ahrq’s effective health care program: applying existing evidence to breast cancer prevention and...

AHRQ’s Effective Health Care Program: AHRQ’s Effective Health Care Program: Applying Existing Evidence to Breast Applying Existing Evidence to Breast

Cancer Prevention and DiagnosisCancer Prevention and Diagnosis

Friday, December 3, 2010Friday, December 3, 2010

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AgendaAgenda

Brief Overview of Patient-Centered Outcomes Brief Overview of Patient-Centered Outcomes Research and AHRQ’s Effective Health Care Research and AHRQ’s Effective Health Care Program-Program- Deborah L. Rogal, Moderator Deborah L. Rogal, Moderator

Comparative Effectiveness of Medications to Comparative Effectiveness of Medications to Reduce Risk of Primary Breast Cancer in Women-Reduce Risk of Primary Breast Cancer in Women- Heidi Nelson, M.D., M.P.H., FACPHeidi Nelson, M.D., M.P.H., FACP

Comparative Effectiveness of Core Needle and Comparative Effectiveness of Core Needle and Open Surgical Biopsy for the Diagnosis of Breast Open Surgical Biopsy for the Diagnosis of Breast Lesions- Lesions- Karen Schoelles, M.D., S.M., FACPKaren Schoelles, M.D., S.M., FACP

Q&A from Audience Q&A from Audience

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Patient-Centered Outcomes Patient-Centered Outcomes Research and AHRQ’s Effective Research and AHRQ’s Effective

Health Care ProgramHealth Care Program

Deborah L. Rogal, M.P.P. Deborah L. Rogal, M.P.P.

AHRQ’s Office of Communications and AHRQ’s Office of Communications and Knowledge TransferKnowledge Transfer

44

Patient-Centered Patient-Centered Outcomes ResearchOutcomes Research

Benefits

Harms

Also known as comparative effectiveness researchAlso known as comparative effectiveness research

Unbiased and practical, evidence-based Unbiased and practical, evidence-based information information

Compares drugs, devices, tests and surgeries, and Compares drugs, devices, tests and surgeries, and approaches to health care approaches to health care – Benefits and harms Benefits and harms – What is known and what isn’tWhat is known and what isn’t

Descriptive, not prescriptiveDescriptive, not prescriptive 55

Horizon Horizon ScanningScanning

EvidenceEvidence NeedNeed

IdentificationIdentification

Evidence Evidence SynthesisSynthesis

EvidenceEvidence GenerationGeneration

StrategiesStrategiesInterventionsInterventionsConditionsConditionsPopulationsPopulations

DisseminationDisseminationTranslationTranslation

ImprovementsImprovements inin

Health CareHealth Care

Research PlatformResearch PlatformInfrastructure – Methods Development – Training Infrastructure – Methods Development – Training

A Framework for A Framework for Patient-Centered Outcomes Patient-Centered Outcomes

ResearchResearch

66

Research Focus: Research Focus: 14 Priority Conditions14 Priority Conditions

Arthritis and nontraumatic joint Arthritis and nontraumatic joint disordersdisorders

CancerCancer

Cardiovascular disease, Cardiovascular disease, including stroke and including stroke and hypertensionhypertension

Dementia, including Dementia, including Alzheimer’s diseaseAlzheimer’s disease

Depression and other mental Depression and other mental health disordershealth disorders

Developmental delays, ADHD Developmental delays, ADHD and autismand autism

Diabetes mellitusDiabetes mellitus

Functional limitations and Functional limitations and disabilitydisability

Infectious disease Infectious disease including HIV/AIDSincluding HIV/AIDS

ObesityObesity

Peptic ulcer disease and Peptic ulcer disease and dyspepsiadyspepsia

Pregnancy including Pregnancy including preterm birthpreterm birth

Pulmonary disease/asthmaPulmonary disease/asthma

Substance abuseSubstance abuse

77

Research Focus: Research Focus: Priority PopulationsPriority Populations

Low-income groupsLow-income groups

Minority groups Minority groups

Women Women

Children Children

The elderly The elderly

Individuals with special health-care needs, such as Individuals with special health-care needs, such as those with disabilities, those who need chronic care or those with disabilities, those who need chronic care or end-of-life care, or those who live in inner-city and rural end-of-life care, or those who live in inner-city and rural areas. areas. 88

Effective Health Care Program Effective Health Care Program Translation ProductsTranslation Products

99

Executive Summary

Web Site

ClinicianGuide

ConsumerGuide Policymaker

Summary

Interactive Case Study

CE Modules

Faculty Slides

Patient Decision Aid(available soon)

