Primary prevention
Chemoprevention is recommended for women at high risk of developing breast cancer.[37][38][39][40]
Tamoxifen is indicated for chemoprevention in pre- and postmenopausal women. Raloxifene and aromatase inhibitors (e.g., anastrozole or exemestane) are recommended for chemoprevention in postmenopausal women only.[37][38][39][40] Some high-risk patients may choose to undergo prophylactic bilateral total mastectomy for breast cancer risk reduction. Risk-reducing mastectomy is usually considered for women if they have a pathogenic or likely pathogenic genetic mutation conferring a high risk for breast cancer, a compelling family history, or prior chest wall radiation at age <30 years.[37][41]
Assessing patient risk
Breast cancer risk reduction measures may be considered following evaluation using the National Cancer Institute’s Breast Cancer Risk Assessment Tool (the Gail model), which determines risk based on current age, age at first menstrual period, number of breast biopsies and whether atypical hyperplasia was found, age at first live birth, and number of first-degree relatives with breast cancer.[42] National Cancer Institute: breast cancer risk assessment tool Opens in new window
The Gail model applies to women ages 35-85 years. It is not accurate in the setting of prior DCIS, lobular carcinoma in situ (LCIS), invasive breast cancer, or BRCA1 or BRCA2 mutation. Risk may be underestimated in black women with previous biopsies and non-US born Hispanic women.
Other risk assessment tools are available (e.g., the BOADICEA model can be used for women with a known BRCA1 or BRCA2 mutation; the IBIS model can be used for women with prior LCIS).[43][44]
Lifestyle measures
Healthy lifestyle including physical activity and a balanced diet may prevent breast cancer.[45] In the Women's Health Initiative randomized controlled study, those who consumed a low-fat diet had a reduced risk of death after a diagnosis of breast cancer compared with those who consumed a usual diet.[46] The positive association between alcohol consumption and breast cancer risk is well established.[47] A study among patients attending breast clinics or screening found low levels of alcohol health literacy in this group. These appointments could provide an opportunity for discussing alcohol use as a modifiable risk factor.[48]
The table that follows summarizes recommendations on the primary prevention of breast cancer in women from National Comprehensive Cancer Network (NCCN) guidance on breast cancer risk reduction.[37] This guideline does not specifically outline criteria for what constitutes a compelling family history of breast cancer but notes that a thorough evaluation is recommended. Magnitude of risk increases with the number of affected relatives in the family, the closeness of the relationship, and the age at which the affected relative was diagnosed. The younger the age at diagnosis of the first- or second-degree relative, the more likely it is that a genetic component is present. It is necessary to consider both the maternal and paternal sides of the family independently for familial patterns of cancer. Risk models that use family history in their risk assessment models are available (e.g., Tyrer-Cuzick, BRCAPro, and CanRisk/BOADICEA). For further information, see NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast and Ovarian.[49]
Prevention of invasive breast cancer in those with breast cancer in situ (e.g., lobular carcinoma in situ) is not covered in this table. Recommendations on screening and surveillance for breast cancer are complex, and they are individualized according to the patient’s personal risk assessment; they are not covered within the table below (see Primary invasive breast cancer [Screening]).
Note that an individual patient may fall into more than one group and so interventions might be additive; please review all population and subpopulation groups to assess all that apply.
Woman with known pathogenic/likely pathogenic gene mutation conferring elevated risk for breast cancer, or with compelling family history of breast cancer
Genetic predispositions conferring a high risk for breast cancer include hereditary breast and ovarian cancer (mutations in BRCA1 and BRCA2), Li-Fraumeni syndrome (TP53), Peutz-Jeghers syndrome (STK11), Cowden syndrome (PTEN), and hereditary diffuse gastric cancer (CDH1).
All
Intervention
Counseling on healthy lifestyle; consider risk-reducing surgery
Lifestyle modification counselling:
Counseling on healthy lifestyle and risk reduction for breast cancer incorporates the following points:
Hormonal contraception; advise that combined estrogen/progestin agents ≥3-5 years' duration of use are associated with an increased risk of breast cancer.
