Breast Cancer Screening (Average Risk Women)

• Breast cancer is the most common cancer in women worldwide. 1 In Australia, one in eight women will develop breast cancer in their lifetime and it is one of the leading causes of mortality with more than 3000 estimated deaths in 2015. 2,3 Males also develop breast cancer, although it is less common (the risk of a male being diagnosed with breast cancer before 85 years was 1 in 688 in 2008)
• The aim of breast cancer screening is early detection of breast cancer so that prognosis can be improved by early intervention
• Breast screening programs are designed such that the benefits of reduced breast cancer mortality are balanced with the potential harms of screening including false-positives, over-diagnosis and radiation exposure
• Risk factors for breast cancer include but are not limited to 4,5
  • Increasing age
  • Female gender - breast cancer occurs 100 times more frequently in women than in men
  • Family history of breast cancer
  • Inherited genetic mutations such as BRCA1, BRCA2, p53,ATM and PTEN
  • Chest irradiation between the ages of 10 and 30 years
  • White race
  • Obesity
  • Dense breast tissue
  • Early menarche or late menopause
  • Alcohol
  • Smoking
• Several risk prediction models have been developed to calculate a woman’s breast cancer risk based on family history and other major risk factors. 6,7 Although a family history of breast cancer is common, only a small percentage of breast cancers will be associated with an inherited genetic mutation. 4 These models are used for risk assessment of individual patients, to decide whether to recommend genetic testing and to predict which patients may benefit from high-risk screening. There are benefits and limitations to each model and calculated risk can vary a great deal according to which model is used. Due to this complexity, stratification of patients by risk should be carried out by health care professionals who specialize in risk assessment. 8,9 One such model is the Familial Risk Assessment-Breast and Ovarian Cancer (FRA-BOC), an online tool which provides an estimation of the risk of developing breast or ovarian cancer, based on family history for unaffected women. The three broad categories of risk are outlined below 10

• This pathway provides guidance regarding breast screening in asymptomatic women who are 'average risk' for breast cancer
• Other broad definitions for women with 'average risk' for breast cancer include women without a personal history of breast cancer, a confirmed or suspected genetic mutation known to increase risk of breast cancer (e.g. BRCA), a history of chest irradiation between the ages of 10 to 30 or women < 20% lifetime risk of breast cancer 1,5

RISK FACTORS 8-10

Multiple factors affect the individual risk for development of breast cancer:

• Female sex
  • Sex ratio approximately 100F:1M
• Age
  • About 80% of patients with breast cancer are individuals aged >50 while at the same time more than 40% of those are more than 65 years old
• Ethnicity
  • Black women and those of Ashkenazi Jewish descent are at higher risk of genetic mutations (see below)
  • Black women are at risk for breast cancer at a younger age
• Age at menarche
  • Early age at menarche is a risk factor
• Age at menopause
  • Early menopause (natural or surgically induced) lowers the risk
• Reproductive history
  • First full-term pregnancy at an early age along with a subsequently increasing number of births are associated with a reduced risk of breast cancer
• Breastfeeding
  • A longer duration of breastfeeding period also reduces the risk
• Obesity
  • Obesity, particularly in post-menopausal women, increases breast cancer risk
• Family History
  • This is a major factor associated with breast cancer risk
  • Approximately 13–19% of patients diagnosed with breast cancer report a first-degree relative affected by the same condition
  • The risk of breast cancer significantly increases with an increasing number of first-degree relatives affected
  • The risk might be higher when the affected relatives are under 50 years old
  • A family history of ovarian cancer - especially those associated with BRCA1 and BRCA2 genetic mutations - might also induce a greater risk of breast cancer
  • Although a family history of breast cancer is common, only a small percentage of breast cancers will be associated with an inherited genetic mutation
• Mammographic density
  • Generally, the greater the breast tissue density the greater the breast cancer risk
• Genetic mutations
  • Two major genetic mutations are associated with a high penetrance - BRCA1 and BRCA2 (mainly inherited in an autosomal dominant manner, however, sporadic mutations are also commonly reported)
  • Other genes with high penetrance include TP53, CDH1, PTEN, and STK11
  • The above also carry an increased risk of ovarian cancer
  • Genes associated with breast cancer but at a lower degree of penetrance compared to BRCA1 and BRCA2 include ATM, PALB2, BRIP1, or CHEK2
• Personal History of breast cancer or non-cancerous breast disease
  • Risk increased with past history of breast cancer
  • Risk increased by history of atypical hyperplasia, carcinoma in situ, as well as other proliferative or non-proliferative lesions
• Previous radiotherapy
  • Increased risk in patients who receive radiation therapy before the age of 30
• Hormone Replacement Therapy (HRT)
  • HRT, especially taken for longer than 5 or 7 years, increases the risk of breast cancer
• Alcohol and Smoking
  • Both excess alcohol consumption and smoking increase breast cancer risk
• White race
  • Breast cancer incidence is highest among white women

