BREAST CANCER DIAGNOSIS BREAST CANCER DIAGNOSIS IN ONE DAY: IN ONE DAY:

THE IGR EXPERIENCETHE IGR EXPERIENCE

Philippe Philippe VielhVielh MD, PhDMD, PhDBreast cancer study group Breast cancer study group

Institut de Institut de CancCancéérologierologie Gustave RoussyGustave RoussyVillejuif, FranceVillejuif, France

1st International 1st International CongressCongress of of BreastBreast DiseaseDisease CentersCenters. . Malesherbes Convention Center, Paris. 28Malesherbes Convention Center, Paris. 28--29 29 JanuaryJanuary 20112011

WHY: CONTEXT IN 2004WHY: CONTEXT IN 2004

�� French breast cancer screening program French breast cancer screening program launched and efficient, BUT : launched and efficient, BUT : �� PostPost--screening care : not organized screening care : not organized

�� Surgical delays : twice as expected and Surgical delays : twice as expected and recommended (3 months instead of 1 month)recommended (3 months instead of 1 month)

�� Evolution of breast care towards non Evolution of breast care towards non palpable lesions: importance of a close palpable lesions: importance of a close collaboration between clinicians collaboration between clinicians radiologists and (radiologists and (cyto)pathologistscyto)pathologists

French and French and EuropeanEuropeanrecommendationsrecommendations

�� PreoperativePreoperative diagnosisdiagnosis of of breastbreast lesionslesionsmandatorymandatory

�� Delay Delay betweenbetween first screening test and first screening test and surgerysurgery << 1 1 monthmonth for cancersfor cancers

�� PreoperativePreoperative multidisplinarymultidisplinary assessmentassessmentmandatorymandatory in in manymany casescases

�� PostoperativePostoperative multidisciplinarymultidisciplinaryassessmentassessment mandatorymandatory

HOW: ORGANISATIONHOW: ORGANISATION

RadiologistRadiologist SurgeonSurgeon OncologistOncologist

Shared diagnosis and decisionShared diagnosis and decision

D1D1Cytopathol

Phone callPhone call

Total agreementTotal agreement No agreement or No agreement or no diagnosisno diagnosis

Appropriate Appropriate treatment or treatment or follow up follow up as requiredas required

Go furtherGo further

35 pts/35 pts/weekweek

Immediate diagnosis as frequent as possibleImmediate diagnosis as frequent as possible

Phone callPhone call

direct patients to the direct patients to the most appropriate most appropriate medical visitmedical visit

Information Information sheetsheetsent to the patientsent to the patient

ItineraryItinerary 1 : 1 : subclinicalsubclinical nodulenodule

PATIENT ARRIVES IN THE UNITPATIENT ARRIVES IN THE UNITPATIENT ARRIVES IN THE UNITPATIENT ARRIVES IN THE UNITPATIENT ARRIVES IN THE UNITPATIENT ARRIVES IN THE UNITPATIENT ARRIVES IN THE UNITPATIENT ARRIVES IN THE UNIT

VISIT OF THE FIRST SPECIALISTVISIT OF THE FIRST SPECIALISTVISIT OF THE FIRST SPECIALISTVISIT OF THE FIRST SPECIALISTVISIT OF THE FIRST SPECIALISTVISIT OF THE FIRST SPECIALISTVISIT OF THE FIRST SPECIALISTVISIT OF THE FIRST SPECIALIST

USUSUSUSUSUSUSUS--------GUIDED FNAGUIDED FNAGUIDED FNAGUIDED FNAGUIDED FNAGUIDED FNAGUIDED FNAGUIDED FNA

COMPLEMENTARY MAMMOGRAM AND/OR USCOMPLEMENTARY MAMMOGRAM AND/OR USCOMPLEMENTARY MAMMOGRAM AND/OR USCOMPLEMENTARY MAMMOGRAM AND/OR USCOMPLEMENTARY MAMMOGRAM AND/OR USCOMPLEMENTARY MAMMOGRAM AND/OR USCOMPLEMENTARY MAMMOGRAM AND/OR USCOMPLEMENTARY MAMMOGRAM AND/OR US

