US Preventive Services Task Force

1. US Preventive Services Task Force Diana Petitti, MD, MPH Arizona State University

2. Today’s outline • Background on the USPSTF • USPSTF Analysis and Recommendation on Breast Cancer Screening

3. U.S. Preventive Services Task Force • 16 member independent, volunteer panel convened by AHRQ • Non-Federal experts in clinical prevention and primary care • Use evidence to create new and updated recommendations on screening, counseling, and medications to prevent illness

4. USPSTF • Relevant to practice of primary care for asymptomatic persons AND average risk persons • Uses systematic, unbiased evidence reviews to gather data on both benefits and harms

5. USPSTF • The USPSTF does not use cost or cost effectiveness data in making recommendations • The USPSTF does not make insurance coverage or policy determinations

6. USPSTF • New member nominations are sought each year from the public and from partner organizations through a Federal Register notice • Requirements for nominees • Expertise in prevention and primary care • Strong experience in critical appraisal of evidence • Primary care experience • New members are named by the AHRQ Director

7. The making of a recommendation • Each systematic review starts with an analytic framework and key questions • Project at this stage is informed by • Previous evidence review and recommendation (if an update) • Topic Prioritization workgroup of the USPSTF • 3-4 member topic workgroup of the USPSTF • Evidence-based practice center (EPC) Principal Investigator and team

8. Analytic Framework on Screening for a Disease

9. USPSTF Recommendations On Breast Cancer Screening

10. Breast Cancer Screening Recommendation • Update of 2002 recommendation begun in 2007 • Two reports commissioned by AHRQ: • An updated systematic review and meta-analysis of trial data, including new information from large databases • A collaborative modeling study from the Cancer Information and Surveillance Network (CISNET)

11. Systematic Evidence Review

12. Updated Systematic Evidence Review- (SER) • PI: Heidi Nelson, Oregon Evidence-based Practice Center (EPC) • Trials of screening with breast cancer mortality as outcome • New trial from UK, updates from older trials • Harms of screening: radiation exposure, pain, adverse psychosocial responses, overdiagnosis, false positive mammograms, additional imaging, biopsies • Using primary data from the Breast Cancer Surveillance Consortium (BCSC).

13. SER Results Film Mammography • 8 screening trials for age 39 – 49 year olds indicate reduced breast cancer mortality in screened women • 1 screening trial for ages 70-74 years indicates no mortality reduction

14. SER Results New evidence for women 40-49 • Age Trial, in United Kingdom • Annual mammography to age 48 yrs vs. ‘usual care’ • Results • Breast cancer mortality RR 0.83 (0.66- 1.04) • Number needed to invite 2,512 (1,1,49- 13,544)

15. SER results New Evidence for Women 40-49 • Additional follow-up for the Gothenburg trial • RCT of mammography among women aged 39-59 in Gothenburg, Sweden in 1982 • Results • Breast cancer mortality RR 0.69 (0.45-1.05)

16. Meta-analysis of Screening Trials of Women Age 39 to 49 Years SER Results Screened Control Relative Risk for Breast Cancer Death (95% CI) Study (yr) Cases/N Cases/N Gothenburg (2003) Kopparberg (1995) Malmo (2002) HIP (1986) Age (2006) CNBSS-1 (2002) Ostergotland (2002) Stockholm (2002) Total 0.69 (0.45, 1.05) 0.72 (0.38, 1.37) 0.73 (0.51, 1.04) 0.78 (0.56, 1.08) 0.83 (0.66, 1.04) 0.97 (0.74, 1.27) 1.05 (0.64, 1.73) 1.47 (0.77, 2.78) 0.85 (0.75, 0.96) 34/11,724 59/14,217 22/9,582 16/5,031 53/13,568 66/12,279 64/13,740 82/13,740 105/53,884 251/106,956 105/25,214 108/25,216 31/10,285 30/10,459 34/14,303 13/8,021 437/152,300 615/195,919 0.2 0.5 1 2 5 Favors screening Favors control 16

17. SER Results 17

18. SER ResultsHarms of Screening Mammography • Radiation – per study very low • Pain – common, transient • Adverse psychosocial responses – anxiety, distress, worry • Overdiagnosis • estimates vary - 9 European studies from 1 to 10%

19. SER ResultsIllustration of Overdiagnosis: Rates of Invasive Cancer and DCIS Invasive Cancer Number per 1000 Women Screened DCIS Age (yrs) 19

20. SER Results: Harms of Screening- Rates of False Positive and False Negative Mammograms 12 10 8 6 4 2 0 False Positive Rates (%) False Negative Age (yrs) 20

21. SER results Breast Self Examination • Benefits: Two trials conducted in countries (China, Russia) without mass mammography screening • No mortality reduction in either trial • Harms • Increased benign biopsy rates in the BSE group compared to controls

22. SER Results Clinical Breast Examination • RCTs in countries without mass mammography screening (one discontinued, two underway) • Canadian trial from the 1980’s compared mammography plus CBE plus BSE versus CBE plus BSE and found no difference in mortality between groups. • Harms- inconclusive data, potential harms include false positives, anxiety, excess imaging and benign biopsies

23. SER Results Digital Mammography and MRI • No studies of MRI screening in average risk women • No trials of digital mammography for screening average risk women. Studies of diagnostic accuracy suggest similar to film mammography and more accurate in younger women and those with dense breasts.