RISK STRATIFICATION

• It is recommended that women undergo risk assessment for breast cancer around the age of 25 years 10-12. NCCN guidelines 12 also recommend clinical breast examination at this encounter.
• There are several established methods of risk stratification 13-16 based on the presence/absence of the recognised risk factors for breast cancer (see above) but also latterly incorporating assessment of breast density and the presence of genetic pathogenic variants such as BRCA1 and BRCA2 13.
• These models are used for risk assessment of individual patients, to decide whether to recommend genetic testing and to predict which patients may benefit from high-risk screening. There are benefits and limitations to each model and calculated risk can vary according to which model is used 14.
• Since numerous factors contribute to risk, no single method of classification or definition is used to classify individual women into a specific category.
• However, most models are based largely on family history of breast cancer, but also incorporate additional factors 10, 12.
• Risk categories are most often defined by estimated life-time risk.
• There has been growing interest in risk-stratified breast screening whereby individualised risk assessment may inform screening frequency, starting age, screening instrument used, or decision not to screen. This has the potential to be beneficial at the population level, but the net health benefit will depend on the particular risk-based strategy and requires further assessment 17.
• One model is the iPrevent breast cancer risk assessment and risk management decision support tool, developed by the Peter MacCallum Cancer Centre in Australia 18, 19, an online tool which provides an estimation of the risk of developing breast cancer. This is one of several tools available that allow women to self-assess their cancer risk 19.
• Clinical evaluations of risk-stratified screening are currently limited and further studies of their clinical usefulness are required 20.
• Breast cancer risk is most frequently divided into three categories (Average, Intermediate and High) 11 although European Society Of Breast Imaging (EUSOBI) guidelines 9 subdivide High risk into “Intermediate High” (women with highly positive family history but without known genetic mutations) and “Very high” (women with high penetrance genetic mutations and women with a history of chest radiotherapy between 10-30 years of age).

Risk Factors 8-10

Multiple factors affect the individual risk for development of breast cancer:

• Female sex
  • Sex ratio approximately 100F:1M
• Age
  • About 80% of patients with breast cancer are individuals aged >50 while at the same time more than 40% of those are more than 65 years old
• Ethnicity
  • Black women and those of Ashkenazi Jewish descent are at higher risk of genetic mutations (see below)
  • Black women are at risk for breast cancer at a younger age 
• Age at menarche
  • Early age at menarche is a risk factor 
• Age at menopause
  • Early menopause (natural or surgically induced) lowers the risk
• Reproductive history 
  • First full-term pregnancy at an early age along with a subsequently increasing number of births are associated with a reduced risk of breast cancer
• Breastfeeding
  • A longer duration of breastfeeding also reduces the risk 
• Obesity
  • Obesity, particularly in post-menopausal women, increases breast cancer risk
• Family History  
  • This is a major factor associated with breast cancer risk
  • Approximately 13–19% of patients diagnosed with breast cancer report a first-degree relative affected by the same condition
  • The risk of breast cancer significantly increases with an increasing number of first-degree relatives affected
  • The risk might be higher when the affected relatives are under 50 years old
  • A family history of ovarian cancer - especially those associated with BRCA1 and BRCA2 genetic mutations - might also induce a greater risk of breast cancer
  • Although a family history of breast cancer is common, only a small percentage of breast cancers will be associated with an inherited genetic mutation 
• Mammographic density
  • Generally, the greater the breast tissue density the greater the breast cancer risk
• Genetic mutations
  • Two major genetic mutations are associated with a high penetrance - BRCA1 and BRCA2 (mainly inherited in an autosomal dominant manner, however, sporadic mutations are also commonly reported)
  • Other genes with high penetrance include TP53, CDH1, PTEN, and STK11
  • The above also carry an increased risk of ovarian cancer
  • Genes associated with breast cancer but at a lower degree of penetrance compared to BRCA1 and BRCA2 include ATM, PALB2, BRIP1, or CHEK2 
• Personal History of breast cancer or non-cancerous breast disease
  • Risk increased with past history of breast cancer
  • Risk increased by history of atypical hyperplasia, carcinoma in situ, as well as other proliferative or non-proliferative lesions
• Previous radiotherapy
  • Increased risk in patients who receive radiation therapy before the age of 30
• Hormone Replacement Therapy (HRT)
  • HRT, especially taken for longer than 5 or 7 years, increases the risk of breast cancer
• Alcohol and Smoking
  • Both excess alcohol consumption and smoking increase breast cancer risk
• White race
  • Breast cancer incidence is highest among white women

