Advertisement
Mayo Clinic Proceedings Home

Supplemental Cancer Screening for Women With Dense Breasts: Guidance for Health Care Professionals

Published:October 19, 2021DOI:https://doi.org/10.1016/j.mayocp.2021.06.001

      Abstract

      Mammography is the standard for breast cancer screening. The sensitivity of mammography in identifying breast cancer, however, is reduced for women with dense breasts. Thirty-eight states have passed laws requiring that all women be notified of breast tissue density results in their mammogram report. The notification includes a statement that differs by state, encouraging women to discuss supplemental screening options with their health care professionals (HCPs). Several supplemental screening tests are available for women with dense breast tissue, but no established guidelines exist to direct HCPs in their recommendation of preferred supplemental screening test. Tailored screening, which takes into consideration the patient’s mammographic breast density and lifetime breast cancer risk, can guide breast cancer screening strategies that are more comprehensive. This review describes the benefits and limitations of the various available supplemental screening tests to guide HCPs and patients in choosing the appropriate breast cancer screening.

      Abbreviations and Acronyms:

      ACR (American College of Radiology), CEM (contrast-enhanced mammography), DBN (dense breast notification), DBT (digital breast tomosynthesis), HCP (health care professional), MBI (molecular breast imaging), MRI (magnetic resonance imaging), 3D (3-dimensional), WBUS (whole-breast ultrasonography)
      Article Highlights
      • Supplemental breast cancer screening methods are intended to detect additional breast cancers in women with dense breast tissue and normal mammography results.
      • Breast tissue composition and breast cancer risk differ among persons, making individualized breast cancer screening important.
      • Women with dense breasts should have a thorough discussion with their health care professionals about the risks and benefits of supplemental dense breast screening. Depending on availability and the patient’s preference, supplemental breast cancer screening considerations can include tomosynthesis, whole-breast ultrasonography, molecular breast imaging, and magnetic resonance imaging.

      Case Vignette

      A 53-year-old postmenopausal woman with a body mass index of 23.1 presents to her primary care physician after recently completing screening mammography with tomosynthesis. The patient is nulliparous with no family history of breast cancer and has never used menopausal hormone therapy. She received a letter regarding her mammogram results, which stated that the mammogram was negative for breast cancer and she has heterogeneously dense breasts. Because density could obscure detection of small masses, she is advised to discuss mammography results with her physician and to undergo consultation regarding supplemental screening. How would you counsel this patient as her physician?
      Breast cancer is the most common cancer of women worldwide. Mammography is the standard imaging tool for breast cancer screening, leading to early detection of breast cancer and a 30% reduction in mortality rate.
      • Pisano E.
      Issues in breast cancer screening.
      Mammography is the only screening test that has shown an effect in breast cancer mortality reduction.
      • Harris R.
      • Yeatts J.
      • Kinsinger L.
      Breast cancer screening for women ages 50 to 69 years a systematic review of observational evidence.
      Mammography has been reported to have a sensitivity of 80% to 95% and a specificity of 88% to 98% for women without dense breast tissue
      • Kerlikowske K.
      • Hubbard R.A.
      • Miglioretti D.L.
      • et al.
      Comparative effectiveness of digital versus film-screen mammography in community practice in the United States: a cohort study.
      • Pisano E.D.
      • Gatsonis C.
      • Hendrick E.
      • et al.
      Diagnostic performance of digital versus film mammography for breast-cancer screening.
      • Lehman C.D.
      • Arao R.F.
      • Sprague B.L.
      • et al.
      National performance benchmarks for modern screening digital mammography: update from the Breast Cancer Surveillance Consortium.
      ; however, the sensitivity can be as low as 30% to 48% in women with extremely dense tissue.
      • Pisano E.
      Issues in breast cancer screening.
      The goal of breast cancer screening is early detection to enable less aggressive breast cancer therapies that reduce morbidity and mortality rates. In situ and invasive disease can be detected with radiologic findings on mammography.
      The radiographic description of breast density provides an estimate of the amount of radiopaque breast tissue of epithelial and stromal elements compared with the amount of radiolucent fatty tissue.
      • Freer P.E.
      • Slanetz P.J.
      • Haas J.S.
      • et al.
      Breast cancer screening in the era of density notification legislation: summary of 2014 Massachusetts experience and suggestion of an evidence-based management algorithm by multi-disciplinary expert panel.
      Fat appears dark on a mammogram; fibroglandular tissue appears white. Breast density is assessed by subjective visual evaluation on mammography, leading to interobserver and intraobserver variability.
      • Keller B.M.
      • Nathan D.L.
      • Gavenonis S.C.
      • Chen J.
      • Conant E.F.
      • Kontos D.
      Reader variability in breast density estimation from full-field digital mammograms: the effect of image postprocessing on relative and absolute measures.
      The Breast Imaging–Reporting and Data System developed by the American College of Radiology (ACR) has the standardized verbiage used by radiologists to classify breast density.
      • Mercado C.L.
      BI-RADS update.
      ,
      • Burkett B.J.
      • Hanemann C.W.
      A review of supplemental screening ultrasound for breast cancer: certain populations of women with dense breast tissue may benefit.
      This system divides it into 4 categories according to the amount of fibroglandular tissue: entirely fatty (a), scattered fibroglandular (b), heterogeneously dense (c), and extremely dense (d).
      • Nevler A.
      • Shabtai E.
      • Rosin D.
      • Hoffman A.
      • Gutman M.
      • Shabtai M.
      Mammographic breast density as a predictor of radiological findings requiring further investigation.
      In approximately 50% of mammography reports in the United States, breast tissue is reported as heterogeneously dense or extremely dense.
      • Nevler A.
      • Shabtai E.
      • Rosin D.
      • Hoffman A.
      • Gutman M.
      • Shabtai M.
      Mammographic breast density as a predictor of radiological findings requiring further investigation.
      Breast density fluctuates throughout a woman’s menstrual cycle
      • White E.
      • Velentgas P.
      • Mandelson M.T.
      • et al.
      Variation in mammographic breast density by time in menstrual cycle among women aged 40-49 years.
      and is not related to breast size, nor can it be gauged by physical examination.
      • Swann C.A.
      • Kopans D.B.
      • McCarthy K.A.
      • White G.
      • Hall D.A.
      Mammographic density and physical assessment of the breast.
      Some associations with increased breast density include the BRCA1 and BRCA2 inherited genetic variants, hormone therapy, younger age,
      • Quandt Z.
      • Flom J.D.
      • Tehranifar P.
      • Reynolds D.
      • Terry M.B.
      • McDonald J.A.
      The association of alcohol consumption with mammographic density in a multiethnic urban population.
      • Burton A.
      • Maskarinec G.
      • Perez-Gomez B.
      • et al.
      Mammographic density and ageing: a collaborative pooled analysis of cross-sectional data from 22 countries worldwide.
      • Sherratt M.J.
      • McConnell J.C.
      • Streuli C.H.
      Raised mammographic density: causative mechanisms and biological consequences.
      • Henry N.L.
      • Chan H.P.
      • Dantzer J.
      • et al.
      Aromatase inhibitor–induced modulation of breast density: clinical and genetic effects.
      • Harris H.R.
      • Tamimi R.M.
      • Willett W.C.
      • Hankinson S.E.
      • Michels K.B.
      Body size across the life course, mammographic density, and risk of breast cancer.
      • Boyd N.F.
      • Melnichouk O.
      • Martin L.J.
      • et al.
      Mammographic density, response to hormones, and breast cancer risk.
      • Warren R.
      Hormones and mammographic breast density.
      and lower body mass index; insulinemic diet (foods that cause greater insulin production) during puberty
      • Jung S.
      • Goloubeva O.
      • Hylton N.
      • et al.
      Intake of dietary carbohydrates in early adulthood and adolescence and breast density among young women.
      ; and alcohol consumption.
      • Quandt Z.
      • Flom J.D.
      • Tehranifar P.
      • Reynolds D.
      • Terry M.B.
      • McDonald J.A.
      The association of alcohol consumption with mammographic density in a multiethnic urban population.
      Breast density decreases with advancing age; the greatest decrease occurs around menopause and is mostly due to involution of glandular tissue.
      • Burton A.
      • Maskarinec G.
      • Perez-Gomez B.
      • et al.
      Mammographic density and ageing: a collaborative pooled analysis of cross-sectional data from 22 countries worldwide.
      Tamoxifen, aromatase inhibitor, and gonadotropin-releasing hormone agonist therapies are associated with reduced breast density, an effect related to their influence on estrogen levels and related effects on the breast.
      • Sherratt M.J.
      • McConnell J.C.
      • Streuli C.H.
      Raised mammographic density: causative mechanisms and biological consequences.
      ,
      • Henry N.L.
      • Chan H.P.
      • Dantzer J.
      • et al.
      Aromatase inhibitor–induced modulation of breast density: clinical and genetic effects.
      Dense breast tissue can obscure underlying breast lesions that have mammographic attenuation similar to dense fibroglandular tissue, called the masking effect.
      • Hooley R.J.
      • Greenberg K.L.
      • Stackhouse R.M.
      • Geisel J.L.
      • Butler R.S.
      • Philpotts L.E.
      Screening US in patients with mammographically dense breasts: initial experience with Connecticut Public Act 09-41.
      ,
      • Mandelson M.T.
      • Oestreicher N.
      • Porter P.L.
      • et al.
      Breast density as a predictor of mammographic detection: comparison of interval- and screen-detected cancers.
      In addition, breast density is considered a modest independent risk factor for breast cancer, with a 5.65-fold increased risk of interval breast cancers compared with women with nondense breasts. Interval cancers are defined as those cancers detected by a woman with symptoms and within 12 months of a normal mammogram. These interval cancers typically have a worse prognosis than screen-detected cancers.
      • Kerlikowske K.
      • Scott C.G.
      • Mahmoudzadeh A.P.
      • et al.
      Automated and clinical breast imaging reporting and data system density measures predict risk for screen-detected and interval cancers: a case-control study.
      Given the limitations of standard mammography for women with dense breasts, the new state-mandated dense breast notifications (DBNs) are intended to motivate patients to discuss personal risk and supplemental screening tests with their health care professionals (HCPs). Supplemental imaging tools for dense breasts have been found to augment breast cancer detection rates by identifying mammographically occult cancers in women with dense breast tissue.
      • Hooley R.J.
      • Greenberg K.L.
      • Stackhouse R.M.
      • Geisel J.L.
      • Butler R.S.
      • Philpotts L.E.
      Screening US in patients with mammographically dense breasts: initial experience with Connecticut Public Act 09-41.
      ,
      • Haas B.M.
      • Kalra V.
      • Geisel J.
      • Raghu M.
      • Durand M.
      • Philpotts L.E.
      Comparison of tomosynthesis plus digital mammography and digital mammography alone for breast cancer screening.
      • Kolb T.M.
      • Lichy J.
      • Newhouse J.H.
      Occult cancer in women with dense breasts: detection with screening US—diagnostic yield and tumor characteristics.
      • Corsetti V.
      • Ferrari A.
      • Ghirardi M.
      • et al.
      Role of ultrasonography in detecting mammographically occult breast carcinoma in women with dense breasts.
      • Drukker K.
      • Horsch K.J.
      • Pesce L.L.
      • Giger M.L.
      Interreader scoring variability in an observer study using dual-modality imaging for breast cancer detection in women with dense breasts.
      • Kelly K.M.
      • Dean J.
      • Comulada W.S.
      • Lee S.J.
      Breast cancer detection using automated whole breast ultrasound and mammography in radiographically dense breasts.
      • Gur D.
      • Abrams G.S.
      • Chough D.M.
      • et al.
      Digital breast tomosynthesis: observer performance study.
      Health care professionals need to be knowledgeable about the supplemental screening options available in their community, including such details as insurance coverage and screening intervals, for shared decision-making that acknowledges the patient’s preferences and values. In this article, we provide background of the DBN laws, benefits and limitations of the supplemental screening modalities, breast cancer risk assessment, and tools available to facilitate a practical, shared decision-making model in primary care.
      We undertook a literature search with the terms breast cancer, supplemental breast cancer screening, tomosynthesis, breast ultrasound, breast MBI, and breast MRI using PubMed and Scopus, published in English from January 1997 through March 2020. We reviewed more than 600 articles of all publication types (eg, peer-reviewed research, systematic reviews, literature reviews, editorials, preprints). They included all relevant articles with reference to the guidelines of major societies, such as ACR, American Cancer Society, National Comprehensive Cancer Network, and American College of Obstetricians and Gynecologists, and citations within the reviewed articles were identified. In total, 161 articles in English, with clinical data of breast density screening and supplemental imaging modalities, are referenced in this manuscript.

