Controversies in Breast Cancer Screening

Transcription

1 Controversies in Breast Cancer Screening Arash Naeim, MD PhD Associate Professor of Medicine Divisions of Hematology-Oncology and Geriatric Medicine David Geffen School of Medicine University of California, Los Angeles

2 How we see the other guys point of view

3 Does mammography save lives? In 2009, >40,000 women died of breast cancer Although not perfect, a high quality mammogram is currently the most effective way to detect breast cancer early. Overall risk of dying from breast cancer has decreased 29% since peak in 1989 In early 1980s, only 13% of US women got mammograms (average tumor size~3cm), in late 1990, 60% of women have mammograms (average size of tumor~2cm)

4 Limitations of Mammography Even when well done, mammography will still miss cases (False Negatives). Breast Density if higher in younger women making finding small breast tumors challenging. False Positive rates are similar in women of all ages (11% in women in their 40s, 10% in their 50s, and 8% in their 60s)

5 Studies on Newer Technologies Digital mammography no screening trials using digital mammography have been published MRI- Limited data on incorporating MRI in breast cancer screening (high risk)

6 Two Controversies Breast Cancer Screening Screening in women age Screening in women over the age of 75

7 Screening in Women Ages 40-50

8 Data limited to randomized controlled trials involves screening only with mammography, only at ages 40-69, and only for averagerisk women.

9 RCT Evidence (Ages 40-69) Relative risk = 0.80 ( ) Radiol Clin North Am 2004; 42:

10 Scientific rigor of RCT experimental design is necessary to establish mortality reduction Magnitude of observed reduction in RCTs is likely to underestimate the actual reduction achieved in the community setting

11 USPSTF Findings Based on A review of evidence by researchers from the Oregon Evidence-based Practice Center A group of computer and medical science experts from 6 universities that evaluated 20 screening strategies beginning and ending at different ages using 1 or 2 year intervals.

12 Computer Models Each of the size complex computer models came up with different answers for the same questions

13 USPSTF Panel Independent Panel of Experts (12 individuals) 10 University or Medical School Professors 6 with degrees in Public Health 3 with PhDs 9 have multiple degrees 1 had 4 degrees Limited clinical experience in the field of cancer detection, diagnosis, or treatment.

14 USPS Taskforce said Using evidence from published international prospective trials clinical trials combined, screening women in their 40s was shown to decrease risk of death by 15-20% Routine Screening of women in their 40s not recommended.

15 Annals Intern Med 2009; 151(10):

16 What the Public Heard Evidence exists that screening women in their 40s decreases relative risk of death by 15% Screening women in their 40s is not recommended. By assigning a Grade C, insurance coverage would not exist.

17 Numbers Needed to Screen to save 1 life in a decade Aged Aged Age

18 Harms of Mammography Screening Radiation oncogenesis Pain (breast compression) False-positives (recall, biopsy) Anxiety Inconvenience Morbidity False-negatives ( false reassurance) Overdiagnosis ( possible future un-insurability until 2014)

19 USPSTF: A decade of screening 1900 women age call backs for reassessment 665 breast biopsies 8 cancers diagnosed 1 life saved

20 2009 USPSTF Report Critically Reviewed RCT data underestimate actual benefits RCT design = invitation to screening (required to eliminate biases). Once benefit is established by RCTs, the true benefit (for women actually screened) is at least 25%-30% higher, because noncompliance and contamination are taken into account.

21 2009 USPSTF Report Critically Reviewed Actual mortality reduction is ~ 30%, all ages USPSTF meta-analysis showing only a 15% mortality reduction at age is the result of: [1] adding the UK Age Trial, limited by single-view incidence screening and failure to biopsy for calcifications [2] excluding the Edinburgh trial [3] retaining the design-flawed Canadian NBSS-1 trial [4] earlier RCTs used inefficient protocols (single-view, 24+ month intervals) whereas second-generation trials (Gothenburg, Malmo) used two-view, month intervals significant 44% & 36% mortality reductions, respectively.

22 2009 USPSTF Report Critically Reviewed Service screening data > modeling data Direct evidence from service screening data (Sweden, Netherlands, Italy) shows the great majority of mortality benefit comes from screening, not advances in treatment.

23 2009 USPSTF Report Critically Reviewed Forego some mortality for ~50% False Positive, age Through modeling, by recommending biennial rather than annual screening for women age 50-74, the USPSTF has chosen to endorse less mortality reduction to obtain an even greater reduction in false positives.