Risk Stratification

• It is recommended that women undergo risk assessment for breast cancer around the age of 25 years (10-12). NCCN guidelines (12) also recommend clinical breast examination at this encounter. 

• There are several established methods of risk stratification (13-16) based on the presence/absence of the recognised risk factors for breast cancer (see above) but also latterly incorporating assessment of breast density and the presence of genetic pathogenic variants such as BRCA1 and BRCA2 (13).

• These models are used for risk assessment of individual patients, to decide whether to recommend genetic testing and to predict which patients may benefit from high-risk screening. There are benefits and limitations to each model and calculated risk can vary according to which model is used (14).

• Since numerous factors contribute to risk, no single method of classification or definition is used to classify individual women into a specific category.

• However, most models are based largely on family history of breast cancer, but also incorporate additional factors (10, 12).

• Risk categories are most often defined by estimated life-time risk.

• There has been growing interest in risk-stratified breast screening whereby individualised risk assessment may inform screening frequency, starting age, screening instrument used, or decision not to screen. This has the potential to be beneficial at the population level, but the net health benefit will depend on the particular risk-based strategy and requires further assessment (17).

• One model is the iPrevent breast cancer risk assessment and risk management decision support tool, developed by the Peter MacCallum Cancer Centre in Australia (18, 19), an online tool which provides an estimation of the risk of developing breast cancer. This is one of several tools available that allow women to self-assess their cancer risk (19).

• Clinical evaluations of risk-stratified screening are currently limited and further studies of their clinical usefulness are required (20).

• Breast cancer risk is most frequently divided into three categories (Average, Intermediate and High) (11) although European Society Of Breast Imaging (EUSOBI) guidelines (9) subdivide High risk into “Intermediate High” (women with highly positive family history but without known genetic mutations) and “Very high” (women with high penetrance genetic mutations and women with a history of chest radiotherapy between 10-30 years of age).

Typically defined as an estimated lifetime risk of < 15%, but by some authorities as 1 in 14 to 1 in 8. This risk category includes over 95% of the female population.

Abbreviations: DBT = Digital Breast Tomosynthesis; CEM = Contrast-enhanced mammography, MRI= Magnetic Resonance Imaging; US= Ultrasonography

^a Lifetime risk

^b Some authorities use 1 in 14 to 1 in 8 (average risk), 1 in 8 to 1 in 4 (intermediate) and 1 in 4 to 1 in 2 (high)

^c Some guidelines, for example NCCN 12, The US Preventive Services Task Force [USPSTF] 21 and the ACR 11, recommend starting screening of average-risk women at age 40. UK guidelines recommend starting at age 50 22.

^d Guidelines differ for average-risk women. For example, ACR 11 and NCCN 12 recommend yearly; USPSTF recommends 2 yearly 21; European Breast Guidelines 23 recommend 2-3 yearly for women aged 45-49, but 2 yearly for women 50-69: Australian guidelines 4 recommend 2 yearly. UK guidelines 22 recommend 3 yearly.