      Background of DBN

      The initial passage of a mandate for DBN occurred in Connecticut in 2009. Since then, 38 states started to mandate DBN, and 5 states also mandate supplemental screening for women with dense breast tissue. On March 27, 2019, the US Food and Drug Administration proposed a rule (Federal Register, Mammography Quality Standards Act, May 7, 2019) that requires all mammography facilities to use standard reporting language to ensure that their reports include information about qualitative assessment of breast density, how breast density may mask cancer on a mammogram, and a reminder to patients with dense breasts to talk with their HCP if they have questions. This rule helps set minimum reporting standards for all states. Every year, 40 million US women in the age group of 40 to 74 years undergo breast cancer screening with mammography. Of these women, 43% have dense breast tissue. The DBN translates into nearly 28 million women obtaining additional breast density information.
      • Sprague B.L.
      • Conant E.F.
      • Onega T.
      • et al.
      Variation in mammographic breast density assessments among radiologists in clinical practice: a multicenter observational study.
      Currently, no breast density notification mandate exists outside the United States.
      A study published in the Journal of the American College of Radiology suggested that DBN helps disseminate information about the limited sensitivity of mammography for women with dense breasts and helps initiate the conversation between patient and HCP about supplemental dense breast screening options.
      • Cappello N.M.
      • Richetelli D.
      • Lee C.I.
      The impact of breast density reporting laws on women's awareness of density-associated risks and conversations regarding supplemental screening with providers.
      Studies have shown that the resulting rate of women pursuing supplemental imaging after DBN continues to be variable
      • Sechopoulos I.
      A review of breast tomosynthesis. Part II. Image reconstruction, processing and analysis, and advanced applications.
      • Mumin N.A.
      • Rahmat K.
      • Fadzli F.
      • et al.
      Diagnostic efficacy of synthesized 2D digital breast tomosynthesis in multi-ethnic Malaysian population.
      • Liao G.J.
      • Hippe D.S.
      • Chen L.E.
      • et al.
      Physician ordering of screening ultrasound: national rates and association with state-level breast density reporting laws.
      • de Lange S.V.
      • Bakker M.F.
      • Monninkhof E.M.
      • et al.
      Reasons for (non)participation in supplemental population-based MRI breast screening for women with extremely dense breasts.
      • Weigert J.
      • Steenbergen S.
      The Connecticut experiment: the role of ultrasound in the screening of women with dense breasts.
      • Berg W.A.
      • Gutierrez L.
      • NessAiver M.S.
      • et al.
      Diagnostic accuracy of mammography, clinical examination, US, and MR imaging in preoperative assessment of breast cancer.
      Reasons may be multifactorial, including incomprehensible language that requires a high literacy level, lack of clear explanation,
      • Miles R.C.
      • Lehman C.
      • Warner E.
      • Tuttle A.
      • Saksena M.
      Patient-reported breast density awareness and knowledge after breast density legislation passage.
      lack of cultural sensitivity,
      US Department of Education, Institute of Education Sciences, National Center for Education Statistics
      A first look at the literacy of America's adults in the 21st century.
      ,
      • Weiss B.D.
      American Medical Association Foundation
      Health literacy: a manual for clinicians.
      and failure to incorporate the preferences and values of the patient.
      • Saraiya A.
      • Baird G.L.
      • Lourenco A.P.
      Breast density notification letters and websites: are they too "dense"?.
      ,
      • Kressin N.R.
      • Gunn C.M.
      • Battaglia T.A.
      Content, readability, and understandability of dense breast notifications by state [erratum appears in JAMA. 2016;315(23):2624].
      Studies have confirmed that the quality of communication may vary on the basis of racial ethnicity learning to increased health care disparities.
      • Kressin N.R.
      • Gunn C.M.
      • Battaglia T.A.
      Content, readability, and understandability of dense breast notifications by state [erratum appears in JAMA. 2016;315(23):2624].
      • Kuhl C.K.
      • Schrading S.
      • Strobel K.
      • Schild H.H.
      • Hilgers R.D.
      • Bieling H.B.
      Abbreviated breast magnetic resonance imaging (MRI): first postcontrast subtracted images and maximum-intensity projection—a novel approach to breast cancer screening with MRI.
      • Ashton C.M.
      • Haidet P.
      • Paterniti D.A.
      • et al.
      Racial and ethnic disparities in the use of health services: bias, preferences, or poor communication?.
      • Eggly S.
      • Barton E.
      • Winckles A.
      • Penner L.A.
      • Albrecht T.L.
      A disparity of words: racial differences in oncologist-patient communication about clinical trials.
      • Street Jr., R.L.
      • Gordon H.S.
      • Ward M.M.
      • Krupat E.
      • Kravitz R.L.
      Patient participation in medical consultations: why some patients are more involved than others.
      • Manning M.
      • Purrington K.
      • Penner L.
      • Duric N.
      • Albrecht T.L.
      Between-race differences in the effects of breast density information and information about new imaging technology on breast-health decision-making.
      In fact, in many instances, the DBN did not specify the type of supplemental test that is recommended and whether it will be covered by insurance carriers, causing confusion among patients and HCPs.

      Supplemental Screening Options

      Several supplemental screening modalities in combination with mammography are more effective than mammography alone for detection of additional breast cancer among women with dense breasts (Table 1).
      • Berg W.A.
      Supplemental screening sonography in dense breasts.
      • Berg W.A.
      • Blume J.D.
      • Cormack J.B.
      • Mendelson E.B.
      Training the ACRIN 6666 Investigators and effects of feedback on breast ultrasound interpretive performance and agreement in BI-RADS ultrasound feature analysis.
      • Kuhl C.K.
      • Strobel K.
      • Bieling H.
      • Leutner C.
      • Schild H.H.
      • Schrading S.
      Supplemental breast MR imaging screening of women with average risk of breast cancer.
      • Kuhl C.K.
      • Schrading S.
      • Leutner C.C.
      • et al.
      Mammography, breast ultrasound, and magnetic resonance imaging for surveillance of women at high familial risk for breast cancer.
      • Kjesbu I.E.
      • Laursen C.B.
      • Graven T.
      • et al.
      Feasibility and diagnostic accuracy of point-of-care abdominal sonography by pocket-sized imaging devices, performed by medical residents.
      • Skaane P.
      • Bandos A.I.
      • Gullien R.
      • et al.
      Comparison of digital mammography alone and digital mammography plus tomosynthesis in a population-based screening program.
      • Phi X.A.
      • Houssami N.
      • Hooning M.J.
      • et al.
      Accuracy of screening women at familial risk of breast cancer without a known gene mutation: individual patient data meta-analysis.
      • Tagliafico A.
      • Mariscotti G.
      • Durando M.
      • et al.
      Characterisation of microcalcification clusters on 2D digital mammography (FFDM) and digital breast tomosynthesis (DBT): does DBT underestimate microcalcification clusters? Results of a multicentre study.
      • Mariscotti G.
      • Houssami N.
      • Durando M.
      • et al.
      Digital breast tomosynthesis (DBT) to characterize MRI-detected additional lesions unidentified at targeted ultrasound in newly diagnosed breast cancer patients.
      • Skaane P.
      • Bandos A.I.
      • Niklason L.T.
      • et al.
      Digital mammography versus digital mammography plus tomosynthesis in breast cancer screening: the Oslo Tomosynthesis Screening Trial.
      • Hruska C.B.
      Molecular breast imaging for screening in dense breasts: state of the art and future directions.
      • Shermis R.B.
      • Redfern R.E.
      • Burns J.
      • Kudrolli H.
      Molecular breast imaging in breast cancer screening and problem solving.
      • Li L.
      • Roth R.
      • Germaine P.
      • et al.
      Contrast-enhanced spectral mammography (CESM) versus breast magnetic resonance imaging (MRI): a retrospective comparison in 66 breast lesions.
      • Barra F.R.
      • Sobrinho A.B.
      • Barra R.R.
      • et al.
      Contrast-enhanced mammography (CEM) for detecting residual disease after neoadjuvant chemotherapy: a comparison with breast magnetic resonance imaging (MRI).
      • Li H.
      • Yin L.
      • He N.
      • et al.
      Comparison of comfort between cone beam breast computed tomography and digital mammography.
      • Berg W.A.
      • Zhang Z.
      • Lehrer D.
      • et al.
      Detection of breast cancer with addition of annual screening ultrasound or a single screening MRI to mammography in women with elevated breast cancer risk.
      • Tagliafico A.S.
      • Calabrese M.
      • Mariscotti G.
      • et al.
      Adjunct screening with tomosynthesis or ultrasound in women with mammography-negative dense breasts: interim report of a prospective comparative trial.
      • Tagliafico A.S.
      • Mariscotti G.
      • Valdora F.
      • et al.
      A prospective comparative trial of adjunct screening with tomosynthesis or ultrasound in women with mammography-negative dense breasts (ASTOUND-2).
      • Friedewald S.M.
      • Rafferty E.A.
      • Rose S.L.
      • et al.
      Breast cancer screening using tomosynthesis in combination with digital mammography.
      • Ciatto S.
      • Houssami N.
      • Bernardi D.
      • et al.
      Integration of 3D digital mammography with tomosynthesis for population breast-cancer screening (STORM): a prospective comparison study.
      • Rafferty E.A.
      • Durand M.A.
      • Conant E.F.
      • et al.
      Breast cancer screening using tomosynthesis and digital mammography in dense and nondense breasts.
      • Lehman C.D.
      • Isaacs C.
      • Schnall M.D.
      • et al.
      Cancer yield of mammography, MR, and US in high-risk women: prospective multi-institution breast cancer screening study.
      • Comstock C.E.
      • Gatsonis C.
      • Newstead G.M.
      • et al.
      Comparison of abbreviated breast MRI vs digital breast tomosynthesis for breast cancer detection among women with dense breasts undergoing screening [erratum appears in JAMA. 2020;323(12):1194].
      • Bakker M.F.
      • de Lange S.V.
      • Pijnappel R.M.
      • et al.
      Supplemental MRI screening for women with extremely dense breast tissue.
      • Jochelson M.S.
      • Pinker K.
      • Dershaw D.D.
      • et al.
      Comparison of screening CEDM and MRI for women at increased risk for breast cancer: a pilot study.
      • Sung J.S.
      • Lebron L.
      • Keating D.
      • et al.
      Performance of dual-energy contrast-enhanced digital mammography for screening women at increased risk of breast cancer.
      • Sorin V.
      • Yagil Y.
      • Yosepovich A.
      • et al.
      Contrast-enhanced spectral mammography in women with intermediate breast cancer risk and dense breasts.
      • Berg W.A.
      • Vourtsis A.
      Screening breast ultrasound using handheld or automatic technique in women with dense breasts.
      One category includes functional imaging, which has the benefit of detection of vascular, molecular, and metabolic changes in breast tissue despite anatomic limitations in the tissue. Several newer technologies and modifications to existing technology are in the pursuit of the ideal supplemental screening test. These technologies and modifications are outside the scope of this article.
      Table 1Comparison of Supplemental BC Screening Modalities
      BC, breast cancer; CDR, clinical data repository; CEM, contrast-enhanced mammography; DBT, digital breast tomosynthesis; IV, intravenous; MBI, molecular breast imaging; MR, magnetic resonance; MRI, magnetic resonance imaging.
      CharacteristicModality (type)
      Ultrasonography
      • Berg W.A.
      Supplemental screening sonography in dense breasts.
      • Berg W.A.
      • Blume J.D.
      • Cormack J.B.
      • Mendelson E.B.
      Training the ACRIN 6666 Investigators and effects of feedback on breast ultrasound interpretive performance and agreement in BI-RADS ultrasound feature analysis.
      • Kuhl C.K.
      • Strobel K.
      • Bieling H.
      • Leutner C.
      • Schild H.H.
      • Schrading S.
      Supplemental breast MR imaging screening of women with average risk of breast cancer.
      • Kuhl C.K.
      • Schrading S.
      • Leutner C.C.
      • et al.
      Mammography, breast ultrasound, and magnetic resonance imaging for surveillance of women at high familial risk for breast cancer.
      • Kjesbu I.E.
      • Laursen C.B.
      • Graven T.
      • et al.
      Feasibility and diagnostic accuracy of point-of-care abdominal sonography by pocket-sized imaging devices, performed by medical residents.
      ,
      • Berg W.A.
      • Zhang Z.
      • Lehrer D.
      • et al.
      Detection of breast cancer with addition of annual screening ultrasound or a single screening MRI to mammography in women with elevated breast cancer risk.
      • Tagliafico A.S.
      • Calabrese M.
      • Mariscotti G.
      • et al.
      Adjunct screening with tomosynthesis or ultrasound in women with mammography-negative dense breasts: interim report of a prospective comparative trial.
      • Tagliafico A.S.
      • Mariscotti G.
      • Valdora F.
      • et al.
      A prospective comparative trial of adjunct screening with tomosynthesis or ultrasound in women with mammography-negative dense breasts (ASTOUND-2).
      ,
      • Berg W.A.
      • Vourtsis A.
      Screening breast ultrasound using handheld or automatic technique in women with dense breasts.
      (anatomic)
      DBT
      A primary screening tool at Mayo Clinic.
      ,
      • Skaane P.
      • Bandos A.I.
      • Gullien R.
      • et al.
      Comparison of digital mammography alone and digital mammography plus tomosynthesis in a population-based screening program.
      • Phi X.A.
      • Houssami N.
      • Hooning M.J.
      • et al.
      Accuracy of screening women at familial risk of breast cancer without a known gene mutation: individual patient data meta-analysis.
      • Tagliafico A.
      • Mariscotti G.
      • Durando M.
      • et al.
      Characterisation of microcalcification clusters on 2D digital mammography (FFDM) and digital breast tomosynthesis (DBT): does DBT underestimate microcalcification clusters? Results of a multicentre study.
      • Mariscotti G.
      • Houssami N.
      • Durando M.
      • et al.
      Digital breast tomosynthesis (DBT) to characterize MRI-detected additional lesions unidentified at targeted ultrasound in newly diagnosed breast cancer patients.
      • Skaane P.
      • Bandos A.I.
      • Niklason L.T.
      • et al.
      Digital mammography versus digital mammography plus tomosynthesis in breast cancer screening: the Oslo Tomosynthesis Screening Trial.
      ,
      • Li H.
      • Yin L.
      • He N.
      • et al.
      Comparison of comfort between cone beam breast computed tomography and digital mammography.
      ,
      • Friedewald S.M.
      • Rafferty E.A.
      • Rose S.L.
      • et al.
      Breast cancer screening using tomosynthesis in combination with digital mammography.
      • Ciatto S.
      • Houssami N.
      • Bernardi D.
      • et al.
      Integration of 3D digital mammography with tomosynthesis for population breast-cancer screening (STORM): a prospective comparison study.
      • Rafferty E.A.
      • Durand M.A.
      • Conant E.F.
      • et al.
      Breast cancer screening using tomosynthesis and digital mammography in dense and nondense breasts.
      (anatomic)
      MBI
      • Hruska C.B.
      Molecular breast imaging for screening in dense breasts: state of the art and future directions.
      ,
      • Shermis R.B.
      • Redfern R.E.
      • Burns J.
      • Kudrolli H.
      Molecular breast imaging in breast cancer screening and problem solving.
      (functional)
      MRI
      • Kuhl C.K.
      • Strobel K.
      • Bieling H.
      • Leutner C.
      • Schild H.H.
      • Schrading S.
      Supplemental breast MR imaging screening of women with average risk of breast cancer.
      ,
      • Berg W.A.
      • Zhang Z.
      • Lehrer D.
      • et al.
      Detection of breast cancer with addition of annual screening ultrasound or a single screening MRI to mammography in women with elevated breast cancer risk.
      ,
      • Lehman C.D.
      • Isaacs C.
      • Schnall M.D.
      • et al.
      Cancer yield of mammography, MR, and US in high-risk women: prospective multi-institution breast cancer screening study.
      • Comstock C.E.
      • Gatsonis C.
      • Newstead G.M.
      • et al.
      Comparison of abbreviated breast MRI vs digital breast tomosynthesis for breast cancer detection among women with dense breasts undergoing screening [erratum appears in JAMA. 2020;323(12):1194].
      • Bakker M.F.
      • de Lange S.V.
      • Pijnappel R.M.
      • et al.
      Supplemental MRI screening for women with extremely dense breast tissue.
      ,
      • Sorin V.
      • Yagil Y.
      • Yosepovich A.
      • et al.
      Contrast-enhanced spectral mammography in women with intermediate breast cancer risk and dense breasts.
      (functional)
      CEM
      • Li L.
      • Roth R.
      • Germaine P.
      • et al.
      Contrast-enhanced spectral mammography (CESM) versus breast magnetic resonance imaging (MRI): a retrospective comparison in 66 breast lesions.
      ,
      • Barra F.R.
      • Sobrinho A.B.
      • Barra R.R.
      • et al.
      Contrast-enhanced mammography (CEM) for detecting residual disease after neoadjuvant chemotherapy: a comparison with breast magnetic resonance imaging (MRI).
      ,
      • Jochelson M.S.
      • Pinker K.
      • Dershaw D.D.
      • et al.
      Comparison of screening CEDM and MRI for women at increased risk for breast cancer: a pilot study.
      ,
      • Sung J.S.
      • Lebron L.
      • Keating D.
      • et al.
      Performance of dual-energy contrast-enhanced digital mammography for screening women at increased risk of breast cancer.
      (functional)
      Incremental CDR per 10001.2-2.71.2-2.76.5-6.99.7-16.513.1-15.5
      Specificity, %42-8269-868375.7-97.493.7-94.1
      Radiation exposureNoYesYesNoYes
      AdvantagesNo exposure to ionizing radiation

