Precision Breast Cancer Screening: Moving from Debate to Wisdom _______Laura Esserman, MD, MBADirector, UCSF Carol Franc Buck Breast Care Center@drlauraessermanSeptember 18, 2019

Diane HeditsianWISDOM Study Research Advocate & Communications Consultant

@dianeheditsian

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Laura Esserman• Has nothing to disclose.

Diane Heditsian• Has nothing to disclose.

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Audience Poll

• How many women are getting mammography screening for breast cancer?

• How many women believe there is complete agreement on when women should start and how often they should be screened?

• How many women know their own breast cancer risk?

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Years of Policy Controversy & ConflictWISDOM will provide data required to inform professional societies and resolve discordant recommendations

Professional Society Screening Age Frequency

USPSTF 40 – 4950 – 74

Shared decision on whether to screen Biennially (for average risk)

ACS 45 – 5555 – until life expectancy < 10 years.

AnnuallyBiennially

ACR / SBI 40 – until life expectancy < 5 -7 years. Annually

NCCN 40 – until life expectancy < 10 years. Annually

ACOG 40 – 4950 – 74

Shared decision on whether to screen Shared decision: Annual or Biennial

ACP (new: April 2019) 40 – 4950 – 74

Shared decision on whether to screen Biennially

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Breast Screening Controversy Puts Women in the Middle

Polarized Views Confuse MDs too

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Old Paradigm

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New Paradigm: Breast Cancer is not a single diseaseTumor progression and Benefit (lack of) from Screening

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Breast Cancer Screening Today• Mired in controversy• Based on 30-year-old medical science• Age-based• Low risk women are over-screened

• false positive recalls and benign biopsies • High-risk women are under-screened missing lethal tumors• Catchy Public Health Messages miss the complexity

• “Mammograms Save Lives” and “Early Detection Saves Lives” • Resource intensive in aggregate: $8 - $10 billion annually

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“One Size Does NOT Fit All”

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Unprecedented Opportunity: Advances in Science and Technology

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What Breast Cancer Screening Could Be: Personalized

• Leverages advances in: • Biology of breast cancer• Risk-assessment • Genetics

• More effective at finding “clinically meaningful” cancers • Personalized and precise for each individual woman• Integrated with risk reduction strategies• More cost-effective

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Comprehensive risk prediction model• Validated high-impact risk factors including

• Exposures/Lifestyle• Breast density• 9 breast cancer genes• SNPs polygenic risk score

• 76303 SNPs

• Tailor screening/prevention plans • Age to start/stop• Frequency• Screening modality• Risk reduction

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Pragmatic Trial Design: Preference Tolerant RCT

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Wisdom Study AimsDetermine if personalized screening (as compared to annual screening):1. Is as safe 2. Is less morbid 3. Is more accepted by women4. Enables prevention5. Has greater health care value

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Risk Reduction: Breast Health Decisions Tool• Automated integration of risk education tool

• Includes risk factors and interventions to lower risk

• Threshold for outreach (personalized arm): Top 2.5 % risk by age group

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Breast Health Decisions Tool

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Transformative Trials That Evolve: WISDOM Study Structure

• All reporting is automated using the WISDOM platform• Offered across several nationwide sites

• California, Dakotas, Iowa, Minnesota, Illinois, Alabama, Louisiana

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PCORI Principles• Results ready in a timely way

• Used a surrogate endpoint- no increase in stage 2B cancers• Tests had to be covered by the study (payors participating)

• Coverage with Evidence Progression model• Compared to annual, cost saving over time• Champion: Blue Cross Blue Shield and self-insured employers

• Stakeholder Engagement• Annual stakeholder meetings to project results• All guideline makers, payors, providers at the table

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Why is this study critical for women?• Answers a big and intractable question • Breast cancer screening can leverage precision

medicine • Begin to learn who is at risk/for what kind of breast cancer • Provides a framework to determine risk, improve screening,

educate/involve women and integrate risk reduction • Breaks down barriers so more women can participate• Answers will be relevant to all communities of women

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What Does it Take For a Paradigm to Shift?

What results will have enough impact to inform guidelines?

What are the right early endpoints?

How best to educate MDs and women?

Annual Stakeholder Meeting: Full day each year

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WISDOM Innovations• Use of established tests in new ways• Coverage with evidence development/progression• Virtual trial design

• Trial comes to the participant not vice versa

• Technology platform with embedded analytics• All stakeholders at the table from beginning

• reduce time to implement trial results

• Risk model is updated as new data emerges• Patient Reported Outcomes• Patient education and risk communication (BHD Tool)• Bioethics Committee & Embedded Ethics Study

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Wisdom Recruitment over time

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Lessons Learned• Opposing views will always be encountered

• Radiology community in US feels that less than“annual screening” hurts women

• Models will always improve• Build an infrastructure that allows study to evolve as knowledge evolves

• Test the concept of personalization based on best knowledge • Allow for improvements in models

• Much more difficult to get payers to partner than anticipated!• Recruiting diverse populations takes a big effort

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Patient-Centered and Inclusive

• Spanish Translation• Outreach Materials

• Plain-language translation

• Materials modified with simpler, 6th

grade reading level

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Everyone Benefits When Everyone Participates

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Thank You to Partners & Stakeholders

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Thank You!Laura Esserman, MD, MBADirector, UCSF Carol Franc Buck Breast Care Center

@drlauraesserman

September 18, 2019

Diane HeditsianWISDOM Study Research Advocate & Communications Consultant

@dianeheditsian