IntroductionAlthough­ mammography­ is­ known­ to­ be­ the­ most­ effective­

form­ of­ breast­ screening,­ it­ has­ limitations.­ In­ particular,­ it­ is­known­ to­have­ limitations­ in­ high-risk­patients­ especially­ those­with­ mammographically­ dense­ breasts­ because­ of­ the­ radio-graphically­occult­nature­of­such­breasts.­It­will­be­presented­that­although­ultrasound­also­has­its­ limitations,­ it­can­have­a­viable­role­in­the­secondary­screening­of­dense­breasts.­The­purpose­of­screening­ will­ be­ defined­ and­ the­ limitations­ of­ mammography­will­be­described­with­particular­relevance­to­breast­density.­The­benefits­and­limitations­of­ultrasound­as­a­screening­tool­will­be­evaluated­after­ review­of­current­ literature­and­ it­will­be­shown­that­the­limitations­of­ultrasound­can­be­minimised­to­achieve­the­best­possible­outcome­for­the­general­population.

The results of breast screeningBreast­screening­is­where­asymptomatic­women­are­imaged­for­

the­early­detection­of­breast­cancer­with­the­aim­of­reducing­the­morbidity­and­mortality­of­breast­cancer.­

It­is­widely­accepted­that­the­primary­method­of­breast­screen-ing­ is­mammography­and­ that­ the­use­of­ultrasound­ is­ the­most­effective­ adjunct­ to­ mammography­ in­ helping­ to­ distinguish­benign­from­malignant­disease.�,2,3,5­Mammography­has­a­screen-ing­ detection­ rate­ of­ between­ 0.20­ per­ cent­ and­ 0.70­ per­ cent­which­is­partly­dependent­on­patient­age.5­

BreastScreen­ Victoria,­ however,­ reports­ in­ its­ 200�­ Annual­Statistical­Report,�2­that­screening­mammography­detects­a­higher­average­ of­ 0.73­ per­ cent­ of­ cancers.­ The­ 40-49-year-old­ age­group,­which­is­more­likely­to­have­dense­breasts,­is­reported­as­having­ a­ 0.38­ per­ cent­ detection­ rate.­ Ultrasound,­ as­ a­ primary­screening­tool,­is­reported­to­detect­approximately­0.30­per­cent­of­breast­cancers.2,3,4,6

Mammography­ has­ its­ limitations­ and­ the­ use­ of­ ultrasound­as­ a­ secondary­ screening­ tool,­ especially­ in­ high­ risk­ patients,­must­be­considered.3,4,5­The­sensitivity­of­an­imaging­modality­is­defined­as­the­percentage­of­cancers­detected­among­all­cancers­detected­ with­ any­ modality.�3­ Mammography­ in­ symptomatic­patients­ is­ reported­ to­have­a­sensitivity­of­up­ to­98­per­cent­ in­women­with­ fatty­breasts.­However,­ in­women­with­very­dense­breasts­it­is­reported­to­diminish­to­a­low­of­only­48­per­cent,­with­an­average­of­78­per­cent.­The­sensitivity­of­ultrasound­in­women­with­dense­breasts­ is­around­75­per­cent.­The­use­of­ultrasound­combined­with­mammography­ in­ these­women­can­ increase­ the­sensitivity­ to­ 97­ per­ cent.�3­Therefore,­ it­ is­ clear­ that­ ultrasound­can­play­a­role­in­the­secondary­screening­of­dense­breasts.

What is a dense breast?The­interpretation­of­the­density­of­a­breast­is­very­subjective.­

Some­ studies­ rate­ the­ denseness­ of­ the­ breast­ according­ to­ the­Breast­Imaging­Reporting­and­Data­System­(BIRADS)­as­set­by­

Ultrasound as a secondary screening tool in mammographically dense breasts

Kylie Griggs

Maroondah­Hospital­Radiology­DepartmentDavey­Drive,­East­Ringwood,­Victoria­3�35,­Australia

Correspondence­email­kgriggs@easternwireless.com.au

Abstract It­is­well­known­that­breast­screening­is­a­part­of­our­society­and­is­designed­to­reduce­the­mortality­and­mor-bidity­ from­breast­cancer.­Mammography­ is­ the­ imaging­modality­of­choice­ in­a­breast-screening­environment.­Both­the­detection­rate­of­mammography­in­a­screening­environment­and­the­sensitivity­of­mammography­in­symptomatic­women­are­known­to­be­greater­than­that­of­ultrasound.­However,­after­a­review­of­literature­both­of­these­are­said­to­increase­when­the­two­imaging­modalities­are­combined.­This­paper­will­present­that­mammography­has­limitations­in­breast­imaging,­especially­in­women­with­dense­breasts­and­that­ultrasound­can­have­a­benefit­as­a­secondary­screening­tool­in­these­women.­It­will­be­shown­that­although­ultrasound­also­has­its­limitations,­these­can­be­minimised­with­the­implementation­of­effective­education­and­imaging­protocols.­

The­ paper­ will­ conclude­ that­ although­ further­ research­ into­ ultrasound­ as­ screening­ tool­ is­ required,­ its­ use­ as­ a­complement­to­mammography­can­only­be­of­benefit­to­the­general­population.