Systematic Review Report

Breast Cancer ResourcesBreast Cancer Resources

1010

Public InvolvementPublic Involvement

Topic Topic GenerationGeneration

Topic Topic DevelopmentDevelopment

Topic Topic RefinementRefinement

Research Research ReviewReview

Research Research Needs Needs

DevelopmentDevelopment

Report Report Translation & Translation & DisseminationDissemination

During the Research ProcessDuring the Research Process

Web Web linkslinks

Newsletter Newsletter blurbsblurbs

Articles Articles or or

commentariescommentaries

Web Web conferencesconferences

Continuing Continuing educationeducation

Disseminating the FindingsDisseminating the Findings

• Nominate topics using the online Nominate topics using the online formform• Participate in key question Participate in key question refinementrefinement• Comment via the Web on draft key Comment via the Web on draft key questions and reportsquestions and reports

1111

Heidi D. Nelson, M.D., M.P.H., FACPHeidi D. Nelson, M.D., M.P.H., FACPResearch ProfessorResearch Professor

Departments of Medical Informatics & Clinical Departments of Medical Informatics & Clinical Epidemiology and MedicineEpidemiology and Medicine

Oregon Evidence-Based Practice CenterOregon Evidence-Based Practice CenterOregon Health & Science UniversityOregon Health & Science University

Comparative Effectiveness of Comparative Effectiveness of Medications to Reduce Risk of Medications to Reduce Risk of

Primary Breast Cancer in WomenPrimary Breast Cancer in Women

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Prevention strategies for breast cancer currently focus on Prevention strategies for breast cancer currently focus on early detection with screening mammography.early detection with screening mammography.

Newer approaches target risk reduction:Newer approaches target risk reduction:– Identification of Identification of BRCABRCA mutation carriers mutation carriers – Prophylactic mastectomy/oophorectomy for high-risk Prophylactic mastectomy/oophorectomy for high-risk

womenwomen– MedicationsMedications

Despite availability of medications that reduce risk of Despite availability of medications that reduce risk of primary breast cancer: primary breast cancer: – Not commonly used in the U.S.Not commonly used in the U.S.– Unclear how to apply results of recently published trials Unclear how to apply results of recently published trials

in clinical practicein clinical practice1313

BackgroundBackground

Comparative effectiveness review was commissioned by Comparative effectiveness review was commissioned by AHRQ for new USPSTF recommendations.AHRQ for new USPSTF recommendations.

Previous recommendations in 2002 include:Previous recommendations in 2002 include:

B Recommendation for High Risk B Recommendation for High Risk

Clinicians should discuss chemoprevention with women at Clinicians should discuss chemoprevention with women at high risk for breast cancer and at low risk for adverse high risk for breast cancer and at low risk for adverse effects of chemoprevention.effects of chemoprevention.

D Recommendation for Low RiskD Recommendation for Low Risk

The USPSTF recommends against routine use of The USPSTF recommends against routine use of tamoxifen or raloxifene for the primary prevention of breast tamoxifen or raloxifene for the primary prevention of breast cancer in women at low or average risk for breast cancer.cancer in women at low or average risk for breast cancer.

1414

BackgroundBackground

Develop & prioritize topicDevelop & prioritize topic Develop key questionsDevelop key questions Collect abstracts and papers by searching for published Collect abstracts and papers by searching for published

and unpublished studies and registries; and soliciting and unpublished studies and registries; and soliciting information from drug companies (to January 2009) information from drug companies (to January 2009)

Select studies based on predetermined eligibility criteria:Select studies based on predetermined eligibility criteria:

– Efficacy: Efficacy: RCTs RCTs

– Harms: Harms: RCTs, observational studiesRCTs, observational studies

– Risk Models: Risk Models: discriminatory and diagnostic accuracy discriminatory and diagnostic accuracy studiesstudies

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Comparative Effectiveness ReviewComparative Effectiveness ReviewSummary of Available Scientific EvidenceSummary of Available Scientific Evidence

Abstract data from studies meeting eligibility criteriaAbstract data from studies meeting eligibility criteria Evaluate studies for quality and applicability using Evaluate studies for quality and applicability using

predefined criteriapredefined criteria Statistically combine results of trials in meta-analyses for Statistically combine results of trials in meta-analyses for

major health outcomesmajor health outcomes Evaluate strength of evidence for each comparator and Evaluate strength of evidence for each comparator and

outcome using GRADE criteriaoutcome using GRADE criteria Interpret results in the context of strengths and limits of Interpret results in the context of strengths and limits of

evidenceevidence Identify future research needsIdentify future research needs

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Comparative Effectiveness ReviewComparative Effectiveness ReviewSummary of Available Scientific EvidenceSummary of Available Scientific Evidence