      Widely accessible

      Reduces interval cancers in dense breasts
      Reduced recall rate

      Coverage by most insurance carriers
      Sestamibi well tolerated

      Alternative for women with MR contraindication

      Lower dose models and biopsy capability under development
      Most sensitive test

      No ionizing radiation

      Reduced interval cancers

      Development of advanced MR techniques underway
      Less costly than MRI

      Less time-consuming than MRI

      More accessible
      DrawbacksHigh recall rates

      Low positive predictive value

      Large number of images to review
      Sensitivity modest in extremely dense breasts

      Modest increase in cost and time than standard mammography
      4 times more radiation than standard mammography

      40-min image acquisition time
      Relatively costly

      Gadolinium contrast agent required

      Cannot be used in morbidly obese patients and those with severe claustrophobia
      Early research and data studies with low number of participants

      IV iodine contrast agent (potential allergy)

      Not widely available
      a BC, breast cancer; CDR, clinical data repository; CEM, contrast-enhanced mammography; DBT, digital breast tomosynthesis; IV, intravenous; MBI, molecular breast imaging; MR, magnetic resonance; MRI, magnetic resonance imaging.
      b A primary screening tool at Mayo Clinic.

       Digital Breast Tomosynthesis

      Tomosynthesis, also known as 3-dimensional (3D) mammography, is a technique whereby the X-ray tube moves in an arc over the breast, allowing acquisition of images from multiple angles while the breast is compressed. These additional thin-section images are typically reconstructed into 1-mm slices to create a 3D image.
      • Niklason L.T.
      • Christian B.T.
      • Niklason L.E.
      • et al.
      Digital tomosynthesis in breast imaging.
      The thin images reduce the overlap of tissues and help with the separation of the breast lesions from the superimposed breast tissue to improve lesion conspicuity.
      • Haas B.M.
      • Kalra V.
      • Geisel J.
      • Raghu M.
      • Durand M.
      • Philpotts L.E.
      Comparison of tomosynthesis plus digital mammography and digital mammography alone for breast cancer screening.
      ,
      • Ho J.M.
      • Jafferjee N.
      • Covarrubias G.M.
      • Ghesani M.
      • Handler B.
      Dense breasts: a review of reporting legislation and available supplemental screening options.
      Studies have shown an additional 1.2 to 2.7 cancers detected per 1000 screening examinations for 3D mammography compared with standard 2-dimensional digital mammography.
      • Ciatto S.
      • Houssami N.
      • Bernardi D.
      • et al.
      Integration of 3D digital mammography with tomosynthesis for population breast-cancer screening (STORM): a prospective comparison study.
      ,
      • Skaane P.
      • Bandos A.I.
      • Gullien R.
      • et al.
      Prospective trial comparing full-field digital mammography (FFDM) versus combined FFDM and tomosynthesis in a population-based screening programme using independent double reading with arbitration.
      ,
      • Lang K.
      • Andersson I.
      • Rosso A.
      • Tingberg A.
      • Timberg P.
      • Zackrisson S.
      Performance of one-view breast tomosynthesis as a stand-alone breast cancer screening modality: results from the Malmö Breast Tomosynthesis Screening Trial, a population-based study.
      Unlike most advanced imaging techniques, digital breast tomosynthesis (DBT) is distinctive because it leads to increased sensitivity with an absolute reduction in recall rates of 0.8% to 3.6%. A reduction in false-positive recall rates of 29% has been noted especially for women younger than 50 years with dense breasts.
      • Kerlikowske K.
      • Scott C.G.
      • Mahmoudzadeh A.P.
      • et al.
      Automated and clinical breast imaging reporting and data system density measures predict risk for screen-detected and interval cancers: a case-control study.
      ,
      • Haas B.M.
      • Kalra V.
      • Geisel J.
      • Raghu M.
      • Durand M.
      • Philpotts L.E.
      Comparison of tomosynthesis plus digital mammography and digital mammography alone for breast cancer screening.
      ,
      • Ho J.M.
      • Jafferjee N.
      • Covarrubias G.M.
      • Ghesani M.
      • Handler B.
      Dense breasts: a review of reporting legislation and available supplemental screening options.
      ,
      • Friedewald S.M.
      • Rafferty E.A.
      • Conant E.F.
      Breast cancer screening with tomosynthesis and digital mammography—reply.
      As of 2016, the National Comprehensive Cancer Network has updated its guidelines to consider annual DBT screening starting at the age of 40 years for women with an average risk of breast cancer.
      • Skaane P.
      • Bandos A.I.
      • Gullien R.
      • et al.
      Comparison of digital mammography alone and digital mammography plus tomosynthesis in a population-based screening program.
      At Mayo Clinic, breast DBT is considered a screening mammogram test and is recommended universally, regardless of breast density.

       Breast Ultrasonography

      Supplemental screening with breast ultrasonography is widely accessible in the United States, does not have ionizing radiation, and allows real-time biopsy of a lesion when necessary.
      • Scheel J.R.
      • Lee J.M.
      • Sprague B.L.
      • Lee C.I.
      • Lehman C.D.
      Screening ultrasound as an adjunct to mammography in women with mammographically dense breasts.
      Accordingly, whole-breast ultrasonography (WBUS) has become a common supplemental screening test recommended by many HCPs.
      • Vaughan C.L.
      • Douglas T.S.
      • Said-Hartley Q.
      • et al.
      Testing a dual-modality system that combines full-field digital mammography and automated breast ultrasound.
      Both handheld ultrasonography and WBUS are comparable in sensitivity and specificity for women with dense breast tissue and normal mammography results.
      • Berg W.A.
      • Zhang Z.
      • Lehrer D.
      • et al.
      Detection of breast cancer with addition of annual screening ultrasound or a single screening MRI to mammography in women with elevated breast cancer risk.
      ,
      • Melnikow J.
      • Fenton J.J.
      • Whitlock E.P.
      • et al.
      Supplemental screening for breast cancer in women with dense breasts: a systematic review for the U.S. Preventive Services Task Force.
      ,
      • Berg W.A.
      • Blume J.D.
      • Cormack J.B.
      • et al.
      Combined screening with ultrasound and mammography vs mammography alone in women at elevated risk of breast cancer [erratum appears in JAMA. 2010;303(15):1482].
      Handheld ultrasonography has the drawback of scan reproducibility and requires a highly trained specialist.
      • Vaughan C.L.
      • Douglas T.S.
      • Said-Hartley Q.
      • et al.
      Testing a dual-modality system that combines full-field digital mammography and automated breast ultrasound.
      ,
      • Merry G.M.
      • Mendelson E.B.
      Update on screening breast ultrasonography.
      ,
      • Berg W.A.
      • Mendelson E.B.
      Technologist-performed handheld screening breast US imaging: how is it performed and what are the outcomes to date?.
      Alone, ultrasonography lacks the spatial resolution of mammography and does not help in the diagnosis of most microcalcifications.
      • Weigert J.
      • Steenbergen S.
      The Connecticut experiment: the role of ultrasound in the screening of women with dense breasts.
      Yet, it effectively differentiates tissues of varying densities (fluid vs soft tissue).
      • Vaughan C.L.
      • Douglas T.S.
      • Said-Hartley Q.
      • et al.
      Testing a dual-modality system that combines full-field digital mammography and automated breast ultrasound.
      The cancers missed on mammography but detected by ultrasonography are reported to be mostly small, node-negative, and invasive breast cancers.
      • Berg W.A.
      Supplemental screening sonography in dense breasts.
      ,
      • Kelly K.M.
      • Richwald G.A.
      Automated whole-breast ultrasound: advancing the performance of breast cancer screening.
      About 1.8 to 4.6 additional breast cancers were detected per 1000 women when WBUS was used for screening asymptomatic women with dense breasts and normal results on mammography.
      • Weigert J.
      • Steenbergen S.
      The Connecticut experiment: the role of ultrasound in the screening of women with dense breasts.
      ,
      • Melnikow J.
      • Fenton J.J.
      • Whitlock E.P.
      • et al.
      Supplemental screening for breast cancer in women with dense breasts: a systematic review for the U.S. Preventive Services Task Force.
      ,
      • Sprague B.L.
      • Stout N.K.
      • Schechter C.
      • et al.
      Benefits, harms, and cost-effectiveness of supplemental ultrasonography screening for women with dense breasts.
      More than 70% of these cancers were less than 10 mm, 90% were stage 0 or 1, and 94% were invasive.
      • Merry G.M.
      • Mendelson E.B.
      Update on screening breast ultrasonography.
      ,
      • Okello J.
      • Kisembo H.
      • Bugeza S.
      • Galukande M.
      Breast cancer detection using sonography in women with mammographically dense breasts.
      Interval cancer rates have been shown to be reduced after ultrasound screening started to be used as a supplemental study.
      • Berg W.A.
      • Blume J.D.
      • Cormack J.B.
      • Mendelson E.B.
      Training the ACRIN 6666 Investigators and effects of feedback on breast ultrasound interpretive performance and agreement in BI-RADS ultrasound feature analysis.
      ,
      • Ohuchi N.
      • Suzuki A.
      • Sobue T.
      • et al.
      Sensitivity and specificity of mammography and adjunctive ultrasonography to screen for breast cancer in the Japan Strategic Anti-cancer Randomized Trial (J-START): a randomised controlled trial.
      These findings suggest that incorporation of screening ultrasonography performed by a trained specialist with a normal screening mammography result is one of the effective supplemental strategies for women with dense breasts or other intermediate risk factors.
      Screening ultrasonography, however, can lead to false-positive results when it is added to mammography. Screening studies have shown a 12% to 15% increase in recall rates with a reported low positive predictive value (9.4%), where false-positive ultrasonography results led to many unnecessary biopsies.
      • Melnikow J.
      • Fenton J.J.
      • Whitlock E.P.
      • et al.
      Supplemental screening for breast cancer in women with dense breasts: a systematic review for the U.S. Preventive Services Task Force.
      ,
      • Merry G.M.
      • Mendelson E.B.
      Update on screening breast ultrasonography.
      Overall, supplemental screening ultrasonography of women with dense breasts allows detection of more breast cancers at an earlier stage, facilitating less radical treatment options and improved survival rates.
      • Berg W.A.
      Supplemental screening sonography in dense breasts.
      The ACR
      • Lee C.H.
      • Dershaw D.D.
      • Kopans D.
      • et al.
      Breast cancer screening with imaging: recommendations from the Society of Breast Imaging and the ACR on the use of mammography, breast MRI, breast ultrasound, and other technologies for the detection of clinically occult breast cancer.
      ,
      • Mainiero M.B.
      • Lourenco A.
      • Mahoney M.C.
      • et al.
      ACR Appropriateness Criteria Breast Cancer Screening.
      recommends ultrasonography as an optional tool for screening of an asymptomatic woman with dense breast tissue at average to intermediate risk for breast cancer and as a supplemental screening tool for high-risk women who cannot tolerate breast magnetic resonance imaging (MRI).
      • Scheel J.R.
      • Lee J.M.
      • Sprague B.L.
      • Lee C.I.
      • Lehman C.D.
      Screening ultrasound as an adjunct to mammography in women with mammographically dense breasts.
      Providers are advised to counsel women about potential limitations before recommending this as a supplemental screening tool. These limitations include the limited positive predictive value, which may result in unnecessary procedures that have benign results, and a relatively high recall rate, which can lead to additional short-term imaging follow-up.

