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Breast cancer chemoprevention: Medicines that reduce breast cancer risk

By Mayo Clinic staff

Original Article:  http://www.mayoclinic.com/health/breast-cancer/WO00092

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Breast cancer chemoprevention: Medicines that reduce breast cancer risk

Preventive medications (chemoprevention) reduce breast cancer risk for women at high risk of developing the disease. Find out how these medications work plus associated side effects and health risks.

By Mayo Clinic staff

If you're at high risk of breast cancer, you may be able to improve your odds of staying cancer-free by taking certain medicines, an approach known as chemoprevention or chemoprophylaxis.

Medication options for breast cancer chemoprevention include tamoxifen or raloxifene (Evista). These medications currently used for breast cancer chemoprevention — as well as new medications that might be future chemoprevention options — are the subject of much ongoing research.

Here's a look at what's known about each of these medications, including how they may work to prevent breast cancer and the possible side effects and health risks.

Tamoxifen

How it works
Tamoxifen blocks the effects of estrogen — a reproductive hormone that influences the growth and development of many breast tumors. Tamoxifen belongs to a class of drugs known as selective estrogen receptor modulators (SERMs), and it reduces the effects of estrogen in most areas of the body, including the breast. In the uterus, tamoxifen acts like an estrogen and encourages the growth of the lining of the uterus. Tamoxifen is usually prescribed as a pill you take once a day by mouth. For breast cancer risk reduction, tamoxifen is typically taken for a total of five years.

Who it's for
Tamoxifen is used to reduce the risk of invasive breast cancer in high-risk women age 35 and older, whether or not they've gone through menopause. Generally speaking, you and your doctor might consider whether chemoprevention with tamoxifen is right for you if:

  • Your Gail model risk score is greater than 1.66 percent. The Gail model is a tool doctors use to predict future risk of developing breast cancer, based on factors such as your age, reproductive history and family history.
  • You're at high risk of developing breast cancer — for instance, you've had a breast biopsy that found precancerous conditions such as atypical ductal hyperplasia, atypical lobular hyperplasia or lobular carcinoma in situ (LCIS).
  • You have a strong family history of breast cancer.
  • You don't have a history of blood clots.
  • You've had a hysterectomy.

Common side effects
Common side effects of tamoxifen include:

  • Hot flashes
  • Vaginal discharge
  • Vaginal dryness
  • Bladder or urinary problems

Risks
Rarely, taking tamoxifen may cause:

  • Blood clots
  • Endometrial cancer or uterine cancer
  • Cataracts
  • Stroke

Taking tamoxifen doesn't guarantee that you'll remain cancer-free. Unless you're at high risk of developing breast cancer, the potential risks of tamoxifen may outweigh the benefits for you.

Raloxifene

How it works
Raloxifene is another drug in the class known as SERMs. It's also prescribed in pill form, to be taken by mouth once a day for five years. Like tamoxifen, raloxifene works by blocking estrogen's effects in the breast and other tissues. Unlike tamoxifen, raloxifene doesn't exert estrogen-like effects on the uterus.

Who it's for
Raloxifene is used to reduce the risk of invasive breast cancer in high-risk women who are past menopause (postmenopausal). You're considered at high risk if you score greater than 1.66 percent on the Gail model. Raloxifene is also used for prevention and treatment of the bone-thinning disease osteoporosis in postmenopausal women.

Common side effects
Common side effects of raloxifene include:

  • Hot flashes
  • Vaginal dryness or irritation
  • Joint and muscle pain
  • Weight gain

Risks
Health risks associated with raloxifene are similar to those associated with tamoxifen. Both drugs carry an increased risk of blood clots, though the risk may be lower with raloxifene. However, raloxifene may be associated with fewer cases of endometrial and uterine cancers than is tamoxifen. Raloxifene may also be linked to fewer strokes than tamoxifen in women at average risk of heart disease. But if you have heart disease or you have multiple risk factors for heart disease, such as high cholesterol, high blood pressure, obesity and smoking, raloxifene may actually increase your risk of strokes.

Aromatase inhibitors

Aromatase inhibitors are commonly used to treat breast cancer that's hormone-receptor positive in postmenopausal women. These drugs aren't widely used for breast cancer chemoprevention, but they may be an option for some women. Aromatase inhibitors are the subject of much ongoing research.