DisseminationDissemination

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1: In adult women without pre-existing breast cancer, what 1: In adult women without pre-existing breast cancer, what is the comparative effectiveness of selective estrogen is the comparative effectiveness of selective estrogen receptor modulators (SERMs) tamoxifen citrate and receptor modulators (SERMs) tamoxifen citrate and raloxifene, and the selective tissue estrogenic activity raloxifene, and the selective tissue estrogenic activity regulator (STEAR) tibolone, when used to reduce risk regulator (STEAR) tibolone, when used to reduce risk for primary breast cancer on improving short-term and for primary breast cancer on improving short-term and long-term outcomes including:long-term outcomes including:– Invasive Breast CancerInvasive Breast Cancer

– Noninvasive Breast Cancer including Ductal Carcinoma in situ Noninvasive Breast Cancer including Ductal Carcinoma in situ (DCIS)(DCIS)

– Breast Cancer MortalityBreast Cancer Mortality

– All-Cause MortalityAll-Cause Mortality

– Osteoporotic FracturesOsteoporotic Fractures

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Key QuestionsKey Questions

Thromboembolic EventsThromboembolic Events Cardiovascular EventsCardiovascular Events Metabolic DisordersMetabolic Disorders Musculoskeletal Musculoskeletal

SymptomsSymptoms Genitourinary OutcomesGenitourinary Outcomes Breast OutcomesBreast Outcomes

Other MalignanciesOther Malignancies Ophthalmologic DisordersOphthalmologic Disorders Gastrointestinal/ Gastrointestinal/

Hepatobiliary DisordersHepatobiliary Disorders Others Impacting Quality Others Impacting Quality

of Lifeof Life

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2: What is the evidence for harms? 2: What is the evidence for harms?


3: How do outcomes vary by heterogeneity in subpopulations?3: How do outcomes vary by heterogeneity in subpopulations?

4: What methods, such as clinical risk assessment models, 4: What methods, such as clinical risk assessment models, have been used to identify women who could benefit from have been used to identify women who could benefit from medications to reduce risk of primary breast cancer?medications to reduce risk of primary breast cancer?

2020


AgeAge Menopausal StatusMenopausal Status Use of Exogenous EstrogenUse of Exogenous Estrogen Risk of Breast CancerRisk of Breast Cancer Ethnicity and RaceEthnicity and Race

21

Drugs to Reduce Drugs to Reduce Breast Cancer RiskBreast Cancer Risk

Tamoxifen Tamoxifen citratecitrate

SERMSERM NolvadexNolvadexSoltamoxSoltamox

Reduce breast cancer risk in Reduce breast cancer risk in high-risk women.high-risk women.

Breast cancer treatment. Breast cancer treatment.

RaloxifeneRaloxifene SERMSERM EvistaEvista Reduce breast cancer risk in Reduce breast cancer risk in high-risk postmenopausal high-risk postmenopausal women.women.

Treatment and prevention of Treatment and prevention of postmenopausal osteoporosis.postmenopausal osteoporosis.

TiboloneTiboloneNot FDA Not FDA approvedapproved

STEARSTEAR LivialLivial Prevention of postmenopausal Prevention of postmenopausal osteoporosis.osteoporosis.

Treatment of vasomotor Treatment of vasomotor menopausal symptoms.menopausal symptoms.

LasofoxifeneLasofoxifeneNot FDA Not FDA approvedapproved

SERMSERM FablynFablyn Under developmentUnder development Reduces bone loss.Reduces bone loss. Reduces LDL cholesterol.Reduces LDL cholesterol.

2121

ComparatorsComparators 9 Primary Prevention Trials9 Primary Prevention TrialsN (Drug vs N (Drug vs Placebo)Placebo)

Tamoxifen vs. Tamoxifen vs. RaloxifeneRaloxifene Study of Tamoxifen & Raloxifene (STAR) Study of Tamoxifen & Raloxifene (STAR) 9872 vs 98759872 vs 9875

Tamoxifen Tamoxifen vs.vs.

PlaceboPlacebo

International Breast Cancer Intervention International Breast Cancer Intervention Study (IBIS-1)Study (IBIS-1) 3579 vs 35753579 vs 3575

National Surgical Adjuvant Breast and National Surgical Adjuvant Breast and Bowel Project P-1 (NSABP-1)Bowel Project P-1 (NSABP-1) 6681 vs 67076681 vs 6707

Royal Marsden Hospital TrialRoyal Marsden Hospital Trial 1238 vs 12331238 vs 1233

Italian TrialItalian Trial 2700 vs 27082700 vs 2708

RaloxifeneRaloxifenevs. vs.

