Dense Breasts, Over-diagnosis, Screening Guideline Controversies & Genetic Risk Stratification The Road to Customized Care

Transcription

1 Dense Breasts, Over-diagnosis, Screening Guideline Controversies & Genetic Risk Stratification The Road to Customized Care Jason Cord, M.D. SCPMG Regional Chief of Breast Imaging PIC for Breast Imaging, Information Technology, and General Radiology, Orange County, Board of Directors Orange County Medical Association 1

2 The Why 2 Breast cancer is the second-leading cause of cancer death among women in the United States. In 2015, an estimated 232,000 women were diagnosed with the disease and 40,000 women died of it. It is most frequently diagnosed among women aged 55 to 64 years, and the median age of death from breast cancer is 68 years Burden of Disease: Approximately 125 new cases of breast cancer and about 22 deaths per 100,000 U.S. women each year. The mean age at diagnosis has remained unchanged at 64 years since the late 1970s.

3 Performance Expectations 1. Evaluate California s dense breast legislation 2. Understand some of the controversy associated with aggressive imaging and over-diagnosis 3. Be able to discuss current various screening clinical guidelines 4. Be able to critically evaluate the politics of guidelines and historic evolution and implications of guidelines 5. Evaluate our current recommendations for those patients at very high known risk (optional, time allowing) 3

4 Performance Expectation #1 Evaluate California s dense breast legislation 4

5 The Past when life was simpler.. Film-screen Mammography is the ubiquitous primary screening imaging modality of choice having surpassed xeromammography. Digital mammography is improving and working hard to be the preliminary imaging modality of choice.

6 Breast Density and Masking Density Sensitivity Almost entirely fatty 88% Scattered densities 82% Heterogeneously dense 69% Extremely dense 62% Sensitivity: the number of cancers detected divided by the total number of cancers present (usually those diagnosed within 1 year) ~463,000 film mammograms Carney, BCSC, 2003

7 Breast Density and Risk Density Relative Risk Prevalence Almost entirely fatty % Scattered densities 1 (reference group) 40% Heterogeneously dense % Extremely dense % Much of this relative risk is due to risk of masking

8 DISPUTE: This is result of screening or improved treatment? Mammography screening benefits 9 RCTs >600,000 women followed for years 20 to 25% relative reduction in breast cancer specific mortality Absolute risk reduction 0.18% or 1.8 per 1000 women screened with annual mammography over 15 years Lifetime risk (USA): 12% (approx 1 in 8) Mortality has declined 28% overall from breast cancer from 1990 thru 2005 at a rate of 2.2% / year (avg.)

9 Mammography screening harms False positive results ~ 10% each round ~ 50% of women after 10 mammograms Time for repeat imaging and breast biopsies Anxiety, decrease in well being Over diagnosis: 10% to 30% of cancer diagnoses Treatment harms with no benefits Radiation exposure 1000 women screened 20 times ages 40 to 75 years 0.86 extra breast cancers and 0.11 extra deaths from BC

10 Digital Mammography (DM) - Improves sensitivity & preserves specificity in dense breast tissue. Replacing film: more than 95% of facilities DMIST Study ,760 women with both film and digital mammography 20,000 with dense breast tissue Statistic Film Digital P Sensitivity 55% 70% 0.02 Specificity 90% 91% 0.09 Area under ROC curve Pisano, NEJM, 2005

11 Digital Mammography (DM) shows comparative sensitivity stabilization* Breast Cancer Surveillance Consortium ~870,000 mammograms at a mix of academic and community practices across the United States Density Sensitivity Film Sensitivity Digital Almost entirely fatty 86% 78% Scattered densities 85% 87% Heterogeneously dense 79% 82% Extremely dense 68% 84% * Decreased Masking Kerlikowske, Ann Intern Med, 2011

12 Results: Digital vs. Film Mammography (Dense Breasts) Outcome (per 1,000 screened) Film Digital Recalls Biopsies Performed Cancers Detected (True Positives) False Positive (with Biopsy) False Positive (without Biopsy) Cancers Missed (Interval Cancers) Cost (per Woman Screened, $)

13 The Present a time with many controversies Film-screen Mammography is extinct but societally and legislatively we are responding to the previous issue of masking. New modalities are working hard to be the supplemental imaging modality of choice.

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15 Controversy #1: CA SB1538 effective April 1, 2013 Women with dense breasts must receive the following language with their results: 15 Your mammogram shows that your breast tissue is dense. Dense breast tissue is common and is not abnormal. However, dense breast tissue can make it harder to evaluate the results of your mammogram and may also be associated with an increased risk of breast cancer. This information about the results of your mammogram is given to you to raise your awareness and to inform your conversations with your doctor. Together, you can decide which screening options are right for you. A report of your results was sent to your physician.

