5/24/16. Current Issues in Breast Cancer Screening. Breast cancer screening guidelines. Outline

Transcription

1 Disclosure information: An Evidence based Approach to Breast Cancer Karla Kerlikowske, MDDis Current Issues in Breast Cancer Screening Grant/Research support from: National Cancer Institute - and - Karla Kerlikowske, MD Profess or of Medic ine and Epidemiology and Biostatis tic s, UCSF Primary care physician at San Francisco VA; VA follows USPSTF guidelines May 24, 2016 Outline Breast cancer screening guidelines Screening mammography Potential benefits vs. harms When to start and stop How often to screen Risk-based screening Breast density legislation Breast cancer screening guidelines ACR, SBI, ACOG -- annual mammogram starting at age 40, with no upper age limit ACS -- start at age 45, annual 45-54, biennial starting at 55, continue if life expectancy >10 years USPSTF, CDC, AAFP -- biennial from Most European countries start biennial screening at age 50 & stop at age 69; Canada q2-3 USPSTF & ACS do not recommend CBE 1

2 Measures of benefits and harms Benefits Relative reduction in breast cancer mortality Deaths averted from cancer or NNS to avert a cancer death Gain in life expectancy Harms Discomfort, cost, anxiety, inconvenience of screening test False-positive imaging and invasive follow-up testing Detection/treatm ent of biologically insignificant lesions Data sources, guideline grading system & member composition, value placed on benefits vs. harms Meta-analyses of screening mammography trials -- film Age RR (95% CI) NNS* ( ) ( ) ( ) ( ) 800 All cause 0.99 ( ) mortality *Number women screened for 10 years to avert a breast cancer death Myers, Jama, 2015; Nelson, Ann Intern Med, 2016 Advanced disease reduced in screened women ages >50 CISNET models Models simulate events in individual life histories Ages No screening Birth Onset Clinically diagnosed X Death from breast cancer Screening Ages >50 Birth Onset Detectable by screening Sc reen diagnosed X Death from other cause Sojourn time Lead time Effect of screening 2

3 Common inputs Background Trends -- SEER CISNET models Unique simulation or analytical model Outputs Breast Cancer Surveillance Consortium Screening - BCSC Treatment -- RCT 6 different breast cancer models BC incidence, mortality, life years gained (LYG), false positives Other common inputs Active registries His toric regis tries False-alarms, benign biopsies & missed cancers/10,000 digital screens False-positives 1, (false alarms) No. biopsies per invasive breast cancer diagnosed False-negatives (missed cancers) Invasive cancer DCIS Model estimates of biennial digital screening mammogram effectiveness Age Deaths No. False Benign averted* screens positives* biopsy* , *per 1,000 women screened biennially Nelson, Ann Intern Med, 2016 Mandelblatt, Ann Intern Med,

4 Model estimates of biennial digital screening mammogram effectiveness Age FP/death Biopsy /death FP/LYG averted averted *False positive = FP ACS rationale for starting screening at 45 Observational studies 20-40% reduction in breast cancer mortality Breast cancer mortality similar 45 vs per 100, per 100, per 100, per 100,000 Harms higher in women vs Mandelblatt, Ann Intern Med, 2016 Oeffinger, Jama, 2015 Lifetime risk of breast cancer death Deaths Risk % averted Overall biennial biennial annual, biennial 0.47 ( ) deaths averted per 1,000 women Age trial per 1,000 women screened Life expectancy for women US female life tables Kerlikowske, Jama Intern Med, 2015; Moss, Lancet Oncol, Oeffinger, Jama,

