Dense Breasts. A Breast Cancer Risk Factor and Imaging Challenge

Transcription

1 Dense Breasts A Breast Cancer Risk Factor and Imaging Challenge Renee Pinsky, MD University of Michigan Department of Radiology Division of Breast Imaging

2 No Disclosures

3 QUIZ: ARE YOU DENSE? a. Breast Imaging question regarding the mammographic appearance of breast tissue. b. Current legislative issue in many states. c. A teenager s disrespectful response when you do not know how to download an app to your smart phone. d. a and b

4 ARE YOU DENSE? Nancy Capello founder 2004 dx d stage 3c breast cancer Normal mammogram 2 months earlier Found out after treatment that she had dense breasts Founded organization

5 Mission Statement: dedicated to informing the public about dense breast tissue and its significance for the early detection of breast cancer.

6 Why are we interested? An average woman s lifetime risk for developing breast cancer is 1: 8

7 INCIDENCE American Cancer Society estimate for 2012 was 229,060 new cases of breast cancer in US 3/4 Invasive cancer 1/4 Ductal Carcinoma In Situ

8 MICHIGAN Incidence NCI State Cancer Profiles ( ) 120 per 100,000 female population/year 6,993 women / year 0.7%/year not significant accessed February 23, 2013

9 INCIDENCE Incidence drop in early 2000 s felt to be related to WHI Report and decreased HRT use. Rate relatively steady for last 10 years.

10 MORTALITY Estimated U.S. breast cancer deaths in 2012 is 39,920

11 USA Female Breast Cancer Mortality Rate -2.2% / year % Screening and Treatment SEER 2011 ACS 2012

12 WHO IS AT RISK? 99 % of breast cancers develop in women Median age 61 years 1 % in men

13 Major Risk Factors for Breast Cancer Increasing age (age 25 = 1 in 19,608 vs. age 45 = 1 in 93) Family history (especially first degree relatives and premenopausal) Personal history Prior breast biopsy with atypia or LCIS Genetic mutations BRCA 1 and 2 (5-10% of all cases. ) Thoracic Radiation Therapy (age < 30) Dense Breasts

14 Other Risk Factors Early menarche (<12yo) Late menopause (> 52/55yo) Late age at first full term pregnancy (> 30yo) Nulliparity Post-menopausal obesity Hormone replacement therapy Estrogen + Progesterone implicated in Women s Health Initiative Study (2003)

15 Mammography Screening Only modality with many years of multiple large randomized clinical trials demonstrating mortality benefit.

16 Mammography Diminished sensitivity in dense breasts compare to fatty. Despite this it has been proven to save lives **The breast density issue should NOT discourage women from getting mammograms**

17 What is Breast density? Assessed on mammography Different X-ray absorption of fibrous and glandular tissue vs fat. Density is the relative amount of white (FG) vs black/gray (fat)

18 How is breast density measured and reported? Visual estimation of density Wolfe s Classification (1976) Hutzel Hospital, Detroit

19 How is breast density measured and reported? Wolfe s Classification-Qualitative N1-mostly fat P1- <¼ of breast is dense P2- >¼ of breast is dense DY- marked mammary dysplasia 37x Greater incidence of cancer in DY vs N1 group Wolfe JN Breast Patterns as a Index of risk for Developing Breast Cancer. AJR 1976:126:

20 How is breast density measured and reported? Visual estimation of density Wolfe s Classification (1976) BI-RADS Computer Assisted MDEST (Mammographic Density ESTimation) Cumulus

21 BI-RADS (Breast Imaging Reporting and Data System) Qualitative 1- Almost entirely fat 2- Scattered fibroglandular densities 3- Heterogeneously dense 4- Extremely dense American College of Radiology. Breast imaging Reporting and Data System (BI-RADS) 4 th Ed. Reston, VA: American College of Radiology: 2003 Ciatto et al The Breast vol 21, issue 4 August 2012, Pages

22 BI-RADS Ciatto et al The Breast vol 21, issue 4 August 2012, Pages

23 Quantitative BI-RADS 1- Almost entirely fat <25% dense 2- Scattered fibroglandular densities 25-50% 3- Heterogeneously dense 50-75% 4- Extremely dense >75% American College of Radiology. Breast imaging Reporting and Data System (BI-RADS) 4 th Ed. Reston, VA: American College of Radiology: 2003 Ciatto et al The Breast vol 21, issue 4 August 2012, Pages

