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 patients should be informed of both the benefits and harms.[174][175]

Screening for male breast cancer

Screening mammography is not routinely performed in men. However, annual screening may be considered for men at higher risk, especially those with a BRCA2 pathogenic or likely pathogenic variant, starting at age 50 years (or 10 years before earliest male breast cancer in the family).[19]​ Men with a BRCA1 or BRCA2 variant should have an annual clinical breast examination, and education and training in self-examination, starting at age 35 years.[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][76]

US guidelines recommend clinical assessment by age 25 years for all women.​[76][111]​​​​[112]​​​​ The American College of Obstetricians and Gynecologists (ACOG) and National Comprehensive Cancer Network (NCCN) guidelines recommend offering clinical assessment to average-risk women aged 25-39 years every 1-3 years, and annually for women aged 40 years and older.[76][112]​​ 

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).[176]​ Breast density should be taken into account if available from prior mammography.[76]

Women 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.[177]

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).[142][178]​​​ Digital breast tomosynthesis (DBT; three-dimensional mammography) may be considered in preference to conventional mammography in a population-based screening programme.[178]​​

US recommendations

US guidelines typically recommend that average-risk women:​[76][112][77]​​​​[179]​​​[180][181]

  • 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.​[76][77][182]​​​​​​​ However, annual screening may increase overdiagnosis.​[76]​​​​​​[77][182][179]​​​[183]

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.[179] A shared decision should be made about when to stop screening after age 75 years.[112]​​

NCCN guidelines recommend screening mammography with DBT (three-dimensional mammography) for women at average risk.[76][179]​​​ The American College of Radiology (ACR) suggests that DBT screening may be used as an alternative to conventional mammography.[183]​ DBT has been found to improve cancer detection and decrease false-positive call back rates compared with two-dimensional mammography alone.[76][184]​​​​[185][186][187]​​​​​​​​​

Women with dense breasts: supplemental screening

​Dense breast tissue is a risk factor for developing breast cancer. Mammographic sensitivity is lower in women with dense breasts; therefore, supplemental imaging may be warranted.[76]​​[77]​​​​​​​​[78][188]

The addition of MRI, DBT, or ultrasound to conventional mammography increases the sensitivity and rate of cancer detection in women with dense breasts.[78]​​[184][189][190]​​​​​

NCCN and ACR guidelines recommend supplemental MRI, in addition to screening with mammography and DBT, for women with extremely dense breasts. Consideration of supplemental MRI is suggested for women with heterogenously dense breasts.[76][78]​ Women with dense breasts (not included in any other higher risk categories) are described as a separate higher risk category in NCCN guidelines (see below).[76]

NCCN guidelines recommend shared decision-making, with counselling on the risks and benefits of supplemental screening, for women with all breast densities and risk categories, taking into account breast density and texture on mammography.[76]

Although supplemental imaging may improve detection of breast cancer, the risk of false-positive results and overdiagnosis is increased.[189][191]​ Some 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 this patient population.​[179][191][192]

​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.[192][193][194]

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.[195] 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.[195]

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.[196]

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:[122]

  • 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, which may include mammography, DBT, and/or MRI (without and with contrast).[19][76]​​​​​​​​​​​​​[111]​​[191][197]​​​​​​​ ​​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 modalities are not available.[76]​ Clinical assessment is encouraged every 6-12 months for most higher-risk women aged ≥25 years.[76]

Recommendations for screening women at higher-risk:[19][76]

  • ≥20% lifetime risk of breast cancer (calculated using a validated risk assessment tool that is includes a full family history; for example, BRCAPro, Tyrer-Cuzick, BOADICEA/CanRisk): annual screening with mammography, DBT, and MRI (without and with contrast) should start by age 40 years (or 10 years before the earliest known breast cancer in the family, but not before age 25 years for MRI and 30 years for mammography).

  • 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). Annual clinical assessment is encouraged from 8 years after radiotherapy for women aged <25 years.

  • Personal history of lobular carcinoma in situ, or atypical ductal or lobular hyperplasia, and ≥20% lifetime risk of breast cancer: annual screening with mammography and DBT, and consideration of supplemental MRI (without and with contrast), starting at age of diagnosis (but not before age 25 years for MRI and 30 years for mammography).

  • 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 age 25 to 29 years, with mammography and DBT added from age 30 to 75 years, and individualised screening from age >75 years.

  • 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 age 20 to 29 years, with mammogram with DBT added from ages 30 to 75 years, and individualised screening >75 years; for Cowden/PTEN hamartoma tumour syndrome, annual mammogram with DBT and MRI (without and with contrast) from age 30 to 75 years, and individualised screening >75 years.

  • 5-year breast cancer risk ≥1.7% using Gail model (age ≥35 years): annual screening mammography with DBT, starting when identified at risk assessment.

  • Dense breast tissue on mammography: annual screening with mammography and DBT should start no later than age 40 years (but not before age 30 years). For women with extremely dense breasts, annual supplemental MRI (without and with contrast) should start at age ≥50 years (with consideration of starting at age ≥40 years, taking into account individual risk and patient preferences). For women with heterogenously dense breasts, supplemental MRI may be considered.​ The optimal frequency of MRI supplemental screening for these women is unknown.

Note that some experts recommend alternating between mammography and MRI at 6-monthly intervals for patients who require annual mammography and MRI.[76]

Genetic evaluation

The NCCN recommends genetic counselling and testing for mutations in 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][124]

The American Society of Breast Surgeons and the USPSTF have published recommendations for genetic testing for breast cancer.​[123][198]

Germline testing for a specific pathogenic variant can be carried out, if known; tailored multigene panel testing is recommended if the variant is unknown.[19]​ Selection of the specific multigene panel should take into account the patient's personal and family history.[19][157]

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).​[199]

Use of this content is subject to our disclaimer