       Molecular Breast Imaging

      Molecular breast imaging (MBI) is a functional nuclear imaging test that uses a tumor-avid radioactive tracer, technetium Tc 99m sestamibi.
      • Hruska C.B.
      • O'Connor M.K.
      Nuclear imaging of the breast: translating achievements in instrumentation into clinical use.
      Among the benefits of functional imaging, markers are used to detect vascular, molecular, and metabolic changes in breast tissue despite anatomic limitations in the breast. Tissues containing cancer cells, which rapidly grow and divide, show increased angiogenesis and mitochondrial concentration resulting in greater uptake of technetium. The US Food and Drug Administration has approved MBI for supplemental screening of women who have dense breasts and normal mammography results.
      • Hruska C.B.
      Molecular breast imaging for screening in dense breasts: state of the art and future directions.
      A prospective clinical study by Rhodes et al,
      • Rhodes D.J.
      • Hruska C.B.
      • Conners A.L.
      • et al.
      Journal club: molecular breast imaging at reduced radiation dose for supplemental screening in mammographically dense breasts.
      supported by similar studies later, showed that the addition of supplemental MBI detected an incremental 7.5 to 8.8 cancers per 1000 women screened, with only a small decrease in specificity.
      • Melnikow J.
      • Fenton J.J.
      • Whitlock E.P.
      • et al.
      Supplemental screening for breast cancer in women with dense breasts: a systematic review for the U.S. Preventive Services Task Force.
      ,
      • Hruska C.B.
      • Conners A.L.
      • Jones K.N.
      • et al.
      Diagnostic workup and costs of a single supplemental molecular breast imaging screen of mammographically dense breasts.
      Mammography with supplemental MBI has shown an additional recall rate of 5.9% to 8.4% and a false-positive rate of 18%.
      • Rhodes D.J.
      • Hruska C.B.
      • Conners A.L.
      • et al.
      Journal club: molecular breast imaging at reduced radiation dose for supplemental screening in mammographically dense breasts.
      ,
      • Houssami N.
      Digital breast tomosynthesis (3D-mammography) screening: data and implications for population screening.
      Currently, women who have findings of dense breasts on mammography have the option for MBI if they do not meet the criteria for MRI of the breast
      • Saslow D.
      • Boetes C.
      • Burke W.
      • et al.
      American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography [erratum appears in CA Cancer J Clin. 2007;57(3):185].
      or they meet the criteria but have contraindications to or do not prefer magnetic resonance screening (Figure). Molecular breast imaging is not recommended for BRCA carriers and patients who have other genetic conditions with radiation sensitivity. Despite promising results clinically, there have been concerns about the higher radiation dose of MBI relative to mammography.
      • Hruska C.B.
      Molecular breast imaging for screening in dense breasts: state of the art and future directions.
      ,
      • Holbrook A.
      • Newel M.S.
      Alternative screening for women with dense breasts: breast-specific gamma imaging (molecular breast imaging).
      • Hruska C.B.
      Let's get real about molecular breast imaging and radiation risk (commentary).
      • Tao A.T.
      • Hruska C.B.
      • Conners A.L.
      • et al.
      Dose reduction in molecular breast imaging with a new image-processing algorithm [erratum appears in AJR Am J Roentgenol. 2019;213(6):1403].
      Dose reduction algorithms and techniques are currently underway and have been promising.
      • Tao A.T.
      • Hruska C.B.
      • Conners A.L.
      • et al.
      Dose reduction in molecular breast imaging with a new image-processing algorithm [erratum appears in AJR Am J Roentgenol. 2019;213(6):1403].
      The relatively lower cost and the absence of nephrotoxic effects caused by the contrast agent make MBI a reasonable option for patients seeking supplemental breast cancer screening.
      • Rauch G.M.
      • Adrada B.E.
      Comparison of breast MR imaging with molecular breast imaging in breast cancer screening, diagnosis, staging, and treatment response evaluation.
      Currently, only selected insurance carriers provide coverage for MBI. In addition, abnormalities detected with MBI require further imaging because MBI image-guided biopsy capabilities, although under development, are not available for clinical use.
      • Adrada B.E.
      • Moseley T.
      • Kappadath S.C.
      • Whitman G.J.
      • Rauch G.M.
      Molecular breast imaging–guided percutaneous biopsy of breast lesions: a new frontier on breast intervention.
      The appropriate screening interval for MBI is unclear, although institutions with the technology are recommending a biennial screening interval to minimize radiation exposure.
      • Hruska C.B.
      Molecular breast imaging for screening in dense breasts: state of the art and future directions.
      ,
      • Rhodes D.J.
      • Hruska C.B.
      • Conners A.L.
      • et al.
      Journal club: molecular breast imaging at reduced radiation dose for supplemental screening in mammographically dense breasts.
      Figure thumbnail gr1
      FigureA 40-year-old woman with heterogeneously dense breasts. A, Baseline screening mammography examination. Two craniocaudal views showing a normal screening mammogram (Breast Imaging–Reporting and Data System category score 1). B, Molecular breast imaging supplemental screening examination 3 months after the normal screening mammogram (A) demonstrates focal uptake in the left central breast mid-depth (arrow). Surgical pathologic analysis reported corresponding 7-mm invasive ductal carcinoma, histologic grade 1, at surgical excision.