16 What it doesn t say You definitely do have an increased risk of breast cancer Because your breasts are dense, you need more screening tests (e.g. whole breast ultrasound, MRI) Breast Care Task Force and Regional Imaging

17 What it should say Increased breast density is a risk factor for breast cancer. Data from the BCSC indicate that, compared with women with average breast density: HD/Dense women 40 to 49 years have relative risk (RR) of 1.23 for developing invasive breast cancer. 50 to 64 years, the RR is to 74 years, the RR is 1.30 However, women with dense breasts who develop breast cancer do NOT have an increased risk for dying from the disease, after adjustment for stage, treatment, method of detection, and other risk factors,

18 Last comments on dense breasts 18 At the present time, 24 states require patient notification of breast density status when mammography is performed In some states, legislation also includes language to be sent to women informing them that they should consider adjunctive screening. No clinical practice guidelines explicitly recommend adjunctive screening in women identified to have dense breasts on an otherwise negative screening mammogram.

19 Performance Expectation #2 Understand some of the controversy associated with aggressive imaging and over-diagnosis 1 9

20 Scope of Over-Diagnosis Discussion Screening vs. Diagnostic Mammography Screening mammography is performed to detect an abnormality Diagnostic mammography is used to further evaluate an abnormality detected at screening or a clinical problem

21 Scope of Over-diagnosis Discussion Screening discussion that follows applies to asymptomatic women aged 40 years or older who do not have preexisting 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 BRCA1 or BRCA2 gene mutation or other familial breast cancer syndrome) or a history of chest radiation at a young age.

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23 What are features of a good screening test? Detects life-threatening disease at an earlier, more curable stage (i.e decrease mortality) It should not change the prevailing prevalence of a given cancer over the long term but when initiated may result in a temporary artificial prevalence increase as the first cohorts cancers are detected sooner (screening is not carcinogenic)

24 What are features of a good screening test? Detect life-threatening disease at an earlier, more curable stage (i.e. decrease mortality) Two prerequisites for screening to reduce the rate of death from cancer: 1,2 A) Screening must advance the time of diagnosis of cancers that are destined to cause death B) Early treatment of the cancers must confer some advantage over treatment at clinical presentation 1. Introduction. In: Morrison AS. Screening in chronic disease. 2nd ed. New York: Oxford University Press, 1992: Welch HG, Black WC. Evaluating randomized trials of screening. J Gen Intern Med 1997;12:

25 What are features of a good screening test? Screening must advance the time of diagnosis of cancers that are destined to cause death Increase the incidence of cancer detected at an early stage (lower mortality demonstrated) Decrease the incidence of cancer presenting at a late stage (higher mortality demonstrated)

26 What are our results What is the buzz? Increase the incidence of cancer detected at an early stage The introduction of screening mammography in the United States has been associated with a doubling in the number of cases of earlystage breast cancer that are detected each year, from 112 to 234 cases per 100,000 women an absolute increase of 122 cases per 100,000 women. (SEER Data)

27 What are our results What is the buzz? Decrease the incidence of cancer presenting at a late stage Late-stage cancer has decreased by 8%, from 102 to 94 cases per 100,000 women. An absolute decrease of 8 cases per 100,000 women. With the assumption of a constant underlying disease burden, only 8 of the 122 additional early-stage cancers diagnosed were expected to progress to advanced disease. (SEER Data)

28 What are our results What is the buzz? Should not change the prevailing prevalence of cancer (screening is not carcinogenic) If early stage diagnosis doubled and late stage disease only decreased 8%, then we are up 42% in the prevailing prevalence??? So the prevalence of cancer is increasing?

29 What are our results What is the buzz? Should not change the prevailing prevalence of cancer (screening is not carcinogenic) If the prevalence of cancer is increasing we should see some uptick in the unscreened population as well since the trend matched prior to screening but we don t see as significant a increase in prevalence in the unscreened. So what is it we are detecting so much more of that must not be as important in survival?

