Risk Management
Chemoprevention and breast cancer
Overview
Chemoprevention is the use of medication to lower the risk or prevent cancer in healthy people. Some chemoprevention medications reduce breast cancer risk. However, just how well these drugs perform in high-risk women depends on each woman’s individual level of risk. Many past studies of these medications focused on women in the general population or women whose risk for breast cancer was based on the Gail Model, a risk assessment tool, therefore the research may not apply to everyone with hereditary cancer risk. When choosing the best risk management option for yourself, you need a clear sense of your risk (a health care team with expertise in managing high-risk patients can help you identify this) and an understanding of the potential benefits and side effects of chemopreventive medications. For more information see our section on risk assessment for breast cancer based on the Gail Model. Studies are ongoing to identify new medications to lower the risk or prevent breast cancer. Please visit our research and clinical trials section for information on these studies.
Tamoxifen
Selective Estrogen Receptor Modulators (SERMs) are a group of drugs that block the effects of estrogen on breast tissue. One SERM, tamoxifen, is the only medication that is FDA approved for decreasing breast cancer risk in high-risk women. A large study found women who took tamoxifen for 5 years lowered their breast cancer risk by one half. This study identified women at high-risk for breast cancer according to the Gail Model. (For more information see our page on the Gail Model). The Gail Model does not take into account certain aspects of hereditary breast and ovarian cancer; therefore the high-risk population from this study may be different than women who are at high risk for breast cancer because of a BRCA mutation. Smaller studies looking at tamoxifen for breast cancer prevention in women with BRCA mutations have been inconclusive. In a study of 19 women with BRCA mutations, women with BRCA 2 mutations who took tamoxifen had a lower breast cancer risk. However, the results were based on only 11 women and were not statistically significant. In the same study, women with BRCA 1 mutations who took tamoxifen did not have any decrease in breast cancer risk. Again the sample size was small (8 women) and the results were not statistically significant.
Studies of BRCA carriers who were diagnosed with cancer in one breast and took Tamoxifen demonstrated a reduced risk for breast cancer in the other breast. One such study showed Tamoxifen lowered the risk for a new breast cancer in the other breast by about 40% in women with BRCA 1 mutations and by about 25% in women with BRCA 2 mutations. However, it is uncertain if the same risk-lowering affect applies to BRCA carriers who have not had cancer or to BRCA mutation carriers whose prior breast cancers did not express estrogen or progesterone receptors.
Tamoxifen may protect bone density and reduce osteoporosis risk in postmenopausal women who cannot take hormone replacement.
Tamoxifen may have some side effects and risks. Women who take this medication are at a slightly higher risk for developing uterine cancer. Tamoxifen can also increase the risk of blood clots, including serious blood clots, particularly in women who smoke or have other risk factors. A recent presentation showed that women with an inherited clotting disorder called “Factor V Lieden” mutation were four times more likely to develop blood clots on tamoxifen than women without this disorder. Tamoxifen may also have less serious side effects such as hot flashes and vaginal dryness.
Experts do not all agree that tamoxifen is appropriate for preventing breast cancer in women with BRCA 1 mutations. Women who consider tamoxifen to lower their risk for breast cancer should discuss the benefits, risks and limitations with their health care team, including experts in managing high-risk women.
Raloxifene
Raloxifene is a medication that blocks the effects of estrogen similar to Tamoxifen. Raloxifene may have many similar benefits to Tamoxifen and lowers the risk for breast cancer in certain high-risk women. The STAR Trial (Study of Tamoxifen and Raloxifene), a large research study which compared Tamoxifen and Raloxifene in certain post-menopausal high-risk women concluded that Raloxifene was as effective as Tamoxifen in reducing invasive breast cancer risk. This study includedonly post-menopausal women who are high-risk based on the risk assessment using the Gail Model , but did not looking specifically at women with BRCA mutations, so the benefits of Raloxifene in BRCA mutation carriers remain uncertain. Raloxifene appears to have fewer side effects than Tamoxifen, including a lower risk for uterine cancer, blood clots and cataracts. One study showed that Raloxifene lowered the risk for uterine cancer by half compared to women who did not take the medication, while Tamoxifen increased the risk for uterine cancer.
