Current Strategies in the Detection of Breast Cancer. Karla Kerlikowske, M.D. Professor of Medicine & Epidemiology and Biostatistics, UCSF

Transcription

1 Current Strategies in the Detection of Breast Cancer Karla Kerlikowske, M.D. Professor of Medicine & Epidemiology and Biostatistics, UCSF

2 Outline ν Screening Film Mammography ν Film ν Digital ν Screening MRI ν Screening ultrasound ν CBE ν BSE

3 Rank of Clinical Preventive Services CPB CE Total ν Tobacco cessation ν Colorectal cancer ν Hypertension ν Influenza ν Pneumococcal ν Cervical cancer ν Breast cancer Maciosek, Am J Prev Med,, 2006

4 Screening Mammography ν Radiological examination to detect unsuspected breast cancer ν Limited to CC and MLO views ν For ASYMPTOMATIC women ν Separates women into low and high probability of cancer ν Further studies needed when abnormality is identified

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7 Screening Mammography Report Assessment Negative Benign finding Needs additional imaging tests Suspicious Malignant % Exams Risk cancer % %.4 50%.1 100%

8 Potential Benefits Prevent deaths from breast cancer Detection of tumor earlier opportunity for less toxic treatment improved cosmesis Decrease overall mortality

9 The efficacy of screening mammography to reduce breast cancer deaths in women compared to women is? 1. Similar 2. Higher 3. Lower 5 73% 14% 14% Similar Higher Lower

10 Meta-regression of Women Aged 40 to 49 16% reduction in breast cancer mortality among screened women at years

11 Efficacy of Mammography for Women 40 to 49 after years Mortality Reduction United Kingdom Mammography 0.83 (95% ) Usual care ref Canadian Mammography + CBE 1.06 (95% ) Usual care ref Moss, Lancet, 2006; Miller, Ann Intern Med, 2002 Number needed to screen for 10 years to avert 1 breast cancer death

12 Case-Control Control Studies in U.S. Communities Women Mortality Reduction Elmore (2005) Mammography 0.92 (95% ) within 3 yrs of dx Usual care ref Norman (2007) Mammography 0.89 (95% ) within 2 yrs of dx Usual care ref

13 Meta-regression of Women Aged 50 to 74 30% reduction in breast cancer mortality among screened women at 5 years Number needed to screen for 20 years to avert 1 breast cancer death

14 Cumulative Breast Cancer Mortality in Screened vs Non-screened Aged Mortality per 1000 person-years Unscreened ο ο ο ο ο ο ο ο ο Screened Time (years) ο

15 Invasive Cancer & DCIS Incidence & Breast Cancer Mortality, Invasive per 100, Screening 24% decrease in breast cancer mortality from Treatment 20 DCIS Year Mortality

16 Five-Year Breast Cancer Survival Rates in U.S. by Stage Stage Localized Regional Distant < < < SEER, 2006

17 Screening & Treatment Decrease Breast Cancer Mortality Number women 100, ,000 Number deaths Deaths averted Screening 4.0 Treatment 4.0 Berry, NEJM, 2005 About 2300 fewer breast cancer deaths in 2006 vs. 1999

18 Total Mortality in Swedish Trials Age after 16 years of Follow-up RR (95% CI) Δ per 100, ( ).95 ( ) 0.98) ( ) 0.97) ( ( ( ( ) 1.07) Nystrom, Lancet,, 2002

19 How often should women aged years should undergo mammography? 1. Every year 2. Every years 3. Every 2 years 4. Every 3 years 5 42% 39% 16% 3% Every year Every 1-2 years Every 2 years Every 3 years

20 Biennial vs. Annual Mammography & Proportion of Late Stage Disease Interval year 21% 21% 17% 14% 2 year 28% 22% 16% 13% White, JNCI, year survival rates 90.4% for annual & 89.2% for biennial Wai, Br J Cancer, 2005

21 Patient Characteristics Influence Breast Cancer Detection

22 HT Increases Rate of Breast Cancer and Advanced Stage Invasive Breast Cancer Advanced Disease Cancer Screen- Non-screen rate detected detected Groups per 1,000 screening exam No HT Estrogen only >5y Estrogen/progestin >5y 6.5* 1.07* 0.74* *P< 0.05 Kerlikowske,, JCO, 2003 Increased rate of ER-positive invasive cancer among women taking E+P >5y