30 Heart of the Controversy Early treatment of the cancers must confer some advantage over treatment at clinical presentation Today, approximately one woman is diagnosed with DCIS for every four women diagnosed with invasive breast cancer 3 Although DCIS is a risk factor for invasive breast cancer, the natural history of DCIS and the likelihood that DCIS will progress to invasive disease is unknown and likely variable in biology. There is no available data on DCIS that is left untreated. However, a review of autopsy records showed that somewhere between 9% and 15% of women have undetected DCIS at death. 4 This supports the idea that a proportion of DCIS occurrences will not progress into invasive cancer or become lifethreatening. The problem is that we do not know how to identify this proportion yet. How best to treat DCIS, and even whether to consider it cancer, remain controversial Allegra CJ, Aberle DR, Ganschow P et al. National Institutes of Health State-of-the-science conference statement: Diagnosis and management of ductal carcinoma in situ September JNCI 2010; 102: Welch HG, Black WC. Using Autopsy Series To Estimate the Disease "Reservoir" for Ductal Carcinoma in Situ of the Breast: How Much More Breast Cancer Can We Find? Annals of Internal Medicine 1997; 127 (11)

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32 Over Diagnosis Estimates: 32 It is not possible to know with certainty what proportion of that increase is due to over diagnosis and what proportion reflects other reasons for a rising incidence. If over diagnosis is the only explanation for the increase, 1 in 3 women diagnosed with breast cancer today is being treated for cancer that would never have been discovered or caused her health problems in the absence of screening. The best estimates from randomized, controlled trials (RCTs) evaluating the effect of mammography screening on breast cancer mortality suggest that 1 in 5 women diagnosed with breast cancer over approximately 10 years will be over diagnosed. Modeling studies conducted by the Cancer Intervention and Surveillance modeling NETwork (CISNET) provide a range of estimates that reflect different underlying assumptions; the median estimate is that 1 in 8 women diagnosed with breast cancer with biennial screening from ages 50 to 74 years will be over diagnosed. The rate increases with an earlier start age or with annual mammography. Even with the conservative estimate of 1 in 8 breast cancer cases being over diagnosed, for every woman who avoids a death from breast cancer through screening, 2 to 3 women will be treated unnecessarily.

33 Other Screening Harms 33 Other principal harms of screening are false-positive results, which require further imaging and often breast biopsy, and false-negative results. Following chart summarizes the rates of these harms per screening round using registry data for digital mammography from the Breast Cancer Surveillance Consortium (BCSC), a collaborative network of 5 mammography registries and 2 affiliated sites with linkages to tumor registries across the United States.

34 Other Screening Harms 34

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36 Performance Expectation #3 Be able to discuss current various screening clinical guidelines 3 6

37 US Preventative Task Force 37 The USPSTF makes recommendations about the effectiveness of specific preventive care services for patients without related signs or symptoms. It bases its recommendations on the evidence of both the benefits and harms of the service, and an assessment of the balance. The USPSTF does not consider the costs of providing a service in this assessment. The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decision making to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms. Current version was published online first at on January 12, 2016.

38 US Preventative Task Force 38 Benefit and Harms of Screening and Early Treatment The USPSTF found adequate evidence that mammography screening reduces breast cancer mortality in women aged 40 to 74 years. The number of breast cancer deaths averted increases with age; women aged 40 to 49 years benefit the least and women aged 60 to 69 years benefit the most. Age is the most important risk factor for breast cancer, and the increased benefit observed with age is at least partly due to the increase in risk. Women aged 40 to 49 years who have a first-degree relative with breast cancer have a risk for breast cancer similar to that of women aged 50 to 59 years without a family history. Direct evidence about the benefits of screening mammography in women aged 75 years or older is lacking.

39 US Preventative Task Force 39 Benefit and Harms of Screening and Early Treatment The USPSTF found adequate evidence that screening for breast cancer with mammography results in harms for women aged 40 to 74 years. The most important harm is the diagnosis and treatment of noninvasive and invasive breast cancer that would otherwise not have become a threat to a woman s health, or even apparent, during her lifetime (that is, over diagnosis and overtreatment). False-positive results are common and lead to unnecessary and sometimes invasive follow-up testing, with the potential for psychological harms (such as anxiety). False-negative results (that is, missed cancer) also occur and may provide false reassurance. Radiation-induced breast cancer and resulting death can also occur, although the number of both of these events is predicted to be low.

40 US Preventative Task Force 40 Benefit Adjunctive Screening Methods The USPSTF found inadequate evidence on the benefits and harms of DBT as a primary screening method for breast cancer. Similarly, the USPSTF found inadequate evidence on the benefits and harms of adjunctive screening for breast cancer using breast ultrasonography, MRI, DBT, or other methods in women identified to have dense breasts on an otherwise negative screening mammogram. In both cases, while there is some information about the accuracy of these methods, there is no information on the effects of their use on health outcomes, such as breast cancer incidence, mortality, or over diagnosis rates.

