Screening Mammography Policy and Politics. Kevin L. Piggott, MD, MPH August 29, 2015

Transcription

1 Screening Mammography Policy and Politics Kevin L. Piggott, MD, MPH August 29, 2015

2 Objectives 1. To review the current recommendations for screening mammography by various national groups 2. To provide a historical context to screening mammography recommendations 3. To review data from major studies on screening mammography from which recommendations were generated 4. To aid the practicing clinician in reconciling the various recommendations

3 Screening mammography (in average risk women) This is not about diagnostic mammography Well studied Ten major randomized trials ~600,000 patients Followed over 10 yrs Very contentious (and has been for decades) How early is too early? When does it make a difference? Is the implication of the statement if only you had just come in a little earlier, true?

4 Epidemiology 220,000 women were diagnosed with breast CA in 2011 ~41,000 deaths in 2011 U.S. Cancer Statistics Working Group. United States Cancer Statistics: Incidence and Mortality Web-based Report. Atlanta: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute; Available at:

5 Age-Adjusted Invasive Cancer Incidence Rates for the 10 Primary Sites with the Highest Rates U.S. Cancer Statistics Working Group. United States Cancer Statistics: Incidence and Mortality Web-based Report. Atlanta: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute; Available at:

6 Age-Adjusted Cancer Death Rates for the 10 Primary Sites with the Highest Rates U.S. Cancer Statistics Working Group. United States Cancer Statistics: Incidence and Mortality Web-based Report. Atlanta: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute; Available at:

7 Chances of the Development of and Death from Breast Cancer within the Next 10 Years. Fletcher SW, Elmore JG. N Engl J Med 2003;348:

8 Recommendations USPSTF Nov 2009 Screening for Breast Cancer Using Film Mammography Population Women aged years Women aged years Women aged 75 years Recommendation Individualize decision to begin biennial screening according to the patient's circumstances and values. Screen every 2 years. Grade: No recommendation. Grade: (Insufficient Evidence) Grade: A single, large comparison study of film and digital mammography (18) demonstrated similar diagnostic accuracy for the 2 methods, although digital mammography was better at detecting lesions in women who were younger than 50 years or premenopausal or had radiographically dense breasts. Pisano ED, Gatsonis C, Hendrick E, Yaffe M, Baum JK, Acharyya S, et al; Digital Mammographic Imaging Screening Trial (DMIST) Investigators Group. Diagnostic performance of digital versus film mammography for breastcancer screening. N Engl J Med. 2005;353:

9 USPSTF - Grade Definition Suggestions for Practice A B C D I Statement The USPSTF recommends the service. There is high certainty that the net benefit is substantial. The USPSTF recommends the service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial. The USPSTF recommends selectively offering or providing this service to individual patients based on professional judgment and patient preferences. There is at least moderate certainty that the net benefit is small. The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined. Offer or provide this service. Offer or provide this service. Offer or provide this service for selected patients depending on individual circumstances. Discourage the use of this service. Read the clinical considerations section of USPSTF Recommendation Statement. If the service is offered, patients should understand the uncertainty about the balance of benefits and harms.