Figure 1 mediolateral oblique views of three different breast densities. Rang-ing from scattered fibroglandular densities in (A) to a heterogeneously dense breast (B) to being an extremely dense breast (C).

Australian­Institute­of­Radiography

The­Radiographer­2006:­53­(�):­20–23

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Clinical practice

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the­American­College­of­Radiologists.Kolb­et al.6­define­the­BIRADS­classification­of­breast­density­

as­being:4­–­being­an­extremely­dense­breast;­3­–­an­heterogeneously­dense­breast;2­–­scattered­fibroglandular­densities­in­the­breast­and;�­–­a­breast­that­is­almost­entirely­fat.­Other­ studies­ simply­ rate­ the­density­of­ the­breast­ into­ three­

categories,­being­dense,­mixed­and­fatty­breast.7,9­The­density­of­the­breast­is­graded­by­visual­means­only.­It­is­clear­that­the­defi-nition­of­a­dense­breast­needs­to­be­defined­objectively­in­order­to­carry­out­studies­on­the­sensitivity­of­ultrasound­in­dense­breasts.­Figure­�­shows­varying­breast­densities.

It­ is­ understood­ that,­ with­ the­ introduction­ of­ digital­ mam-mography­ and­ computer­ aided­ detection­ (CAD),­ the­ denseness­of­a­breast­will­be­able­to­be­defined­more­objectively,­however,­the­ use­ of­ digital­ mammography­ may­ also­ reduce­ the­ effect­ of­breast­density­on­the­sensitivity­of­mammography.6­It­is­reported­that­ the­different­definitions­of­breast­density­ in­varying­studies­may­be­ the­cause­for­varying­results­and,­as­breast­parenchyma­density­can­vary­ in­ the­same­patient,­ the­difficulty­of­definition­will­always­be­there.­

The limitations of mammographyMammography­ is­ based­ on­ the­ contrast­ differences­ between­

fatty­and­glandular­tissue.­The­glandular­areas­in­the­breast­show­as­areas­of­increased­density.­However,­mammographically,­breast­cancers­can­also­show­as­areas­of­increased­density.­Therefore,­in­dense­breasts,­cancers­may­be­radiographically­occult.­Although­the­biological­basis­is­unclear,­it­is­suggested­that­the­denseness­of­the­breast­contributes­to­breast­cancer­risk,4­and­in­understand-ing­this­failure­of­mammography­in­imaging­dense­breasts­other­imaging­modalities­need­to­be­considered.9­

A­study­by­the­Wesley­Breast­Clinic7­suggested­that­the­num-ber­of­mammographically­occult­cancers­per­�000­mammograms­was­almost­twice­as­many­in­dense­breasts­as­in­average­density­breasts,­which­is­why­ultrasound­must­be­considered­as­a­second-ary­ screening­ tool.­ Mammography­ also­ has­ limitations­ related­to­patient­age,­ the­use­of­hormone­ replacement­ therapy­and­ the­location­of­a­ lesion­ in­ the­breast,4­ these­all­affect­ the­sensitivity­of­mammography.­

With­ much­ publicity­ today­ about­ the­ effectiveness­ of­ breast­imaging­and­the­increased­knowledge­of­our­patients,­it­is­of­con-cern­that­mammography­alone­cannot­always­satisfy­and­reassure­the­patient­who­is­at­high­risk­of­breast­cancer.2

Ultrasound as a breast-imaging toolUltrasound­in­breast­imaging­is­a­very­useful­adjunct­to­mam-

mography­ as­ it­ can­ help­ to­ classify­ the­ nature­ of­ lesions­ seen­in­ the­ breast.­ Stavros­ et al.��­ showed­ in­ their­ landmark­ study­that­ sonography­ improves­ the­ specificity­ of­ diagnoses­ of­ breast­lesions,­ both­ benign­ and­ malignant.­ It­ is­ the­ most­ common­complement­ to­ mammography­ and­ can­ often­ be­ necessary­ for­complete­evaluation­of­the­breast.

Ultrasound­ is­ the­ recommended­ adjunct­ for­ mammographi-cally­dense­breasts­as­ fibroglandular­ tissue­appears­hyperechoic­and­breast­cancers­usually­present­as­hypoechoic.­Therefore,­it­is­thought­that­cancers­can­be­well­visualised­in­this­background.4,6­

See­Figures­2­and­3.­Ultrasound­has­fewer­limitations­when­it­comes­to­patient­age­

and­positioning.­Unlike­mammography,­ the­ location­of­ a­ lesion­in­ the­ breast­ is­ of­ decreased­ significance­ with­ ultrasound­ usu-ally­providing­easy­access­ for­guiding­needle­core­biopsies­and­localisations.