41 US Preventative Task Force 41 The USPSTF concludes with moderate certainty that the net benefit of screening mammography in women aged 50 to 74 years is moderate. The USPSTF concludes with moderate certainty that the net benefit of screening mammography in the general population of women aged 40 to 49 years, while positive, is small. The USPSTF concludes that the evidence on mammography screening in women age 75 years and older is insufficient, and the balance of benefits and harms cannot be determined. The USPSTF concludes that the evidence on DBT as a primary screening modality for breast cancer is insufficient, and the balance of benefits and harms cannot be determined. The USPSTF concludes that the evidence on adjunctive screening for breast cancer using breast ultrasound, MRI, DBT, or other methods in women identified to have dense breasts on an otherwise negative screening mammogram is insufficient, and the balance of benefits and harms cannot be determined.

42 USPTF When start screening? 42 Concludes that while there are harms of mammography, the benefit of screening mammography outweighs the harms by at least a moderate amount from age 50 to 74 years and is greatest for women in their 60s. For women in their 40s, the number who benefit from starting regular screening mammography is smaller and the number experiencing harm is larger compared with older women. The benefit still outweighs the harms, but to a smaller degree; this balance may therefore be more subject to individual values and preferences than it is in older women. Must weigh a very important but infrequent benefit (reduction in breast cancer deaths) against a group of meaningful and more common harms (over diagnosis and overtreatment, unnecessary and sometimes invasive follow-up testing and psychological harms associated with false-positive test results, and false reassurance from false-negative test results). Women who value the possible benefit of screening mammography more than they value avoiding its harms can make an informed decision to begin screening.

43 USPTF When start screening? 43 It is, however, a false dichotomy to assume that the only options are to begin screening at age 40 or to wait until age 50 years. As women advance through their 40s, the incidence of breast cancer rises. The balance of benefit and harms may also shift accordingly over this decade, such that women in the latter half of the decade likely have a more favorable balance than women in the first half. The CISNET models suggest that most of the benefit of screening women aged 40 to 49 years would be realized by starting screening at age 45. (origin of ACS position)

44 USPTF Risk factors and initiation of screening considerations Advancing age is the most important risk factor for breast cancer in most women, but epidemiologic data from the BCSC suggest that having a firstdegree relative with breast cancer is associated with an approximately 2- fold increased risk for breast cancer in women aged 40 to 49 years. The CISNET models suggest that for women with about a 2-fold increased risk for breast cancer, starting annual digital screening at age 40 years results in a similar harm-to-benefit ratio (based on number of false-positive results or over diagnosed cases per 1000 breast cancer deaths avoided) as beginning biennial digital screening at age 50 years in average-risk women. (origin of SCPMG high risk consensus statement) This approach has not been formally tested in a clinical trial; therefore, there is no direct evidence that it would result in net benefit similar to that of women aged 50 to 74 years. However, given the increased burden of disease and potential likelihood of benefit, women aged 40 to 49 years who have a known first-degree relative (parent, child, or sibling) with breast cancer may consider initiating screening earlier than age 50 years. 44

45 USPTF Risk factors and initiation of screening considerations Many other risk factors have been associated with breast cancer in epidemiologic studies, but most of these relationships are weak or inconsistent and would not likely influence how women value the tradeoffs of the potential benefits and harms of screening. Risk calculators, such as the National Cancer Institute s Breast Cancer Risk Assessment Tool (available at have good calibration between predicted and actual outcomes in groups of women but are not accurate at predicting an individual woman s risk for breast cancer. 45

46 USPTF -How Often to Screen? No clinical trials compared annual mammography with a longer interval in women of any age. In the randomized trials that demonstrated the effectiveness of mammography in reducing breast cancer deaths in women aged 40 to 74 years, screening intervals ranged from 12 to 33 months. No clear trend for greater benefit in trials of annual mammography, but other differences between the trials preclude certainty that no difference in benefit exists. Available observational evidence evaluating the effects of varying mammography intervals found no difference in the number of breast cancer deaths between women aged 50 years or older who were screened biennially versus annually. Regardless of the starting age for screening, the models consistently predict a small incremental increase in the number of breast cancer deaths averted when moving from biennial to annual mammography, but also a large increase in the number of harms. Concludes that for most women, biennial mammography screening provides the best overall balance of benefit and harms. 46

47 USPTF -How Often to Screen? 47

48 USPTF When do we stop? 48 Screening in Women Aged 75 Years or Older: The USPSTF found insufficient evidence to assess the balance of benefits and harms of screening mammography in women aged 75 years or older. CISNET models suggest that biennial mammography screening may potentially continue to offer a net benefit after age 74 years among women with no or low comorbidity but no randomized trials of screening included women in this age group