24 How good are we at estimating density? 706 mammograms Assessed inter-observer agreement for cancer detection and breast density using BI- RADS Observed agreement-75% Agreement expected by chance-39% Κ=0.59 ( ) Moderate agreement Kerlikowske 1998 JNCI

25 Subjective BI-RADS Moderate reproducibility Qualitative > Quantitative More reliable in the lowest and highest density. (Cat 1 and 4)

26 2-D vs. 3-D Example of cranio-caudal image mammographic density readings in the 2-D threshold percent density and the volumetric Standard Mammographic Form methods. Aitken Z et al. Screen Film Mammographic Density and Breast Cancer Risk: A Comparison of the Volumetric Standard Mammographic Form and the Interactive Threshold Measurement Methods Cancer Epidemiol Biomarkers Prev 2010;19:

27 Computerized methods Aitkin cancers/661 controls Compared % density 2D semi automated system with 3D fully automated system % density 2D method better at predicting risk of cancer.

28 Density measurements No perfect measure yet BIRADS Current clinical standard Subjective Automated systems not ready for the clinic

29 Distribution of Breast Density 587,369 women >1 million mammo exams Looking at 5 year breast cancer risk BIRADS breast density # of women % 1 57, , , ,995 9 Adapted from Breast Cancer Risk by Breast Density, Menopause, and Postmenopausal Hormone Therapy Use, Kerlikowske K. et al J Clin Onc August 20, 2010 vol. 28 no

30 Breast Density # of women Predominantly fatty Scattered densities Heterogeneously Dense Extremely Dense Breast Density

31 Density and Breast Cancer Risk MASKING- Dense tissue hiding a cancer on a mammogram

32 Density and Breast Cancer Risk

33 Density and Breast Cancer Risk

34 RT LT Palpable left breast mass 36 years old Heterogeneously dense

35 Density and Breast Cancer Risk Intrinsic increased risk of Cancer

36 Density and Breast Cancer Risk Wolfe x risk McCormack x risk Meta analysis 11 studies >14,000 cases Wolfe, JN Risk for Breast Cancer Development Determined by Mammographic Parenchymal Pattern. Cancer 1976 May: 37(5) McCormack, VA et al, Breast Density and Parenchymal Patterns as Markers of Breast Cancer Risk. Cancer Epidem Biomarkers Prev 2006; 15:

37 Association of Density classifications with breast cancer risk in general (incidence and prevalence) Relative risk McCormack V A, and dos Santos Silva I Cancer Epidemiol Biomarkers Prev 2006;15: by American Association for Cancer Research

38 Density and Breast Cancer Risk Wolfe x risk McCormack x risk Boyd odds ratio Risk >75% dense vs < 10% dense Boyd NF, Mammographic Density and the Risk and Detection of Breast Cancer N Engl J Med 356;3January 18,2007

39 So far What is breast density How is it measured Importance in breast cancer risk Extremely dense breasts- highest risk

40 What is being done with this information?

41 Breast Density Imaging Patient Counseling Patient demand Legislation

42 Breast Imaging Digital Mammography X ray image converted into an electronic signal > projected on screen > manipulated 85% of units in USA are digital

43 Breast Imaging Digital Mammography DMIST Trial ~43,000 women/33 centers/2 years Accuracy- Film Screen vs Digital Pisano,ED et al, Diagnostic Performance of Digital vs Film Mammography for Breast Cancer Screening N Engl J Med 2005; 353:

44 Breast Imaging Digital Mammography DMIST Trial Accuracy higher for digital imaging Under age 50 Dense breasts (>50% dense) Pre or peri-menopausal

45 Film Screen Digital

46 Supplemental Screening In addition to mammography!

47 Breast Ultrasound Hand held US Inexpensive Available User dependent Time consuming

48 Screening US Kolb ,712 women/dense breasts Screening Mammogram Screening hand held US PE

49 Screening US Kolb: Cancers in dense breasts- Sensitivity Mammo alone-64% US alone- 37% PE alone- 28% Mammo + US- 97.3% Mammo + PE- 74.7% P<.001 False + approx 5%

50 ACRIN 666 Screening US Screening mammogram Screening US 2637 Women High risk AND >50% dense Based on personal hx, previous high risk biopsy, Gail model Berg WA, et al, Combined Screening With Ultrasound and Mammography vs Mammography Alone in Women at Elevated Risk of Breast Cancer JAMA, 2008; 299,

