Primary prevention

Options for the primary prevention of breast cancer include risk-reducing agents (hormone therapies) and surgery (mastectomy and salpingo-oophorectomy). These options should be discussed with women at risk for breast cancer, and decisions should be based on shared decision-making.

Women should be advised of healthy lifestyle measures that may reduce their risk, such as limiting alcohol consumption, keeping physically active, maintaining a healthy weight, and, if appropriate, breastfeeding.

Breast cancer risk assessment

Risk assessment should be used to identify women at higher risk, and guide screening, risk reduction strategies, and genetic evaluation.[55][76]​​​​ 

A validated assessment tool may be used to estimate a woman's risk of developing invasive breast cancer:[55][76]​​ 

US guidelines recommend clinical assessment by age 25 years for all women.​[76][111][112]​​​​ Clinical assessment should include risk assessment, counselling on breast awareness and healthy lifestyle, and may include a breast exam.

Risk-reduction options should be discussed with women at increased risk of breast cancer who have a life expectancy ≥10 years, including those who have:​[55][76]​​​[113]

  • ≥20% lifetime risk of breast cancer calculated using a validated risk assessment tool that is primarily based on family history (e.g., BRCAPro, Tyrer-Cuzick, BOADICEA/CanRisk), or

  • A history of radiotherapy with exposure to breast tissue between age 10 and 30 years, or

  • A personal history of lobular carcinoma in situ, or atypical ductal or lobular hyperplasia, or

  • A strong family history of breast cancer or a known or likely pathogenic variant associated with increased risk for breast cancer (e.g., BRCA1, BRCA2, TP53, PALB2, PTEN, STK11, or CDH1), or

  • Increased risk based on a validated risk-assessment tool; for example, 5-year breast cancer risk ≥1.7% using the BCRAT (age ≥35 years); or 10-year risk of ≥5% using Tyrer-Cuzick model, or

  • Dense breast tissue on mammography.

Risk-reducing agents

Selective oestrogen receptor modulators (tamoxifen and raloxifene) and aromatase inhibitors (exemestane and anastrozole) are recommended as risk-reducing agents for women aged ≥35 years at increased risk for invasive oestrogen receptor-positive breast cancer (e.g., 5-year breast cancer risk ≥1.7% using Gail model; 10-year risk of ≥5% using Tyrer-Cuzick model).[55][113][114][115][116][117][118][119] [ Cochrane Clinical Answers logo ] ​ In particular, risk-reducing agents are strongly recommended for women with atypical hyperplasia or a history of lobular carcinoma in situ.[55]

For pre-menopausal women (≥35 years) at increased risk of breast cancer, tamoxifen is recommended. Tamoxifen is teratogenic and should be avoided in pregnancy or in women planning a pregnancy.[55][113]

Tamoxifen, raloxifene, exemestane, or anastrozole are options for post-menopausal women.[55][113]​​ Exemestane and anastrozole are not currently approved by the US Food and Drug Administration (FDA) for breast cancer risk reduction.

Risks and benefits of risk-reduction agents should be discussed, including adverse effects and age-dependent risks, and a shared decision made. The National Comprehensive Cancer Network (NCCN) advises that tamoxifen is a superior choice of risk reduction agent for most post-menopausal women. However, consideration of adverse effects may lead some women to choose raloxifene in preference to tamoxifen.[55][120]​​​​​[121]​ 

​The USPSTF specifically recommends against the routine use of risk-reducing agents for women who are not at increased risk for breast cancer.[114]

Investigations before starting a risk-reducing agent

Women with an intact uterus require a gynaecological evaluation before starting tamoxifen, to ensure there is no abnormal uterine bleeding that requires further investigation.

Post-menopausal women require an assessment of bone density (dual energy x-ray absorptiometry [DXA]) before treatment and should be offered raloxifene or tamoxifen in preference to aromatase inhibitors if they have low bone mineral density.[55]

Women who do not desire risk-reducing therapy should be invited for screening according to national guidelines.

Risk-reducing mastectomy

Risk-reducing mastectomy should be discussed with women who have any of the following:[19][55]​​​​[122]​​ 

  • A known or likely pathogenic genetic variant in a high-penetrance breast cancer susceptibility gene (e.g., BRCA1, BRCA2, TP53, PALB2, PTEN, STK11, or CDH1)

  • A strong family history

  • Prior radiotherapy with exposure to breast tissue at aged <30 years

Prophylactic mastectomy in BRCA carriers is associated with reduced breast cancer incidence and reduced breast cancer mortality.[123] Risk-reducing mastectomy is most beneficial when carried out in women aged between 30 and 55 years.[122]​

Women considering surgery should undergo multi-disciplinary evaluation and receive counselling on the potential psychosocial impact of risk-reducing mastectomy. Immediate breast reconstruction is an option for many women undergoing risk-reducing mastectomy.[55] Nipple-sparing mastectomy may be an alternative option to total mastectomy.[122]