PlaceboPlacebo

Multiple Outcomes of Raloxifene Multiple Outcomes of Raloxifene (MORE/CORE)(MORE/CORE) 5129 vs 25765129 vs 2576

Raloxifene Use for the Heart (RUTH)Raloxifene Use for the Heart (RUTH) 5044 vs 50575044 vs 5057

Tibolone vs. Tibolone vs. PlaceboPlacebo

Long-term Intervention on Fractures with Long-term Intervention on Fractures with Tibolone (LIFT)Tibolone (LIFT) 2249 vs 22572249 vs 2257

Lasofoxifene Lasofoxifene vs. Placebovs. Placebo

Postmenopausal Evaluation and Risk Postmenopausal Evaluation and Risk Reduction with Lasofoxifene (PEARL)Reduction with Lasofoxifene (PEARL) 2852 vs 28522852 vs 2852

Meta-Analysis of Meta-Analysis of Placebo-Controlled TrialsPlacebo-Controlled Trials

Invasive Breast CancerInvasive Breast Cancer

FavorsDrug

FavorsPlacebo

0.125 0.25 1 2

Study (yr)Study (yr)Risk Ratio Risk Ratio

(95% CI)(95% CI)

TamoxifenTamoxifen NSABP P-1 (2005)NSABP P-1 (2005) 0.57 (0.46-0.70)0.57 (0.46-0.70)

IBIS (2007)IBIS (2007) 0.74 (0.58-0.94)0.74 (0.58-0.94)

Marsden (2007)Marsden (2007) 0.78 (0.58-1.04)0.78 (0.58-1.04)

Italian (2007)Italian (2007) 0.80 (0.56-1.15)0.80 (0.56-1.15)

Tamoxifen combinedTamoxifen combined 0.70 (0.59-0.82)0.70 (0.59-0.82)

RaloxifeneRaloxifene MORE (2004)MORE (2004) 0.34 (0.22-0.50)0.34 (0.22-0.50)

RUTH (2006)RUTH (2006) 0.56 (0.38-0.83)0.56 (0.38-0.83)

Raloxifene combinedRaloxifene combined 0.44 (0.27-0.71)0.44 (0.27-0.71)

TiboloneTibolone LIFT (2008)LIFT (2008) 0.32 (0.13-0.80)0.32 (0.13-0.80)

LasofoxLasofox PEARL (2010)PEARL (2010) 0.15 (0.04-0.50)0.15 (0.04-0.50)

0.5 2323

2424

Summary of BenefitsSummary of BenefitsEvents Prevented in Placebo-Controlled TrialsEvents Prevented in Placebo-Controlled Trials

Major Clinical Major Clinical

OutcomeOutcomeTamoxifenTamoxifen

(5 trials)(5 trials)RaloxifeneRaloxifene

(2 trials)(2 trials)TiboloneTibolone

(1 trial) (1 trial) Lasofoxi-Lasofoxi-

fene* (1)fene* (1)

Invasive Breast Invasive Breast

CancerCancer8/1,000*8/1,000* 9/1,0009/1,000 10/1,00010/1,000 7/1,0007/1,000

Estrogen Receptor + Estrogen Receptor + 8/1,0008/1,000 8/1,0008/1,000 NANA 7/1,0007/1,000

Estrogen Receptor -Estrogen Receptor - xx xx NANA xx

Noninvasive CancerNoninvasive Cancer xx xx NANA xx

All-Cause DeathAll-Cause Death xx xx NANA xx

Vertebral FractureVertebral Fracture xx 7/1,0007/1,000 44/1,00044/1,000 47/1,00047/1,000

Nonvertebral FractureNonvertebral Fracture 3/1,0003/1,000 xx 34/1,00034/1,000 29/1,00029/1,000

**Per 1000 women-years assuming 5 years of treatment.

2525

Summary of BenefitsSummary of BenefitsEvents Prevented in STAR Head-to-Head TrialEvents Prevented in STAR Head-to-Head Trial

Major Clinical OutcomeMajor Clinical OutcomeRaloxifene vs Raloxifene vs

Tamoxifen 2010Tamoxifen 2010

Invasive Breast CancerInvasive Breast Cancer More with RaloxifeneMore with Raloxifene

Estrogen Receptor + Estrogen Receptor +

Estrogen Receptor -Estrogen Receptor -

Noninvasive CancerNoninvasive Cancer No DifferenceNo Difference

All-Cause DeathAll-Cause Death No DifferenceNo Difference

Vertebral FractureVertebral Fracture

Nonvertebral FractureNonvertebral Fracture

Outcomes in SubgroupsOutcomes in Subgroups

TamoxifenTamoxifen Reduces breast cancer:Reduces breast cancer:

– Age (≤50/>50)Age (≤50/>50)– Pre/post menopausalPre/post menopausal– Estrogen use (yes/no)Estrogen use (yes/no)– Family history of breast Family history of breast

cancer (with/without)cancer (with/without)– LCIS or atypical LCIS or atypical

hyperplasiahyperplasia In National Surgical Adjuvant In National Surgical Adjuvant