How they work
Aromatase inhibitors are a class of medicines that reduce the amount of estrogen in your body, depriving breast cancer cells of the fuel they need to grow and thrive. Three aromatase inhibitors are currently used in the treatment of postmenopausal women with breast cancer: anastrozole (Arimidex), exemestane (Aromasin) and letrozole (Femara). These medications are used after breast cancer surgery to prevent breast cancer from returning (recurring) in postmenopausal women with estrogen- or progesterone-responsive tumors.

Who it's for
Aromatase inhibitors have been studied and shown to be effective in postmenopausal women to treat breast cancer and to prevent breast cancer recurrence. Aromatase inhibitors are not intended for preventing breast cancer recurrence in women who still have menstrual cycles.

Aromatase inhibitors are being studied to see if they may reduce the risk of breast cancer in high-risk women, such as those with a family history of breast cancer or a history of precancerous breast lesions. Studies have shown promise in these high-risk women. Based on these results, some women and their doctors may choose to use aromatase inhibitors to reduce the risk of breast cancer, though these drugs aren't approved for this use.

Common side effects
Common side effects of aromatase inhibitors include:

  • Hot flashes
  • Vaginal dryness
  • Joint and muscle pain
  • Headache
  • Fatigue

Risks
Aromatase inhibitors raise the risk of:

  • Broken bones (fractures)
  • Osteoporosis

Because aromatase inhibitors are a newer class of medications, not much is yet known about long-term health risks, such as heart disease. As more results from research studies become available, doctors will have a better idea of the long-term health implications for these drugs and their effectiveness in breast cancer chemoprevention.

Other areas of research

Aspirin and other pain relievers
Several studies have looked into whether common over-the-counter painkillers, such as aspirin, ibuprofen (Advil, Motrin, others) and naproxen sodium (Aleve), may reduce the risk of breast cancer.

Study results are mixed. Some research has found that women who had breast cancer and who regularly take these pain relievers have a slightly decreased risk of breast cancer recurrence. But other studies haven't shown a significant association between breast cancer risk and these pain relievers.

It remains unknown whether aspirin and other pain relievers help protect against breast cancer, and if so, exactly how they do so. Because some pain relievers, such as celecoxib (Celebrex) and naproxen sodium (Aleve), may increase the risk of heart attack and stroke, talk with your doctor to weigh the potential benefits versus the risks of taking these medications in your situation.

Vitamin D
Studies are examining whether vitamin D may have some role in preventing breast cancer and breast cancer recurrence. Preliminary research has shown that vitamin D may have anticancer properties. Early studies in breast cancer survivors linked lower than normal vitamin D levels to an increased risk of cancer recurrence. More studies are needed to understand the action and potential benefits of vitamin D.

References
  1. Breast cancer risk reduction. Fort Washington, Pa.: National Comprehensive Cancer Network. http://www.nccn.org/professionals/physician_gls/PDF/breast_risk.pdf. Accessed Dec. 28, 2010.
  2. American Society of Clinical Oncology clinical practice guideline update on the use of pharmacologic interventions including tamoxifen, raloxifene and aromatase inhibition for breast cancer risk reduction. American Society of Clinical Oncology. http://jco.ascopubs.org/cgi/content/full/27/19/3235. Accessed Dec. 28, 2010.
  3. Wickerham DL. Breast cancer chemoprevention: Progress and controversy. Surgical Oncology Clinics of North America. 2010;19:463.
  4. Medicines to reduce breast cancer risk. American Cancer Society. http://www.cancer.org/acs/groups/cid/documents/webcontent/002585-pdf.pdf. Accessed Dec. 29, 2010.
  5. Harris RE, et al. Breast cancer and nonsteroidal anti-inflammatory drugs: Prospective results from the Women's Health Initiative. Cancer Research. 2003;63:6096.
  6. Terry MB, et al. Association of frequency and duration of aspirin use and hormone receptor status with breast cancer risk. Journal of the American Medical Association. 2004;291:2433.
  7. Agrawal A, et al. NSAIDs and breast cancer: A possible prevention and treatment strategy. International Journal of Clinical Practice. 2008;62:444.
  8. Pruthi S (expert opinion). Mayo Clinic, Rochester, Minn. Oct. 18, 2011.
  9. Vogel VG, et al. Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: The NSABP study of tamoxifen and raloxifene (STAR) P-2 trial. JAMA. 2006;295:2727.
  10. Giovannucci E, et al. Role of vitamin and mineral supplementation and aspirin use in cancer survivors. Journal of Clinical Oncology. 2010;28:4081.
  11. Goss PE, et al. Exemestane for breast-cancer prevention in postmenopausal women. The New England Journal of Medicine. 2011;25:2381.
WO00092 Oct. 21, 2011

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