49 Who supports USPTF guidelines: 49 The American College of Physicians The American Academy of Family Physicians The 2013 Well-Woman Task Force assembled by the American Congress of Obstetricians and Gynecologists The Canadian Task Force on Preventive Health Notably, the USPSTF is in agreement with all other major professional organizations about the importance of regular mammography screening for women aged 50 to 74 years. The USPSTF found that most of the benefit of mammography screening is realized with biennial screening. The newly released recommendations from the American Cancer Society also support biennial screening, at intervals of 1 to 2 years in women in their 50s, 60s, and 70s. National breast cancer screening programs in the United Kingdom, the Netherlands, Switzerland, Poland, Norway, Luxembourg, Germany, Finland, Denmark, and Belgium offer mammography screening every 2 to 3 years for women aged 50 up to 74 years. Many European countries adhere to recommendations from the International Agency for Research on Cancer, which recently updated its guidelines to promote screening starting at age 50 years.

50 ACS Recommendations: 50 Women ages 40 to 44 should have the choice to start annual breast cancer screening with mammograms (x-rays of the breast) if they wish to do so. Women age 45 to 54 should get mammograms every year. Women 55 and older should switch to mammograms every 2 years, or can continue yearly screening. Screening should continue as long as a woman is in good health and is expected to live 10 more years or longer. All women should be familiar with the known benefits, limitations, and potential harms linked to breast cancer screening. They also should know how their breasts normally look and feel and report any breast changes to a health care provider right away. Some women because of their family history, a genetic tendency, or certain other factors should be screened with MRIs along with mammograms. (The number of women who fall into this category is very small.) Talk with a health care provider about your risk for breast cancer and the best screening plan for you.

51 SCPMG Recommendations: 51 Deviations from guidelines are appropriate in specific cases, yet exceptions to the guidelines should be infrequent when there is strong direct medical evidence closely linked to health outcomes. In more controversial clinical subjects with weaker or indirect evidence, occasional exceptions are appropriate and anticipated. Clinical Practice Guideline recommendations are not intended to be used as standards for utilization management or performance. SCPMG providers are responsible for applying recommendations to the specific clinical characteristics of each patient. In all clinical situations, SCPMG physicians have authority and autonomy in planning and directing the care of patients.

52 SCPMG Recommendations: 52 Breast Cancer Risk Factors that alter our screening interval: Asymptomatic women are considered to be at high risk if they have one or more of the following risk factors: Personal history of breast cancer (including ductal carcinoma in situ). Consensus-based Breast biopsy showing atypical hyperplasia or lobular neoplasia (lobular carcinoma in situ). Evidence-based First degree relative diagnosed with breast cancer. Evidencebased Women who have been tested and found to have a clinically significant alteration in a BRCA gene associated with increased risk for the development of breast cancer, or who have a first degree relative who has been tested and found to have such an alteration, or a first- or second-degree relative with early-onset (diagnosis before age 50) breast cancer and/or ovarian cancer (at any age). Consensus-based Prior chest radiation therapy. Consensus-based

53 SCPMG Recommendations: 53 Mammography Screening in Asymptomatic Women Without Breast Cancer Risk Factors (Essentially USPTF recs) Routine mammography screening is recommended for asymptomatic women aged For women aged 75 and older, offer mammography in the context of a shared decision making approach, taking into consideration life expectancy, patient preference, existing comorbidities, and clinician judgment. For women under age 40, routine mammography screening is not recommended. For women aged 40 49, offer mammography in the context of a shared decision making approach, taking into consideration life expectancy, patient preference, existing comorbidities, and clinician judgment. The screening frequency for mammography is every 1 2 years.

54 SCPMG Recommendations: 54 Mammography Screening in Asymptomatic Women With Selected Breast Cancer Risk Factors (upgrade to baseline USPTF) Annual mammography screening is recommended as is CBE. Age to initiate mammography: Personal history of breast cancer (including ductal carcinoma in situ) starts at age of diagnosis Breast biopsy showing atypical hyperplasia or lobular neoplasia (lobular carcinoma in situ) starts at age of diagnosis First degree relative diagnosed with breast cancer start 5 10 years earlier than the affected family member's age at diagnosis, or by age 40 Genetic risk: Clinically significant alteration in a BRCA1 or BRCA2 gene in the patient or a first degree relative, or family history of breast cancer in a first or second-degree relative (diagnosed before the age of 50) and/or ovarian cancer (diagnosed at any age) start the year the alteration was found in the patient or 5 10 years earlier than the affected family member's age at diagnosis (but not before age 30), taking into consideration individual circumstances and patient preferences. Prior chest radiation therapy start at age 25

