Medications for reducing breast cancer risk Hui Gao, M.D., Ph.D, Harbin Medical University When healthy people take medications to reduce their risk of developing breast cancer, it is called chemoprevention. Now there are several medications available for chemoprevention; however, they all have some side effects. This article will give a brief review of these medications. What medications can reduce the risk of breast cancer?
Several medications can be used as chemoprevention to reduce the risk of breast cancer in women who are at increased risk of developing the disease. These medications belong to two groups: •Selective estrogen receptor modulators (SERM): tamoxifen and raloxifene. •Aromatase inhibitors (AIs): exemestane and anastrozole. How do the medications work?
Some breast cancers have hormone receptors, on the cancer cell membranes, which allow these hormones to stimulate cancer cell growth and proliferation. Medications which can block these receptors or reduce the production of the hormone may function protectively on breast tissue by inhibiting cell growth. The hormone receptors on the breast cancers are either estrogen receptor called ER-positive, or progestin receptor called PR-positive. The preventive medications all function by interfering with the effects of estrogen. SERMs work by blocking the estrogen receptor on the breast tissue, so that estrogen can not bind to the receptor. Aromatase inhibitors work by inhibiting a key enzyme (aromatase) which is responsible for producing estrogen. Thus, the level of estrogen was reduced in the body, and the fuel for breast cancer is taken away. How effective are these medications?
Tamoxifen: Studies have shown that tamoxifen can prevent hormone-responsive breast cancers from developing in women at high risk for the disease. In general, tamoxifen, daily use for five years, reduces the risk of developing invasive breast cancer by about 50%, and reduces the risks of non-invasive breast cancer by about 33%. However tamoxifen has no effect on estrogen receptor negative breast cancer. Raloxifene: Raloxifene is currently used for osteoporosis in postmenopausal women. Several studies suggest that in postmenopausal women with high-risk of breast cancer, raloxifene can reduce the risk of developing ER-positive breast cancer. Compared with tamoxifen, raloxifene was slightly less effective at preventing breast cancers; however it also showed fewer serious side effects associated with tamoxifen. Raloxifene has been tested only in postmenopausal women; its benefit in premenopausal women is still not clear. Additionally, like tamoxifen, it has no effect on estrogen receptor negative breast cancer. Aromatase inhibitors are newer drugs that are used to treat advanced breast cancer or help keep breast cancer recurring. One study of the AI exemestane for preventing breast cancer in high-risk women showed that it can reduce the risk of breast cancer by about 65%. Aromatase inhibitors are also only effective in preventing estrogen What are the risks in taking these medications?
Tamoxifen is a complex drug. It belongs to a family called selective estrogen response modifier (SERM). It acts like an anti-estrogen in some tissues such as breasts, but acts like estrogen in other tissues such as uterus. The anti- estrogen effects cause the most common, menopause-like side effects, such as hot flashes and night sweats. Its estrogen-like effects can cause serious problems such as cancer of the uterus, especially after menopause. It is important for women who are taking tamoxifen to talk with their doctors about the risk of uterine cancer. Women taking tamoxifen are at higher risk of blood clots such as a deep venous thrombosis (DVT), or stroke. Those with a history of blood clots or those at increased risk of developing a blood clot should talk to their doctor about the increased risk of blood clots with tamoxifen. Raloxifene and tamoxifen have similar side profiles. The risk of developing a serious side effect, such as uterine cancer or blood clots is generally lower with raloxifene. Some short-term side effects of aromatase inhibitors are similar to those caused by tamoxifen and raloxifene, including hot flashes and vaginal dryness. Muscle, joint pain and headaches occur more often with aromatase inhibitors. However, they do have fewer problems with serious side effects such as blood clots or uterine cancer. Aromatase inhibitors can accelerate osteoporosis. Aromatase inhibitors have been available for a shorter period of time, therefore less is known about their long-term effects. Currently, aromatase inhibitors are not FDA approved to be used to reduce breast cancer risk. They are currently used either to treat advanced breast cancer or given after surgery to help prevent breast cancer from coming back. They may soon be approved for use to prevent breast cancer. Who should consider taking medications to reduce their breast cancer risk?
Your doctor may use the Breast Cancer Risk Assessment Tool (Gail model) to calculate your risk of developing breast cancer, prior to initiating therapy to lower your risk. However, having breast cancer risk factors does not necessarily mean that cancer is inevitable. Many women with risk factors may never develop breast cancer, therefore it is important that you discuss the risks and benefits of chemoprevention. In general, you might think about taking medications to lower your risk if one or more of the following is true: • Age greater than 60 • Breast biopsy showed high-risk conditions, such as lobular carcinoma in situ (LCIS) or atypical hyperplasia. • Inherited mutation in breast cancer genes: BRCA1 and BRCA2. • Two or more family members with breast cancer, especially before age of 50 • Calculated five-year risk for breast cancer is 1.66% or higher for women age 35 to 59 years Who should not take tamoxifen and raloxifene?
Tamoxifen and raloxifene is not recommended for every woman. Women should talk with their to make the best Women with the following problems should be cautious: •History of blood clots •Currently on anticoagulant or blood-thinning medications (such as warfarin, Coumadin or heparin) •History of high blood pressure, obesity, diabetes; or smokers •Younger than 35 years old •Younger than 60 years old with no increased risk for breast cancer •Have been diagnosed with any type of uterine cancer or atypical hyperplasia •Are taking hormone replacement therapy or an aromatase inhibitor •Pregnant or plan to, or breastfeeding (tamoxifen may cross placenta and cause birth defects) •Taking oral contraceptives or other hormonal method of birth control What to monitor if taking tamoxifen and raloxifene
Women who use tamoxifen or raloxifene should be closely monitored: •Annual gynecologic examination, including a breast examination, mammogram and Pap smear. The following should be immediately reported to your doctor: •Abnormal gynecologic symptoms, such as irregular menstrual cycle, abnormal vaginal bleeding/spotting, or pelvic pain. •Signs or symptoms of blood clots, such as calf tenderness or swelling, and severe shortness of breath for no reason. In conclusion:
Chemoprevention provides a way to decrease the risk of developing breast cancer in women who have known high- risk for the disease. All chemoprevention has possible side effects, and these drugs may not be right for everyone who is at high-risk for breast cancer. If you are thinking about taking one of them, be sure you talk with your doctor about your breast cancer risk, potential benefits and side effects of these medicines. Also keep in mind that your risk of developing breast cancer can change over time. 1. U.S. Preventive Services Task Force. Chemoprevention of breast cancer: recommendations and rationale. Ann 2. Guidelines for cancer prevention from the National Comprehensive Cancer Network (NCCN) available online at www.nccn.org (Accessed on June 10, 2011). 3. Visvanathan K, Chlebowski RT, Hurley P, et al. 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. J Clin Oncol 2009; 27:3235. 4. Breast cancer risk asssessment tool available online at www.cancer.gov/bcrisktool/ (Accessed July 7, 2009). 5. American Society of Clinical Oncology (www.cancer.net/portal/site/patient) 6. National Comprehensive Cancer Network (www.nccn.com/default.asp) 7. National Cancer Institute (www.nci.nih.gov) 8. American Cancer Society (www.cancer.org)

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