Aromatase inhibitors
Aromatase inhibitors are medications used to keep post-menopausal women from producing estrogen in their fat cells and adrenal cells. These drugs are used as adjuvant (additional) therapy for preventing breast cancer recurrence in women with cancers that are estrogen or hormone receptor positive. Common aromatase inhibitors include anastrozole (Arimidex), letrozole (Femara), and exemestane (Aromasin). The Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial, studied anastrozole as an adjuvant treatment for women with breast cancer. The trial found anastrozole reduced the risk of developing a new cancer in the other breast by 58 percent. This study did not look specifically at women with BRCA mutations, so the benefits of Arimidex to prevent breast cancer in this population remain uncertain.
Unlike SERM medications, aromatase inhibitors do not improve bone density. In fact, they may actually accelerate bone loss in post-menopausal women. However, aromatase inhibitors appear to cause fewer side effects than, and do not appear to have the risk of blood clots or uterine cancer as seen with Tamoxifen.
Clinical trials are studying whether aromatase inhibitors can reduce post-menopausal, high-risk women’s likelihood of developing breast cancer. Some of these studies are looking at women with BRCA mutations. Results from this research will not be available for several years. To enroll or learn more about clinical trials for chemoprevention, visit our section on clinical trials.
Nonsteroidal anti-inflammatory medications
Nonsteroidal anti-inflammatory drugs (NSAIDs) are medications used for pain relief. This category includes many common over-the-counter painkillers, such as aspirin, ibuprofen (Advil, Motrin) and naproxen sodium (Aleve). Several studies have tried to determine whether aspirin and other NSAIDs reduce breast cancer risk. The Women’s Health Initiative studied the use of NSAIDs by women over the age of 50. Those who used aspirin on a regular basis had a 21% decreased chance of developing breast cancer than women who did not regularly use the medication .Regular use of ibuprofen was associated with a 49% risk reduction in breast cancer risk. This lowered risk also applied to women with a family history of breast cancer (first-degree female relatives only: mother, sister or daughter). However, the study did not specifically focus on women who had BRCA mutations or had evidence of a hereditary breast and ovarian cancer syndrome.This study was “observational” only, meaning although women who regularly took NSAIDs were less likely to develop breast cancer, the study does not prove NSAIDs are responsible for the reduced risk of breast cancer. A clinical trial is needed to show that NSAID use lessens the risk for breast cancer. For more information on the types of research studies see our section on clinical trials and research.
Certain NSAIDs increase the risk for death from heart disease. A recent clinical trial studying whether Celebrex could lessen the risk for colon polyps was discontinued when there were more heart disease and heart-disease related deaths in participants who took the medication compared to participants who took a placebo. The risk was still low for death by heart disease: about 3% of people who were on the highest dose, and 2% risk for people on the lower dose. In that particular study, however, the benefits of Celebrex were not believed to outweigh the risks.
Clinical trials are looking at whether nonsteroidal anti-inflammatory agents can decrease breast cancer risk in high-risk women, including some studies looking at women with BRCA mutations. Results from this research will not be available for several years. To enroll or learn more about clinical trials for chemoprevention, visit our section on chemoprevention clinical trials.
Statins
Statins are medications commonly used to lower cholesterol. A recent study showed women taking statins had a 51% reduction of breast cancer risk. This study was “observational” and “retrospective” only: although women who took statins on a regular basis were less likely to develop breast cancer, researchers cannot be certain that taking statins is responsible for the decreased risk. A clinical trial is needed in order to show that statin use lowers the risk for breast cancer. For more information on the types of research studies see our section on chemoprevention clinical trials.
Deslorelin
Deslorelin is a medication that prevents the ovaries from producing estrogen. Research studies have shown that lowering estrogen levels through removal of the ovaries can lower the risk for breast cancer, particularly in women with BRCA mutations. Since Deslorelin prevents the ovaries from producing estrogen, there is reason to believe that it will also protect against breast cancer, however, unlike surgical removal of the ovaries, Deslorelin's effect on the ovaries is reversible: that means when a woman stops taking the medication, her ovaries will begin to make estrogen again. One preliminary study which studied the effects of Deslorelin on premenopausal women with BRCA mutations, showed that Deslorelin can decrease the density of breasts as seen on a mammogram. Increased breast density has been linked to breast cancer risk and also makes it more difficult for a radiologist to read mammograms of the breasts. Although this study is encouraging, more research is needed to show that Deslorelin lowers the risk for breast cancer.
