Screening

Early detection is highly effective in reducing mortality associated with breast cancer. However, screening can lead to overdiagnosis and overtreatment of breast disease, and women should be informed of both the benefits and harms.[166]

Screening mammography is not routinely performed in men, but may be considered for men at higher risk, especially those with a BRCA2 pathogenic or likely pathogenic variant.[19]

Initial breast cancer risk assessment

Breast cancer risk assessment should be used to identify women at higher risk and guide screening, risk reduction strategies, and genetic evaluation. A validated assessment tool may be used:​[55][103]

US guidelines recommend clinical assessment by age 25 years for all women.​[103][104]​​​[105][106]​​ The American College of Obstetricians and Gynecologists (ACOG) and National Comprehensive Cancer Network (NCCN) guidelines recommend offering clinical assessment to women aged 25-39 years every 1-3 years, and annually for women aged 40 years and older.[103][105]​ 

Clinical assessment should include risk assessment, counselling on breast awareness and healthy lifestyle, and may include a breast examination. The National Breast and Cervical Cancer Early Detection Program in the US found that adding clinical breast examination to mammography led to an increase in breast cancer detection rate, such that 5% of cancers were detected by clinical breast examination alone initially (i.e., where screening mammogram had been negative, benign, or probably benign).[167]

Woman at average risk: mammography screening recommendations

In the UK, the National Health Service offers breast screening mammography every 3 years to women between the ages of 50 and 71 years.[168]

The European Commission Initiative on Breast Cancer (ECIBC) recommends mammography screening every 2 years for average-risk women aged 50-69 years. Consideration of screening is also suggested for women aged 45-49 years (every 2 or 3 years) and women aged 70-74 years (every 3 years).[135][169]​​ Digital breast tomosynthesis (DBT; three-dimensional mammography) may be considered in preference to conventional mammography in a population-based screening programme.[169]​​

US recommendations

US guidelines typically recommend that average-risk women:​[103][105][136]​​​[170]​​​

  • Start regular (annual or biennial) bilateral mammography screening at age 40 years.

  • Continue regular breast screening, irrespective of age, unless they have severe comorbidities and/or limited life expectancy (<10 years), or make an informed shared decision to stop.

Reduction in breast cancer mortality varies by screening regimen; mortality reduction is greater when screening starts at 40 years compared with 45 or 50 years, and when done annually rather than biennially.[106][171]​​​​ However earlier, more frequent screening may increase over diagnosis.​[103][106]​​​​[136]

The American Cancer Society (ACS) and the ACOG recommend shared decision-making about when to start regular screening mammography, starting at age 40 years if they wish, and with all women starting screening by 45 years or no later than 50 years.[105][172]

Most US guidelines do not give an upper age limit for screening; the evidence for or against screening in women aged 75 and over is limited.[170] A shared decision should be made about when to stop screening after age 75 years.[105]​​

NCCN guidelines recommend screening mammography with DBT (three-dimensional mammography) for women at average risk.[103][170]​​ The American College of Radiology (ACR) suggests that DBT may be used as an alternative to conventional mammography or for supplemental screening.[106][173]​​ DBT has been found to improve cancer detection and decrease false-positive call back rates compared with two-dimensional mammography alone.[103][174]​​​[175][176][177]​​​​​​​​

Women with dense breasts: supplemental screening

​Dense breast tissue is a risk factor for developing breast cancer, and mammographic sensitivity is lower in women with dense breasts; therefore, supplemental imaging may be warranted.[103]​​[136][137][173]​​​​ The addition of MRI, DBT, or ultrasound to conventional mammography increases the sensitivity and rate of cancer detection in women with dense breasts.[173][174][178][179]​​​​

Although supplemental imaging may improve detection of breast cancer, the risk of false-positive results and overdiagnosis is increased.[180][178]​​​​​​​​ 

​Guidelines do not recommend routine use of supplemental MRI or ultrasound in screening average-risk women with dense breasts, due to a lack of evidence showing a benefit in these women.[103][170]​​​​[180][181]​​​​​​​