       Magnetic Resonance Imaging

      In the high-risk population, MRI has higher sensitivity than mammography or ultrasonography alone for breast cancer detection. The ACR recommends MRI in conjunction with mammography for screening of high-risk women who have a lifetime risk of breast cancer that exceeds 20% on the basis of the Tyrer-Cuzick risk assessment model, also called the International Breast Cancer Intervention Study (IBIS) Tool.
      • Merry G.M.
      • Mendelson E.B.
      Update on screening breast ultrasonography.
      ,
      • Ozanne E.M.
      • Drohan B.
      • Bosinoff P.
      • et al.
      Which risk model to use? Clinical implications of the ACS MRI screening guidelines.
      Women who are carriers of the BRCA1 and BRCA2 gene variant, Li-Fraumeni syndrome, or Cowden syndrome and those who received mantle radiation for Hodgkin lymphoma should be considered at high risk.
      • Saslow D.
      • Boetes C.
      • Burke W.
      • et al.
      American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography [erratum appears in CA Cancer J Clin. 2007;57(3):185].
      Other genetic mutations, such as TP53, PTEN, SKT11, CDH1, MSH1, MSH2, MLH1,
      • Ford D.
      • Easton D.F.
      • Stratton M.
      • et al.
      Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium.
      ,
      • Frey M.K.
      • Kopparam R.V.
      • Ni Zhou Z.
      • et al.
      Prevalence of nonfounder BRCA1/2 mutations in Ashkenazi Jewish patients presenting for genetic testing at a hereditary breast and ovarian cancer center.
      PSM2, EPCAM, PALB2, CHEK2, and ATM, have also been associated with an increased lifetime risk of breast cancer, and therefore these patients should be considered for annual MRI and mammography. Several other genes that may increase the risk of breast cancer, such as BARD1, BRIP1, MRE11, RAD50, NBS1,
      • Couch F.J.
      • Hart S.N.
      • Sharma P.
      • et al.
      Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer.
      RAD51, MUTYH, NF1, and NBN, have been identified. However, additional studies are needed to better characterize their penetrance and risk. Conversations about annual MRI and mammography should be conducted with these women.
      The ACR recently expanded its recommendations for annual supplemental MRI for women with a personal history of breast cancer diagnosed at 50 years of age or younger and for women with the diagnosis of breast cancer who have dense breasts.
      • Cho N.
      • Han W.
      • Han B.K.
      • et al.
      Breast cancer screening with mammography plus ultrasonography or magnetic resonance imaging in women 50 years or younger at diagnosis and treated with breast conservation therapy.
      For these women with a history of breast cancer, MRI has a considerably higher sensitivity than mammography alone: a cancer detection rate of 10 to 29 cancers per 1000 patients and a reduced interval cancer rate.
      • Lehman C.D.
      • Lee J.M.
      • DeMartini W.B.
      • et al.
      Screening MRI in women with a personal history of breast cancer.
      • Schacht D.V.
      • Yamaguchi K.
      • Lai J.
      • Kulkarni K.
      • Sennett C.A.
      • Abe H.
      Importance of a personal history of breast cancer as a risk factor for the development of subsequent breast cancer: results from screening breast MRI.
      • Gweon H.M.
      • Cho N.
      • Han W.
      • et al.
      Breast MR imaging screening in women with a history of breast conservation therapy.
      • Monticciolo D.L.
      • Newell M.S.
      • Moy L.
      • Niell B.
      • Monsees B.
      • Sickles E.A.
      Breast cancer screening in women at higher-than-average risk: recommendations from the ACR.
      Breast MRI can allow increased detection of clinically important mammographically and sonographically occult cancers. In a systematic review of studies of women who underwent MRI after mammography with normal results, the sensitivity was reported as 71% to 100%
      • Warren R.M.
      • Pointon L.
      • Caines R.
      • et al.
      What is the recall rate of breast MRI when used for screening asymptomatic women at high risk?.
      • Lehman C.D.
      Role of MRI in screening women at high risk for breast cancer.
      • O'Neill S.M.
      • Rubinstein W.S.
      • Sener S.F.
      • et al.
      Psychological impact of recall in high-risk breast MRI screening.
      • Cott Chubiz J.E.
      • Lee J.M.
      • Gilmore M.E.
      • et al.
      Cost-effectiveness of alternating magnetic resonance imaging and digital mammography screening in BRCA1 and BRCA2 gene mutation carriers.
      • Le-Petross H.T.
      • Whitman G.J.
      • Atchley D.P.
      • et al.
      Effectiveness of alternating mammography and magnetic resonance imaging for screening women with deleterious BRCA mutations at high risk of breast cancer.
      and the specificity as 78% to 94%; the positive predictive value of performed biopsies was 22% to 63%.
      • Kuhl C.K.
      • Strobel K.
      • Bieling H.
      • Leutner C.
      • Schild H.H.
      • Schrading S.
      Supplemental breast MR imaging screening of women with average risk of breast cancer.
      ,
      • O'Neill S.M.
      • Rubinstein W.S.
      • Sener S.F.
      • et al.
      Psychological impact of recall in high-risk breast MRI screening.
      ,
      • Le-Petross H.T.
      • Whitman G.J.
      • Atchley D.P.
      • et al.
      Effectiveness of alternating mammography and magnetic resonance imaging for screening women with deleterious BRCA mutations at high risk of breast cancer.
      ,
      • Berg W.A.
      Tailored supplemental screening for breast cancer: what now and what next?.
      The MRI study led to an additional 8.2 to 15.9 cancers detected per 1000 examinations, and in women with extremely dense tissue, MRI has led to lower interval cancer rates.
      • Kuhl C.K.
      • Strobel K.
      • Bieling H.
      • Leutner C.
      • Schild H.H.
      • Schrading S.
      Supplemental breast MR imaging screening of women with average risk of breast cancer.
      ,
      • Kuhl C.K.
      • Schrading S.
      • Leutner C.C.
      • et al.
      Mammography, breast ultrasound, and magnetic resonance imaging for surveillance of women at high familial risk for breast cancer.
      ,
      • Phi X.A.
      • Houssami N.
      • Hooning M.J.
      • et al.
      Accuracy of screening women at familial risk of breast cancer without a known gene mutation: individual patient data meta-analysis.
      ,
      • Lehman C.D.
      Role of MRI in screening women at high risk for breast cancer.
      ,
      • Cott Chubiz J.E.
      • Lee J.M.
      • Gilmore M.E.
      • et al.
      Cost-effectiveness of alternating magnetic resonance imaging and digital mammography screening in BRCA1 and BRCA2 gene mutation carriers.
      ,
      • Phi X.A.
      • Tagliafico A.
      • Houssami N.
      • Greuter M.J.W.
      • de Bock G.H.
      Digital breast tomosynthesis for breast cancer screening and diagnosis in women with dense breasts—a systematic review and meta-analysis.
      • Riedl C.C.
      • Luft N.
      • Bernhart C.
      • et al.
      Triple-modality screening trial for familial breast cancer underlines the importance of magnetic resonance imaging and questions the role of mammography and ultrasound regardless of patient mutation status, age, and breast density.
      • Lo G.
      • Scaranelo A.M.
      • Aboras H.
      • et al.
      Evaluation of the utility of screening mammography for high-risk women undergoing screening breast MR imaging.
      • Warner E.
      • Messersmith H.
      • Causer P.
      • Eisen A.
      • Shumak R.
      • Plewes D.
      Systematic review: using magnetic resonance imaging to screen women at high risk for breast cancer.
      Most women enrolled in these studies had other risk factors in addition to denser breasts. In a prospective trial of women with average breast cancer risk, supplemental breast MRI showed an incremental cancer detection rate of 15.5 per 1000 screened patients and across all breast density groups.
      • Kuhl C.K.
      • Strobel K.
      • Bieling H.
      • Leutner C.
      • Schild H.H.
      • Schrading S.
      Supplemental breast MR imaging screening of women with average risk of breast cancer.
      Data are still lacking to support annual MRI screening of women who are at intermediate risk, defined as a 15% to 20% lifetime risk.
      • Mainiero M.B.
      • Lourenco A.
      • Mahoney M.C.
      • et al.
      ACR Appropriateness Criteria Breast Cancer Screening.
      At this time, such MRI studies probably will not be reimbursed by insurance, and patients can incur considerable out-of-pocket expenses; however, this may change with more evidence. In a 2017 study, a magnetic resonance screening study by Kuhl et al
      • Kuhl C.K.
      • Strobel K.
      • Bieling H.
      • Leutner C.
      • Schild H.H.
      • Schrading S.
      Supplemental breast MR imaging screening of women with average risk of breast cancer.
      reported an additional 22.6 cancers per 1000 screenings in the prevalent screening round, with subsequent incident rounds showing a clinical data repository of 6.9 per 1000.
      In a study assessing the reasons for nonparticipation in MRI scans offered to high-risk women, participants stated that MRI is inconvenient, can induce claustrophobia,
      • Nguyen X.V.
      • Tahir S.
      • Bresnahan B.W.
      • et al.
      Prevalence and financial impact of claustrophobia, anxiety, patient motion, and other patient events in magnetic resonance imaging.
      and provokes anxiety about its test results.
      • de Lange S.V.
      • Bakker M.F.
      • Monninkhof E.M.
      • et al.
      Reasons for (non)participation in supplemental population-based MRI breast screening for women with extremely dense breasts.
      Magnetic resonance imaging is not widely available, is costly, and is time-consuming.
      • Mainiero M.B.
      • Lourenco A.
      • Mahoney M.C.
      • et al.
      ACR Appropriateness Criteria Breast Cancer Screening.
      ,
      • O'Flynn E.A.
      • Ledger A.E.
      • deSouza N.M.
      Alternative screening for dense breasts: MRI.
      In addition, some patients cannot undergo breast MRI because of an incompatible implantable device.
      • Russo R.J.
      • Costa H.S.
      • Silva P.D.
      • et al.
      Assessing the risks associated with MRI in patients with a pacemaker or defibrillator.
      The annual exposure to gadolinium (the contrast agent used in MRI) and its cumulative toxicity, especially for younger women, have raised concerns.
      • Kuhl C.K.
      • Strobel K.
      • Bieling H.
      • Leutner C.
      • Schild H.H.
      • Schrading S.
      Supplemental breast MR imaging screening of women with average risk of breast cancer.
      ,
      • McDonald R.J.
      • McDonald J.S.
      • Kallmes D.F.
      • et al.
      Intracranial gadolinium deposition after contrast-enhanced MR imaging.
      ,
      • Runge V.M.
      Safety of the gadolinium-based contrast agents for magnetic resonance imaging, focusing in part on their accumulation in the brain and especially the dentate nucleus.
      Studies are underway to evaluate the long-term implications of MRI with gadolinium.
      As with the other imaging modalities discussed, false-positive MRI test results can lead to unnecessary tests with additional costs and anxiety.
      • Lee J.M.
      • Ichikawa L.
      • Valencia E.
      • et al.
      Performance benchmarks for screening breast MR imaging in community practice.
      Therefore, when appropriate, patient-provider discussions about annual breast MRI screening should take place. Ongoing studies are evaluating advanced MRI techniques, sequences, improved spatial resolution, and decreased scan times to reduce false-positive results and to improve the true value of screening MRI
      • Lee J.M.
      • Ichikawa L.
      • Valencia E.
      • et al.
      Performance benchmarks for screening breast MR imaging in community practice.
      • Mann R.M.
      • Kuhl C.K.
      • Moy L.
      Contrast-enhanced MRI for breast cancer screening.
      • Mann R.M.
      • Cho N.
      • Moy L.
      Breast MRI: state of the art.
      for average-risk women with dense breasts.
      • Tosteson A.N.A.
      An abbreviated MRI protocol for breast cancer screening in women with dense breasts: promising results, but further evaluation required prior to widespread implementation.

       Contrast-Enhanced Mammography

      Contrast-enhanced mammography (CEM) is a new and emerging diagnostic imaging tool. In the United States, however, CEM has limited availability. Standard low-energy and recombined, subtracted mammography images are obtained in standard views after injection of iodinated contrast material. Similar to MRI, CEM provides high-resolution anatomic and physiologic contrast-enhanced information to evaluate tumor neovascularity.
      • Gennaro G.
      • Bernardi D.
      • Houssami N.
      Radiation dose with digital breast tomosynthesis compared to digital mammography: per-view analysis.
      ,
      • Patel B.K.
      • Lobbes M.B.I.
      • Lewin J.
      Contrast enhanced spectral mammography: a review.
      Compared with 2-dimensional mammography alone for women, CEM has shown superior diagnostic accuracy.
      • Sorin V.
      • Yagil Y.
      • Yosepovich A.
      • et al.
      Contrast-enhanced spectral mammography in women with intermediate breast cancer risk and dense breasts.
      Compared with MRI, CEM shows similar sensitivity and better specificity at a considerably lower cost and is expected to be applied more widely because of its many potential clinical uses.
      • Xing D.
      • Lv Y.
      • Sun B.
      • et al.
      Diagnostic value of contrast-enhanced spectral mammography in comparison to magnetic resonance imaging in breast lesions.
      Large-scale multi-institutional prospective trials and CEM-guided biopsy technology need to be investigated further.
      • Li L.
      • Roth R.
      • Germaine P.
      • et al.
      Contrast-enhanced spectral mammography (CESM) versus breast magnetic resonance imaging (MRI): a retrospective comparison in 66 breast lesions.
      ,
      • Covington M.F.
      • Pizzitola V.J.
      • Lorans R.
      • et al.
      The future of contrast-enhanced mammography.
      • Chou C.P.
      • Lewin J.M.
      • Chiang C.L.
      • et al.
      Clinical evaluation of contrast-enhanced digital mammography and contrast enhanced tomosynthesis—comparison to contrast-enhanced breast MRI.
      • Luczynska E.
      • Heinze-Paluchowska S.
      • Hendrick E.
      • et al.
      Comparison between breast MRI and contrast-enhanced spectral mammography.
      At this time, CEM is not used as a supplemental screening tool in otherwise average-risk women with dense breasts, except under off-label or research purposes.