55 ACOG/SBI/ACR Recommendations: 55 Screening mammography every year for women aged years Screening mammography every year for women aged 50 years or older Breast Self-Awareness has the potential to detect palpable breast cancer and can be recommended (ACOG ONLY, minimized by ACR/SBI) Clinical Breast Exam every year for women aged 19 or older

56 Performance Expectation #4 Be able to critically evaluate the politics of guidelines and historic evolution and implications of guidelines 5 6

57 Insurance Coverage and Access to Mammography 57 When published there was expressed concern that a C recommendation from the USPSTF might create a financial barrier for some women in their 40s who wish to undergo mammography screening after making an informed decision. These commenters asked the USPSTF to change its recommendation to a B to guarantee insurance coverage for these women. The Affordable Care Act mandates that persons with private health plans receive coverage without copayment or coinsurance for preventive services that have a USPSTF A or B recommendation. Recommendations from the USPSTF are based on its interpretation of the science regarding the potential benefits and harms of a preventive service; a C recommendation means that the USPSTF has concluded that there is at least moderate certainty of a small net benefit to the service, whereas a B recommendation means that there is either high certainty that the net benefit is moderate or moderate certainty that the net benefit is moderate to substantial.

58 Insurance Coverage and Access to Mammography 58 The USPSTF found in 2009 and again in 2016 that there is moderate certainty of a small net benefit to starting breast cancer screening before age 50 years because of the balance of benefit and harms outlined in this recommendation statement. The USPSTF could not give a B recommendation for screening in women aged 40 to 49 years because the science did not support moderate or high certainty of moderate or substantial net benefit in this age group. The role of the USPSTF is to assess the scientific evidence for preventive services; it is not within its mandate to reinterpret the science and inflate the net benefit of mammography screening solely to ensure insurance coverage of the service for women with private insurance plans. The USPSTF recommends that women in their 40s who understand the potential harms of mammography screening but place a higher value on the potential benefit have the option to begin screening. The USPSTF appreciates that, in the absence of full or partial insurance coverage, fewer women may make that choice, but those determinations are made by payers and legislators. Private and public payers have the option of providing coverage (as most do), and legislators have the option of requiring coverage (as they have done in the past and again in the 2016 Consolidated Appropriations Act)

59 Evidence-Based vs Politically Mandated Care 59 Although the 2009 ACA mandated insurance coverage for USPSTF-recommended preventive services, it went further for mammography screening Instead of relying on the most recent USPSTF guidelines, Congress amended the ACA to require the Department of Health and Human Services (DHHS) to use its 2002 guidelines, which recommended screening every 1 to 2 years starting at age 40 years.

60 Evidence-Based vs Politically Mandated Care 60 Last year, in draft form the USPSTF again provisionally recommended biannual screening for women beginning at age 50. Yet, on December 18, included within a $1.15 trillion fiscal year (FY) 2016 Consolidated Appropriations Act (HR 2029), Congress again required the use of USPSTF s 2002 guidelines. In other words, a political body required the DHHS to follow outdated scientific guidance.

61 Societal risks of politically motivated mandates relating to public health guidelines 61 A C grade is commonly misunderstood. It does not advise against screening, but rather it indicates moderate certainty that there is small population-level benefit. Clinicians should discuss C-rated services with patients using an individualized assessment of the patients risk factors and preferences. Irrespective of USPSTF recommendations, most insurers have offered mammography coverage for women aged 40 through 49 years.

62 Societal risks of politically motivated mandates relating to public health guidelines 62 Often USPSTF guidelines are framed as government rationing of beneficial health services as a cost-saving measure. Task Force uses a rigorous scientific methodology focusing on net health benefits and does not take economic cost into account. Stakeholders, with conflicts of interest, lobbied for mammography mandated coverage The Medical Imaging and Technology Alliance said a coverage mandate would safeguard access to this important life-saving technology The American College of Radiology framed the Task Force s recommendations as potentially causing women in their 40s to develop illness and die of cancer.

63 Societal risks of politically motivated mandates relating to public health guidelines 63 There is a real risk that Congress could further erode the Task Force s independence. The House s version of 2016 omnibus spending bill (which was not included in the final legislation) would have denied funding for any future USPSTF mammography recommendation. Some members of Congress have gone further, proposing to alter the Task Force s composition to include stakeholders from the medical products manufacturing community.