23 Trend of HT and Breast Cancer HT use 13% annual decrease in ER-positive breast cancer from ER Positive ER Negative Year of Screening Mammogr Rate of HT Use per 1,000 Mammograms Kerlikowske, JNCI,, 2007

24 BI-RADS BI-RADS 1 Almost entirely fat 8.7% BI-RADS 2 Scattered densities 47.4% BI-RADS 3 Heterogeneously dense 38.6% BI-RADS 4 Extremely dense 5.2%

25 Rate of cancer per 1,000 screening exams increases with high breast density y Screen Non-screen BIRADS detected detected Kerlikowske, NEJM,, 2007 Higher risk of advanced disease in women with BI-RADS 4 density

26 Performance of Screening Mammography by Family History Measure Family Hx+ Family Hx- Cancer/1000 exams Sensitivity % Abnormals % Biopsies/1000 exams Kerlikowske, Ann Intern Med, 2000

27 Potential Consequences of Undergoing Screening Mammography

28 What is the chance a woman will have an abnormal result after 10 screening exams? 1. 5% 2. 12% 3. 30% 49% 31% 20% 5% 12% 30%

29 ν ν ν ν ν Potential Consequences False positives multiple work-ups in healthy women creates anxiety morbidity from invasive procedures more likely to undergo repeat screening & perform BSE Detection of biologically insignificant lesions results in unnecessary surgery & radiation Rate of treatment higher in screened women results in 25-35% more surgery and radiation Intense pain with breast compression % 15% Radiation induced cancer 1 per 10,000 women screened annually for 10 yrs

30 Performance of Screening Mammography by Age Measure Positive % PPV % Sensitivity % Yankaskas,, Radiology, 2005

31 Mammography Outcomes After 10yrs of Annual Screening AGE Positive % False-positive % Biopsy % Kerlikowske, JNCI,, 1997

32 Factors Influence Risk of False-Positive or Negative Mammography Test False positive > 3 breast biopsies Family history E+P hormone use No comparison films > 2 years since last screen Obesity False negative > 3 breast biopsies E+P hormone use High breast density Breast implants Younger age Rapid tumor growth Christiansen, JNCI,, 2000; Banks, BMJ,, 2004

33 Sensitivity of Digital vs Screen-Film N Digital Film < 50 yr % > 50 yr % Premenopausal % Postmenopausal % Dense % Nondense % N Engl J Med 2005; 353: [10/27/05]

34 Annual volume Higher Specificity if Interpret High Volume of Exams Focus on SM False-positives 12.9% 11.5% 7.6% 6.8% 750 Low 12.9% 1000 Low 11.5% 1000 High 7.6% 4000 High 6.8% Smith-Bindman Bindman,, JNCI, 2005

35 Invasive Cancer & DCIS Incidence & Breast Cancer Mortality, Invasive per 100, Screening 1 in 1300 screening exams diagnosed with DCIS 20 DCIS Year Mortality

36 Data Suggesting DCIS of Low Malignant Potential ν ν ν ν 15% of lesions progress to invasive cancer over 10 years Risk of death 1% to 2% over 10 years with all types of treatment Prevalent among women who die of other causes (~15%) Breast cancer incidence has not decreased in relation to increase in DCIS

37 Screen-detected DCIS and Invasive cancer per 1,000 exams increase with age Age DCIS Rate* Invasive cancer Rate* *Per 1000 screens

38 Risk of Invasive Cancer & DCIS after 10yrs of Screening AGE Invasive cancer % DCIS % Kerlikowske, JNCI, 1997

39 70 yo women with DCIS not likely to die of breast cancer in next 10y Risk of Death in 10 years Breast Cancer Other Mammography 1.2% 25.2% Low grade DCIS 0.8% 25.6% High grade DCIS 2.0% 25.2% Kerlikowske, JNCI, 2003

40 The benefits of mammography outweigh the harms for women aged? years years and older years 67% 21% 4% 8% years years 40 and older years

41 Cost-effectiveness of Screening Age Group Cost/yr of life saved 40 to 49 $150, to 69 $21, to 79 $73,900 Cost-effective < $50,000 Salzmann & Kerlikowske, Ann Intern Med,, 1997 & Kerlikowske, JAMA,, 1999