5 Stopping ages based on comorbidities Comorbidities None Mild Moderate Severe Stopping age Mild: history of MI, acute MI, ulcer, or rheumatologic disease Moderate: vascular disease, cardiovascular disease, paralysis or diabetes, or combinations of diabetes with MI, ulcer, or rheumatologic disease Severe: AIDS, COPD, mild liver disease, severe liver disease, chronic renal failure, dementia, or congestive heart failure Lansdorp-Vogelaar, Ann Intern Med, 2014 Overdiagnosis & overtreatment from screening mammography Cases not clinically detected in the absence of screening because of lack of progression or death from other causes Canadian National Breast Screening Studies 22% of invasive cancers 37% invasive + DCIS CISNET 12% of detected cases 20-year breast cancer mortality 3.3% regardless of treatment type for DCIS Miller, BMJ, 2014; Mandelblatt, Ann Intern Med, 2016 Model estimates of digital screening mammogram effectiveness by interval Age & Interval Deaths* averted LYG Mandelblatt, Ann Intern Med, 2016 FP* Over* diagnosis y 1 y , y y 1 y , y *per 1,000 women screened over screening period Risk-based screening to optimize clinical outcomes Implement prevention strategies based on individual disease risk to: Maximize potential benefits of intervention Minimize harms for those with no or minimal benefit from interventions Important for uncommon diseases if screening test has modest efficacy 5

6 BCSC model ONLINE includes strong & prevalent risk factors Breast Imaging Reporting and Data System (BI-RADS) a a b b c c d d Almost entirely fat Scattered fibroglandul ar densities Heterogeneously dense Extremely dense 5-year risk (%) for 45-49y women BCSC No Family Hx Family Hx Density 5-yr risk No bx Bx No bx Bx a b c d Average risk 1.4% in next 5 years for woman years Tice, Ann Intern Med, 2008; Tice, JCO, 2015 Mammography Strategies Age (Cost-Effectiveness Threshold $50,000 per QALY Gained) 20% offer biennial screening with BCSC risk >1.4% Dense breasts & 1-2 risk factors Scattered density & 2 risk factors Schousboe, Ann Intern Med, 2011 BI-RADS-c or d + 1 or 2 risk factors BI-RADS-b + 2 risk factors BI-RADS-c or d + 0 risk factors BI-RADS-b + 0 or 1 risk factor BI-RADS-a Mammo Every 2 Years None Until Age 50 6

7 5-year risk (%) for 50-54y women BCSC No Family Hx Family Hx Density 5-yr risk No bx Bx No bx Bx a b c d Tice, Ann Intern Med, 2008; Tice, JCO, 2015 Mammography Strategies Age (Cost-Effectiveness Threshold $50,000 per QALY Gained) 60% offer biennial screening with BCSC risk >1.4% Dense breasts Scattered density & 1-2 risk factors 40% of women offered q3-4y screening with BCSC risk <1.4% Sc housboe, Ann Intern Med, 2011 BI-RADS-c or -d BI-RADS-b + 1 or 2 risk factors BI-RADS-b + 0 risk factor BI-RADS-a + 1 or 2 risk factors BI-RADS-a + 0 risk factor Mammo Every 2 years Mammo Every 3-4 Years Mammo age 60 Deaths averted depend on density and risk Deaths averted per 1000 women aged years Low density & low risk: screen biennial or triennial High density or high risk: screen annual Almost a Scattered b Hetero. c Extremely d Entirely Fat Densities BI-RADS Breast Dense Density Dense Trentham-Dietz and Kerlikowske (In press) Annual Biennial Triennial Risk-based strategy better harm-benefit ratios Outcome Risk-based vs Biennial Life expectancy +0.5% False positives -23% Overdiagnosis -12% False-negatives -22% Screen frequency 40% q3 100% q2 43% q2 18% q1 Vilaprinyo, Plos One,