LUNCHLUNCHLUNCHLUNCHLUNCHLUNCHLUNCHLUNCH

RESULTSRESULTSRESULTSRESULTSRESULTSRESULTSRESULTSRESULTS AT BACK VISIT TO THE FIRST SPECIALISTAT BACK VISIT TO THE FIRST SPECIALISTAT BACK VISIT TO THE FIRST SPECIALISTAT BACK VISIT TO THE FIRST SPECIALISTAT BACK VISIT TO THE FIRST SPECIALISTAT BACK VISIT TO THE FIRST SPECIALISTAT BACK VISIT TO THE FIRST SPECIALISTAT BACK VISIT TO THE FIRST SPECIALIST

PATIENT LEAVES WITH ALL SURGICAL APPOINTMENTSPATIENT LEAVES WITH ALL SURGICAL APPOINTMENTSPATIENT LEAVES WITH ALL SURGICAL APPOINTMENTSPATIENT LEAVES WITH ALL SURGICAL APPOINTMENTSPATIENT LEAVES WITH ALL SURGICAL APPOINTMENTSPATIENT LEAVES WITH ALL SURGICAL APPOINTMENTSPATIENT LEAVES WITH ALL SURGICAL APPOINTMENTSPATIENT LEAVES WITH ALL SURGICAL APPOINTMENTS

VISIT OF SURGEONVISIT OF SURGEONVISIT OF SURGEONVISIT OF SURGEONVISIT OF SURGEONVISIT OF SURGEONVISIT OF SURGEONVISIT OF SURGEON

REVIEW OF PREVIOUS IMAGING, CONCERTED DECISIONREVIEW OF PREVIOUS IMAGING, CONCERTED DECISIONREVIEW OF PREVIOUS IMAGING, CONCERTED DECISIONREVIEW OF PREVIOUS IMAGING, CONCERTED DECISIONREVIEW OF PREVIOUS IMAGING, CONCERTED DECISIONREVIEW OF PREVIOUS IMAGING, CONCERTED DECISIONREVIEW OF PREVIOUS IMAGING, CONCERTED DECISIONREVIEW OF PREVIOUS IMAGING, CONCERTED DECISION

BLOOD TESTS, FIRST EXTENSION ASSESSMENTSBLOOD TESTS, FIRST EXTENSION ASSESSMENTSBLOOD TESTS, FIRST EXTENSION ASSESSMENTSBLOOD TESTS, FIRST EXTENSION ASSESSMENTSBLOOD TESTS, FIRST EXTENSION ASSESSMENTSBLOOD TESTS, FIRST EXTENSION ASSESSMENTSBLOOD TESTS, FIRST EXTENSION ASSESSMENTSBLOOD TESTS, FIRST EXTENSION ASSESSMENTS

FNA + NEEDLE CORE BIOPSYFNA + NEEDLE CORE BIOPSYFNA + NEEDLE CORE BIOPSYFNA + NEEDLE CORE BIOPSYFNA + NEEDLE CORE BIOPSYFNA + NEEDLE CORE BIOPSYFNA + NEEDLE CORE BIOPSYFNA + NEEDLE CORE BIOPSY + FROZEN SAMPLE+ FROZEN SAMPLE+ FROZEN SAMPLE+ FROZEN SAMPLE+ FROZEN SAMPLE+ FROZEN SAMPLE+ FROZEN SAMPLE+ FROZEN SAMPLE