^e See ACR guide specific to women with dense breasts 24. DBT (if available) is usually appropriate as supplemental screening in average risk women with dense breasts. CEM and MRI are alternatives. The ACR reports disagreement regarding the role of Breast US.

Breast Awareness

• Although breast self-examination has been promoted for many years as a screening method to diagnose breast cancer at an early stage, studies have shown that self-detection does not reduce breast cancer-specific mortality 30 and self-examination is no longer routinely recommended 4, 26.
• However, more than half of breast cancers are diagnosed after investigation of a breast change found by the woman or by her doctor 31, hence women are recommended to be aware of the normal look and feel of her breasts and report new or unusual changes to the doctor 4, 30.
• No single method for women to use when checking their breasts is recommended over another 4, 31.
• In 2015 the International Agency for Research on Cancer (IARC) Working Group concluded that there was inadequate evidence that breast self-examination reduces breast cancer mortality when taught or when practiced competently and regularly 5.

• Age for Initiation of Screening (Average Risk Women)

  • There is a general consensus among the various guidelines that average risk women between the ages of 50 and 74 years should be on a breast screening program.
  • With regard to average-risk women aged 40-49, there is no clear consensus.
  • Several USA guidelines recommend screening starting at age 40, including the US Preventive Services Task Force (USPSTF) 21, 25, the ACR 11, and the National Comprehensive Cancer Network 12, among others. The American Cancer Society supports screening from the age of 45 26.
  • Several of the European guidelines do not recommend screening in average-risk women aged 40-49 years, although the European Commission Initiative on Breast Cancer (ECIBC) does recommend screening for 45-49 year olds 23.
  • The 2016 USPSTF recommendations did not support screening for 40-49 year olds but the 2024 iteration has changed the recommendation to support this 21, 25, 27. This does not appear to be based on any data other than that the incidence of breast cancer diagnoses has increased in recent years. However, this does not necessarily equate with an increase in mortality and, it has been pointed out, that an increase in screening is, in itself, a cause of an apparent increase in the disease 27.
  • In Australia the screening program invites women of 50-74 years. Women of 40-49 years are eligible to receive free mammography but do not receive invitations to attend 4.
  • Women of 40-49 years and, indeed, of all ages are, in the Australian recommendations, encouraged to be “Breast Aware” 4.
  • Therefore, the question of screening women of 40-49 years of age of average risk remains contentious.

  Age of stopping screening

  • Many guidelines suggest stopping screening at the age of 75 years 28, stating that there is insufficient evidence to support screening above this age.
  • Some guidelines qualify this by recommending that a decision to discontinue be individualised, based on a shared decision between screenee and doctor, and should take into account the patient’s co-morbidity, life expectancy, etc. eg ACS 26, ACOG 29, and ACR 11.

• Although breast self-examination has been promoted for many years as a screening method to diagnose breast cancer at an early stage, studies have shown that self-detection does not reduce breast cancer-specific mortality 30 and self-examination is no longer routinely recommended 4, 26.
• However, more than half of breast cancers are diagnosed after investigation of a breast change found by the woman or by her doctor 31, hence women are recommended to be aware of the normal look and feel of her breasts and report new or unusual changes to the doctor 4, 30.
• No single method for women to use when checking their breasts is recommended over another 4, 31
• In 2015 the International Agency for Research on Cancer (IARC) Working Group concluded that there was inadequate evidence that breast self-examination reduces breast cancer mortality when taught or when practiced competently and regularly 5.