64 Benefits of Evidence-Based 64 Preventive Care Relying on scientific evidence to guide preventive care coverage is a surprisingly recent idea (outside of KP) Prior to the ACA, insurers had discretion to determine what screening, counseling, and vaccinations to cover as they currently do for all health services Insurers paid for some preventive services that were shown to be ineffective, such as chest radiography for lung cancer screening in smokers and electrocardiography for coronary heart disease screening in low-risk adults. In contrast, most insurers did not pay for certain highly effective services, such as counseling for smoking cessation or alcohol misuse.

65 Societal risks of politically motivated 65 mandates relating to public health guidelines When Congress required DHHS to link insurance coverage policy to outdated public health guidance, it was making a scientific judgment for which it is distinctly unqualified. In effect, legislators implicitly concluded that a rigorous assessment of numerous research studies during the past 14 years is not relevant to women s health today.

66 Societal risks of politically motivated 66 mandates relating to public health guidelines The ACA improved the public s health by guaranteeing that insurers provide uniform, cost-free access to preventive services based on modern evidence of effectiveness. The public s health is best served when women s personal decisions about screening are informed by evidence rather than political considerations. Congress s paternalistic response to USPSTF mammography screening recommendations vividly illuminates the social costs of politically mandated care. Rather than benefiting women, political interference with science can discourage shared decision making, increase harms from screening, and foster public doubt about the value and integrity of science.

67 Performance Expectation #5 Drowning for time? Click the clock! Evaluate our current recommendations for those patients at very high known risk (optional, time allowing, click here) 6 7

68 What imaging studies do we recommend for prevention and early detection in BRCA carriers? Applied risk stratification.

69 What is BRCA 1 and 2? BRCA1 and BRCA2 are human genes that produce tumor suppressor proteins. These proteins help repair damaged DNA Play a role in ensuring the stability of the cell s genetic material When either of these genes is mutated, its protein product either is not made or does not function correctly & DNA damage may not be repaired properly Result is cells are more likely to develop additional genetic alterations that can lead to cancer

70 BRCA + vs. Average risk? Average Risk: American Women 1 in 8 will develop breast cancer 12.15% of women born today Over 87% will NOT develop breast Cancer European Women 1 in 9 11% of women born today 89% will not develop breast cancer 2% risk of ovarian cancer BRCA (1/2) + (females) Higher risk of breast cancer 55-65% BRCA1& 45% BRCA 2 50% by age 50 Younger earlier breast cancer Different breast cancer biology Triple negative, high grade Imaging characteristics can be benign - round with well defined borders Higher risk of ovarian cancer - 16% to 60%

71 BRCA + vs. Average risk? Average Risk: American Women 1 in 8 will develop breast cancer 12.15% of women born today Over 87% will NOT develop breast Cancer European Women 1 in 9 11% of women born today 89% will not develop breast cancer 2% risk of ovarian cancer BRCA + (males) Higher lifetime risk of male breast cancer Especially with the BRCA2 mutation 7% lifetime risk of developing breast cancer Similar to women in the general population for whom screening is recommended. Should we be screening BRCA 2 + men? May also have a higher risk of developing prostate cancer +/- pancreatic

72 Prevention vs. Surveillance Prevention: Occurs BEFORE a breast cancer develops Lowers RISK of breast cancer occurrence Only considered an option in greater than average risk patients Surveillance: Seeks to detect small, node negative breast cancer early AFTER it occurs Does NOT alter RISK or PREVENT breast cancer Hopes to MINIMIZE mortality Is not EQUAL to prevention - fundamentally different! Customized to risk level

73 Prevention - Prophylactic mastectomy Before develop breast cancer Removal of both breasts Reduces the risk of breast cancer by estimated 90% (So post-operative risk is around 10% due to un-excisable residual tissue)

74 Surveillance after prophylactic mastectomy Is it recommended? No Is it reasonable With 90% risk reduction, risk is lower than women in the general population for which MRI screening is not recommended However, every cell has the BRCA mutation No definitive answer, but thought not necessary

75 Surveillance Techniques Mammography is the backbone of breast cancer screening leading to early diagnosis Mortality reduction by 30% Downgrade in stage at detection (overall rise in early stage cancers and DCIS

76 What about breast density in BRCA + Women? No data on impact of breast density in BRCA positive women Risk increase due to breast density is minimal compared to risk due to mutation Nevertheless, important to be aware of issues included in breast cancer risk assessment

77 Surveillance Techniques What about over diagnosis? More controversial issue with average risk patients In average risk patients 1 in 5 may be over diagnosis BRCA patients have less over diagnosis because Their pretest probability of disease (i.e. risk) is MUCH higher They get cancers younger and earlier than average They get more aggressive, triple negative, disease Tumor biology and appearance generally more challenging