Breast and Bowel Project Breast and Bowel Project (NSABP)(NSABP) P-1, cancer rates P-1, cancer rates were highest and risk reduction were highest and risk reduction greatest:greatest:– Prior atypical hyperplasiaPrior atypical hyperplasia– Highest modified Gail Highest modified Gail

model risk category (>5%)model risk category (>5%)

RaloxifeneRaloxifene Reduces breast cancer:Reduces breast cancer:

– Age (≤60/>60 or ≤65/>65) Age (≤60/>60 or ≤65/>65) – Age at menarcheAge at menarche– ParityParity– Age at first live birthAge at first live birth– Body mass index (≤25/>25)Body mass index (≤25/>25)

2626

2727

Summary of HarmsSummary of HarmsEvents Caused in Placebo-Controlled TrialsEvents Caused in Placebo-Controlled Trials


OutcomeOutcomeTamoxifenTamoxifen

(5 trials)(5 trials)RaloxifeneRaloxifene

(2 trials)(2 trials)TiboloneTibolone

(1 trial) (1 trial) Lasofoxi-Lasofoxi-

fene (1)fene (1)

Thromboembolic Thromboembolic

eventsevents4/1,000*4/1,000* 7/1,0007/1,000 xx 8/1,0008/1,000

Coronary heart Coronary heart

disease disease xx xx xx

12/1,000 12/1,000

lessless

StrokeStroke xx xx 11/1,00011/1,0007/1,000 7/1,000

lessless

Endometrial Endometrial

cancercancer4/1,0004/1,000 xx NANA NANA

CataractsCataracts 3/1,000**3/1,000** xx NANA NANA

*Per 1000 women-years assuming 5 years of treatment.**Results from NSABP P-1 trial.

2828

Summary of HarmsSummary of HarmsEvents Caused in STAR Head-to-Head TrialEvents Caused in STAR Head-to-Head Trial


OutcomeOutcomeRaloxifene vs Tamoxifen Raloxifene vs Tamoxifen

20102010

Thromboembolic eventsThromboembolic events More with TamoxifenMore with Tamoxifen

Coronary heart disease Coronary heart disease

StrokeStroke

Endometrial cancerEndometrial cancer More with TamoxifenMore with Tamoxifen

CataractsCataracts More with TamoxifenMore with Tamoxifen

Common Side EffectsCommon Side Effects

TamoxifenTamoxifen Hot FlashesHot Flashes Vaginal Symptoms Vaginal Symptoms

(discharge, dryness)(discharge, dryness) Leg CrampsLeg Cramps Bladder Control Bladder Control

ProblemsProblems

RaloxifeneRaloxifene Hot FlashesHot Flashes Leg CrampsLeg Cramps

MusculoskeletalMusculoskeletal ProblemsProblems Weight GainWeight Gain

LasofoxifeneLasofoxifene Leg CrampsLeg Cramps Hot FlashesHot Flashes Vaginal CandidiasisVaginal Candidiasis

2929

TiboloneTibolone Vaginal BleedingVaginal Bleeding Reduces Hot Reduces Hot

FlashesFlashes

AgeAge Age at MenarcheAge at Menarche Age at First BirthAge at First Birth Family History of Breast Cancer in First Degree Family History of Breast Cancer in First Degree

RelativeRelative History of Atypical HyperplasiaHistory of Atypical Hyperplasia Prior Breast BiopsiesPrior Breast Biopsies

cancer.gov/bcrisktool/cancer.gov/bcrisktool/

Selecting Candidates for TherapySelecting Candidates for TherapyRisk Based on Gail Model (≥1.67% 5-year RiskRisk Based on Gail Model (≥1.67% 5-year Risk))

3030

False Positive Rate (1-Specificity)

1.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0

Tru

e P

osi

tive

Rat

e (S

ensi

tivi

ty)

0 .1 .2 .3 .4 .5 .6 .7 .8 .9 1.0

ExcellentGoodWorthless

0.55-0.66

Summary of Risk Model ResultsSummary of Risk Model ResultsDiscriminatory Accuracy (16 studies of 9 models)Discriminatory Accuracy (16 studies of 9 models)

3131

Questions Questions





3232

Comparative Effectiveness of Core Comparative Effectiveness of Core Needle and Open Surgical Biopsy for the Needle and Open Surgical Biopsy for the

Diagnosis of Breast LesionsDiagnosis of Breast Lesions

Karen Schoelles M.D., S.M., FACPKaren Schoelles M.D., S.M., FACP

Director, ECRI Institute Evidence-based Practice Director, ECRI Institute Evidence-based Practice CenterCenter

3333

ObjectivesObjectives

To describe the process of developing To describe the process of developing this comparative effectiveness reviewthis comparative effectiveness review

To describe the findings of the reviewTo describe the findings of the review To describe the implications of the To describe the implications of the

reviewreview

3434

Women referred for biopsy after detection of a

breast abnormality

Adverse events related

to biopsy procedure

Diagnosis/ classification of

breast abnormality

1

2

Core-needle or open biopsy?