• There are multiple international expert consensus guidelines 28 including, but not limited to:
  • US Preventative Services task force (USPDTF) 2024 21, 31
  • European Commission Initiative on Breast Cancer (ECIBC) European Guidelines 2020 23
  • European Society of Breast Imaging (EUSOBI) 2024 9
  • American College of Radiology (ACR) 2023 11, 32
  • Cancer Australia 2015 4
  • American College of Physicians (ACP) 2019 30
  • American College of Obstetricians and Gynecologists (ACOG) 2017 29
  • National Comprehensive Cancer Network (NCCN) 2024 12
  • American Cancer Society (ACS) 2015 26
  • European Society of Medical Oncology (ESMO) 2019 33
• Mammography is the only screening modality to have been shown, to date, in many trials, to decrease breast cancer modality 11, 34, 35
• Therefore, all of the above guidelines recommend mammography as the primary screening modality in average-risk women, but inevitably there are variations in details of recommendations among the different guidelines 28, particularly in relation to screening interval, whether that frequency should vary with the age of the screenee, and the age at which screening should start in average-risk women. There is also some variation in the definition of risk groups. The evidence comparing the effectiveness of these different parameters in breast screening strategies is inconclusive 36.
• BreastScreen Australia invites women aged 50-74 for 2-yearly mammograms, with women aged 40-49 or 75 and over also eligible to attend if they wish 7.

1. Mammography
   • Analogue (film/screen) mammography has largely been replaced by digital mammography
   • The advantages of digital mammography over film mammography are 35:
     • The ability to post-process the image by changing contrast and magnification
     • Greater contrast resolution
     • Lower average radiation dose
     • The ability to store and send images electronically
   • A recently published Australian study 37 has reported that,with the transition to digital mammography, the screen-detected cancer rate increased but this has not been accompanied by a reduction in interval cancer detection rates
   • Standard mammography involves two views: cranio-caudal and medio-lateral oblique
   • The diagnostic accuracy of mammography is enhanced through the use of magnification views (magnified, coned compression views, DBT), which visualise only a small area of breast tissue but gives better contrast resolution and spatial detail. These additional views are usually only done to work-up suspected abnormalities, not de novo, due to additional radiation dose.
   • Standardised reporting systems such as the Breast Imaging Reporting and Data System (BI-RADS) by the American College of Radiology have been developed to improve communication between physicians 38
   • Another standardised reporting system currently in use in Australia requires a description of the following characteristics
     • Location
     • Size
     • Mass lesions - shape, margins, associated calcifications
     • Asymmetric density
     • Significant calcification - distribution, shape
     • Architectural distortion
   • Mammography is not as sensitive in detecting abnormal lesions in dense breast tissue 9, 12, 24, 39
   • One of the potential harms of breast screening is over-diagnosis, that is, detection of cancer through screening that would not have led to symptomatic breast cancer throughout a woman’s life if not detected by screening 11, 40. This has the potential to lead to unnecessary investigations and overtreatment.
   • The reported frequency of overdiagnosis has varied widely in the literature 11. Estimates allowing for breast cancer risk, trends in cancer incidence and lead time bias range from 1-10%.
   • Breast Screen Australia quotes a figure of about 10% of invasive breast cancers found through screening may not become life-threatening (i.e. overdiagnosis) 41
   • Approximately 10% of screening mammograms result in a recall for further assessment, although <2% result in percutaneous biopsy 11
   • False-positive findings are another potential harm - the 10-year cumulative probability of a false-positive mammogram is reported to be 7% with annual and 4.8% with biennial screening 1
   • The radiation exposure (2 views of each breast) is estimated to be an effective dose of 0.7mSv 41 and hence risk of malignancy secondary to mammography is believed to be low
2. Digital Breast Tomosynthesis (Dbt)
   
   • DBT is a quasi-3D x-ray technique that involves multiple low-dose projections acquired across an arc over each breast 9. These images are reconstructed into a series of stacked images, as well as providing a “synthetic” mammogram or a full-field digital mammogram 11.
   • DBT has been shown in several international trials to increase cancer detection rates (CDR) and decreased recall rates compared with mammography, summarised below 11, 24, 31. However, results have varied across screening settings, and currently there is limited and conflicting evidence on interval cancer rates (a surrogate for screening effectiveness).
   • A 2023 review 42 concluded that CDR improves the most in biennial screening settings, with little or no improvement in annual screening
   • Incremental increase in cancer detection of 1.6-3.2 per 1000 DBT screening exams and 2.2% pooled decrease in recall rate, compared to digital mammography
   • Recall rates are decreased with DBT in situations where there is a background of high recall settings – most studies reported from the USA 9, 42, 43
   • In Europe, where there is a background of fewer recalls, DBT has resulted in no difference, or slightly higher recall rates 9, 43
   • DBT is increasingly used in the USA and Europe 9
   • However, any benefits of DBT are limited in women with very high breast density
   • There is some evidence that DBT increases detection of indolent , slow-growing tumours, thus perhaps increasing the overdiagnosis rate 9
   • The synthetic mammograms produced using 2D reconstructions of DBT datasets can be used as an alternative to 2D mammography projections, thereby avoiding the additional dose associated with performing separate 2D mammograms 9
   • Studies of the rates of interval cancers after DBT are showing mixed results (43-50)
   • ACR and NCCN recommend DBT 11, 12
   • A prospective trial comparing hybrid DBT/mammography with standard mammography is underway in 2024 in Australia 51.