10 USPSTF 2015 Draft: Recommendation Summary This recommendation applies to asymptomatic women age 40 years and older who do not have pre-existing breast cancer or a previously diagnosed high-risk breast lesion and who are not at high risk for breast cancer because of a known underlying genetic mutation (such as a BRCA mutation or other familial breast cancer syndrome) or a history of chest radiation at a young age. Population Recommendation Grade (What's This?) Women ages 50 to 74 years The USPSTF recommends biennial screening mammography for women ages 50 to 74 years. The USPSTF recommends the service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial. Women ages 40 to 49 years The decision to start screening mammography in women prior to age 50 years should be an individual one. Women who place a higher value on the potential benefit than the potential harms may choose to begin biennial screening between the ages of 40 and 49 years. For women at average risk for breast cancer, most of the benefit of mammography will result from biennial screening during ages 50 to 74 years. Of all age groups, women ages 60 to 69 years are most likely to avoid a breast cancer death through mammography screening. Screening mammography in women ages 40 to 49 years may reduce the risk of dying of breast The USPSTF recommends against cancer, but the number of deaths averted is much smaller than in older women and the number routinely providing the service. There may of false-positive tests and unnecessary biopsies are larger. be considerations that support providing All women undergoing regular screening mammography are at risk for the diagnosis and the service in an individual patient. There is treatment of noninvasive and invasive breast cancer that would otherwise not have become a at least moderate certainty that the net threat to her health, or even apparent, during her lifetime (known as overdiagnosis ). This risk benefit is small. is predicted to be increased when beginning regular mammography before age 50 years. Women with a parent, sibling, or child with breast cancer may benefit more than average-risk women from beginning screening between the ages of 40 and 49 years. Women age 75 years and older The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening mammography in women age 75 years and older. The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined. All women The USPSTF concludes that the current evidence is insufficient to assess the benefits and harms of tomosynthesis (3-D mammography) as a screening modality for breast cancer. Women with dense breasts The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of adjunctive screening for breast cancer using breast ultrasound, magnetic resonance imaging (MRI), tomosynthesis, or other modalities in women identified to have dense breasts on an otherwise negative screening mammogram.

11 American Cancer Society*; Women age 40 and older should have a mammogram every year and should continue to do so for as long as they are in good health. arly/cancerscreeningguidelines/americancancer-society-guidelines-for-the-earlydetection-of-cancer *At one time, the ACS used to run an ad stating, If a woman doesn t have a mammogram, she needs more than her breasts examined

12 ACOG; Based on the incidence of breast cancer, the sojourn time for breast cancer growth, and the potential reduction in breast cancer mortality, the College recommends that women aged 40 years and older be offered screening mammography annually.

13 American College of Radiology; For average-risk women, annual screening mammography is indicated starting at age 40.

14 National Cancer Institute; Women age 40 years and older should have mammography every 1-2 years. ing/breast/healthprofessional

15 National Comprehensive Cancer Network; Women age 40 years and older should have mammography annually

16 Huh? What to recommend? There is a delicate balance between benefit and harm Reasonable clinicians and patients may come to different conclusions even when presented the same scenario Thus, it is imperative to have a discussion with your patients.

17 Benefit Assumption #1 Being screened regularly for breast cancer will reduce a woman s risk of dying from breast cancer

18 The HIP study Health Ins Plan of NY with the National Cancer Institute (NCI) Population - 62,000 women aged in randomized study Intervention annual mammogram and clinical breast exam; control group received neither Therefore could not isolate benefit of mammogram alone Also there was an increased awareness to early treatment of breast CA By the end of 18 years from entry, the study group had about a 25% lower breast cancer mortality among women aged and at time of entry than did the control group. However, to a large extent the difference among the year-olds occurred in the subgroup with breast cancer diagnosed after these women had passed their 50th birthday. Therefore, the benefit would likely have been the same had they initiated mammography screening at 50 yo. Amongst women in their forties when diagnosed with breast CA, there was no reduction in mortality

19 1973 Both the NCI and the American Cancer Society (ACS) launched a nationwide effort for screening mammography All women age 35 and older were encouraged to have screening mammography

20 1976 Due to concerns regarding radiation exposure of radiosensitive tissue in young women, the recommendation was changed women 50 were encouraged to have screening mammograms and no longer included yo However, mammography then exposed women to higher amounts of radiation than now.

