Breast Cancer: Preventive Medications -- Women Not at Increased Risk


General

Grade: D The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. Discourage the use of this service.

Specific Recommendations

The USPSTF recommends against the routine use of medications, such as tamoxifen or raloxifene, for risk reduction of primary breast cancer in women who are not at increased risk for breast cancer. 

Frequency of Service

No information available.

Risk Factor Information

Assessment of Breast Cancer Risk If a family history of breast cancer or a personal history of breast biopsy is found during the usual patient assessment, clinicians may consider further evaluation using a breast cancer risk assessment tool. Risk assessment tools specifically for family history of breast cancer are available elsewhere (www.uspreventiveservicestaskforce.org). The National Cancer Institute has developed a Breast Cancer Risk Assessment Tool (available at www.cancer.gov/bcrisktool) that is based on the Gail model and estimates the 5-year incidence of invasive breast cancer in women on the basis of characteristics entered into a risk calculator. This tool helps identify women who may be at increased risk for the disease. Other risk assessment models have been developed by the Breast Cancer Surveillance Consortium (BCSC), Rosner and Colditz, Chlebowski, Tyrer and Cuzick, and others. Examples of risk factors elicited by risk assessment tools include patient age, race or ethnicity, age at menarche, age at first live childbirth, personal history of DCIS or LCIS, number of first-degree relatives with breast cancer, personal history of breast biopsy, body mass index, menopause status or age, breast density, estrogen and progestin use, smoking, alcohol use, physical activity, and diet. These models are not recommended for use in women with a personal history of breast cancer, a history of radiation treatment to the chest, or a possible family history of mutations in the BRCA1 or BRCA2 genes. Only a small fraction of women are at increased risk for breast cancer. Most who are at increased risk will not develop the disease, and most cases will arise in women who are not identified as being at increased risk. Risk assessment should be repeated when there is a significant change in breast cancer risk factors. There is no single cutoff for defining increased risk. Most clinical trials defined increased risk as a 5-year risk for invasive breast cancer of 1.66% or greater, as determined by the BCPT (Breast Cancer Prevention Trial). At this cutoff, however, many women would not have a net benefit from risk-reducing medications. Freedman and colleagues developed risk tables that incorporate the BCPT estimate of a woman's breast cancer risk as well as her age, race or ethnicity, and presence of uterus. On the basis of the Freedman risk–benefit tables for women aged 50 years or older (Figures 2 to 5), the USPSTF concludes that many women with an estimated 5-year breast cancer risk of 3% or greater are likely to have more benefit than harm from using tamoxifen or raloxifene, although the balance depends on age, race or ethnicity, the medication used, and whether the patient has a uterus. Assessment of Risk for Adverse Effects In general, women taking medications for breast cancer risk reduction are less likely to experience a VTE if they are younger and have no other predisposition to thromboembolic events. Women with a personal or family history of venous thromboembolism are at higher risk for these adverse effects. Women without a uterus are not at risk for tamoxifen-related endometrial cancer. Women with a uterus should have a baseline gynecologic examination prior to starting tamoxifen, with regular followup after the end of treatment.


Clinical

Patient Population Under Consideration

This recommendation applies to asymptomatic women aged 35 years or older without a prior diagnosis of breast cancer, ductal carcinoma in situ (DCIS), or lobular carcinoma in situ (LCIS). Neither tamoxifen nor raloxifene should be used in women who have a history of thromboembolic events (deep venous thrombosis, pulmonary embolus, stroke, or transient ischemic attack). The USPSTF has issued separate recommendations for women with BRCA gene mutations (available at www.uspreventiveservicestaskforce.org).

Assessment of Breast Cancer Risk

If a family history of breast cancer or a personal history of breast biopsy is found during the usual patient assessment, clinicians may consider further evaluation using a breast cancer risk assessment tool. Risk assessment tools specifically for family history of breast cancer are available elsewhere (www.uspreventiveservicestaskforce.org). The National Cancer Institute has developed a Breast Cancer Risk Assessment Tool (available at www.cancer.gov/bcrisktool) that is based on the Gail model and estimates the 5-year incidence of invasive breast cancer in women on the basis of characteristics entered into a risk calculator. This tool helps identify women who may be at increased risk for the disease. Other risk assessment models have been developed by the Breast Cancer Surveillance Consortium (BCSC), Rosner and Colditz, Chlebowski, Tyrer and Cuzick, and others. Examples of risk factors elicited by risk assessment tools include patient age, race or ethnicity, age at menarche, age at first live childbirth, personal history of DCIS or LCIS, number of first-degree relatives with breast cancer, personal history of breast biopsy, body mass index, menopause status or age, breast density, estrogen and progestin use, smoking, alcohol use, physical activity, and diet. These models are not recommended for use in women with a personal history of breast cancer, a history of radiation treatment to the chest, or a possible family history of mutations in the BRCA1 or BRCA2 genes. Only a small fraction of women are at increased risk for breast cancer. Most who are at increased risk will not develop the disease, and most cases will arise in women who are not identified as being at increased risk. Risk assessment should be repeated when there is a significant change in breast cancer risk factors. There is no single cutoff for defining increased risk. Most clinical trials defined increased risk as a 5-year risk for invasive breast cancer of 1.66% or greater, as determined by the BCPT (Breast Cancer Prevention Trial). At this cutoff, however, many women would not have a net benefit from risk-reducing medications. Freedman and colleagues developed risk tables that incorporate the BCPT estimate of a woman's breast cancer risk as well as her age, race or ethnicity, and presence of uterus. On the basis of the Freedman risk–benefit tables for women aged 50 years or older (Figures 2 to 5), the USPSTF concludes that many women with an estimated 5-year breast cancer risk of 3% or greater are likely to have more benefit than harm from using tamoxifen or raloxifene, although the balance depends on age, race or ethnicity, the medication used, and whether the patient has a uterus.