Alcohol; advise that any alcohol intake increases the risk for breast cancer and is best avoided.
Exercise; advise people to be active daily and to avoid being sedentary.
Weight control; advise that in postmenopausal individuals a body mass index (BMI) >25 can incrementally increase breast cancer risk.
Consideration of risk-reducing surgery:
Decisions are based on shared decision making.
Risk-reducing mastectomy may be considered in select circumstances where the risk of breast cancer is very high, for example in individuals with a pathogenic variant in a high-penetrance breast cancer susceptibility gene or with a strong family history of breast cancer. There is no established benefit of risk-reducing mastectomy in individuals with pathogenic/likely pathogenic variants in moderate- or low-penetrance breast cancer susceptibility genes in the absence of a compelling family history.
Risk estimation is a complex and individualized process; there is no established risk cutoff for decision making regarding risk-reducing mastectomy. Individualized management is important.
Bilateral salpingo-oophorectomy for the purposes of breast (and ovarian) cancer risk reduction may be considered in individuals with a BRCA1 or BRCA2 mutation.
It is recommended that people considering either bilateral mastectomy or bilateral salpingo-oophorectom undergo multidisciplinary evaluation prior to surgery so as to become well informed about all treatment alternatives, the risks and benefits of risk reduction surgery, and various reconstruction options available after bilateral mastectomy. Immediate breast reconstruction is an option for many women undergoing risk-reducing mastectomy.
Goal
Reduced risk of breast cancer; promotion of overall health
Lifestyle modifications:
Alcohol: it is recommended that alcohol is best avoided; there is no known safe limit of alcohol consumption.
Exercise: it is recommended that people take part in 150-300 minutes of moderate-intensity physical activity per week; exceeding the upper limit is optimal.
Weight control: maintenance of a healthy body weight and BMI is recommended.
Woman age ≤30 years, with history of therapeutic chest wall radiation
All
Intervention
Counseling on healthy lifestyle; consider risk-reducing surgery
Lifestyle modification counseling:
Counseling on healthy lifestyle and risk reduction for breast cancer incorporates the following points:
Hormonal contraception; advise that combined estrogen/progestin agents ≥3-5 years' duration of use are associated with an increased risk of breast cancer.
Alcohol; advise that any alcohol intake increases the risk for breast cancer and is best avoided.
Exercise; advise people to be active daily and to avoid being sedentary.
Weight control; advise that in postmenopausal individuals, a BMI >25 can incrementally increase breast cancer risk.
Consideration of risk-reducing surgery:
Decisions are based on shared decision making.
Risk-reducing mastectomy may be considered in select circumstances where the risk of breast cancer is very high, including in those with a history of therapeutic chest wall radiation encompassing the chest/breast area before age 30 years (e.g., to treat Hodgkin’s disease).
Risk estimation is a complex and individualized process; there is no established risk cutoff for decision making regarding risk-reducing mastectomy. Individualized management is important.
Bilateral salpingo-oophorectomy for the purposes of breast (and ovarian) cancer risk reduction may be considered in individuals with a BRCA1 or BRCA2 mutation.
It is recommended that people considering either bilateral mastectomy or bilateral salpingo-oophorectomy undergo multidisciplinary evaluation prior to surgery so as to become well informed about all treatment alternatives, the risks and benefits of risk reduction surgery, and various reconstruction options available after bilateral mastectomy. Immediate breast reconstruction is an option for many women undergoing risk-reducing mastectomy.
Goal
Reduced risk of breast cancer; promotion of overall health
Lifestyle modifications:
Alcohol: it is recommended that alcohol is best avoided; there is no known safe limit of alcohol consumption.
Exercise: it is recommended that people take part in 150-300 minutes of moderate-intensity physical activity per week; exceeding the upper limit is optimal.
Weight control: maintenance of a healthy body weight and BMI is recommended.