21 1988 ACS and NCI revise their recommendations to begin annual screening mammography at 40 Mammography equipment had improved with reduction in radiation HIP study re-analyzed and it was felt that women in their forties do benefit

22 1992 Canadian National Breast Screening Study Design similar to HIP study Focused only on women Result Screening mammography did not reduce deaths from breast cancer

23 1993 ACS re-confirms its recommendations to screen young women 9 major studies had been completed by this time and it remained inconclusive as to the benefit of screening mammography in women <50 yo. NCI convenes an international workshop to summarize the trials (not to make recommendations) Conclusion For women aged 40 49, randomized controlled trials of breast cancer screening show no benefit 5 7 years after entry. At years, benefit is uncertain and, if present, marginal; thereafter, it is unknown. For women aged 50 69, screening reduces breast cancer mortality by about a third. Currently available data for women age 70 or older are inadequate to judge the effectiveness of screening

24 1997 The Director of the NCI convened a 13 member panel to make a consensus recommendation Conclusion The data currently available do not warrant a universal recommendation for mammography for all women in their forties. Each woman should decide for herself whether to undergo mammography.... Given both the importance and complexity of the issues involved in assessing the evidence, a woman should have access to the best possible relevant information regarding both benefits and risks, presented in an understandable and usable form.

25 1997 Suzanne Fletcher, MD 336 (16);

26 USPSTF Summary of Recommendations The U.S. Preventive Services Task Force (USPSTF) recommends screening mammography, with or without clinical breast examination (CBE), every 1-2 years for women aged 40 and older. The USPSTF recommends the service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial.

27 USPSTF Summary of Recommendations The USPSTF recommends against routine screening mammography in women aged 40 to 49 years. The decision to start regular, biennial screening mammography before the age of 50 years should be an individual one and take into account patient context, including the patient s values regarding specific benefits and harms. (Grade C recommendation)

28 USPSTF

29 USPSTF

30 From: A Systematic Assessment of Benefits and Risks to Guide Breast Cancer Screening Decisions JAMA. 2014;311(13): doi: /jama Table Title: Pooled Results from Randomized Clinical Trials on Mortality Reductions With Mammography Screening by Age Group Date of download: 8/24/2015 Copyright 2015 American Medical Association. All rights reserved.

31 USPSTF

32 40-49 Pos Mamm Pos Breast CA Neg Breast CA PPV= 2.6% Neg Mamm Sens = 72.2% Spec = 90.2% 10,000 NPV= 99.9% Pos Breast CA = invasive CA and DCIS

33 50-59 Pos Mamm Pos Breast CA Neg Breast CA PPV= 5.1% Neg Mamm Sens = 81.0% Spec = 91.3% 10,000 NPV= 99.9% Pos Breast CA = invasive CA and DCIS

34 60-69 Pos Mamm Pos Breast CA Neg Breast CA PPV= 7.6% Neg Mamm Sens = 82.3% Spec = 92.0% 10,000 NPV= 99.8% Pos Breast CA = invasive CA and DCIS

35 70-79 Pos Mamm Pos Breast CA Neg Breast CA PPV= 10.3% Neg Mamm Sens = 84.0% Spec = 93.1% 10,000 NPV= 99.8% Pos Breast CA = invasive CA and DCIS

36 80-89 Pos Mamm Pos Breast CA Neg Breast CA PPV= 12.5% Neg Mamm Sens = 85.9% Spec = 94.0% 10,000 NPV= 99.8% Pos Breast CA = invasive CA and DCIS