As­ an­ imaging­ tool,­ ultrasound­ has­ limitations­ that­ make­ it­unsuitable­ for­ use­ as­ a­ primary­ screening­ modality.­ Ultrasound­cannot­ detect­ microcalcifications­ and­ is­ operator­ dependent.­ It­is­reported­as­not­being­cost­effective­as­a­screening­modality­if­performed­by­radiologists.3

Stavros3­also­reports­a­medico­legal­disincentive­for­perform-ing­whole­breast­ultrasound­in­the­United­States.­He­states­that:

‘A­radiologist­can­be­held­liable­only­for­a­missed­cancer­that­lies­in­the­part­of­the­breast­that­was­examined­sonographically.­He­or­she­cannot­be­held­liable­for­a­missed­cancer­that­lies­in­a­part­of­ the­breast­ that­was­not­examined­sonographically.­Thus,­certain­ American­ radiologists­ have­ tended­ to­ avoid­ scanning­areas­other­than­the­immediate­area­of­clinical­or­mammographic­concern.’3

Ultrasound,­however,­needs­further­ investigation­ if­ it­ is­ to­be­used­as­a­secondary­screening­tool.­

There­ are­ no­ hard­ data­ on­ the­ effectiveness­ of­ sonographic­screening.­Ultrasound­needs­ to­be­explored­further­as­a­second-ary­ screening­ tool­ with­ newer­ high­ resolution­ equipment­ and­improved­scan­technique.2,3

Madjar2­conducted­a­small­pilot­study­on­asymptomatic­women­that­showed­that­ultrasound­was­a­feasible­option­for­secondary­screening.­He­also­showed­that­operator­skill­can­be­ transferred­with­effective­education­and­training,­thus­partly­overcoming­the­issue­of­operator­dependence.­Madjar­also­believes­the­extra­cost­of­ultrasound­ is­ justified­ in­high­ risk­patients,­ as­does­Stavros.3­Stavros­reports­the­cost­of­cancer­found­by­ultrasound­is­similar­

Figure 2 mediolateral (A) and craniocaudal (B) views of a 52-year-old woman with heterogeneously dense breasts. The mammogram was normal while an ultra-sound (C) revealed an invasive ductal carcinoma in the right breast at 10 o’clock. The carcinoma is hypoechoic in a hyperechoic background.

Ultrasound as a secondary screening tool in mammographically dense breasts

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to­the­cost­of­cancer­found­at­screening­mammography­and­that­ultrasound­is­viable­when­the­mammogram­is­negative­in­a­high­risk­patient.

Crystal­ et al.4­ also­ reports­ the­ effectiveness­ of­ ultrasound­ as­a­ secondary­ screening­ tool.­ Their­ study­ shows­ a­ 0.46­ per­ cent­cancer­detection­rate­for­screening­ultrasound.­They­believe­that­ultrasound­is­not­cost­effective­for­all­patients­but­has­the­poten-tial­ to­be­beneficial­ for­patients­with­dense­breasts.­Their­ study­achieved­a­high­rate­because­of­the­high­number­of­patients­with­dense­breasts.­It­ is­believed­that­if­ there­had­been­more­patients­with­less­fatty­breasts­the­detection­rate­would­not­have­been­as­high­with­ultrasound­and­would,­ therefore,­not­be­as­cost­effec-tive.­The­study­by­Crystal­et al.­also­used­modern­high­resolution­equipment­as­they­recognised­the­need­for­this.­However,­Crystal­et al.­recognise­the­need­for­further­studies­in­this­area­to­repro-duce­ their­ results­ and­ to­ look­ at­ the­ cost­ effectiveness­ of­ ultra-sound.­Of­course­the­cost­of­ultrasound­as­a­screening­modality­will­ vary­ between­ countries­ depending­ on­ different­ regulations.­The­true­benefit­from­ultrasound­‘cannot­be­determined­other­than­by­performance­of­a­randomised­control­trial­(RCT)­using­death­as­the­end­point’.4­A­RCT­is­actually­unlikely­in­today’s­times­as­women­are­better­informed­and,­therefore,­there­is­more­likely­to­be­ less­ compliance­ resulting­ in­ contamination.­ It­ is­ known­ that­women­who­volunteer­for­a­trial­but­who­are­assigned­to­the­con-trol­group­are­likely­to­seek­information­outside­the­trial­and­will­therefore,­ receive­ the­ examination­ anyway.­ This­ contamination­would­likely­affect­the­difference­in­mortality­between­groups.5­