       Breast Cancer Risk Assessment Calculators

      An assessment of a woman’s lifetime risk of breast cancer may help guide discussions about the appropriate breast cancer screening options for her. Depending on a woman’s lifetime risk of breast cancer, her risk can be stratified into high (>20%), intermediate (15% to 20%), and average (<15%).
      • Amir E.
      • Freedman O.C.
      • Seruga B.
      • Evans D.G.
      Assessing women at high risk of breast cancer: a review of risk assessment models.
      The American Cancer Society has recommended models that incorporate histories of first- and second-degree relatives (eg, BRCAPRO computer program, Tyrer-Cuzick, Claus) to identify high-risk women who qualify for additional annual screening MRI scans
      • Ozanne E.M.
      • Drohan B.
      • Bosinoff P.
      • et al.
      Which risk model to use? Clinical implications of the ACS MRI screening guidelines.
      (Table 2).
      • Wang X.
      • Huang Y.
      • Li L.
      • Dai H.
      • Song F.
      • Chen K.
      Assessment of performance of the Gail model for predicting breast cancer risk: a systematic review and meta-analysis with trial sequential analysis.
      • Turhan E.
      • Yasli G.
      Breast cancer risk evaluation by utilizing Gail model and association between breast cancer risk perception with early diagnosis applications among midwives and nurses working in primary health services.
      • Sa-Nguanraksa D.
      • Sasanakietkul T.
      • O-Charoenrat C.
      • Kulprom A.
      • O-Charoenrat P.
      Gail model underestimates breast cancer risk in Thai population.
      • Nickson C.
      • Procopio P.
      • Velentzis L.S.
      • et al.
      Prospective validation of the NCI Breast Cancer Risk Assessment Tool (Gail model) on 40,000 Australian women.
      • Berry D.A.
      • Iversen Jr., E.S.
      • Gudbjartsson D.F.
      • et al.
      BRCAPRO validation, sensitivity of genetic testing of BRCA1/BRCA2, and prevalence of other breast cancer susceptibility genes.
      • Stevanato K.P.
      • Pedroso R.B.
      • Iora P.
      • et al.
      Comparative analysis between the Gail, Tyrer-Cuzick and BRCAPRO models for breast cancer screening in Brazilian population.
      • Mazzola E.
      • Blackford A.
      • Parmigiani G.
      • Biswas S.
      Recent enhancements to the genetic risk prediction model BRCAPRO.
      • Grant R.C.
      • Holter S.
      • Borgida A.
      • et al.
      Comparison of practice guidelines, BRCAPRO, and genetic counselor estimates to identify germline BRCA1 and BRCA2 mutations in pancreatic cancer.
      • Elsayegh N.
      • Barrera A.M.
      • Muse K.I.
      • et al.
      Evaluation of BRCAPRO risk assessment model in patients with ductal carcinoma in situ who underwent clinical BRCA genetic testing.
      • Boughey J.C.
      • Hartmann L.C.
      • Anderson S.S.
      • et al.
      Evaluation of the Tyrer-Cuzick (International Breast Cancer Intervention Study) model for breast cancer risk prediction in women with atypical hyperplasia.
      • Vianna F.S.L.
      • Giacomazzi J.
      • Oliveira Netto C.B.
      • et al.
      Performance of the Gail and Tyrer-Cuzick breast cancer risk assessment models in women screened in a primary care setting with the FHS-7 questionnaire.
      • McCarthy A.M.
      • Guan Z.
      • Welch M.
      • et al.
      Performance of breast cancer risk-assessment models in a large mammography cohort.
      [The Claus model for estimating lifetime cumulative risk for breast cancer in women with a positive family anamnesis].
      • Eoh K.J.
      • Park J.S.
      • Park H.S.
      • et al.
      BRCA1 and BRCA2 mutation predictions using the BRCAPRO and Myriad models in Korean ovarian cancer patients.
      Women at high risk should be encouraged to undergo annual supplemental breast MRI screening in addition to regular annual screening mammography either together or in 6-month intervals, irrespective of breast density.
      • Le-Petross H.T.
      • Whitman G.J.
      • Atchley D.P.
      • et al.
      Effectiveness of alternating mammography and magnetic resonance imaging for screening women with deleterious BRCA mutations at high risk of breast cancer.
      ,
      • Barlow W.E.
      • White E.
      • Ballard-Barbash R.
      • et al.
      Prospective breast cancer risk prediction model for women undergoing screening mammography.
      Table 2Risk Prediction Models
      CharacteristicRisk prediction model
      BCRAT or Gail
      • Wang X.
      • Huang Y.
      • Li L.
      • Dai H.
      • Song F.
      • Chen K.
      Assessment of performance of the Gail model for predicting breast cancer risk: a systematic review and meta-analysis with trial sequential analysis.
      • Turhan E.
      • Yasli G.
      Breast cancer risk evaluation by utilizing Gail model and association between breast cancer risk perception with early diagnosis applications among midwives and nurses working in primary health services.
      • Sa-Nguanraksa D.
      • Sasanakietkul T.
      • O-Charoenrat C.
      • Kulprom A.
      • O-Charoenrat P.
      Gail model underestimates breast cancer risk in Thai population.
      • Nickson C.
      • Procopio P.
      • Velentzis L.S.
      • et al.
      Prospective validation of the NCI Breast Cancer Risk Assessment Tool (Gail model) on 40,000 Australian women.
      BRCAPRO
      • Berry D.A.
      • Iversen Jr., E.S.
      • Gudbjartsson D.F.
      • et al.
      BRCAPRO validation, sensitivity of genetic testing of BRCA1/BRCA2, and prevalence of other breast cancer susceptibility genes.
      • Stevanato K.P.
      • Pedroso R.B.
      • Iora P.
      • et al.
      Comparative analysis between the Gail, Tyrer-Cuzick and BRCAPRO models for breast cancer screening in Brazilian population.
      • Mazzola E.
      • Blackford A.
      • Parmigiani G.
      • Biswas S.
      Recent enhancements to the genetic risk prediction model BRCAPRO.
      • Grant R.C.
      • Holter S.
      • Borgida A.
      • et al.
      Comparison of practice guidelines, BRCAPRO, and genetic counselor estimates to identify germline BRCA1 and BRCA2 mutations in pancreatic cancer.
      • Elsayegh N.
      • Barrera A.M.
      • Muse K.I.
      • et al.
      Evaluation of BRCAPRO risk assessment model in patients with ductal carcinoma in situ who underwent clinical BRCA genetic testing.
      ,
      • Eoh K.J.
      • Park J.S.
      • Park H.S.
      • et al.
      BRCA1 and BRCA2 mutation predictions using the BRCAPRO and Myriad models in Korean ovarian cancer patients.
      Tyrer-Cuzick
      • Boughey J.C.
      • Hartmann L.C.
      • Anderson S.S.
      • et al.
      Evaluation of the Tyrer-Cuzick (International Breast Cancer Intervention Study) model for breast cancer risk prediction in women with atypical hyperplasia.
      • Vianna F.S.L.
      • Giacomazzi J.
      • Oliveira Netto C.B.
      • et al.
      Performance of the Gail and Tyrer-Cuzick breast cancer risk assessment models in women screened in a primary care setting with the FHS-7 questionnaire.
      • McCarthy A.M.
      • Guan Z.
      • Welch M.
      • et al.
      Performance of breast cancer risk-assessment models in a large mammography cohort.
      Claus
      • McCarthy A.M.
      • Guan Z.
      • Welch M.
      • et al.
      Performance of breast cancer risk-assessment models in a large mammography cohort.
      ,
      [The Claus model for estimating lifetime cumulative risk for breast cancer in women with a positive family anamnesis].
      General description
      • RR data calculated using case-controlled studies of women receiving mammograms from mammography screening
      • Calibrated to US incidence rates
      • Genetic model parameters estimated from meta-analysis of published studies
      • Rates for non-BRCA carriers
      • Calibrated to US incidence rates
      • RR data and other measures obtained from published studies
      • Calibration done with incidence rates from the United Kingdom
      • Measures for the genetic model are obtained from population-based case studies that enrolled young patients with breast cancer
      • Calibrated to US incidence rates
      Advantages
      • Easy to use
      • Widely available
      • Includes hormonal, reproductive, and personal history of BC; no first-degree relatives with BC
      • Requires family pedigree
      • Well calibrated
      • Includes extensive FH
      • Predicts risk of invasive BC and DCIS
      • Version 8 has dense breast tissue as a risk factor
      • Predicts risk of invasive BC and DCIS
      Drawbacks
      • Cannot be used for MRI needs assessment
      • Insufficient data on FH, so less precise for women with strong FH of BC
      • Less precise for older and non-White women
      • Modest sensitivity and specificity
      • Complex to use
      • Predicts risk for invasive BC only
      • Time-consuming
      • Not validated
      Websitehttps://bcrisktool.cancer.govhttps://www4.utsouthwestern.edu/breasthealth/cagenehttps://ibis.ikonopedia.com/
      Patient exclusions
      • Prior BC, DCIS, LCIS
      • Chest irradiation
      • BRCA1 carrier
      • None
      • None
      • No first- or second-degree relatives with BC
      • First-degree relatives with ovarian cancer
      Risk assessment information
      • 5-y and lifetime risk
      • Personal risk of BC
      • Age 35-90 y
      • Age ≤110 y
      • 5-y, 10-y, and lifetime risk
      • Personal risk and risk of gene variant carrier
      • Age 19-85 y
      • Lifetime risk
      • Personal risk
      • Age 20-79 y
      BC, breast cancer; BCRAT, Breast Cancer Risk Assessment Tool; DCIS, ductal carcinoma in situ; FH, family history; LCIS, lobular carcinoma in situ; MRI, magnetic resonance imaging; RR, relative risk.
      A few models include modifiable lifestyle risk factors, such as alcohol intake, body mass index, hormone therapy,
      • Nickson C.
      • Procopio P.
      • Velentzis L.S.
      • et al.
      Prospective validation of the NCI Breast Cancer Risk Assessment Tool (Gail model) on 40,000 Australian women.
      ,
      • Valero M.G.
      • Zabor E.C.
      • Park A.
      • et al.
      The Tyrer-Cuzick model inaccurately predicts invasive breast cancer risk in women with LCIS.
      ,
      • Ozanne E.M.
      • Howe R.
      • Mallinson D.
      • Esserman L.
      • Van't Veer L.J.
      • Kaplan C.P.
      Evaluation of National Comprehensive Cancer Network guideline-based Tool for Risk Assessment for breast and ovarian Cancer (N-TRAC): a patient-reported survey for genetic high-risk assessment for breast and ovarian cancers in women.
      and exercise, that improve the breast cancer risk predictive capability. Risk assessment tools do not always identify the same at-risk groups, and because they use different risk factors that are weighted differently, they can give different risk estimates for the same woman.
      • Ozanne E.M.
      • Howe R.
      • Mallinson D.
      • Esserman L.
      • Van't Veer L.J.
      • Kaplan C.P.
      Evaluation of National Comprehensive Cancer Network guideline-based Tool for Risk Assessment for breast and ovarian Cancer (N-TRAC): a patient-reported survey for genetic high-risk assessment for breast and ovarian cancers in women.
      Risks are usually predicted for 5 years, 10 years, or lifetime.
      The Gail model, also called the National Cancer Institute Breast Cancer Risk Assessment Tool, is popular and widely used in the United States.
      • Nickson C.
      • Procopio P.
      • Velentzis L.S.
      • et al.
      Prospective validation of the NCI Breast Cancer Risk Assessment Tool (Gail model) on 40,000 Australian women.
      ,
      • Warwick J.
      • Birke H.
      • Stone J.
      • et al.
      Mammographic breast density refines Tyrer-Cuzick estimates of breast cancer risk in high-risk women: findings from the placebo arm of the International Breast Cancer Intervention Study I.
      Most clinicians use the Gail model to identify patients at high risk and to provide counseling about chemoprevention. It should not be used for risk assessment for MRI screening eligibility (Table 2). Currently, no single validated risk model incorporates all the risk factors and performs consistently well for women of all races. No single model is appropriate for all subgroups, and the need still exists to develop an improved model with better predictive capability. Investigators of risk models are attempting to include breast density as a risk factor in their algorithms because it improves the risk predictive capability and discriminatory power of these models.
      • Warwick J.
      • Birke H.
      • Stone J.
      • et al.
      Mammographic breast density refines Tyrer-Cuzick estimates of breast cancer risk in high-risk women: findings from the placebo arm of the International Breast Cancer Intervention Study I.
      For instance, the modified Tyrer-Cuzick risk assessment model version 8
      • Brentnall A.R.
      • Harkness E.F.
      • Astley S.M.
      • et al.
      Mammographic density adds accuracy to both the Tyrer-Cuzick and Gail breast cancer risk models in a prospective UK screening cohort.
      includes breast density, which improves its sensitivity. Until a better model is available, it is reasonable for HCPs to be familiar with 1 or 2 family-based risk factor models, such as Tyrer-Cuzick or BRCAPRO, to estimate a woman’s lifetime risk for breast cancer.

      Discussion

      Supplemental breast cancer screening methods are intended to detect additional breast cancers in women with dense breasts and normal mammography results.
      • Burkett B.J.
      • Hanemann C.W.
      A review of supplemental screening ultrasound for breast cancer: certain populations of women with dense breast tissue may benefit.
      Breast tissue composition and breast cancer risk differ among women, making individualized breast cancer screening important. Screening mammography is known to reduce breast cancer mortality rates.
      • Cohen S.L.
      • Margolies L.R.
      • Schwager S.J.
      • et al.
      Early discussion of breast density and supplemental breast cancer screening: is it possible?.
      Women should be informed that dense breast tissue is common and can be seen in nearly 50% of women. Women with dense breasts should have a thorough discussion with their HCPs about the risks and benefits of supplemental dense breast screening. Depending on availability and the patient’s preference, common supplemental screening considerations can include MBI, MRI, and WBUS.
      When considering a population-based supplemental screening modality, the HCP needs to recognize that the technique should be widely available, easily accessible, and relatively inexpensive; should show high specificity and high sensitivity; and should be associated with minimal radiation exposure. Health care professionals need to be aware of the cost-effectiveness, local availability, and insurance coverage of various supplemental screening procedures to limit substantial out-of-pocket expense for patients.
      • Nevler A.
      • Shabtai E.
      • Rosin D.
      • Hoffman A.
      • Gutman M.
      • Shabtai M.
      Mammographic breast density as a predictor of radiological findings requiring further investigation.
      The ideal supplemental screening method may vary for the individual patient on the basis of availability and risk factors. Direct comparisons of the different supplemental screening tests are limited in light of varying costs and practicality of the randomized trials. Additional studies that focus on the outcomes, including breast cancer mortality and interval breast cancer rates, are needed.
      • Siu A.L.
      U.S. Preventive Services Task Force
      Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement [erratum appears in Ann Intern Med. 2016;164(6):448].
      Although the available medical society guidelines attempt to help HCPs determine which women would benefit from supplemental screening and which supplemental imaging test is most appropriate, clear directions and recommendations are limited. The lack of consensus guidelines from societies leads to confusion among HCPs and patients alike.

      Conclusion

      Health care professionals are positioned to have patient-provider discussions about mammographic breast density and breast cancer risk factors. As such and where appropriate, HCPs can serve as a key resource to counsel interested patients about supplemental screening modalities known to improve breast cancer detection for women with dense breasts. This discussion should include the benefits of early detection of otherwise mammographically occult breast cancer, which are weighed against the harms of supplemental screening, such as false-positive results that can lead to increased patient recalls, patient anxiety, and false-positive biopsy findings.
      • Kerlikowske K.
      • Miglioretti D.L.
      • Vachon C.M.
      Discussions of dense breasts, breast cancer risk, and screening choices in 2019.
      ,
      • Richman I.B.
      • Busch S.H.
      Advising women about supplemental screening after dense breast notification: still no easy answers.
      In addition to shared decision-making, HCPs should take this opportunity to counsel their patients on risk-reducing lifestyle modifications, such as maintenance of an ideal body weight through diet and regular exercise and a limitation of alcohol intake.
      • Quandt Z.
      • Flom J.D.
      • Tehranifar P.
      • Reynolds D.
      • Terry M.B.
      • McDonald J.A.
      The association of alcohol consumption with mammographic density in a multiethnic urban population.
      ,
      • Arthur R.
      • Kirsh V.A.
      • Kreiger N.
      • Rohan T.
      A healthy lifestyle index and its association with risk of breast, endometrial, and ovarian cancer among Canadian women.