37 Table 3. Estimated Benefits and Harms of Mammography Screening for 10,000 Women Who Undergo Annual Screening Mammography Over a 10-Year Period a Age, y No. of Breast Cancer Deaths Averted With Mammography Screening Over Next 15 y b No. (95% CI) With 1 False-Positive Result During the 10 y c ,130 (5,940 6,310) No. (95% CI) With 1 False Positive Resulting in a Biopsy During the 10 y c No. of Breast Cancers or DCIS Diagnosed During the 10 y That Would Never Become Clinically Important (Overdiagnosis) d 700 ( )? 104 e ,130 (5,800 6,470) ,970 (4,780 5,150) No. = number; CI = confidence interval; DCIS = ductal carcinoma in situ. 940 (740 1,150) 980 (840 1,130) a Adapted from Pace and Keating.[1] b Number of deaths averted are from Welch and Passow.[2] The lower bound represents breast cancer mortality reduction if the breast cancer mortality relative risk were 0.95 (based on minimal benefit from the Canadian trials [3,4]), and the upper bound represents the breast cancer mortality reduction if the relative risk were 0.64 (based on the Swedish 2-County Trial [5]). c False-positive and biopsy estimates and 95% confidence intervals are 10-year cumulative risks reported in Hubbard et al. [6] and Braithwaite et al.[7] d Overdiagnosed cases are calculated by Welch and Passow.[2] The lower bound represents overdiagnosis based on results from the Malmö trial,[8] whereas the upper bound represents the estimate from Bleyer and Welch.[9] e The lower-bound estimate for overdiagnosis reported by Welch and Passow [2] came from the Malmö study.[8] The study did not enroll women younger than 50 years.

38 Chances of False Positive Mammograms, Need for Biopsies, and Development of Breast Cancer among 1000 Women Who Undergo Annual Mammography for 10 Years. Fletcher SW, Elmore JG. N Engl J Med 2003;348:

39 Chances of Breast-Cancer Related Outcomes among 1000 Women Who Undergo Annual Mammography for 10 Years. Fletcher SW, Elmore JG. N Engl J Med 2003;348:

40 Cochrane review Screening for breast cancer with mammography. Gøtzsche PC 1, Jørgensen KJ. Author information Abstract BACKGROUND: A variety of estimates of the benefits and harms of mammographic screening for breast cancer have been published and national policies vary. OBJECTIVES: To assess the effect of screening for breast cancer with mammography on mortality and morbidity. SEARCH METHODS: We searched PubMed (22 November 2012) and the World Health Organization's International Clinical Trials Registry Platform (22 November 2012). SELECTION CRITERIA: Randomised trials comparing mammographic screening with no mammographic screening. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data. Study authors were contacted for additional information. MAIN RESULTS: Eight eligible trials were identified. We excluded a trial because the randomization had failed to produce comparable groups. The eligible trials included 600,000 women in the analyses in the age range 39 to 74 years. Three trials with adequate randomization did not show a statistically significant reduction in breast cancer mortality at 13 years (relative risk (RR) 0.90, 95% confidence interval (CI) 0.79 to 1.02); four trials with suboptimal randomization showed a significant reduction in breast cancer mortality with an RR of 0.75 (95% CI 0.67 to 0.83). The RR for all seven trials combined was 0.81 (95% CI 0.74 to 0.87). We found that breast cancer mortality was an unreliable outcome that was biased in favor of screening, mainly because of differential misclassification of cause of death. The trials with adequate randomization did not find an effect of screening on total cancer mortality, including breast cancer, after 10 years (RR 1.02, 95% CI 0.95 to 1.10) or on all-cause mortality after 13 years (RR 0.99, 95% CI 0.95 to 1.03).Total numbers of lumpectomies and mastectomies were significantly larger in the screened groups (RR 1.31, 95% CI 1.22 to 1.42), as were number of mastectomies (RR 1.20, 95% CI 1.08 to 1.32). The use of radiotherapy was similarly increased whereas there was no difference in the use of chemotherapy (data available in only two trials). AUTHORS' CONCLUSIONS: If we assume that screening reduces breast cancer mortality by 15% and that overdiagnosis and overtreatment is at 30%, it means that for every 2000 women invited for screening throughout 10 years, one will avoid dying of breast cancer and 10 healthy women, who would not have been diagnosed if there had not been screening, will be treated unnecessarily. Furthermore, more than 200 women will experience important psychological distress including anxiety and uncertainty for years because of false positive findings. To help ensure that the women are fully informed before they decide whether or not to attend screening, we have written an evidence-based leaflet for lay people that is available in several languages on Because of substantial advances in treatment and greater breast cancer awareness since the trials were carried out, it is likely that the absolute effect of screening today is smaller than in the trials. Recent observational studies show more overdiagnosis than in the trials and very little or no reduction in the incidence of advanced cancers with screening.