Clinical trials are looking at whether Deslorelin can decrease breast cancer risk in high-risk women, including some studies looking at women with BRCA mutations .Results from this research will not be available for several years. To enroll or learn more about clinical trials for chemoprevention, visit our section on chemoprevention clinical trials.
Fenretinide
Fenretinide is a medication related to Vitamin A. Research studies suggest Fenretinide might reduce the risk of several types of cancers. Results of a 15 year Italian study on women who were already diagnosed with breast cancer showed that women who took Fenretinide for 5 years lowered their risk for a second breast cancer in the same or the opposite breast. Fenretinide seemed to work best on premenopausal women, with women under the age of 40 having a 50% reduction in risk for a second cancer. The protective benefit of Fenretinide continued even after women stopped the medication. Although the study suggests that Fenretinide lowers the risk of breast cancer, there is not enough research yet to say that Fenretinide can prevent breast cancer in high-risk women who have never had cancer. This study did not look exclusively at women with BRCA mutations, so it is unknown if the medication will be as effective for BRCA mutation carriers as it is for premenopausal breast cancer survivors in general. Fenretinide is not available in the United States.
Clinical trials
ClinicalTrials.gov
This site, produced by the U.S. National Library of Medicine (NLM), provides
patients, family members, and members of the public easy and free access to
information on clinical studies for a wide range of diseases and conditions.
(Link includes search for: breast AND cancer AND prevention)
Anastrozole in Preventing Breast Cancer in Postmenopausal Women at Increased Risk of Breast Cancer
Note: This study is only open to women in the United Kingdom.
Letrozole in Preventing Breast Cancer in Postmenopausal Women
Genestein in Preventing Breast Cancer in Women at High Risk for Breast Cancer
Exemestane in Treating Postmenopausal Women at High Risk for Invasive Breast Cancer
Exercise in Preventing Breast Cancer in Healthy Young Women
Other websites
Tamoxifen: Questions and Answers
Produced by the National Cancer Institute.
Chemoprevention:
A therapy for women at high risk of breast cancer
The Mayo Clinic, provides this overview of chemoprevention options for high-risk
women.
Anastrozole
shows promise for breast cancer chemoprevention
A summary of the rationale behind the use of Anastrozole (a type of medication
called an "aromatase inhibitor") to prevent breast cancer in high-risk
women.
Further reading - articles (advanced reading)
Fifteen-year
results of a randomized phase III trial of fenretinide to prevent second
breast cancer
U. Veronesi, L. Mariani, A. Decensi, F. Formelli, T.
Camerini, R. Miceli, M. G. Di Mauro, A. Costa, E. Marubini, M. B. Sporn
and G. De Palo. Annals of Oncology. Volume 17, Number 7: p. 1065-1071,
July, 2006.
Statins
reduce breast cancer risk: a case control study in US female veterans
R.
Kochhar, V. Khurana, H. Bejjanki, G. Caldito, C. Fort American Society
of Clinical Oncologists. (abstract # 514), May 2005. (Annual conference
proceedings abstract)
Factor
V Leiden (FVL) mutations and thromboembolic events (TE) in women with breast
cancer on adjuvant tamoxifen
J. E. Garber, S. Halabi, E. Kaplan, S.
Edge, L. Dressler, E. Paskett, N. Berliner, Cancer and Leukemia Group.
American Society of Clinical Oncologists. (abstract # 508), May 2005. (Annual
conference proceedings abstract)
Cardiovascular
risk associated with celecoxib in a clinical trial for colorectal adenoma
prevention
SD Solomon, McMurray JJ, Pfeffer MA, Wittes J, Fowler R,
Finn P, Anderson WF, Zauber A, Hawk E, Bertagnolli M; Adenoma Prevention
with Celecoxib (APC) Study Investigators. New
England Journal of Medicine.
Volume 17, Number 11: p. 1071-80, March 2005.
Results
of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after
completion of 5 years' adjuvant treatment for breast cancer
Anthony
Howell, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, Hoctin-Boes G,
Houghton J, Locker GY, Tobias JS; ATAC Trialists' Group. Lancet. Volume
365, Number 9453: p. 60-62, January 2005.