24. CISNET Modeling Data

25. Advantages of (Collaborative) Modeling • Models can “test” strategies not feasible in the population • Models can “test” strategies in large samples • Models can ask “what if” questions • Multiple models can use common data (“experimental conditions”) and: • “Replicate” experiments • Control the experimental conditions • Provide sense of qualitative ranking • Provide range of plausible quantitative effects • Results can inform practice and policy debates

26. Overview of CISNET Breast Cancer Models Original Objective:Assess Impact of Screening and/or Adjuvant Therapy on Breast Cancer Mortality Population Inputs (Common to all models) • Dissemination of Adjuvant Therapy • Dissemination of Mammography • Change in Background Risk • Mortality from Other Causes Model Specific Inputs and Assumptions Predicted Mortality • Efficacy of Treatment • Tumor Growth Rates & MetastaticSpread • Operating Characteristics of Screening (e.g., sensitivity, lead time) • Consequences of Screening (e.g., stage • shift, over diagnosis) • Post Diagnosis Survival by Tumor Characteristics • For: • Treatment Alone • Screening Alone • Treatment and Screening

27. Outcome Measures -Benefits • Two primary measures of benefit of screening (vs. no screening): • % reduction in breast cancer mortality • Life years gained (per 1000 women) • Secondary metrics: • Additional change in effect for screening at ages younger or older than 50 to 69. .

28. Outcome Measures-Resources and Harms • Resources required: • Number of screening mammograms • Exposure to harms: • False positive screens • Number of un-necessary biopsies • Detection of tumors never destined to cause breast cancer death (“over diagnosis”) • (NO measure of morbidity or decrement in QOL)

29. % Benefit Maintained Moving from Annual to Biennial Screening by Strategy and Model ~70 to 98% of benefit maintained screening biennial

30. A 40-84 A 50-84 B 50-84 B 50-79 B 60-69 Efficiency FrontierNon-dominated Strategies (% Mortality Decline)– Exemplar Model Model S A 40-79 A 50-79 B 40-79 B 50-74 B 50-69

31. Harms: Screen Detection of Invasive Tumors Never Destined to Cause Cancer Death by Age • Model assumes that all invasive cancers progress with different age-specific lead times • Percent dying in lead time increases steeply in older age due to: • High rate of death from other illnesses • Longer lead time in older age Annual Screening Ages 40-84 Model D

32. Harms: Screen Diagnosis of Tumors Never Destined to Cause Cancer Death • Two models (E, W) include: • Some DCIS/small local tumors that never progress (“low malignant potential”) • Screen detection of progressive invasive cancers where death occurs in the lead time from other illness • These models project “over-diagnosis” rates several orders of magnitude higher than models without “low malignant potential” tumors • Overall, there is uncertainty for this potential harm due to limited primary data upon which to base models

33. Potential Harms: False Positive Results, Unnecessary Biopsies Based on published age-specific specificity in BCSC: • False positives increase in linear fashion with number of mammograms performed (~8.3% rate; varies by age) • If 9 screens ~0.8 false + per woman • If 18 screens ~1.5 false + • If 36 screens ~3.0 false + • Adding 10 years screening in younger women adds > 2x as many false positives as adding 10 years at older ages. • ~ 7% of false positives lead to “unnecessary” biopsy

34. Balance Sheet of Potential Benefits & Harms Starting Ages Shaded =dominated by other strategies *% over-diagnosed invasive cancers within the strategy divided by all cancer cases occurring over life time from age 40. Probability of over-diagnosis is ~10 times higher in models E and W with explicit LMP

35. Balance Sheet of Potential Benefits & Harms Stopping Ages *% over-diagnosed invasive cancers within the strategy divided by all cancer cases occurring over life time from age 40. Probability of over-diagnosis is ~10 times higher in models E and W with explicit LMP. Shaded=dominated by other strategies

36. USPSTF Assessment- Grades Net Benefit (Benefit – Harms)

37. Summary of New USPSTF recommendations • Biennial screening mammography between 50 and 74 years (B grade) • The decision to start regular screening before the age of 50 should be an individual one and take into account patient context, including values regarding specific benefits and harms (C grade) • Previous recommendation was to screen women 40 and older every 1 to 2 years

38. Summary of New USPSTF recommendations • The USPSTF concludes evidence is insufficient to assess the additional benefits and harms of screening mammography in women 75 years or older (I statement) • Previous recommendation had no ending date (applied to women 40 and older) • Insufficient evidence on the additional benefits and harms of clinical breast examination beyond mammography in women 40 or older (I statement) • This is unchanged from previous

39. Summary of New USPSTF recommendations • USPSTF recommends against clinicians teaching women how to perform breast self-examination (D grade) • Previous recommendation: teaching BSE was given an Insufficient Evidence rating • Insufficient evidence to assess additional benefits and harms for • digital mammography or • magnetic resonance imaging (I statement) • These new modalities were not mentioned in the 2002 recommendation

40. Questions and Discussion