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45 Among 10,000 women screened for 10 yrs, the number who: Age Benefit (avoid breast Ca death) Don't Benefit Benefit (avoid breast Ca death)

46 Benefit Assumption # 2 Mammography reduces the risk of developing metastatic Breast CA. Not specifically addressed in any study SEER (Surveillance, Epidemiology and End Results) registry data shows that 90% of women that develop metastatic breast CA die of it Thus metastatic breast CA and death are similar outcomes

47 Benefit Assumption #3 Screening mammography will result in the need for less aggressive treatment if breast CA is found It has actually led to 20% more mastectomies

48 Harms False reassurance Some people believe that a negative mammogram assures that they do not have breast cancer ~25 % (21.2% in the data shown earlier in 2x2 tables) of breast cancers are not detected by mammography In reality, it only reduces the risk that you have a breast cancer by about 75% The test itself is uncomfortable if not outright painful for some.

49 Harms (cont.) False positives results 11% of screening mammograms are read as abnormal. Breast cancer is found in 3% of abnormal mammograms Therefore, ~10.7% are false positive results in additional studies and expense Mammograms (spot compression or additional views) Ultrasounds MRI s Biopsies After 10 mammograms, 49% (95% CI of 40 64) will have had a false + leading to needle or open biopsy (Elmore JG, Barton MB, Moceri VM, Polk S, Arena PJ, Fletcher SW. Ten-year risk of false positive screening mammograms and clinical breast examinations. NEJM 1998;338: ) In anxiety/distress

50 Harms (cont.) Advancing the time of diagnosis without influencing the long term outcome A mammographically detected CA can be A clinically important cancer that is more curable when found early A clinically important cancer that is not more curable when when found early In which case the mammogram is not beneficial The person is just turned into a breast cancer patient earlier An overdiagnosis Again not beneficial One estimate placed it at 31% of diagnoses Bleyer A, Welch HG. N Engl J Med 2012;367:

51 Welch GW, Schwartz LM, Woloshin S. Over-Diagnosed Making People Sick in the Pursuit of Health. Beacon Press 2011

52 Use of Screening Mammography and Incidence of Stage- Specific Breast Cancer in the United States, Bleyer A, Welch HG. N Engl J Med 2012;367:

53 Absolute Change in the Incidence of Stage-Specific Breast Cancer among Women 40 Years of Age or Older after the Introduction of Screening Mammography. Bleyer A, Welch HG. N Engl J Med 2012;367:

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55 Aschwanden, C. Why I m Opting out of Mammography. JAMA Int Med 2015;175(2):

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57 Michigan Dense Breast Law HB st state to enact a breast density law a classic example of where science and political pressure collide There is no consensus on what constitutes a dense breast There is no consensus on what alternative imaging should be offered (if any) Went into effect June 1, 2015 If a patient s mammogram demonstrates dense breast tissue, that patient must receive notification that includes the following verbiage: Your mammogram shows that your breast tissue is dense. Dense breast tissue is very common and is not abnormal. However, dense breast tissue can make it harder to find cancer through a mammogram. Also, dense breast tissue may increase your risk for breast cancer. This information about the result of your mammogram is given to you to raise your awareness. Use this information to discuss with your health care provider whether other supplemental tests in addition to your mammogram may be appropriate for you, based on your individual risk. A report of your results was sent to your ordering physician. If you are self-referred, a report of your results was sent to you in addition to this summary.

58 Recommendations Regarding Breast-Cancer Screening in Women. Fletcher SW, Elmore JG. N Engl J Med 2003;348:

59 U.S. Women's Perceptions of the Effects of Mammography Screening on Breast-Cancer Mortality as Compared with the Actual Effects. Biller-Andorno N, Jüni P. N Engl J Med 2014;370:

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