Assessment of Risk for Adverse Effects

In general, women taking medications for breast cancer risk reduction are less likely to experience a VTE if they are younger and have no other predisposition to thromboembolic events. Women with a personal or family history of venous thromboembolism are at higher risk for these adverse effects.Women without a uterus are not at risk for tamoxifen-related endometrial cancer. Women with a uterus should have a baseline gynecologic examination prior to starting tamoxifen, with regular followup after the end of treatment.

Medications for Breast Cancer Risk Reduction

Selective estrogen receptor modulators (tamoxifen and raloxifene) have been shown to reduce the incidence of invasive breast cancer in several randomized, controlled trials. Tamoxifen has been approved for this use in women aged 35 years or older, and raloxifene has been approved for this use in postmenopausal women.The usual daily doses for tamoxifen and raloxifene are 20 mg and 60 mg, respectively, for 5 years. Aromatase inhibitors (exemestane) have not been approved by the FDA for this indication and are therefore beyond the scope of this recommendation.Tamoxifen is not recommended for use in combination with hormone therapy or hormonal contraception or in women who are pregnant, those who may become pregnant, or breastfeeding mothers.

Other Approaches to Prevention

The USPSTF recommendation on risk assessment, genetic counseling, and genetic testing for BRCA-related cancer can be found at www.uspreventiveservicestaskforce.org. Clinical trials of tamoxifen and raloxifene have not been conducted specifically in women who are BRCA mutation carriers.

Other Resources

The National Cancer Institute provides information about potential ways to prevent cancer, including lifestyle and diet changes (available at www.cancer.gov/cancertopics/pdq/prevention/breast/Patient and www.cdc.gov/cancer/breast/basic_info/prevention.htm). The USPSTF does not endorse any particular risk prediction model. However, the BCPT model (www.cancer.gov/bcrisktool) and the BCSC model (https://tools.bcsc-scc.org/BC5yearRisk) can be used by clinicians and patients as part of the process of shared, informed decision making. Both models have been calibrated in U.S. populations.

Other Considerations

Implementation

In order to identify patients for whom the potential benefits of risk-reducing medications could outweigh potential risks, clinicians should first identify patients who may be at increased risk for breast cancer (see Assessment of Breast Cancer Risk). Clinicians may use this opportunity to educate all women about their risk for developing breast cancer; studies have shown that women tend to overestimate their individual breast cancer risk. For women whose 5-year projected risk for breast cancer is 3% or greater, clinicians should identify those for whom the potential benefits of risk-reducing medications may outweigh the potential risks. In doing so, clinicians should consider the woman's age, comorbid conditions, presence of uterus, and risks for thromboembolic or medication-related adverse events. Clinicians may refer to risk–benefit tables to complement clinical assessment (Figures 2-5).Clinicians should clearly discuss the potential benefits and risks of risk-reducing medications with women for whom the former may outweigh the latter. Clinicians should then strive to ensure that patients make a fully informed decision that incorporates their personal values and preferences, including their concerns about breast cancer and specific medication-related adverse events.

Research Needs and Gaps

Research to improve the ability to assess and accurately predict a woman's chance of developing breast cancer over a defined period is needed. The ideal candidates for risk-reducing medications are women who have not only a high probability of developing breast cancer over a defined period but also a low probability of thromboembolic and other medication-related adverse events. Models that can more precisely predict both of these events should be developed. Clinical trials that provide more information about the safety and effectiveness of other medications for breast cancer risk reduction, such as aromatase inhibitors and tibolone, are needed. The aromatase inhibitor exemestane reduced the incidence of invasive breast cancer in postmenopausal women who were at moderately increased risk for the disease. There were no significant differences in the incidence of osteoporosis, cardiovascular events, other types of cancer, or death. However, these findings were reported from a randomized, clinical trial with a median follow-up of 3 years and will require long-term assessment. IBIS-II (International Breast Cancer Intervention Study II), an ongoing British study, is comparing the aromatase inhibitor anastrozole with placebo in women who are at increased risk for breast cancer. Additional research could help clarify the optimum treatment duration, timing, and dose. Future studies should examine the benefits and harms of risk-reducing medications in racially diverse patient populations.

Rationale

No information available.


Others

In 2013, the American Society of Clinical Oncology recommended that tamoxifen should be discussed as an option to reduce risk for ER-positive breast cancer in women aged 35 years or older who are at increased risk for breast cancer. It also recommended that raloxifene and exemestane should be discussed as options for breast cancer risk reduction in postmenopausal women. In 2013, the National Institute for Health and Care Excellence recommended that clinicians offer tamoxifen or raloxifene for 5 years to postmenopausal women with a uterus who are at high risk for breast cancer unless they have a history of or may be at increased risk for thromboembolic disease or endometrial cancer. The guideline also included recommendations for different age and risk groups. In 2011, the American Cancer Society recommended that women who are considering medications for breast cancer risk reduction should discuss their personal health situations with their physicians. In 2001, the Canadian Task Force on Preventive Health Care recommended that women who are at high risk for breast cancer should receive counseling about the risks and benefits of tamoxifen for cancer prevention; it found fair evidence to recommend against the use of tamoxifen in women who are at low or normal risk for breast cancer.


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