Breast
cancer and nonsteroidal anti-inflammatory drugs: Prospective results from
the women’s health initiative
Randall E. Harris, Rowan T. Chlebowski,
Rebecca D. Jackson, David J. Frid, Joao L. Ascenseo, Garnet Anderson, Aimee
Loar, Rebecca J. Rodabough, Emily White and Anne McTiernan. Cancer
Research.
Volume: 63, Issue 18: p. 6096-6101, September 15, 2003.
A
gonadotropin-releasing hormone agonist (Gnrha)-based chemoprevention regimen
that reduces mammographic density in Brca carriers while maintaining good
quality of life (Qol), bone density, and reproductive options
J. Weitzel,
S. Buys, M. C. Pike, A. Daniels, G. Ursin, J. R. Daniels, D. J. MacDonald,
K. R. Blazer, D. V. Spicer. American Society
of Clinical Oncologists. Volume
22: p. 94, (abstract # 374), June 2003. (Annual conference proceedings
abstract)
Effects
of Tamoxifen on benign breast disease in women at high risk for breast
cancer
Elizabeth Tan-Chiu, Jiping Wang, Joseph P. Costantino, Soonmyung
Paik, Cheryl Butch, D. Lawrence Wickerham, Bernard Fisher, Norman Wolmark. Journal
of the National Cancer Institute. Volume 95, Number 4: p. 302-307,
February 2003. (Full text)
Oral
contraceptives and the risk of breast cancer in BRCA1 and BRCA2 mutation
carriers
Steven A. Narod, Marie-Pierre Dubé, Jan Klijn, Jan
Lubinski, Henry T. Lynch, Parviz Ghadirian, Diane Provencher, Ketil Heimdal,
Pal Moller, Mark Robson, Kenneth Offit, Claudine Isaacs, Barbara Weber,
Eitan Friedman, Ruth Gershoni-Baruch, Gad Rennert, Barbara Pasini, Theresa
Wagner, Mary Daly, Judy E. Garber, Susan L. Neuhausen, Peter Ainsworth,
Hakan Olsson, Gareth Evans, Michael Osborne, Fergus Couch, William D. Foulkes,
Ellen Warner, Charmaine Kim-Sing, Olufunmilayo Olopade, Nadine Tung, Howard
M. Saal, Jeffrey Weitzel, Sofia Merajver, Marion Gauthier-Villars, Helena
Jernstrom, Ping Sun, Jean-Sebastien Brunet. Journal
of the National Cancer Institute. Volume 94, Number 23: p. 1773-1779, December 2002.
Tamoxifen
and breast cancer incidence among women with inherited mutations in BRCA1
and BRCA2
Mary-Claire King, PhD; Sam Wieand, PhD; Kathryn Hale, BS;
Ming Lee, PhD; Tom Walsh, PhD; Kelly Owens, PhD; Jonathan Tait, MD, PhD;
Leslie Ford, MD; Barbara K. Dunn, MD, PhD; Joseph Costantino, DrPH; Lawrence
Wickerham, MD; Norman Wolmark, MD; Bernard Fisher, MD. Journal
of the American Medical Association. Volume 286: p. 2251-2256, November 2001.
Tamoxifen and risk of contralateral breast cancer in BRCA1 And BRCA2 mutation carriers: A case-control study Narod SA, Brunet JS, Ghadirian P, Robson M, Heimdal K, Neuhausen SL, Stoppa-Lyonnet D, Lerman C, Pasini B, de los Rios P, Weber B, Lynch H, Hereditary Breast Cancer Clinical Study Group. Lancet. Volume 356, Issue 9245: p. 1876-81, December 2000.
Tamoxifen
for prevention of breast cancer: Report of the National Surgical Adjuvant
Breast and Bowel Project P-1 Study
Bernard Fisher, Joseph P. Costantino,
D. Lawrence Wickerham, Carol K. Redmond, Maureen Kavanah, Walter M. Cronin,
Victor Vogel, André Robidoux, Nikolay Dimitrov, James Atkins, Mary
Daly, Samuel Wieand, Elizabeth Tan-Chiu, Leslie Ford, Norman Wolmark, and
other National Surgical Adjuvant Breast and Bowel Project Investigators.
Journal of the National Cancer Institute. Volume 90, Number 18: p. 1371-1388,
September 1998.