Woman with elevated risk of breast cancer based on validated risk assessment model (e.g., ≥1.7% 5-year risk as defined by the Breast Cancer Risk Assessment Tool [BCRAT])
For most women age ≥35 years, the BCRAT (formerly termed the Gail model) is recommended for risk assessment for breast cancer. The NCCN panel has adopted the ≥1.7% 5-year actuarial breast cancer risk as defined by the modified BCRAT as a reasonable discrimination threshold to identify those eligible for risk-reducing therapy. Note that the BCRAT is not an appropriate breast cancer risk assessment tool for certain patient groups, including those with a genetic mutation conveying a high risk of breast cancer, e.g., BRCA1/2, TP53, or PTEN mutation; those with a strong family history of breast cancer; and those who received thoracic radiation to treat Hodgkin disease (e.g., mantle radiation). Risk models that use family history in their risk assessment models are available, and include Tyrer-Cuzick, BRCAPro, and CanRisk/BOADICEA.
All
Intervention
Counseling on healthy lifestyle; consider risk-reducing surgery
Counseling on healthy lifestyle and risk reduction for breast cancer incorporates the following points:
Hormonal contraception; advise that combined estrogen/progestin agents ≥3-5 years' duration of use are associated with an increased risk of breast cancer.
Alcohol; advise that any alcohol intake increases the risk for breast cancer and is best avoided.
Exercise; advise people to be active daily and to avoid being sedentary.
Weight control; advise that in postmenopausal individuals a BMI >25 can incrementally increase breast cancer risk.
Goal
Reduced risk of breast cancer; promotion of overall health
Lifestyle modifications:
Alcohol: it is recommended that alcohol is best avoided; there is no known safe limit of alcohol consumption.
Exercise: it is recommended that people take part in 150-300 minutes of moderate-intensity physical activity per week; exceeding the upper limit is optimal.
Weight control: maintenance of a healthy body weight and BMI is recommended.
Age ≥35 years; life expectancy of ≥10 years; with 5-year risk by the BCRAT ≥1.7% and <3%
Intervention
Consider risk-reducing agent
It is recommended that risk-reducing agents are considered and discussed when the 5-year risk by the BCRAT is ≥1.7%.
Decisions are based on shared decision making.
It is recommended that clinicians discuss the risks and benefits of risk reduction agents, including adverse effects and age-dependent risks, as part of this process.
Risk-reducing agents include:
Tamoxifen
Raloxifene
Anastrozole
Exemestane
Risk-reducing agents are suitable for individuals age ≥35 years only as the utility of these agents in those younger than 35 years is unknown.
Tamoxifen is the only risk-reducing agent indicated for premenopausal women. In postmenopausal women, any of tamoxifen, raloxifene, anastrozole, or exemestane may be used. Tamoxifen is a teratogen and is contraindicated during pregnancy and in individuals planning a pregnancy.
Tamoxifen is a superior choice of risk reduction agent for most postmenopausal women. However, consideration of adverse effects may lead to the choice of raloxifene over tamoxifen for some patients, for example postmenopausal patients with a uterus and those at risk for developing cataracts.
Women with an intact uterus require a gynecological evaluation before starting tamoxifen to ensure there is no abnormal uterine bleeding that requires further investigation.
Postmenopausal women require an assessment of bone density (dual energy x-ray absorptiometry [DXA]) before treatment; raloxifene or tamoxifen is indicated in preference to an aromatase inhibitor (anastrozole or exemestane) if they have low bone mineral density, because reduced bone mineral density is a common adverse effect of aromatase inhibitor therapy.
Exemestane and anastrozole are not currently approved for breast cancer risk reduction.
Goal
Reduced risk of breast cancer; attainment of favorable risk:benefit ratio
The optimal duration of therapy is yet to be established:
For those taking tamoxifen, a period of 5 years appears to be appropriate for breast cancer risk reduction.
For those taking raloxifene, continuing therapy beyond 5 years may be an approach to maintain the risk reduction activity of the agent; seek specialist advice with respect to this decision
The optimal duration of therapy with an aromatase inhibitor is unknown.