42 Current Status of Screening Mammography Recommendations ν Most major U.S. organizations (ACS, ACR, NCI, AMA, USPSTF) recommend screening starting at age 40 ν Canada and most European countries recommend or have organized programs that start screening at age 50 and stop at age 69 ν No upper age limit for most U.S. organizations (ACS, ACR, NCI, USPSTF)

43 Recommendations by USPSTF ν Screening mammography, with or without clinical breast examination, every 1 to 2 years for women aged 40 and older. B recommendation ν The precise age at which the benefits from screening justify the potential harms is a subjective judgment & should take into account patient preferences. Clinicians should inform women about the potential benefits (reduced chance of dying of breast cancer), potential harms (eg, false-positive results, unnecessary biopsies), & limitations of the test that apply to women their age. Humphrey, Ann Intern Med, 2002

44 Recommendations for Women ν ACP: For women aged 40-49, 49, the evidence that screening mammography reduces mortality from breast cancer is weaker, and the absolute benefit of mammography is smaller, than it is for older women ν Inform women of benefits and harms ν Periodically assess risk of breast cancer ν Decision to screen based on potential benefits and harms, patient preferences, and risk profile Qaeseem,, Ann Intern Med, 2007

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46 Women at high risk of breast should undergo which screening tests? 1. Mammography, clinical breast examination (CBE), ultrasound 2. Mammography and ultrasound 3. Mammography and MRI 4. Mammography, CBE and MRI 34% 9% 17% 40%

47 Screening Mutation Carriers with MRI Mammo Sono MRI CBE All Sensitivity % Specificity % Sensitivity higher for MRI than mammography (71-100%), specificity lower Negative LR for mammography + MRI lower than mammography alone Warner, JAMA,, 2004; Warner, Ann Intern Med,, 2008

48 ACRIN Trial 6666 ν High risk asymptomatic women with dense breasts ν Mammography + Ultrasound ν Independent readings ν N= 41 breast cancer ν PPV mammography % (21/276) ν PPV ultrasound % (12/337) ν PPV mammo + ultrasound % (8/436) Berg, JAMA,, 2008

49 MRI Testing Does Not Affect Survival in Early Stage Invasive Cancer or DCIS Mammography Mammography + MRI 8-year outcomes % % Local recurrence 4 3 Overall survival Breast cancer survival Contralateral 6 6 Solin, JCO,, 2008

50 Average-risk risk women should undergo which breast examinations in addition to mammography? 1. Clinical breast examinations (CBE) 2. Breast self examinations (BSE) 3. CBE and BSE 4. None of the above 12% 11% 55% 21%

51 Clinical Breast Exam & Mammography CBE Mortality Reduction YES 20% NO 24% Sensitivity of CBE only 22% Kerlikowske, JAMA,, 1995; Fenton, JNCI Monogr,, 2005

52 Outcomes From Screening with CBE AGE > 50 False-positive 1 exam 6.0% 2-3.5% 5 exams 21% 11% 10 exams 34% 19% Elmore, NEJM,, 1998

53 Canadian Screening Mammography Trial in Women 50 to 59 mammo + CBE CBE Invasive cancer DCIS Tumor < 20 mm 53% 40% Node positive 31% 35% Breast cancer deaths RR= 1.02 Miller, JNCI,, 2000

54 Clinical Trials of Breast-Self Exam China Russia UK No. women 266, , ,496 Age (y) Follow-up (y) Breast cancer RR= 1.04 RR= 1.0 RR=.99 mortality 2-fold more benign biopsies in screening than control group

55 Maximize Chance of Benefit & Minimize Chance of Harm ν Inform women of potential benefits and consequences of breast cancer screening ν Mammography at high volume facility ν Screen every 2 years from or ten mammograms in woman s s lifetime ν Consider CBE in women who refuse mammography ν Stop mammography screening at age 70, consider CBE if request ongoing screening ν Sufficient evidence to not recommend BSE

56 Additional Recommendations ν Annual screening for women aged who choose to undergo mammography ν Digital mammography may be more accurate in those aged 40-49, 49, premenopausal or with dense breasts ν Mutation carriers may benefit from both MRI & mammography ν Ultrasound is not a recommended test for screening for breast cancer

57 Thank You