3

Treat or followup or return to

routine screening?

Change in clinical decisions

Adverse events related to treatment or followup tests

Results of additional testing

Clear surgical margins

Response to treatment

Cosmetic results

Patient population

Intervention and Comparator of interest

Diagnostic thinking and Therapeutic decision making

Patient outcome efficacy

Diagnostic Accuracy

Survival

Recurrence

Quality of life

Total number of surgical procedures

required

P C O

Intermediate Outcomes

Patient-oriented Outcomes

I

Analytic FrameworkAnalytic Framework

3535

PopulationPopulation

Asymptomatic women with an abnormality Asymptomatic women with an abnormality identified on self-exam or by clinician examidentified on self-exam or by clinician exam

Asymptomatic women with an abnormality Asymptomatic women with an abnormality identified by screening imagingidentified by screening imaging Ultrasound – solid or mixedUltrasound – solid or mixed Mammography – typically BI-RADS® 4Mammography – typically BI-RADS® 4

3636

ACR Breast Imaging Reporting ACR Breast Imaging Reporting and Data System (BI-RADS®)and Data System (BI-RADS®)

0: Need additional imaging evaluation and/or prior 0: Need additional imaging evaluation and/or prior mammograms for comparisonmammograms for comparison

1: Negative1: Negative 2: Benign finding2: Benign finding 3: Probably benign; initial short-interval follow-up 3: Probably benign; initial short-interval follow-up

suggestedsuggested 4: Suspicious abnormality. Biopsy should be considered4: Suspicious abnormality. Biopsy should be considered 5: Highly suggestive of malignancy. Appropriate action 5: Highly suggestive of malignancy. Appropriate action

should be takenshould be taken 6: Known biopsy-proven malignancy6: Known biopsy-proven malignancy

3737

Intervention: Core Needle Intervention: Core Needle Biopsy (CNB)Biopsy (CNB)

Hollow core needle inserted percutaneouslyHollow core needle inserted percutaneously Usually 11-, 14-, or 16-gauge needlesUsually 11-, 14-, or 16-gauge needles Lesion located by palpation or imaging Lesion located by palpation or imaging

(stereotactic mammography, ultrasound, or MRI) (stereotactic mammography, ultrasound, or MRI) during the procedureduring the procedure

May be inserted multiple times or only once if May be inserted multiple times or only once if using vacuum assistanceusing vacuum assistance

3838

Comparator: Open Surgical Comparator: Open Surgical BiopsyBiopsy

Excisional: Attempted complete removal of Excisional: Attempted complete removal of abnormalityabnormality

Incisional: Sample of the abnormalityIncisional: Sample of the abnormality

Nonpalpable lesions: May first use imaging to Nonpalpable lesions: May first use imaging to place marking wire, carbon particles, dye, etc. place marking wire, carbon particles, dye, etc. which is then used by the surgeon to identify which is then used by the surgeon to identify the lesion in the operating roomthe lesion in the operating room

3939

Comparator: Clinical Comparator: Clinical Follow-UpFollow-Up

Clinical and imaging followup for at least Clinical and imaging followup for at least 6 months6 months

4040

MethodsMethods

4141

Searches: biopsy, breast biopsy, breast diseases, breast cancer, breast tumor, excision, incisional, large core, Mammotome (Ethicon Endosurgery, Cincinnati, OH), needle biopsy, percutaneous biopsy, stereotactic breast biopsy, surgery, etc. (September 2009)

Articles identified: 1224

Articles retrieved: 589

Studies included: 107

Abstracts screened for potential relevance

Full articles screened against inclusion criteria

635 excluded at abstract level

482 excluded articles

Evaluation of the Risk of Bias Evaluation of the Risk of Bias in Individual Studiesin Individual Studies

Based on the QUADAS tool: BMC Med Res Based on the QUADAS tool: BMC Med Res Methodol 2003 Nov 10;3(1):25. PMID: 14606960Methodol 2003 Nov 10;3(1):25. PMID: 14606960 4242

Test CharacteristicsTest Characteristics

Sensitivity, specificity – commonly understoodSensitivity, specificity – commonly understood Sensitivity = TP/(TP+FN)Sensitivity = TP/(TP+FN) Specificity = TN/(FP+TN)Specificity = TN/(FP+TN)

Predictive values – incorporates prevalencePredictive values – incorporates prevalence Positive predictive value = TP/(TP+FP)Positive predictive value = TP/(TP+FP) Negative predictive value = TN/(FN+TN)Negative predictive value = TN/(FN+TN)