It is recommended that follow-up after treatment with a risk reduction agent encompasses management of adverse symptoms or complications, including:
Endometrial cancer
Retinopathy and cataract formation
Loss of bone mineral density
Thromboembolic disease and stroke
Management of hot flashes
Age ≥35 years; life expectancy of ≥10 years; with 5-year risk by the BCRAT of at least 3% or a 10-year risk by the International Breast Cancer Intervention Study (IBIS)/Tyrer-Cuzick of at least 5%
Intervention
Recommend risk-reducing agent
Decisions are based on shared decision making.
It is recommended that clinicians discuss the risks and benefits of risk reduction agents, including adverse effects and age-dependent risks as part of this process.
Risk-reducing agents include:
Tamoxifen
Raloxifene
Anastrozole
Exemestane
Risk-reducing agents are suitable for individuals age ≥35 years only as the utility of these agents in those younger than 35 years is unknown.
Tamoxifen is the only risk-reducing agent indicated for premenopausal women. In postmenopausal women, any of tamoxifen, raloxifene, anastrozole, or exemestane may be used. Tamoxifen is a teratogen and is contraindicated during pregnancy and in individuals planning a pregnancy.
Tamoxifen is a superior choice of risk reduction agent for most postmenopausal women. However, consideration of adverse effects may lead to the choice of raloxifene over tamoxifen for some patients.
Women with an intact uterus require a gynecological evaluation before starting tamoxifen, to ensure there is no abnormal uterine bleeding that requires further investigation.
Postmenopausal women require an assessment of bone density (dual energy x-ray absorptiometry [DXA]) before treatment; raloxifene or tamoxifen is indicated in preference to an aromatase inhibitor (anastrozole or exemestane) if they have low bone mineral density, because reduced bone mineral density is a common adverse effect of aromatase inhibitor therapy.
Exemestane and anastrozole are not currently approved for breast cancer risk reduction.
Goal
Reduced risk of breast cancer; attainment of favorable risk:benefit ratio
The optimal duration of therapy is yet to be established:
For those taking tamoxifen, a period of 5 years appears to be appropriate for breast cancer risk reduction.
For those taking raloxifene, continuing therapy beyond 5 years may be an approach to maintain the risk reduction activity of the agent; seek specialist advice with respect to this decision.
The optimal duration of therapy with an aromatase inhibitor is unknown.
It is recommended that follow-up after treatment with a risk reduction agent encompasses management of adverse symptoms or complications, including:
Endometrial cancer
Retinopathy and cataract formation
Loss of bone mineral density
Thromboembolic disease and stroke
Management of hot flashes
Secondary prevention
Avoiding hormone replacement therapy could reduce recurrence, new breast cancer, or progression of ductal carcinoma in situ (DCIS) to invasive breast cancer.[12][148] History of DCIS is a risk factor for future cancer in the same breast. Hormone replacement therapy (HRT) is not advised for this population. If DCIS develops during HRT, alternatives should be sought to treat menopausal symptoms.
Selective estrogen receptor modulators such as tamoxifen can be used to prevent recurrence or new breast cancer.[128]
[ 
]
Tamoxifen can be taken for up to 5 years.
In women at increased breast cancer risk, raloxifene has been shown to decrease the risk of new invasive breast cancer, but the benefit in reducing DCIS risk is less.[12] Thus, raloxifene has been approved by the Food and Drug Administration in high-risk postmenopausal women and in women at risk for osteoporosis to prevent invasive breast cancer. Treatment with raloxifene for more than 4 years has been tested, and prolonged use does not appear to be harmful in the context of osteoporosis.[149]
Aromatase inhibitors have also been shown to decrease risk of recurrence after DCIS.
Women with lobular carcinoma in situ (LCIS) are considered high-risk (based on the Gail model) and should be offered chemoprevention to reduce the risk of invasive cancer, discussing the benefits and risks of the intervention. NCCN guidelines recommend tamoxifen for premenopausal women. Tamoxifen, raloxifene, exemestane, or anastrozole are options for postmenopausal women. The NCCN advises that tamoxifen is a superior choice of risk-reduction agent for most postmenopausal women.[37] However, consideration of adverse effects may lead some patients to choose raloxifene.
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