For women who decline risk-reducing mastectomy, risk-reducing agents may be considered for women with BRCA1 or BRCA2 variants.[122]​ However, evidence for risk-reducing agents is lacking for all pathogenic variants and for women with prior radiation therapy.[55]​ Recommendations for screening according to risk should be followed.[55]​​[122]​​ See Screening.​​​​

Contralateral prophylactic mastectomy is not recommended for patients diagnosed with unilateral breast cancer, unless they already meet criteria for risk-reducing mastectomy based on high familial or genetic risk.[124] One meta-analysis found that there was no absolute reduction in the risk of metachronous contralateral breast cancer in patients who received a contralateral prophylactic mastectomy, compared with those who did not have the procedure. In patients with elevated familial or genetic risk, contralateral prophylactic mastectomy significantly decreased the risk of metachronous contralateral breast cancer, compared with no procedure, but there was no improvement in breast cancer mortality or overall survival.[125]

Risk-reducing salpingo-oophorectomy

While risk-reducing mastectomy has been found to decrease breast cancer risk by >90% in high-risk patients, the role of risk-reducing bilateral salpingo-oophorectomy (RRSO) in reducing the risk of breast cancer remains uncertain.[126][127][128][129][130][131][132][133]​​​​

Early studies in women with BRCA mutations reported a reduction in risk of breast cancer of approximately 50% with RRSO.[129][130]​​​​ However, subsequent studies with more robust methodology found no evidence for a protective effect with RRSO.[132][133]​​​​ One Cochrane review found very low-certainty evidence that RRSO improves overall survival in women with BRCA1/2 mutations.[131]​ Subgroup analyses of the individual pathological variants found that RRSO decreased breast cancer-related mortality in women with a BRCA1 mutation, but not in those with a BRCA2 mutation.[131]​ These results should be interpreted with caution. One large case series reported reduced risk of breast cancer with RRSO in women carrying a BRCA1 or a BRCA2 mutation, but with diminishing benefit after 5 years.[134]

For women with variants associated with ovarian and breast cancer, guidelines recommend RRSO for ovarian and breast cancer risk reduction. This may be considered at age 35-40 years, upon completion of childbearing, in women with a BRCA1 mutation.[19]​​​​​​ BRCA2 variants are associated with later ovarian cancer onset, and consideration may be given to delaying RRSO until age 40-45 years in these patients. For women with a BRIP1, RAD51C, or RAD51D mutation, RRSO is recommended at age 45-50 years. Discussions should start earlier if there is a family history of early-onset ovarian cancer.[19][122]​​​​​​ RRSO may be considered at age 45-50 years in women with a PALB2 mutation; expert guidance is recommended.[19]

Women considering surgery should undergo multidisciplinary evaluation and receive counselling on the potential psychosocial impact of RRSO, including consideration of reproductive wishes and advice on premature menopause for women who are pre-menopausal.[19][122]​​​​

Secondary prevention

For patients diagnosed with unilateral breast cancer, contralateral prophylactic mastectomy is not recommended unless they already meet criteria for risk-reducing mastectomy based on high familial or genetic risk.[124]​ One meta-analysis found that there was no absolute reduction in the risk of metachronous contralateral breast cancer in patients who received a contralateral prophylactic mastectomy, compared with those who did not have the procedure.[125]

Risk-reduction strategies, including contralateral prophylactic mastectomy, should be discussed with patients with a known genetic predisposition for breast cancer, particularly those at higher risk of contralateral breast cancer.[19][499]​​ Women at higher risk of contralateral breast cancer include those with BRCA1, BRCA2, or TP53 mutations, or with Li-Fraumeni syndrome.[19]​ There is limited evidence that women with a CHEK2 variant, or with PALB2 variant ER-negative breast cancer, are at increased risk of contralateral breast cancer.​[19][500][501]​​ Risk of contralateral disease is typically lower in post-menopausal patients.

Screening following completion of breast-conserving surgery

Annual mammography (conventional and/or DBT) is recommended, beginning 6 months or more after breast-conserving surgery.[124][488]​​ Annual surveillance mammography is associated with reduced mortality compared with no annual mammography in this clinical scenario.[502][503]

Women at higher risk (e.g., with a BRCA1 or BRCA2 mutation) treated for breast cancer, and who have chosen breast-conserving surgery should be offered continued age-appropriate intensive screening.[19]​ See Screening.

Screening after mastectomy

Imaging is not typically recommended for screening purposes following bilateral mastectomy (with or without reconstruction [autologous or non-autologous]).[124][489]​​

Women who have had unilateral mastectomy are offered regular screening of the contralateral native breast according to risk; breast MRI (without and with contrast) may be considered, especially for those at higher risk.[197][124][143]​​[489]​​​​​​

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