LUNCHLUNCHLUNCHLUNCHLUNCHLUNCHLUNCHLUNCH

PATIENT LEAVES WITH APPOINTMENTS FOR MEDICAL PATIENT LEAVES WITH APPOINTMENTS FOR MEDICAL PATIENT LEAVES WITH APPOINTMENTS FOR MEDICAL PATIENT LEAVES WITH APPOINTMENTS FOR MEDICAL PATIENT LEAVES WITH APPOINTMENTS FOR MEDICAL PATIENT LEAVES WITH APPOINTMENTS FOR MEDICAL PATIENT LEAVES WITH APPOINTMENTS FOR MEDICAL PATIENT LEAVES WITH APPOINTMENTS FOR MEDICAL ONCOLOGIST VISIT AND CHEMOTHERAPYONCOLOGIST VISIT AND CHEMOTHERAPYONCOLOGIST VISIT AND CHEMOTHERAPYONCOLOGIST VISIT AND CHEMOTHERAPYONCOLOGIST VISIT AND CHEMOTHERAPYONCOLOGIST VISIT AND CHEMOTHERAPYONCOLOGIST VISIT AND CHEMOTHERAPYONCOLOGIST VISIT AND CHEMOTHERAPY

ItineraryItinerary 2 : large mass2 : large mass

PATIENT ARRIVES IN THE UNITPATIENT ARRIVES IN THE UNITPATIENT ARRIVES IN THE UNITPATIENT ARRIVES IN THE UNITPATIENT ARRIVES IN THE UNITPATIENT ARRIVES IN THE UNITPATIENT ARRIVES IN THE UNITPATIENT ARRIVES IN THE UNIT

VISIT OF FIRST SPECIALISTVISIT OF FIRST SPECIALISTVISIT OF FIRST SPECIALISTVISIT OF FIRST SPECIALISTVISIT OF FIRST SPECIALISTVISIT OF FIRST SPECIALISTVISIT OF FIRST SPECIALISTVISIT OF FIRST SPECIALIST

RESULTSRESULTSRESULTSRESULTSRESULTSRESULTSRESULTSRESULTS AT BACK VISIT TO THE ONCOLOGISTAT BACK VISIT TO THE ONCOLOGISTAT BACK VISIT TO THE ONCOLOGISTAT BACK VISIT TO THE ONCOLOGISTAT BACK VISIT TO THE ONCOLOGISTAT BACK VISIT TO THE ONCOLOGISTAT BACK VISIT TO THE ONCOLOGISTAT BACK VISIT TO THE ONCOLOGIST

VISIT OF FIRST SPECIALISTVISIT OF FIRST SPECIALISTVISIT OF FIRST SPECIALISTVISIT OF FIRST SPECIALISTVISIT OF FIRST SPECIALISTVISIT OF FIRST SPECIALISTVISIT OF FIRST SPECIALISTVISIT OF FIRST SPECIALISTExplanationsExplanationsExplanationsExplanationsExplanationsExplanationsExplanationsExplanations on on on on on on on on breastbreastbreastbreastbreastbreastbreastbreast lesionslesionslesionslesionslesionslesionslesionslesions, diagnostic , diagnostic , diagnostic , diagnostic , diagnostic , diagnostic , diagnostic , diagnostic procedureprocedureprocedureprocedureprocedureprocedureprocedureprocedure

and and and and and and and and potentialpotentialpotentialpotentialpotentialpotentialpotentialpotential diagnostics and implicationsdiagnostics and implicationsdiagnostics and implicationsdiagnostics and implicationsdiagnostics and implicationsdiagnostics and implicationsdiagnostics and implicationsdiagnostics and implications

STEREOTACTIC MACROBIOPSYSTEREOTACTIC MACROBIOPSYSTEREOTACTIC MACROBIOPSYSTEREOTACTIC MACROBIOPSYSTEREOTACTIC MACROBIOPSYSTEREOTACTIC MACROBIOPSYSTEREOTACTIC MACROBIOPSYSTEREOTACTIC MACROBIOPSY

PATIENT LEAVES WITH MEDICALPATIENT LEAVES WITH MEDICALPATIENT LEAVES WITH MEDICALPATIENT LEAVES WITH MEDICALPATIENT LEAVES WITH MEDICALPATIENT LEAVES WITH MEDICALPATIENT LEAVES WITH MEDICALPATIENT LEAVES WITH MEDICALAND SURGICAL APPOINTMENTSAND SURGICAL APPOINTMENTSAND SURGICAL APPOINTMENTSAND SURGICAL APPOINTMENTSAND SURGICAL APPOINTMENTSAND SURGICAL APPOINTMENTSAND SURGICAL APPOINTMENTSAND SURGICAL APPOINTMENTS