Procedures Generally not Recommended For Average Risk Women With Non-Dense Breasts

• Clinical breast examination
  • High-quality evidence is lacking from clinical trials that population-based screening using clinical breast examination (CBE) is effective in reducing the number of deaths from breast cancer 4
  • Randomised controlled trials (RCTs) of screening at a population level using clinical breast examination compared to no screening have been undertaken but have not reported results on breast cancer mortality 4
  • In 2015 the IARC Working Group 5 concluded that there was inadequate evidence that clinical breast examination reduces breast cancer mortality, and noted that in three trials in which women were randomly assigned to receive either clinical breast examination or no screening, breast cancers detected at baseline and in the early years of the trials tended to be of a smaller size and less advanced stage in the former group of women than in the latter
  • For women who are not participating in regular mammographic screening, regular clinical breast examination may offer some benefit 12
  • RCTs comparing incremental CBE versus mammographic screening have not been performed 12
  • The majority of international guidelines no longer recommend ongoing CBE as part of a screening programme for average-risk women
• Other modalities – not indicated in average risk women with non-dense breasts
• Breast Ultrasonography
  • In average-risk women with non-dense breasts, US does not add to the CDR 52
• MRI and Contrast-enhanced mammography

• Frequency of screening recommendations for average-risk women vary from 1-3 years
• The majority of international guidelines recommend either annual or biennial screening 28
• Among those recommending annual screening are the ACR 32, NCCN 12, and the American Cancer Society 26
• USPSTF recommends biennial screening 21, 27
• European Commission Initiative on Breast Cancer (ECIBC) recommends 2-yearly screening for 50-69 year olds 23
• ESMO recommends 1-2 yearly screening 33
• Cancer Australia supports 2-yearly screening 4
• Some guidelines eg. ECIBC 33 suggest varying intervals according to women’s age, decreasing the frequency to 3-yearly in older women

This subject is beyond the scope of this article

• Although overall sensitivity of mammography is in the range of 70-85%, the sensitivity can vary significantly with breast density. The sensitivity of mammography is higher in women with fatty breast parenchyma 24, 39.
• Mammography is less sensitive in women with dense breasts 24
• Younger women tend to have denser breasts
• Dense breast tissue is an independent risk factor for breast cancer. Women with dense breasts have a higher risk than those with non-dense (fatty) breast
• Breast density category on mammography should always be reported
• Breast density can be scored on a scale from very low density (mostly fatty tissue) to mostly dense (mostly glandular/connective tissue)
• The most commonly used scale is the American College of Radiology’s Breast Imaging Reporting and Data System (BI-RADS) 38, 53, which scores density by categories A, B, C or D -
  • Type A (almost entirely fatty): around 10% of women
  • Type B (scattered areas of fibroglandular density): roughly 40% of women
  • Type C (heterogeneously dense): 40% of women have this type of mammographic density, which is considered dense and may obscure small cancers
  • Type D (extremely dense): around 10% of women have extremely dense breasts, which lowers the sensitivity of mammography.