​However, NCCN guidelines recommend that supplemental screening with ultrasound or MRI (in addition to screening mammography with DBT) may be considered for average-risk women aged ≥40 years with heterogeneous or extremely dense breasts, taking into account risk and patient preference.[103] The ACR suggests that DBT is usually appropriate for supplemental screening in average-risk women with dense breasts, and that ultrasound may be appropriate in some cases.[173]​​

For higher-risk women with dense breasts, the US guidelines recommend supplemental screening with annual MRI (without and with contrast) in combination with mammography and DBT.[103][173]​ Abbreviated MRI (without and with contrast) or ultrasound may be considered as alternative options to MRI, although they have lower sensitivity.[173]​​​

​In the US, the Food and Drug Administration (FDA) requires that all mammography reports sent to the clinician and patient should include an assessment of a patient’s breast density to inform decision-making regarding supplemental screening.[181][182][183]

Women at higher risk

In the UK, women at very high risk are offered annual surveillance, including early MRI screening, through the National Health Service breast screening programme.[184] Very-high-risk women are defined as women with a lifetime risk of ≥40% due to a genetic abnormality or who received radiotherapy to breast tissue, such as:​

  • Women with a germline pathological variant in a high-risk gene (e.g., BRCA1, BRCA2, TP53, homozygous for ATM, PALB2, PTEN, STK11 or CDH1), or

  • Women who have received radiotherapy to breast tissue during treatment for Hodgkin's and non-Hodgkin's lymphoma between the ages of 10 and 35 years.

Most women at very high risk are offered MRI, starting at age 25 or 30 years (depending on the specific variant or age of radiotherapy), with annual mammography added at age 40 years. From age 51 years, mammography is continued and the decision to perform MRI is based on annual review of breast density.[184]

Women with a TP53 variant (Li-Faumeni syndrome) start annual MRI at 20 years. Those who are homozygous for ATM start annual MRI at 25 years. MRI is continued until age 70 years.[185]

UK National Institute for Health and Care Excellence (NICE) guidelines recommend additional surveillance for women at moderate risk (defined as 17% to 29% lifetime risk) and at high risk (defined as >30% lifetime risk), based on assessment of risk and the presence of known or likely genetic mutation.[28]​​​

  • Moderate-risk women: offer annual mammography from age 40 to 49 years; consider annual mammography from age 50 to 59 years; offer screening as for average-risk women from age 60 years.

  • High risk and unlikely to be a BRCA or TP53 carrier: consider annual mammography from age 30 to 39 years; offer annual mammography from age 40 to 59 years; offer screening as for average-risk women from age 60 years.

  • High risk and likely or known BRCA mutation: offer annual MRI and consider annual mammography from age 30 to 39 years; offer annual MRI and mammography from age 40 to 49 years; offer annual mammography (with consideration of MRI only if the woman has dense breasts) from age 50 to 59 years; offer screening as for average-risk women from age 60 years (except women with a known BRCA mutation who should continue annual mammography until age 69 years).

  • High risk and likely or known TP53 mutation: offer annual MRI from age 20 to 49 years; consider annual MRI for known carriers from age 50 to 69 years; offer screening as for average-risk women for likely carriers from age 50 years (with consideration of MRI only if the woman has dense breasts).

European guidelines recommend intensified screening, including breast MRI, for women with increased risk of hereditary breast cancer:[116]

  • For those with a BRCA1, BRCA2, PALB2, CDH1, PTEN, or STK11 mutation, intensified screening should start at age 30 years, or 5 years younger than the youngest family member with breast cancer. Annual screening intervals are recommended, although 6-monthly screening may be considered for women with BRCA1.

  • For those with a TP53 mutation, annual intensified breast screening should start from age 20 years.