Likelihood ratios – independent of prevalence, but clinical use requires assessment of Likelihood ratios – independent of prevalence, but clinical use requires assessment of pre-test probability pre-test probability

Disease Present Absent Test Results Positive True positives (TP) False positives (FP)

Negative False negatives (FN) True negatives (TN)

4343

Test CharacteristicsTest Characteristics

Likelihood ratio – useful for comparing testsLikelihood ratio – useful for comparing tests Positive likelihood ratio =Positive likelihood ratio = (TP/(TP+FN))/(FP/(FP+TN))(TP/(TP+FN))/(FP/(FP+TN)) Negative likelihood ratio =Negative likelihood ratio = (FN/(TP+FN))/(TN/(FP+TN)) (FN/(TP+FN))/(TN/(FP+TN))

For this evaluation, not missing a cancer was For this evaluation, not missing a cancer was considered the most important outcome, reflected by: considered the most important outcome, reflected by: Sensitivity, Negative Predictive Value and Negative Sensitivity, Negative Predictive Value and Negative

Likelihood RatioLikelihood Ratio

Disease Present Absent Test Results Positive True positives (TP) False positives (FP)

Negative False negatives (FN) True negatives (TN)

4444

0.0010.0020.0050.010.020.050.10.20.51251020501002005001000

Likelihood Ratio

0.1

0.20.30.50.71

235710

20304050607080

9093959798

9999.399.599.799.8

99.9

Po

st-t

est P

roba

bili

ty (

%)

0.1

0.20.30.50.7

1

2357

10

20304050607080

9093959798

9999.399.599.799.8

99.9

Pre

-te

st P

rob

abili

ty (

%)

Prior Prob (%) = 30

LR_Positive = 54Post_Prob_Pos (%) = 96

LR_Negative = 0.04Post_Prob_Neg (%) = 2

Fagan's Nomogram

0.0010.0020.0050.010.020.050.10.20.51251020501002005001000

Likelihood Ratio

0.1

0.20.30.50.71

235710

20304050607080

9093959798

9999.399.599.799.8

99.9

Po

st-t

est P

roba

bili

ty (

%)

0.1

0.20.30.50.7

1

2357

10

20304050607080

9093959798

9999.399.599.799.8

99.9

Pre

-te

st P

rob

abili

ty (

%)

Prior Prob (%) = 30

LR_Positive = 54Post_Prob_Pos (%) = 96

LR_Negative = 0.04Post_Prob_Neg (%) = 2

Fagan's NomogramFagan TJFagan TJLetter: Nomogram for Bayes Letter: Nomogram for Bayes theorem. N Engl J Med 1975; theorem. N Engl J Med 1975; 293:257.293:257.

http://www.cebm.net/http://www.cebm.net/index.aspx?o=1161index.aspx?o=1161

Interactive version:Interactive version:

Fagan’s NomogramFagan’s Nomogram

4545

0 0.05 0.1 0.15 0.2 0.25 0.3

Negative likelihood ratios

Freehand automated gun

US vacuum-assisted

US automated gun

Stereotactic automated gun

Stereotactic vacuum-assisted

Open surgical

4747

0 10 20 30 40 50

DCIS underestimation percentage

US automated gun



Open surgical

DCIS: Ductal carcinoma in situDCIS: Ductal carcinoma in situ4848

0 10 20 30 40 50 60

ADH underestimation percentage

US automated gun



Open surgical

ADH: Atypical ductal hyperplasiaADH: Atypical ductal hyperplasia4949

Overall Strength of Evidence for Overall Strength of Evidence for Each Question-Outcome PairEach Question-Outcome Pair

Risk of bias in the studies included to answer the Risk of bias in the studies included to answer the questionquestion

Quantity of evidence (number of studies and patients)Quantity of evidence (number of studies and patients) Consistency of the findings across and within studiesConsistency of the findings across and within studies Robustness of the results (sensitivity analyses)Robustness of the results (sensitivity analyses) Possible grades: high, moderate, low, or insufficientPossible grades: high, moderate, low, or insufficient

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Summary of Key Accuracy Summary of Key Accuracy FindingsFindings

Type of biopsy

Number of missed cancers expected for every 1,000 biopsies

Risk of malignancy following a “benign” test result

Number of malignancies expected per 1,000 biopsy diagnoses of “high risk” lesion

Number of invasive cancers expected per 1,000 biopsy diagnoses of DCIS

Strength of evidence supporting the conclusion

Open surgical

3 to 6 0 to 1% 0 0 Not rated


24 to 73 3.4 to 10%

Insufficient data to estimate

Low

US guidance automated gun

6 to 9 1 to 2% 234 to 359 271 to 450

Low

Stereotactic guidance automated gun

3 to 13 0.5 to 2% 357 to 517 180 to 321

Low

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Summary of Key Accuracy Summary of Key Accuracy FindingsFindings