Kolb­et al.6­found­a­0.30­per­cent­detection­rate­for­screening­ultrasound­alone.­They­ found­ that­ the­ size­and­stage­of­cancers­detected­was­not­statistically­different­to­those­detected­by­screen-ing­mammography.­They­agree­that,­because­of­the­limitations­of­mammography,­a­secondary­screening­method­needs­to­be­investi-gated­as­finding­cancers­by­mammography­is­just­as­beneficial­as­finding­them­by­ultrasound.­Again,­it­is­thought­that­more­studies­using­high­resolution­equipment­need­to­be­performed­to­assess­whether­ the­ benefits­ of­ the­ increased­ detection­ outweigh­ the­increased­costs­and­time­associated­with­secondary­screening.

Minimising the limitations of ultrasoundThe­main­concern­for­ultrasound­is­the­fact­that­it­is­so­opera-

tor­dependent.­However,­it­can­also­be­argued­that­mammography­is­ operator­ dependent­ as­ well.­ The­ introduction­ of­ guidelines­for­ a­ screening­ program­ including­ comprehensive­ training­ and­accreditation­ for­ mammographers­ has­ helped­ to­ overcome­ this­problem.­It­has­already­been­stated­that­Madjar2­demonstrated­in­

his­study­that­good­ultrasound­technique­can­be­learned­and­trans-ferred.­There­is­no­reason­why,­with­the­availability­of­dedicated­breast­ ultrasound­ training­ programs,­ that­ the­ effect­ of­ operator­dependence­can­be­minimised­in­a­controlled­screening­environ-ment.­ Standards­ for­ ultrasound­ examinations­ of­ the­ breast­ are­already­set­by­various­bodies­such­as­ the­Australian­Society­for­Ultrasound­ in­Medicine­and­ the­International­Breast­Ultrasound­School­to­ensure­a­systematic­approach­to­the­imaging­process.

Previous­studies­report­an­increased­cost­of­ultrasound­screen-ing­ because­ of­ a­ radiologist­ performing­ the­ scan.3,4,6­ These­ are­overseas­ studies.­ The­ author­ believes­ that,­ with­ the­ quality­ of­sonography­in­Australia,­in­conjunction­with­continued­education­standards­as­set­by­the­Australiasian­Sonographers­Accreditation­Registry,­there­is­no­reason­why­feasible­studies­cannot­be­under-taken­ with­ sonographers­ rather­ that­ sonologists­ in­ this­ country.­This­would­ reduce­ the­previously­noted­high­ cost­ of­ secondary­screening­ ultrasound.­ The­ time­ taken­ for­ screening­ ultrasound­and­ the­ increased­anxiety­ level­of­patients­undertaking­an­extra­test­has­been­reported­as­a­negative­aspect­in­ultrasound­screen-ing.­ However,­ the­ time­ for­ a­ screening­ ultrasound­ examination­has­been­reported­as­between­4–�5­min­with­an­average­of­only­7­min.4­Also,­if­the­screening­ultrasound­is­performed­immediately­following­ the­mammogram,­ thus­negating­ the­need­ for­a­ recall,­time­is­saved­and­the­effect­of­adverse­psychological­consequenc-es­from­a­recall­is­reduced.4

ConclusionIt­has­been­shown­that­screening­mammography­has­its­ limi-

tations­especially­ in­high-risk­patients­ such­as­ those­with­dense­breasts.­Because­of­ these­ limitations,­ it­ is­ generally­ agreed­ that­a­secondary­screening­option­needs­to­be­considered.­We­need­to­improve­our­ability­to­detect­breast­cancers­in­mammographically­dense­breast­to­satisfy­the­expectations­of­the­general­population.­Ultrasound,­although­it­has­its­own­limitations,­is­a­viable­option­as­ a­ secondary­ screening­ tool­ as­ it­ has­ been­ shown­ to­ improve­cancer­detection­rates­in­this­high-risk­group.­It­is­known,­though,­that­more­research­needs­to­be­carried­out­to­prove­its­effective-ness­and­to­reproduce­the­encouraging­results­already­obtained.­

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4­ Crystal­P,­Strano­SD,­Shcharynski­S,­Koretz­MJ.­Using­sonography­to­screen­

Figure 3 Mediolateral (A) and craniocaudal (B) views of a 48-year-old woman with dense breasts. The mammogram was normal while the ultrasound revealed a tubular carcinoma with invasive components in the left breast at the 12.30 position. There were no clinical indications.

Kylie Griggs

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The Radiographer ­23

women­ with­ mammographically­ dense­ breasts.­ Am J Roentgenol­ 2003;­ �8�­(�):­�77–82.

5­ Gordon­PB.­Ultrasound­for­breast­cancer­screening­and­staging.­Radiolog Clin Nth Am­2002;­40­(3):­43�–4�.

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