US recommendations

US guidelines recommend more intensive screening for higher-risk women, with mammography, DBT, and MRI (without and with contrast).[19][103]​​​​​​​​​​​[104][106][180]​​​​​ ​​Contrast-enhanced mammography or molecular breast imaging are also options for higher-risk breast cancer screening; they may be considered if MRI is not suitable. Whole breast ultrasound is an option if these are not available.[103]

Recommendations for screening women at higher-risk:[19][103]

  • ≥20% lifetime risk of breast cancer (calculated using a validated risk assessment tool that is primarily based on family history: for example, BRCAPro, Tyrer-Cuzick, BOADICEA/CanRisk): annual screening with mammography, DBT, and MRI (without and with contrast) should start at age 40 years, or when identified at risk assessment, or 10 years before the earliest known breast cancer in the family (but not before age 25 years).

  • History of radiotherapy with exposure to breast tissue between the aged of 10 and 30 years: annual screening with mammography, DBT, and MRI (without and with contrast) should start 8 years after radiotherapy (but not before age 25 years).

  • Personal history of lobular carcinoma in situ, or atypical ductal or lobular hyperplasia: annual screening with mammography and DBT, and consideration of supplemental MRI (without and with contrast) may be considered if they have a ≥20% lifetime risk of breast cancer, starting at age of diagnosis (but not before age 25 years).

  • Known or likely high-risk genetic mutation (e.g., BRCA1, BRCA2) or a first-degree relative with a BRCA mutation: annual MRI (without and with contrast) from aged 25 to 29 years, with mammography added from age 30 to 75 years, and individualised screening >75 years. Annual mammography may be considered for men with a known or likely BRCA mutation, starting at age 50 years or 10 years before the earliest known male breast cancer in the family.

  • Diagnosis of Li-Fraumeni syndrome (TP53 mutation), Cowden syndrome/PTEN hamartoma tumour syndrome, or a first degree relative with one of these syndromes: for Li-Fraumeni syndrome, annual MRI (without and with contrast) from aged 20 to 29 years, with mammogram added from aged 30 to 75 years, and individualised screening >75 years; for Cowden/PTEN hamartoma tumour syndrome, annual mammogram and MRI (without and with contrast) from aged 30 to 75 years, and individualised screening >75 years.

  • 5-year breast cancer risk ≥1.7% using Gail model; or 10-year risk of ≥5% using IBIS/Tyrer-Cuzick model: annual screening mammography with DBT, starting when identified at risk assessment.

Genetic evaluation

The NCCN recommends genetic counselling and testing for high-penetrance breast cancer susceptibility genes (e.g., BRCA1, BRCA2, CDH1, PALB2, PTEN, STK11, and TP53) in the following women at high-risk for hereditary breast cancer:[19]

  • With any blood relative with a known pathogenic/likely pathogenic variant in a cancer susceptibility gene.

  • With a personal history of breast cancer and any of the following specific features:

    • Diagnosed aged ≤50 years

    • Ashkenazi Jewish ancestry

    • Triple-negative breast cancer, or multiple primary (synchronous or metachronous) breast cancers, or lobular breast cancer (with a personal or family history of diffuse gastric cancer).

  • With a personal history of breast cancer and a strong family history, including:

    • ≥1 close blood relative diagnosed with breast cancer at aged ≤50 years, or with male breast cancer, ovarian or pancreatic cancer, or prostate cancer (with metastatic, or high- or very high-risk group) at any age; or

    • ≥3 diagnoses of breast and/or prostate cancer on the same side of the family (including the patient being assessed).

  • With a strong family history of breast cancer (first- or second-degree relative with specific features as above).

  • Who meet the testing criteria for Li-Fraumeni syndrome, or Cowden syndrome/PTEN hamartoma tumour syndrome.

  • With >5% probability of a BRCA1 or BRCA2 pathogenic/likely pathogenic variant based on prior probability models (e.g., Tyrer-Cuzick, BRCAPro, CanRisk).

All male patients with breast cancer at any age should have genetic testing.[19][118]

The American Society of Breast Surgeons and the USPSTF have published recommendations for genetic testing for breast cancer.​[117][186]

The results of genetic testing should be used to guide screening and risk reduction strategies, and inform cascade screening (genetic counselling and testing in blood relatives of individuals who have been identified with specific genetic mutations). Hereditary breast cancer has been identified by the US Centers for Disease Control and Prevention as a high-priority syndrome for cascade screening.[187][188]

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