78 Mammography and BRCA + Patients Annual mammogram beginning at age However, nearly all cancers detected with mammography not visible with MRI are Ductal Carcinoma in Situ (DCIS) Sensitivity of MRI for invasive cancer nearly 100% (BUT NOT) Young breast tissue is radiosensitive Rare to see DCIS in BRCA1, but not rare in BRCA2 Perhaps BRCA2 should have annual mammography but not as clear with BRCA1 patients

79 Mammography and BRCA + Patients Mammography utilizes ionizing radiation Women with BRCA mutation are likely more sensitive to the effects of radiation Do not do mammography in women with P53 mutation due to the marked radiosensitivity As risk based screening increases, perhaps we should consider different screening protocols based on types of cancers, radiosensitivity, specific characteristics of mutation carriers

80 BRCA 1 vs BRCA 2 Population Tumors are biologically different BRCA 1 Triple negative (ER/PR/Her2Neu) More aggressive, high grade and larger at presentation Less likely to be associated with DCIS More likely to have smooth margins May make detection at screening mammography more difficult BRCA 2 are more similar to sporadic cancers

81 Special Issues in BRCA 1 Population Early age at presentation Relatively benign mammographic appearance Dense breast tissue Less DCIS Concern for radiation exposure Value of mammography in addition to MRI? Should we be screening with MRI only?

82 How could we use multiple modalities in screening BRCA+ Women? Mammography and U/S at one point Surveillance of young woman Many with dense breast tissue MRI six months later MRI remains the most sensitive means of detecting breast cancer However, is there a benefit to imaging BRCA+ women with more than mammography at six month intervals?

83 High Risk Screening - BRCA Add MRI Early age (25-30) Annually Timing of MRI and mammography? Mammo and MRI once annually Alternate with 6 month intervals Consider add US at the time of mammo for dense breasts

84 Current Considerations for BRAC + Mammography Screening mammography detects < ½ breast cancers in BRCA + women In routinely screened BRACA patients, ½ cancers have already spread to the nodes at time of detection Imaging younger patients means imaging denser breasts which contributes to mammographic limitations This is basis for argument in favor of prevention and supplemental imaging

85 85 BRCA Specific Conclusions Surveillance: Annual Mammography (? use in BRCA 1) Consider ultrasound at time of mammography Annual MRI - alternating q6mo Risk in post mastectomy patients similar to general population so no need for special imaging patterns; however, low threshold for obtaining imaging for any complaint as they can get cancer In patients who cannot undergo MRI consider BSGI at low dose of radiotracer

86 Faculty Contact Information 86 Jason Cord, M.D. Physician in Charge, Radiology IT, Breast Imaging, and General Radiology Regional Chair, Breast Imaging SCPMG- Orange County

87 87 Last Planned Slide

88 88

89 MRI More sensitive than mammography and ultrasound for the detection of breast cancer Cancers detected are more frequently node negative and small American Cancer Society Based on the evidence from studies of MR screening high risk women, and the limitations of mammography and CBE alone, the ACS recommends annual MR screening in conjunction with mammography in women at significantly increased risk of breast cancer.

90 Comparing Sensitivity

91 Limitations of MRI Widespread use limited by multiple factors Cost-effectiveness Proven mortality benefit Difficulty in interpretation Length of exam Patient factors Contrast contraindications (renal insufficiency) Incompatible hardware Obesity &/or Claustrophobia

92 Reasons MRI is not an option? 15 20% of women CANNOT or WILL NOT undergo MRI Even high risk Body habitus Implantable device Renal insufficiency Severe claustrophobia

93 The Future Directions Abridged Breast MRI (AB-MRI) Breast MRI time-consuming to acquire and interpret resulting in higher cost Typical study takes up to 40 mins to acquire, generates hundreds of images to interpret An abbreviated protocol to increase access Early arterial phase Best to visualize enhancement of DCIS and IDC

94 Abridged Breast MRI (AB-MRI) Kuhl et al (2014) Proof-of-concept prospective study True screening MRI AB-MRI protocol Axial T1-weighted GRE pre-contrast and first (immediate) postcontrast phase Subtracted (FAST) images MIP generated

95 Ultrasound Detection of Cancers Studies have confirmed that the addition of hand-held screening ultrasound to mammography in women with dense breasts in a largely a high risk population significantly increases breast cancer detection 2 to 5 cancers per 1000 women screened Presume similar rates with automated technique