vaginal bleeding

Known side effects of raloxifene:

  • blood clots- for every 1,000 women, 2-3 will develop a potentially dangerous blood clot
  • hot flashes
  • vaginal dryness
  • joint pain
  • leg cramps

Sources: [3], [8]

Compared to raloxifene, women taking tamoxifen have a greater risk of developing serious blood clots, but both drugs have about the same increased risk for other heart-related side effects and bone fractures. Women who took tamoxifen had a more than 1% increased risk for developing cataracts compared to women who took raloxifene.

Most important, taking tamoxifen for five years can increase a woman’s lifetime risk of developing endometrial cancer from about 3% to about 7%.[9] Raloxifene does not.[9]

For premenopausal women, tamoxifen has significantly worse side effects than raloxifene. However, tamoxifen can be taken by either pre-menopausal or post-menopausal women, while raloxifene is only approved for post-menopausal women.

Bottom Line

If you are afraid of developing breast cancer because of a family history or other reasons, it is important to understand the limited benefits as well as the risks of hormonal therapy.  As noted above, the absolute benefit in terms of lower risks is often only about 1% (for example, lowering your risk from 4% to 3% chances of developing cancer, or from 2% to 1%).

Although research has consistently shown that both tamoxifen and raloxifene can decrease risk for developing breast cancer, these results have only been significant for post-menopausal women with an increased risk of getting breast cancer. The higher your risk of developing breast cancer (because of the BRCA genes, family history, or other reasons) the more likely that the benefits will outweigh the risks for you.  But even that depends on your other health risks.  For example, if you are already at high risk of developing blood clots, you probably don’t want to take a hormone treatment that increases that risk even more.

If you are not impressed by the benefits of hormonal treatment to prevent breast cancer, think about other strategies such as reducing how much alcohol you drink, losing a few pounds, eating more fresh fruit, vegetables, and whole grains, and exercising. Our articles about preventing breast cancer can be found here. These strategies reduce your chances of developing cancer as well as reducing your chances of dying from heart disease – which kills more women every year than breast cancer.

All articles are reviewed and approved by Dr. Diana Zuckerman and other senior staff.

References:

  1. What Is Hormonal Therapy for Breast Cancer? (2016, July 20). Retrieved from http://www.breastcancer.org/treatment/hormonal/what_is
  2. The Study of Tamoxifen and Raloxifene (STAR): Questions and Answers. (2010, April 9). Retrieved from https://www.cancer.gov/types/breast/research/star-trial-results-qa
  3. About the Tool. (n.d.). Retrieved from https://www.cancer.gov/bcrisktool/about-tool.aspx
  4. Jones ME. et al. Smoking and risk of breast cancer in the Generations Study cohort. Breast Cancer Research. 2017;19:118. https://doi.org/10.1186/s13058-017-0908-4
  5. Vogel, V. G., Costantino, J. P., Wickerham, D. L., & Cronin, W. M. (2010). Re: Tamoxifen for Prevention of Breast Cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. Cancer Prevention Research, 3(63), 1504-1504. doi:10.1093/jnci/94.19.1504
  6. Tan-Chiu, E., Wang, J., Costantino, J. P., Paik, S., Butch, C., Wickerham, D. L., . . . Wolmark, N. (2003). Effects of Tamoxifen on Benign Breast Disease in Women at High Risk for Breast Cancer. JNCI Journal of the National Cancer Institute, 95(4), 302-307. doi:10.1093/jnci/95.4.302
  7. Vogel, V. G. (2018). Primary Prevention of Breast Cancer. The Breast, 219-236. doi:10.1016/b978-0-323-35955-9.00016-7
  8. Bushnell, C. D., & Goldstein, L. B. (2004). Risk of ischemic stroke with tamoxifen treatment for breast cancer: A meta-analysis. Neurology, 63(7), 1230-1233. doi:10.1212/01.wnl.0000140491.54664.50
  9. Cancer Stat Facts: Uterine Cancer. (n.d.). Retrieved from https://seer.cancer.gov/statfacts/html/corp.html
  10. Swerdlow, A. J., & Jones, M. E. (2005). Tamoxifen Treatment for Breast Cancer and Risk of Endometrial Cancer: A Case-Control Study. JNCI Journal of the National Cancer Institute, 97(5), 375-384. doi:10.1093/jnci/dji057