8 5/24/16 Legislation mandates women be notified of dense breasts Women notified regardless of age or other breast cancer risk factors, ~47% of screened women BIRADS ScreenDensity detected a 1.2 b c d 27.6 million women with dense breast in U.S. Kerlikowske, Ann Intern Med, 2015; Sprague, JNCI, 2014 BCSC Risk Calculator exists as iphone & ipad app Allows users to view app on their portable device App is free Search on BCSC Interval cancer* Film Digital % of interval cancers in women with BI-RADS c or d *per 1,000 women screened Kerlikowske, NEJM, 2007; Henderson, AJR, 2015 Half of women with dense breasts have low 5-year risk % of women with dense breasts have low to average risk Almost entirely fat 67 Scattered densities 38 Hetero. Dense 23 Extremely dense 19 Average: > Intermediate: BCSC 5-year risk % Low: 0-1 5/ 24/ 16 High: >2.5 Tice, JCO, Percentage in 5-Year Risk Group Notifications suggest discussing need for supplemental imaging with your primary provider High breast density masks interval invasive tumors Breas t Cancer Surveillance Cons ortium 1 11 Kerlikowske, Ann Intern Med,

9 High risk, high density interval cancer rate >1 per 1000 exams Interval Cancer Rate (Per 1,000 Screens) BCSC 5-year risk % % of women with dense breasts at high risk of missed cancer Almost entirely fat Scattered densities Hetero. dense Extremely dense Low: Average: > Intermediate: High: >2.5% N/A Kerlikowske, Ann Intern Med, 2015 High rate of stage IIb or higher in high risk, high density BCSC BI-RADS density risk % a b c d > > % of women with dense breasts at high risk of interval advanced cancer 5/24/16 34 Kerlikowske, Ann Intern Med, 2015 Alternative imaging strategies for women with dense breasts Change screening frequency Screening ultrasound -- hand held; whole breast Tomosynthesis (3D) Breast MRI Odds of late stage disease with 2 vs. 1 year screening interval Age Heterogeneously Extremely group dense dense ( ) 1.89 ( ) Dense No HT 1.21 ( ) E+P 1.56 ( ) E only 1.19 ( ) Kerlikowske, Jama Intern Med,

10 Low cancer detection for women with dense breasts by ultrasound Parris Hooley Weigert Exams Cancers Biopsy rate % Cancer rate % NNS Whole breast US for women with dense breasts 1.9 per 1000 exams Supplemental screening ultrasound is expensive Digital mammography + ultrasound 10,000 women dense breasts 12 rounds of screening Cost per QALY -- $338,000 Additional 3 deaths averted 3500 more false-positive biopsies NNS 3300 to avert 1 breast cancer death Hooley, Radiology, 2012;Weigert, Breas t J, 2012;Parris, Breast J, 2012;Brem, Radiology, 2014 Sprague, Ann Intern Med, 2014 Cancer detection for women with dense breasts by tomosynthesis Digital Digital + Tomo Exams 278, ,414 Invasive cancer rate* Non-dense Dense *per 1,000 exams, P< Rafferty, JAMA, 2016 Tomosynthesis cost-effective with decrease in recall rate Digital mammography + tomosynthesis 10,000 women dense breasts 12 rounds of screening Cost per QALY -- $53,893 4,051 fewer false-positives Additional 5 deaths averted NNS 2000 to avert 1 additional breast cancer death Lee, Radiology,

11 Cancer detection with supplemental imaging in women with dense breasts Tomo US Exams Cancers Biopsy rate % Cancer rate % NNS Cancer detection higher with US after negative digital mammogram Maximize chance of benefit & minimize chance of harm Inform women of potential benefits and harms of breast cancer screening Offer screening every 2 years from or 13 mammograms in woman s lifetime Consider stopping screening before 70 for women with moderate to severe comorbidities Consider screening every 2 years for women aged with breast cancer risk of averagerisk woman in her fifties (5-year risk 1.4%) Tagliafico, J Clin Oncol, 2016 Future guidelines Risk assessment to identify women at high and low cancer risk for targeted screening Supplemental screening strategies for women with dense breasts based on breast cancer risk and risk of interval cancer Thank you 11

12 Risk of late stage disease with 2 vs. 1 year screening interval Late Tumor Lymph Factor stage >15mm positive % % % Premenopausal +28* +21* +15 Postmenopausal * -11 *P< 0.05 White, JNCI, 2004; Hubbard, Ann Intern Med, 2011; Miglioretti, Jama Oncol,