ItineraryItinerary 3 : 3 : microcalcificationsmicrocalcifications

PATIENT ARRIVES IN THE UNITPATIENT ARRIVES IN THE UNITPATIENT ARRIVES IN THE UNITPATIENT ARRIVES IN THE UNITPATIENT ARRIVES IN THE UNITPATIENT ARRIVES IN THE UNITPATIENT ARRIVES IN THE UNITPATIENT ARRIVES IN THE UNIT

REVIEW OF PREVIOUS IMAGINGREVIEW OF PREVIOUS IMAGINGREVIEW OF PREVIOUS IMAGINGREVIEW OF PREVIOUS IMAGINGREVIEW OF PREVIOUS IMAGINGREVIEW OF PREVIOUS IMAGINGREVIEW OF PREVIOUS IMAGINGREVIEW OF PREVIOUS IMAGINGCONCERTED DECISIONCONCERTED DECISIONCONCERTED DECISIONCONCERTED DECISIONCONCERTED DECISIONCONCERTED DECISIONCONCERTED DECISIONCONCERTED DECISION

CLINICAL RESULTSCLINICAL RESULTS

�� Quantitative dataQuantitative data

�� Qualitative dataQualitative data

�� PatientPatient’’ss satisfaction datasatisfaction data

NumbersNumbers

�� > 6000 > 6000 womenwomen seenseen atat the one stop the one stop unitunit

�� MedianMedian delaydelay betweenbetween first phone call first phone call and first and first visitvisit: 11 : 11 daysdays

�� Cancer rate Cancer rate atat one stop unit: > 65%one stop unit: > 65%

�� 20% calcifications, 70% 20% calcifications, 70% solidsolid masses masses

�� USUS--guidedguided FNA: 60% FNA: 60% initiallyinitially, > 80% , > 80% currentlycurrently

Several successive Several successive evaluationsevaluations

Age

0

20

40

60

80

100

1 24 47 70 93 116

139

162

185

208

231

254

277

300

323

346

Age

Les ion Size (mm )

0

50

100

150

200

250

300

1 29 57 85 113 141 169 197 225 253 281 309 337

Taille (mm )s

Median age: 56 yrsMedian age: 56 yrs

Median Median lesion size: 15 mmlesion size: 15 mm

FNA for FNA for solidsolid massesmasses

PerfectPerfect concordance concordance isis mandatorymandatory

ClinicianClinician RadiologistRadiologist PathologistPathologist

DIAGNOSTIC DIAGNOSTIC CONCORDANCECONCORDANCE

A single discordant A single discordant elementelement: go : go furtherfurther ++++++

MultidisciplinarityMultidisciplinarity ++++++

FNA: FNA: resultsresults

UnsatisfactoryUnsatisfactory specimensspecimens : 2%: 2%

Suspect : 8%Suspect : 8%

Cancer : 55%Cancer : 55%

BenignBenign : 35%: 35%

(As a (As a meanmean on on severalseveral successive successive evaluationsevaluations))

Cancer : 80%Cancer : 80%

Fx positive: 0.1%Fx positive: 0.1%

Fx Fx negativenegative : 3%: 3%

PatientPatient’’ss satisfactionsatisfaction

2

7

24

47

30

3

0

10

20

30

40

50

60

1 2 3 4 5 x

90% 90% 90% 90% 90% 90% 90% 90% overalloveralloveralloveralloveralloveralloveralloverall satisfiedsatisfiedsatisfiedsatisfiedsatisfiedsatisfiedsatisfiedsatisfiedfair good very

goodexcellentno

ClinicalClinical resultsresults

�� MeanMean delaydelay phone callphone call--first first visitvisit : : 11 11 daysdays