Type of biopsy

Number of missed cancers expected for every 1,000 biopsies

Risk of malignancy following a “benign” test result

Number of malignancies expected per 1,000 biopsy diagnoses of “high risk” lesion

Number of invasive cancers expected per 1,000 biopsy diagnoses of DCIS

Strength of evidence supporting the conclusion

Open surgical4

3 to 6 0 to 1% 0 0 Not rated

MRI guidance automated gun

Insufficient data to estimate Insufficient

US guidance vacuum-assisted

2 to 56 0.3 to 8% Insufficient data to estimate Low

Stereotactic guidance vacuum-assisted

1 to 6 0.1 to 1% 177 to 264 111 to 151 Low

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Type of biopsyAnalysis results

If analysis overestimated sensitivity by 1%(e.g., sensitivity 97% rather than 98%)




6% 6% 8% 9%

Ultrasound guidance automated gun

1% 1% 3% 5%

Stereotactic guidance automated gun

1% 1% 3% 5%

Ultrasound guidance vacuum-assisted

2% 2% 3% 6%

Stereotactic guidance vacuum‑assisted

0.4% 0.8% 3% 5%

Post-Biopsy Probability of Having Post-Biopsy Probability of Having Cancer After A Negative Core-Needle Cancer After A Negative Core-Needle

Biopsy ResultBiopsy Result

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For Additional InformationFor Additional Information

Clinician Guide:Clinician Guide:

http://www.effectivehealthcare.ahrq.gov/index.cfm/http://www.effectivehealthcare.ahrq.gov/index.cfm/search-for-guides-reviews-and-reports/?search-for-guides-reviews-and-reports/?pageaction=displayproduct&productID=406pageaction=displayproduct&productID=406

Full Report:Full Report:

http://www.effectivehealthcare.ahrq.gov/index.cfm/http://www.effectivehealthcare.ahrq.gov/index.cfm/search-for-guides-reviews-and-reports/?search-for-guides-reviews-and-reports/?pageaction=displayproduct&productID=370pageaction=displayproduct&productID=370

Manuscript:Manuscript:Bruening W, Fontanarosa J, Tipton K, Treadwell JR, Launders J, Bruening W, Fontanarosa J, Tipton K, Treadwell JR, Launders J, Schoelles K. Systematic review: comparative effectiveness of core-Schoelles K. Systematic review: comparative effectiveness of core-needle and open surgical biopsy to diagnose breast lesions. Ann needle and open surgical biopsy to diagnose breast lesions. Ann Intern Med. 2010 Feb 16;152(4):238-46. Epub 2009 Dec 14. PMID: Intern Med. 2010 Feb 16;152(4):238-46. Epub 2009 Dec 14. PMID: 2000874220008742

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Questions Questions





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For more information about…For more information about…

AHRQ’s Effective Health Care Program: AHRQ’s Effective Health Care Program: www.effectivehealthcare.ahrq.gov.www.effectivehealthcare.ahrq.gov.

Accessing these FREE resources through Accessing these FREE resources through AHRQ’s Publications Clearinghouse: AHRQ’s Publications Clearinghouse: (800) 358-9295.(800) 358-9295.

E-mail notices: E-mail notices: http://www.effectivehealthcare.ahrq.gov/index.cfm/http://www.effectivehealthcare.ahrq.gov/index.cfm/join-the-email-list1/. join-the-email-list1/.

If you have a question about utilizing AHRQ If you have a question about utilizing AHRQ resources please e-mail us at: resources please e-mail us at: [email protected][email protected].

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Upcoming Web ConferencesUpcoming Web Conferences

Monday, December 6 at 2 p.m. ET. Monday, December 6 at 2 p.m. ET.

Applying Existing Evidence to Cardiac CareApplying Existing Evidence to Cardiac Care

Monday, December 13 at 11 a.m. ET. Monday, December 13 at 11 a.m. ET.

Evidence-Based Medicine for Pharmacists Evidence-Based Medicine for Pharmacists in the Patient-Centered Medical Homein the Patient-Centered Medical Home

Tuesday, December 14 at 12 p.m. ET. Tuesday, December 14 at 12 p.m. ET.

Applying Existing Evidence to Diabetes CareApplying Existing Evidence to Diabetes Care

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Thank you!Thank you!

Thank you for joining us today! Thank you for joining us today! Please take a moment to provide us Please take a moment to provide us

feedback at the end of this event. feedback at the end of this event. A recording and transcript for today’s A recording and transcript for today’s

event will be available on the AHRQ event will be available on the AHRQ Web site. Web site.

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ahrq’s effective health care program: applying existing evidence to breast cancer prevention and...

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