      Case Vignette, Continued

      The patient has a 2.8% 10-year risk and a lifetime risk of 10.2% of breast cancer, based on the Tyrer-Cuzick risk assessment model. Her risk was slightly below the average. She completed screening mammography with tomography, with no report of abnormalities. For informed decision-making, the patient was counseled about her individualized breast cancer risk and had a patient-provider discussion about the benefits and drawbacks of supplemental screening methods. This led to an opportunity for her physician to discuss lifestyle modifications that reduce breast cancer risk and to reinforce the recommendation for routine mammography screening.

      Acknowledgments

      We thank Sandhya Pruthi, MD, Professor, General Internal Medicine, Mayo Clinic, Rochester, Minnesota, for her valuable suggestions.

      Supplemental Online Material

      References

        • Pisano E.
        Issues in breast cancer screening.
        Technol Cancer Res Treat. 2005; 4: 5-9
        • Harris R.
        • Yeatts J.
        • Kinsinger L.
        Breast cancer screening for women ages 50 to 69 years a systematic review of observational evidence.
        Prev Med. 2011; 53: 108-114
        • Kerlikowske K.
        • Hubbard R.A.
        • Miglioretti D.L.
        • et al.
        Comparative effectiveness of digital versus film-screen mammography in community practice in the United States: a cohort study.
        Ann Intern Med. 2011; 155: 493-502
        • Pisano E.D.
        • Gatsonis C.
        • Hendrick E.
        • et al.
        Diagnostic performance of digital versus film mammography for breast-cancer screening.
        N Engl J Med. 2005; 353: 1773-1783
        • Lehman C.D.
        • Arao R.F.
        • Sprague B.L.
        • et al.
        National performance benchmarks for modern screening digital mammography: update from the Breast Cancer Surveillance Consortium.
        Radiology. 2017; 283: 49-58
        • Freer P.E.
        • Slanetz P.J.
        • Haas J.S.
        • et al.
        Breast cancer screening in the era of density notification legislation: summary of 2014 Massachusetts experience and suggestion of an evidence-based management algorithm by multi-disciplinary expert panel.
        Breast Cancer Res Treat. 2015; 153: 455-464
        • Keller B.M.
        • Nathan D.L.
        • Gavenonis S.C.
        • Chen J.
        • Conant E.F.
        • Kontos D.
        Reader variability in breast density estimation from full-field digital mammograms: the effect of image postprocessing on relative and absolute measures.
        Acad Radiol. 2013; 20: 560-568
        • Mercado C.L.
        BI-RADS update.
        Radiol Clin North Am. 2014; 52: 481-487
        • Burkett B.J.
        • Hanemann C.W.
        A review of supplemental screening ultrasound for breast cancer: certain populations of women with dense breast tissue may benefit.
        Acad Radiol. 2016; 23: 1604-1609
        • Nevler A.
        • Shabtai E.
        • Rosin D.
        • Hoffman A.
        • Gutman M.
        • Shabtai M.
        Mammographic breast density as a predictor of radiological findings requiring further investigation.
        Isr Med Assoc J. 2016; 18: 32-35
        • White E.
        • Velentgas P.
        • Mandelson M.T.
        • et al.
        Variation in mammographic breast density by time in menstrual cycle among women aged 40-49 years.
        J Natl Cancer Inst. 1998; 90: 906-910
        • Swann C.A.
        • Kopans D.B.
        • McCarthy K.A.
        • White G.
        • Hall D.A.
        Mammographic density and physical assessment of the breast.
        AJR Am J Roentgenol. 1987; 148: 525-526
        • Quandt Z.
        • Flom J.D.
        • Tehranifar P.
        • Reynolds D.
        • Terry M.B.
        • McDonald J.A.
        The association of alcohol consumption with mammographic density in a multiethnic urban population.
        BMC Cancer. 2015; 15: 1094
        • Burton A.
        • Maskarinec G.
        • Perez-Gomez B.
        • et al.
        Mammographic density and ageing: a collaborative pooled analysis of cross-sectional data from 22 countries worldwide.
        PLoS Med. 2017; 14: e1002335
        • Sherratt M.J.
        • McConnell J.C.
        • Streuli C.H.
        Raised mammographic density: causative mechanisms and biological consequences.
        Breast Cancer Res. 2016; 18: 45
        • Henry N.L.
        • Chan H.P.
        • Dantzer J.
        • et al.
        Aromatase inhibitor–induced modulation of breast density: clinical and genetic effects.
        Br J Cancer. 2013; 109: 2331-2339
        • Harris H.R.
        • Tamimi R.M.
        • Willett W.C.
        • Hankinson S.E.
        • Michels K.B.
        Body size across the life course, mammographic density, and risk of breast cancer.
        Am J Epidemiol. 2011; 174: 909-918
        • Boyd N.F.
        • Melnichouk O.
        • Martin L.J.
        • et al.
        Mammographic density, response to hormones, and breast cancer risk.
        J Clin Oncol. 2011; 29: 2985-2992
        • Warren R.
        Hormones and mammographic breast density.
        Maturitas. 2004; 49: 67-78
        • Jung S.
        • Goloubeva O.
        • Hylton N.
        • et al.
        Intake of dietary carbohydrates in early adulthood and adolescence and breast density among young women.
        Cancer Causes Control. 2018; 29: 631-642
        • Hooley R.J.
        • Greenberg K.L.
        • Stackhouse R.M.
        • Geisel J.L.
        • Butler R.S.
        • Philpotts L.E.
        Screening US in patients with mammographically dense breasts: initial experience with Connecticut Public Act 09-41.
        Radiology. 2012; 265: 59-69
        • Mandelson M.T.
        • Oestreicher N.
        • Porter P.L.
        • et al.
        Breast density as a predictor of mammographic detection: comparison of interval- and screen-detected cancers.
        J Natl Cancer Inst. 2000; 92: 1081-1087
        • Kerlikowske K.
        • Scott C.G.
        • Mahmoudzadeh A.P.
        • et al.
        Automated and clinical breast imaging reporting and data system density measures predict risk for screen-detected and interval cancers: a case-control study.
        Ann Intern Med. 2018; 168: 757-765
        • Haas B.M.
        • Kalra V.
        • Geisel J.
        • Raghu M.
        • Durand M.
        • Philpotts L.E.
        Comparison of tomosynthesis plus digital mammography and digital mammography alone for breast cancer screening.
        Radiology. 2013; 269: 694-700
        • Kolb T.M.
        • Lichy J.
        • Newhouse J.H.
        Occult cancer in women with dense breasts: detection with screening US—diagnostic yield and tumor characteristics.
        Radiology. 1998; 207: 191-199
        • Corsetti V.
        • Ferrari A.
        • Ghirardi M.
        • et al.
        Role of ultrasonography in detecting mammographically occult breast carcinoma in women with dense breasts.
        Radiol Med. 2006; 111: 440-448
        • Drukker K.
        • Horsch K.J.
        • Pesce L.L.
        • Giger M.L.
        Interreader scoring variability in an observer study using dual-modality imaging for breast cancer detection in women with dense breasts.
        Acad Radiol. 2013; 20: 847-853
        • Kelly K.M.
        • Dean J.
        • Comulada W.S.
        • Lee S.J.
        Breast cancer detection using automated whole breast ultrasound and mammography in radiographically dense breasts.
        Eur Radiol. 2010; 20: 734-742
        • Gur D.
        • Abrams G.S.
        • Chough D.M.
        • et al.
        Digital breast tomosynthesis: observer performance study.
        AJR Am J Roentgenol. 2009; 193: 586-591
        • Sprague B.L.
        • Conant E.F.
        • Onega T.
        • et al.
        Variation in mammographic breast density assessments among radiologists in clinical practice: a multicenter observational study.
        Ann. Intern. Med. 2016; 165: 457-464
        • Cappello N.M.
        • Richetelli D.
        • Lee C.I.
        The impact of breast density reporting laws on women's awareness of density-associated risks and conversations regarding supplemental screening with providers.
        J Am Coll Radiol. 2019; 16: 139-146
        • Sechopoulos I.
        A review of breast tomosynthesis. Part II. Image reconstruction, processing and analysis, and advanced applications.
        Med Phys. 2013; 40: 014302
        • Mumin N.A.
        • Rahmat K.
        • Fadzli F.
        • et al.
        Diagnostic efficacy of synthesized 2D digital breast tomosynthesis in multi-ethnic Malaysian population.
        Sci Rep. 2019; 9: 1459
        • Liao G.J.
        • Hippe D.S.
        • Chen L.E.
        • et al.
        Physician ordering of screening ultrasound: national rates and association with state-level breast density reporting laws.
        J Am Coll Radiol. 2020; 17: 15-21
        • de Lange S.V.
        • Bakker M.F.
        • Monninkhof E.M.
        • et al.
        Reasons for (non)participation in supplemental population-based MRI breast screening for women with extremely dense breasts.
        Clin Radiol. 2018; 73: 759.e1-759.e9
        • Weigert J.
        • Steenbergen S.
        The Connecticut experiment: the role of ultrasound in the screening of women with dense breasts.
        Breast J. 2012; 18: 517-522
        • Berg W.A.
        • Gutierrez L.
        • NessAiver M.S.
        • et al.
        Diagnostic accuracy of mammography, clinical examination, US, and MR imaging in preoperative assessment of breast cancer.
        Radiology. 2004; 233: 830-849
        • Miles R.C.
        • Lehman C.
        • Warner E.
        • Tuttle A.
        • Saksena M.
        Patient-reported breast density awareness and knowledge after breast density legislation passage.
        Acad Radiol. 2019; 26: 726-731
        • US Department of Education, Institute of Education Sciences, National Center for Education Statistics
        A first look at the literacy of America's adults in the 21st century.
        https://nces.ed.gov/NAAL/PDF/2006470.PDF
        Date accessed: November 2, 2020
        • Weiss B.D.
        • American Medical Association Foundation
        Health literacy: a manual for clinicians.
        http://lib.ncfh.org/pdfs/6617.pdf
        Date accessed: November 2, 2020
        • Saraiya A.
        • Baird G.L.
        • Lourenco A.P.
        Breast density notification letters and websites: are they too "dense"?.
        J Am Coll Radiol. 2019; 16: 717-723
        • Kressin N.R.
        • Gunn C.M.
        • Battaglia T.A.
        Content, readability, and understandability of dense breast notifications by state [erratum appears in JAMA. 2016;315(23):2624].
        JAMA. 2016; 315: 1786-1788
        • Kuhl C.K.
        • Schrading S.
        • Strobel K.
        • Schild H.H.
        • Hilgers R.D.
        • Bieling H.B.
        Abbreviated breast magnetic resonance imaging (MRI): first postcontrast subtracted images and maximum-intensity projection—a novel approach to breast cancer screening with MRI.
        J Clin Oncol. 2014; 32: 2304-2310
        • Ashton C.M.
        • Haidet P.
        • Paterniti D.A.
        • et al.
        Racial and ethnic disparities in the use of health services: bias, preferences, or poor communication?.
        J Gen Intern Med. 2003; 18: 146-152
        • Eggly S.
        • Barton E.
        • Winckles A.
        • Penner L.A.
        • Albrecht T.L.
        A disparity of words: racial differences in oncologist-patient communication about clinical trials.
        Health Expect. 2015; 18: 1316-1326
        • Street Jr., R.L.
        • Gordon H.S.
        • Ward M.M.
        • Krupat E.
        • Kravitz R.L.
        Patient participation in medical consultations: why some patients are more involved than others.
        Med Care. 2005; 43: 960-969
        • Manning M.
        • Purrington K.
        • Penner L.
        • Duric N.
        • Albrecht T.L.
        Between-race differences in the effects of breast density information and information about new imaging technology on breast-health decision-making.
        Patient Educ Couns. 2016; 99: 1002-1010
        • Berg W.A.
        Supplemental screening sonography in dense breasts.
        Radiol Clin. North Am. 2004; 42 (vi): 845-851
        • Berg W.A.
        • Blume J.D.
        • Cormack J.B.
        • Mendelson E.B.
        Training the ACRIN 6666 Investigators and effects of feedback on breast ultrasound interpretive performance and agreement in BI-RADS ultrasound feature analysis.
        AJR Am J Roentgenol. 2012; 199: 224-235
        • Kuhl C.K.
        • Strobel K.
        • Bieling H.
        • Leutner C.
        • Schild H.H.
        • Schrading S.
        Supplemental breast MR imaging screening of women with average risk of breast cancer.
        Radiology. 2017; 283: 361-370
        • Kuhl C.K.
        • Schrading S.
        • Leutner C.C.
        • et al.
        Mammography, breast ultrasound, and magnetic resonance imaging for surveillance of women at high familial risk for breast cancer.