24 2009 USPSTF Report Defenders USPSTF is independent and non-political USPSTF panel members are unbiased No consideration of costs of screening Clinicians to discuss screening w/ women Does not oppose insurance coverage

25 2009 USPSTF Report Critics Screens per life saved = surrogate for cost

26 May 11, 2010

27 May 11, 2010

28 July 14, 2010

29 Norway Study Kalager et al. NEJM 363(13): Sept 2010

30 Norway Study

31 What to Do?

32

33 Op-Ed in LA Times by H. Gilbert Welch debate persists despite 50 years of research involving more than 600,000 women in 10 randomized trials, each involving about 10 years of follow-up. No screening test has been more exhaustively studied. That the debate persists in the face of this wealth of data tells you something: Screening mammography must be a close call. (Note that doctors don't debate about the value of treating really high blood pressure; that issue was settled more than 40 years ago with a trial of less than 200 men in less than two years).

34 Breast Cancer Screening in Older Patients

35 Uncertainty about Breast Cancer Screening in Older Adults None of the 8 RCTs of screening mammography included women over age 74 Extrapolate data on efficacy of screening to older women Data from RCTs not always applicable to an individual patient Trials do not address individual characteristics (e.g., poor health) that may change likelihood of benefit vs. harm from screening

36 Approach to cancer screening one-sizefits-all approach based on age doesn t make sense The Past In the late 1990 s guidelines were based on age cutoffs and were conflicting Mammography Guidelines (until 2002) USPSTF: Stop mammography at age 70 American College of Physicians: Stop at age 75 American Geriatrics Society: Stop at age 85 American Cancer Society: Never stop

37 Ann Intern Med. 2009;151: USPSTF Guidelines

38 USPSTF Rationale Insufficient evidence to recommend for or against screening mammography in women 75+ No older women in RCTs of mammography Higher percentage of less aggressive cancers may decrease benefit of finding cancer earlier Yet breast cancer is a leading cause of death in older women Lower life expectancy among women 75+ What to do when insufficient evidence from RCTs? Look at indirect evidence

39 Indirect Evidence Supports extrapolating benefits of screening beyond age 74: Mammograms more sensitive/specific with age Screening benefit increases with age in RCTs RR=0.86 ( ); NNS=1339 for years RR=0.68 ( ); NNS=377 for years Many healthy women age 75+ live a long time Should individualize screening decisions in older women based on life expectancy & preferences

40 Approach for Individualized Decisions Estimate life expectancy Determine potential benefits of screening Determine potential harms of screening Weigh potential benefits and harms according to an individual s values and preferences Walter LC. JAMA 2001;285:

41 Great Variation in Life Expectancy for Women of Similar Ages Years Life Expectancy for Women Age (years) Top 25th Percentile 50th Percentile Lowest 25th Percentile Walter LC. JAMA 2001;285:

42 Lag-Time to Benefit Benefit of screening does NOT occur immediately Screening results in benefit by finding cancers at an early stage, which would have caused symptoms or killed a person years later A life expectancy of > 5 yrs is required to have some chance of survival benefit from screening RCTs of mammography show survival curves of screened vs. unscreened do not separate significantly until > 5 years after start of screening

43 Lag-Time to Benefit: Mammography RCTs RCTs in women aged years Screening Control Mortality/ 100,000 Cumulative Breast Cancer Mortality by Study Group Time (years) Nystrom L. Lancet. 2002:

44 Harms of Screening Immediate Older women with life expectancy < 5 years Unlikely to benefit from breast cancer screening Increased risk for experiencing harm from screening Complications due to inaccurate test results Identification and treatment of clinically unimportant disease that would never have progressed to symptoms in patient s lifetime Psychological distress

45 Harm of Finding Clinically Unimportant Cancers 80 y/o woman with severe dementia from multiple strokes who underwent screening mammography on enrollment Abnormal mammogram 2 biopsy attempts inconclusive results Underwent surgery ductal carcinoma in situ Developed wound infection daily trips to wound clinic for 3 months Second surgery to close wound Died of large stroke 9 months later Walter LC. J Gen Intern Med 2001:

46 Impact of Cognitive Impairment on Use of Screening Mammography 18% of women 70+ with severe cognitive impairment were screened Represents > 120,000 mammograms Mehta K, Am J Pub Health % of women 70+ with severe cognitive impairment who were married and had high net worth were screened Flurry of press no controversy Giving mammograms to elderly, cognitively impaired women with only a few years to live may not be as outrageous as giving annual Pap tests to women without a cervix but it's pretty darn close. Newsweek, Sharon Begley

47 Preferences Since many decisions in older patients are close calls, need to consider values/preferences Harms look larger to some people Cognitive or sensory problems may make procedures more difficult, painful or frightening Non-mortality benefits considered more substantial to some women (e.g., peace of mind ) Different from public health strategy (e.g., guideline panels) in which experts weigh benefits/risks and decide what is best for a population

48 Individualized Decisions Do Screen Don t Screen Likelihood of Benefit Likelihood of Harm Patient Preferences (moveable fulcrum)

49 Thanks Lawrence Bassett, MD Elizabeth T.H. Fontham, MD Louise Walter, MD