�� If FNA If FNA isis unsatisfactoryunsatisfactory, , suspicioussuspicious or discordant : or discordant :

cancan bebe repeatedrepeated immediatelyimmediately and/or on site and/or on site corecore

needleneedle biopsybiopsy performedperformed))

�� RegardingRegarding solidsolid lesionslesions, , exact exact diagnosisdiagnosis cancan bebe

made in one made in one dayday in 87% of casesin 87% of cases, and , and soso the the

treatmenttreatment plan and plan and appointmentsappointments givengiven to patientto patient

�� For calcifications, For calcifications, diagnosisdiagnosis isis obtainedobtained and and givengiven

to patient to patient afterafter a maximum ofa maximum of 12 12 daysdays

�� SystematicSystematic reviewreview of images by of images by radiologistradiologist: : multifocalitymultifocality evidencedevidenced in in somesome casescases

�� MultifocalityMultifocality:: provedproved the the samesame dayday((mastectomymastectomy indicatedindicated))

�� Initiation of Initiation of generalgeneral workwork--upup

�� MultidisciplinaryMultidisciplinary approachapproach

�� Screening for inclusion in Screening for inclusion in clinicalclinical trialstrials

�� BankingBanking of a of a vastvast majoritymajority of of samplessampleswithwith patients patients writtenwritten informedinformed consent consent ((leftoversleftovers): ): translationaltranslational researchresearch ++++++

NeedsNeeds, , requirementsrequirements, , and and potentialpotential problemsproblems

�� NeedNeed wellwell--trainedtrained senior senior physiciansphysicians

�� SophisticatedSophisticated organisationorganisation

�� Trust in the Trust in the otherother doctorsdoctors of the teamof the team

�� ModestyModesty and team spirit and team spirit mandatorymandatory

�� Permanent Permanent qualityquality control control necessarynecessary

�� Diagnostic Diagnostic sometimessometimes givengiven tootoo quicklyquickly??

RESEARCH ASPECTSRESEARCH ASPECTS

�� Imaging: Imaging: contrastcontrast doppler, doppler, angioangio--mammographymammography, , tomosynthesistomosynthesis, , opticoptic imagingimaging

�� PsychocognitivePsychocognitive

�� Health Health economicseconomics

�� TranslationalTranslational researchresearch

157.11 157.11 -- 237.91 237.91 €€185 185 €€USUS--guidedguided corecore needleneedlebiopsybiopsy

18.75 18.75 -- 45.30 45.30 €€27 27 €€USUS--guidedguided FNAFNA

7.5 7.5 -- 21.17 21.17 €€11 11 €€FNA for palpable FNA for palpable lesionlesion

MinMin--MaxMaxMedianMedian

OverallOverall measuredmeasured costscosts (all (all includedincluded))

MeasureMeasure of direct of direct costscosts

Overall cost for the 697 lesions (670 patients) for an exact diagnosis (including biopsies and surgeries where necessary): 56.463 56.463 €€

Overall cost if 697 biopsies had been used (withno false positive or false negative result):

123.950 123.950 €€

TranslationalTranslational researchresearch

•• Is FNAC an adequate material for Is FNAC an adequate material for molecular tests?molecular tests?

•• Development of prognostic, Development of prognostic, predictive and diagnostic predictive and diagnostic biomarkersbiomarkers

Diagnostic Diagnostic biomarkersbiomarkersusingusing splicingsplicing arrayarray

�� ManyMany exons are exons are differentiallydifferentially expressedexpressedby by breastbreast cancer and cancer and benignbenign lesionslesions

�� TheseThese alternative alternative transcriptstranscripts are are detectabledetectable on on materialmaterial obtainedobtained by FNA by FNA and and maymay contributecontribute to to increaseincreasesensitivitysensitivity and and specificityspecificity of of breastbreastcancer cancer cytodiagnosiscytodiagnosis

AndrAndréé F, et al. Lancet F, et al. Lancet OncolOncol. 2009,10:381. 2009,10:381--9090