        J Clin Oncol. 2005; 23: 8469-8476
        • Kjesbu I.E.
        • Laursen C.B.
        • Graven T.
        • et al.
        Feasibility and diagnostic accuracy of point-of-care abdominal sonography by pocket-sized imaging devices, performed by medical residents.
        J Ultrasound Med. 2017; 36: 1195-1202
        • Skaane P.
        • Bandos A.I.
        • Gullien R.
        • et al.
        Comparison of digital mammography alone and digital mammography plus tomosynthesis in a population-based screening program.
        Radiology. 2013; 267: 47-56
        • Phi X.A.
        • Houssami N.
        • Hooning M.J.
        • et al.
        Accuracy of screening women at familial risk of breast cancer without a known gene mutation: individual patient data meta-analysis.
        Eur J Cancer. 2017; 85: 31-38
        • Tagliafico A.
        • Mariscotti G.
        • Durando M.
        • et al.
        Characterisation of microcalcification clusters on 2D digital mammography (FFDM) and digital breast tomosynthesis (DBT): does DBT underestimate microcalcification clusters? Results of a multicentre study.
        Eur Radiol. 2015; 25: 9-14
        • Mariscotti G.
        • Houssami N.
        • Durando M.
        • et al.
        Digital breast tomosynthesis (DBT) to characterize MRI-detected additional lesions unidentified at targeted ultrasound in newly diagnosed breast cancer patients.
        Eur Radiol. 2015; 25: 2673-2681
        • Skaane P.
        • Bandos A.I.
        • Niklason L.T.
        • et al.
        Digital mammography versus digital mammography plus tomosynthesis in breast cancer screening: the Oslo Tomosynthesis Screening Trial.
        Radiology. 2019; 291: 23-30
        • Hruska C.B.
        Molecular breast imaging for screening in dense breasts: state of the art and future directions.
        AJR Am J Roentgenol. 2017; 208: 275-283
        • Shermis R.B.
        • Redfern R.E.
        • Burns J.
        • Kudrolli H.
        Molecular breast imaging in breast cancer screening and problem solving.
        Radiographics. 2017; 37: 1309-1606
        • Li L.
        • Roth R.
        • Germaine P.
        • et al.
        Contrast-enhanced spectral mammography (CESM) versus breast magnetic resonance imaging (MRI): a retrospective comparison in 66 breast lesions.
        Diagn Interv Imaging. 2017; 98: 113-123
        • Barra F.R.
        • Sobrinho A.B.
        • Barra R.R.
        • et al.
        Contrast-enhanced mammography (CEM) for detecting residual disease after neoadjuvant chemotherapy: a comparison with breast magnetic resonance imaging (MRI).
        Biomed Res Int. 2018; 2018: 8531916
        • Li H.
        • Yin L.
        • He N.
        • et al.
        Comparison of comfort between cone beam breast computed tomography and digital mammography.
        Eur J Radiol. 2019; 120: 108674
        • Berg W.A.
        • Zhang Z.
        • Lehrer D.
        • et al.
        Detection of breast cancer with addition of annual screening ultrasound or a single screening MRI to mammography in women with elevated breast cancer risk.
        JAMA. 2012; 307: 1394-1404
        • Tagliafico A.S.
        • Calabrese M.
        • Mariscotti G.
        • et al.
        Adjunct screening with tomosynthesis or ultrasound in women with mammography-negative dense breasts: interim report of a prospective comparative trial.
        J Clin Oncol. 2016; 34: 1882-1888
        • Tagliafico A.S.
        • Mariscotti G.
        • Valdora F.
        • et al.
        A prospective comparative trial of adjunct screening with tomosynthesis or ultrasound in women with mammography-negative dense breasts (ASTOUND-2).
        Eur J Cancer. 2018; 104: 39-46
        • Friedewald S.M.
        • Rafferty E.A.
        • Rose S.L.
        • et al.
        Breast cancer screening using tomosynthesis in combination with digital mammography.
        JAMA. 2014; 311: 2499-2507
        • Ciatto S.
        • Houssami N.
        • Bernardi D.
        • et al.
        Integration of 3D digital mammography with tomosynthesis for population breast-cancer screening (STORM): a prospective comparison study.
        Lancet Oncol. 2013; 14: 583-589
        • Rafferty E.A.
        • Durand M.A.
        • Conant E.F.
        • et al.
        Breast cancer screening using tomosynthesis and digital mammography in dense and nondense breasts.
        JAMA. 2016; 315: 1784-1786
        • Lehman C.D.
        • Isaacs C.
        • Schnall M.D.
        • et al.
        Cancer yield of mammography, MR, and US in high-risk women: prospective multi-institution breast cancer screening study.
        Radiology. 2007; 244: 381-388
        • Comstock C.E.
        • Gatsonis C.
        • Newstead G.M.
        • et al.
        Comparison of abbreviated breast MRI vs digital breast tomosynthesis for breast cancer detection among women with dense breasts undergoing screening [erratum appears in JAMA. 2020;323(12):1194].
        JAMA. 2020; 323: 746-756
        • Bakker M.F.
        • de Lange S.V.
        • Pijnappel R.M.
        • et al.
        Supplemental MRI screening for women with extremely dense breast tissue.
        N Engl J Med. 2019; 381: 2091-2102
        • Jochelson M.S.
        • Pinker K.
        • Dershaw D.D.
        • et al.
        Comparison of screening CEDM and MRI for women at increased risk for breast cancer: a pilot study.
        Eur J Radiol. 2017; 97: 37-43
        • Sung J.S.
        • Lebron L.
        • Keating D.
        • et al.
        Performance of dual-energy contrast-enhanced digital mammography for screening women at increased risk of breast cancer.
        Radiology. 2019; 293: 81-88
        • Sorin V.
        • Yagil Y.
        • Yosepovich A.
        • et al.
        Contrast-enhanced spectral mammography in women with intermediate breast cancer risk and dense breasts.
        AJR Am J Roentgenol. 2018; 211: W267-W274
        • Berg W.A.
        • Vourtsis A.
        Screening breast ultrasound using handheld or automatic technique in women with dense breasts.
        J Breast Imaging. 2019; 1: 283-296
        • Niklason L.T.
        • Christian B.T.
        • Niklason L.E.
        • et al.
        Digital tomosynthesis in breast imaging.
        Radiology. 1997; 205: 399-406
        • Ho J.M.
        • Jafferjee N.
        • Covarrubias G.M.
        • Ghesani M.
        • Handler B.
        Dense breasts: a review of reporting legislation and available supplemental screening options.
        AJR Am J Roentgenol. 2014; 203: 449-456
        • Skaane P.
        • Bandos A.I.
        • Gullien R.
        • et al.
        Prospective trial comparing full-field digital mammography (FFDM) versus combined FFDM and tomosynthesis in a population-based screening programme using independent double reading with arbitration.
        Eur Radiol. 2013; 23: 2061-2071
        • Lang K.
        • Andersson I.
        • Rosso A.
        • Tingberg A.
        • Timberg P.
        • Zackrisson S.
        Performance of one-view breast tomosynthesis as a stand-alone breast cancer screening modality: results from the Malmö Breast Tomosynthesis Screening Trial, a population-based study.
        Eur Radiol. 2016; 26: 184-190
        • Friedewald S.M.
        • Rafferty E.A.
        • Conant E.F.
        Breast cancer screening with tomosynthesis and digital mammography—reply.
        JAMA. 2014; 312: 1695-1696
        • Scheel J.R.
        • Lee J.M.
        • Sprague B.L.
        • Lee C.I.
        • Lehman C.D.
        Screening ultrasound as an adjunct to mammography in women with mammographically dense breasts.
        Am J Obstet Gynecol. 2015; 212: 9-17
        • Vaughan C.L.
        • Douglas T.S.
        • Said-Hartley Q.
        • et al.
        Testing a dual-modality system that combines full-field digital mammography and automated breast ultrasound.
        Clin Imaging. 2016; 40: 498-505
        • Melnikow J.
        • Fenton J.J.
        • Whitlock E.P.
        • et al.
        Supplemental screening for breast cancer in women with dense breasts: a systematic review for the U.S. Preventive Services Task Force.
        Ann Intern Med. 2016; 164: 268-278
        • Berg W.A.
        • Blume J.D.
        • Cormack J.B.
        • et al.
        Combined screening with ultrasound and mammography vs mammography alone in women at elevated risk of breast cancer [erratum appears in JAMA. 2010;303(15):1482].
        JAMA. 2008; 299: 2151-2163
        • Merry G.M.
        • Mendelson E.B.
        Update on screening breast ultrasonography.
        Radiol Clin North Am. 2014; 52: 527-537
        • Berg W.A.
        • Mendelson E.B.
        Technologist-performed handheld screening breast US imaging: how is it performed and what are the outcomes to date?.
        Radiology. 2014; 272: 12-27
        • Kelly K.M.
        • Richwald G.A.
        Automated whole-breast ultrasound: advancing the performance of breast cancer screening.
        Semin Ultrasound CT MR. 2011; 32: 273-280
        • Sprague B.L.
        • Stout N.K.
        • Schechter C.
        • et al.
        Benefits, harms, and cost-effectiveness of supplemental ultrasonography screening for women with dense breasts.
        Ann Intern Med. 2015; 162: 157-166
        • Okello J.
        • Kisembo H.
        • Bugeza S.
        • Galukande M.
        Breast cancer detection using sonography in women with mammographically dense breasts.
        BMC Med Imaging. 2014; 14: 41
        • Ohuchi N.
        • Suzuki A.
        • Sobue T.
        • et al.
        Sensitivity and specificity of mammography and adjunctive ultrasonography to screen for breast cancer in the Japan Strategic Anti-cancer Randomized Trial (J-START): a randomised controlled trial.
        Lancet. 2016; 387: 341-348
        • Lee C.H.
        • Dershaw D.D.
        • Kopans D.
        • et al.
        Breast cancer screening with imaging: recommendations from the Society of Breast Imaging and the ACR on the use of mammography, breast MRI, breast ultrasound, and other technologies for the detection of clinically occult breast cancer.
        J Am Coll Radiol. 2010; 7: 18-27
        • Mainiero M.B.
        • Lourenco A.
        • Mahoney M.C.
        • et al.
        ACR Appropriateness Criteria Breast Cancer Screening.
        J Am Coll Radiol. 2013; 10: 11-14
        • Hruska C.B.
        • O'Connor M.K.
        Nuclear imaging of the breast: translating achievements in instrumentation into clinical use.
        Med Phys. 2013; 40: 050901
        • Rhodes D.J.
        • Hruska C.B.
        • Conners A.L.
        • et al.
        Journal club: molecular breast imaging at reduced radiation dose for supplemental screening in mammographically dense breasts.
        AJR Am J Roentgenol. 2015; 204: 241-251
        • Hruska C.B.
        • Conners A.L.
        • Jones K.N.
        • et al.
        Diagnostic workup and costs of a single supplemental molecular breast imaging screen of mammographically dense breasts.
        AJR Am J Roentgenol. 2015; 204: 1345-1353
        • Houssami N.
        Digital breast tomosynthesis (3D-mammography) screening: data and implications for population screening.
        Expert Rev Med Devices. 2015; 12: 377-379
        • Saslow D.
        • Boetes C.
        • Burke W.
        • et al.
        American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography [erratum appears in CA Cancer J Clin. 2007;57(3):185].
        CA Cancer J Clin. 2007; 57: 75-89
        • Holbrook A.
        • Newel M.S.
        Alternative screening for women with dense breasts: breast-specific gamma imaging (molecular breast imaging).
        AJR Am J Roentgenol. 2015; 204: 252-256
        • Hruska C.B.
        Let's get real about molecular breast imaging and radiation risk (commentary).
        Radiol Imaging Cancer. 2019; 1: e190070
        • Tao A.T.
        • Hruska C.B.
        • Conners A.L.
        • et al.
        Dose reduction in molecular breast imaging with a new image-processing algorithm [erratum appears in AJR Am J Roentgenol. 2019;213(6):1403].
        AJR Am J Roentgenol. 2020; 214: 185-193
        • Rauch G.M.
        • Adrada B.E.
        Comparison of breast MR imaging with molecular breast imaging in breast cancer screening, diagnosis, staging, and treatment response evaluation.
        Magn Reson Imaging Clin N Am. 2018; 26: 273-280
        • Adrada B.E.
        • Moseley T.
        • Kappadath S.C.
        • Whitman G.J.
        • Rauch G.M.
        Molecular breast imaging–guided percutaneous biopsy of breast lesions: a new frontier on breast intervention.
        J Breast Imaging. 2020; 2: 484-491
        • Ozanne E.M.
        • Drohan B.
        • Bosinoff P.
        • et al.
        Which risk model to use? Clinical implications of the ACS MRI screening guidelines.
        Cancer Epidemiol Biomarkers Prev. 2013; 22: 146-149
        • Ford D.
        • Easton D.F.
        • Stratton M.
        • et al.
        Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium.
        Am J Hum Genet. 1998; 62: 676-689