• Digital Beast Tomosynthesis (DBT), where available, is recommended over 2D mammography
  • ACR, in addition to stating that digital mammography or DBT are appropriate as primary screening modalities, recommends DBT (over 2-D mammography) in women with dense breasts but concludes that there is, as yet, inconclusive evidence for supplemental screening in average risk women 32; this is also the conclusion of a recent systematic review of existing clinical guidelines 54.
  • The TOmosynthesis plus SYnthesized MAmmography (TOSYMA) trial revealed higher invasive cancer detection rates with digital breast tomosynthesis + synthesized mammography than with digital mammography in dense breasts, relatively and absolutely most marked among women with extremely dense breasts 55.
• About 40-50% of women have heterogeneously or extremely dense breasts 9
• The relative increase in cancer in dense breasts is thought to be 4.6 % 56
• Supplemental screening tests, in addition to DBT, may be indicated in average-risk women with dense breasts -
  • Supplemental tests include (see later for details):
    • Contrast-enhanced digital mammography
    • Whole Breast Ultrasound/Automated Breast Ultrasound (ABUS)
    • MRI
    • Sestamibi MBI (not widely available)
• The question of supplemental screening in this large group of women has not been fully resolved -
  • Recommendations among international expert consensus guidelines vary (see table below)
  • A 2024 editorial stated that there is “an urgent need for evidence on the topic of supplemental screening with ultrasound or MRI for women with dense breasts” 57
  • Interim results from an RCT published in 2025 reported that Abbreviated MRI and contrast-enhanced mammography detected three times as many invasive cancers compared with ABUS, with cancers being half the size, concluding that supplemental imaging could lead to earlier detection of cancer in women with dense breasts. The study could not estimate the level of overdiagnosis 58.

Supplemental screening tests:

• Digital Breast Tomosynthesis (DBT) (recommended over 2D mammography) -
  • ACR, in addition to stating that digital mammography or DBT are appropriate as primary screening modalities, recommends DBT (over 2-D mammography) in women with dense breasts but concludes that there is limited evidence for supplemental screening in average risk women 32.
• Contrast-enhanced digital mammography (CEM) -
  • A systematic review 59 confirmed the potential of CEM as a supplemental screening imaging modality, even for intermediate-risk women, including females with dense breasts and a history of breast cancer. This study found CEM and contrast-enhanced MRI (CE-MRI) to be equally accurate. There is insufficient data for a general recommendation in the screening setting, although ACR guidelines suggest CEM as an option as a supplemental screening test 24.
  • As noted above, interim results from an RCT published in 2025 reported that Abbreviated MRI and CEM detected three times as many invasive cancers compared with ABUS 58.
• Whole Breast Ultrasound -
  • Mammography plus ultrasound (US) (versus mammography alone) tends to increase the cancer detection rate (CDR) while increasing the recall and biopsy rates and decreasing specificity and has had a variable effect on interval cancer rate 9, 24.
  • Most guidelines do not support the use of US as a supplemental test in average risk women with dense breasts and a normal mammogram
• MRI -
  • US Preventive Services Task Force (USPSTF) concludes that there is currently insufficient evidence for or against US or MRI following an otherwise negative mammogram 21
  • European Society Of Breast Imaging (EUSOBI) supports the use of supplemental scanning with MRI every 2-3 years in women with extremely dense breast tissue 9
  • European Commission Initiative on Breast Cancer (ECIBC) Guidelines do not recommend US or MRI 23
  • As noted above, interim results from an RCT published in 2025 reported that Abbreviated MRI and CEM detected three times as many invasive cancers compared with ABUS 58
  • A further study among women with dense breasts reported that abbreviated breast MRI, compared with DBT, was associated with a significantly higher rate of invasive breast cancer detection 60
  • In a 2023 systematic review and metaanalysis the pooled data showed that MRI was the best supplemental imaging modality in women at average risk or intermediate risk for breast cancer with dense breasts who were mammographically negative for cancer 61.
• Sestamibi MBI is not widely available
• BreastScreen Australia 53 does not routinely provide additional screening for women with dense breasts. BreastScreen services in different Australian states vary regarding advising women of their mammographic density. In some states if they are identified as having dense breasts, women are given follow-up information and advised to see their GP who will then generally perform a clinical breast examination and organise US. However, the evidence for this practice is limited.
• Supplemental tests, if indicated, should be performed in addition to DBT

TABLE: Recommendations regarding supplemental screening for average-risk women with dense breasts