PerspectivesPerspectives

Fine Needle Aspirate(less then 1 min)

Total RNA extraction(< 2 hours)

RNA amplification(< 7 hours)

Fragmentation and labelling(< 2.5 hours)

Hybridisation(16 hours)

Affymetrix Gene Chip station(washes, staining and scanning)

(< 4 hours)

RNA qualification(< 30 min)

GO/ no GO

Diagnostic result

40% of biopsy

Fine Needle Aspirate(less then 1 min)

Total RNA extraction(< 2 hours)

RNA amplification(< 7 hours)

Fragmentation and labelling(< 2.5 hours)

Hybridisation(16 hours)

Affymetrix Gene Chip station(washes, staining and scanning)

(< 4 hours)

RNA qualification(< 30 min)

GO/ no GO

Diagnostic result

40% of biopsy

BenignBenign or or malignantmalignant??

ThanksThanks to:to:�� Les Les ééquipes mquipes m éédicales: Corinne dicales: Corinne BalleyguierBalleyguier , Voichita Suciu, Clarisse , Voichita Suciu, Clarisse DromainDromain , Daniel Vanel, , Daniel Vanel, EladiEladi Bayou, Jean Bayou, Jean

RRéémi mi GarbayGarbay , France , France RochardRochard , Damienne , Damienne CastaigneCastaigne , Catherine Uzan, S, Catherine Uzan, S éébastien bastien GouyGouy , Andr, Andr ééa a CavalcantiCavalcanti , Hugo , Hugo MarsigliaMarsiglia , C, Cééline Bourgier, Patrice Chaurin, Fabrice Andrline Bourgier, Patrice Chaurin, Fabrice Andr éé, Marc , Marc SpielmannSpielmann , Julien Domont, et les autres qui sont , Julien Domont, et les autres qui sont partis ou que jpartis ou que j ’’oublieoublie

�� Les Les ééquipes soignantes: Pascale, Anna, Annaquipes soignantes: Pascale, Anna, Anna --Maria, Claudine, Nathalie, Coralie, FranMaria, Claudine, Nathalie, Coralie, Fran ççoise, Muriel, et Marie Paule oise, Muriel, et Marie Paule EtcheverryEtcheverry et Olivia et Olivia RibardiRibardi èèrere

�� Les assistantes mLes assistantes m éédicales: Nathalie, Marie Ange, dicales: Nathalie, Marie Ange, VVééronicaronica , St, Stééphanie, Sandrine, Virginie, Martine, Audrey, phanie, Sandrine, Virginie, Martine, Audrey, Johanne, Anne Sophie, et Christine ProustJohanne, Anne Sophie, et Christine Proust

�� Les filles de lLes filles de l ’’accueil: Marie Claire, Brigitteaccueil: Marie Claire, Brigitte�� Les techniciens de cytopathologie: Anne Marie, Serg eLes techniciens de cytopathologie: Anne Marie, Serg e�� Les manips radioLes manips radio�� Les dames en roseLes dames en rose�� Le service dLe service d ’’oncopsychologieoncopsychologie : Sarah : Sarah DauchyDauchy , Franck , Franck ZenasniZenasni , les psychologues, les psychologues�� GGéérard de rard de PouvourvillePouvourville et son et son ééquipe, Eric Noelquipe, Eric Noel�� Le dLe d éépartement de BSE: Stephan Michiels, Ellen Benhamou, Christine Lapartement de BSE: Stephan Michiels, Ellen Benhamou, Christine La ruerue�� La business Unit sein de lLa business Unit sein de l ’’UPRES EA 3535: VUPRES EA 3535: V ééronique Scott, Isabelle Laurent, ainsi que Vladimir ronique Scott, Isabelle Laurent, ainsi que Vladimir LazarLazar , Mahasti , Mahasti

SaghatchianSaghatchian�� Le dLe d éépartement partement BiopathBiopath , le d, le d éépartement dpartement d ’’ Imagerie, le plateau de consultationImagerie, le plateau de consultation