51 ACRIN 666 Screening US 4.2 additional cancers/1000 women supplemental yield by adding US Berg WA, et al, Combined Screening With Ultrasound and Mammography vs Mammography Alone in Women at Elevated Risk of Breast Cancer JAMA, 2008; 299,

52 Screening US False + PPV Mammo alone % US alone % Mammo + US % ACRIN 666

53 Connecticut Experience First Year after RU Dense Law 935 Women All risk levels Hand held whole breast 63 biopsies or aspirations 3/63 malignant All <1cm All post menopausal 1 cancer per risk category

54 Connecticut Experience Cancer detection rate: 3/1000 PPV- 6.5% (low)

55 Screening US Benefits: Available Inexpensive No radiation Down sides: Time to perform study 19 minutes bilateral (ACRIN) Qualified physician/tech shortages False + Not standardized

56 Speeds up exam Automated US Assisted robotic guidance of probe over breast U- Systems SonixEmbrace

57 Kelly et al, ,425 studies Automated US Increased cancer detection from 3.6 to 7.2/1000 compared to mammo alone 7-8 minutes physician time PPV biopsy = 38.4%

58 MRI Magnetic Resonance Imaging Increased availability in past 10 years

59 MRI

60 MRI 50 yo Extensive non mass like enhancement DCIS

61 MRI CC MAG 62 yo Heterogeneously dense, 25% lifetime risk, screening

62 MRI MR Biopsy- High grade DCIS.

63 Benefits MRI High sensitivity for cancer Not affected by density No Radiation

64 Down sides MRI IV contrast required False + Claustrophobia Availability Cost Berg WA Detection of Breast Cancer with Addition of annual Screening Ultrasound or a Single Screening MRI to Mammography in Women with Elevated Breast Cancer Risk JAMA 2012 ; 307:

65 Berg 2012 MRI Expanded ACRIN trial: high risk AND dense Added MRI screening after 3 rounds of M/US Berg WA Detection of Breast Cancer with Addition of annual Screening Ultrasound or a Single Screening MRI to Mammography in Women with Elevated Breast Cancer Risk JAMA 2012 ; 307:

66 Results MRI 612 women in MRI added group 16/612 had Cancer 9/16 (56%) seen only on MRI Median size 8mm All staged- node negative Supplemental cancer yield of MRI- 14.7/1000 Berg WA Detection of Breast Cancer with Addition of annual Screening Ultrasound or a Single Screening MRI to Mammography in Women with Elevated Breast Cancer Risk JAMA 2012 ; 307:

67 Berg 2012 Added MRI to ACRIN 666 Sensitivity Specificity PPV Recall Rate Mammo alone Mammo + US 56% 89% 29% 11% 94% 74% 11% 16% MRI 100% 70% 19% 31% Berg WA Detection of Breast Cancer with Addition of annual Screening Ultrasound or a Single Screening MRI to Mammography in Women with Elevated Breast Cancer Risk JAMA 2012 ; 307:

68 MRI Current recommendation for screening MRI (NCCN) High risk women >20% lifetime risk of cancer

69 Cost of supplemental studies

70 Berg 2012 Despite its higher sensitivity, the addition of screening MRI rather than ultrasound to mammography in broader populations of women at intermediate risk with dense breasts may not be appropriate, particularly when the current high false positive rates, cost, and reduced tolerability of MRI are considered. Berg WA Detection of Breast Cancer with Addition of annual Screening Ultrasound or a Single Screening MRI to Mammography in Women with Elevated Breast Cancer Risk JAMA 2012 ; 307:

71 Emerging Technologies Tomosynthesis Molecular Imaging

72 Tomosynthesis Digital x-ray mammogram Multiple projections produced by x- ray source that moves in an arc

73 Tomosynthesis Basic technologic principles of breast tomosynthesis. Park J M et al. Radiographics 2007;27:S231-S by Radiological Society of North America

74 Tomosynthesis Digital x-ray mammogram Multiple projections produced by x- ray source that moves in an arc Interpretation of multiple slices thin through breast like CT or MRI

75 Tomosynthesis U. Of M. Case 1 All tomo images courtesy of: Marilyn A. Roubidoux, MD *U. of Michigan Research GE Prototype

76 Tomosynthesis DBT *U. of Michigan Research GE Prototype U. Of M. Case 1 All tomo images courtesy of: Marilyn A. Roubidoux, MD

77 Tomosynthesis DBT slices Case 1 Marilyn A. Roubidoux, MD

78 Tomosynthesis DBT slice U. Of M. Case 2 Marilyn A. Roubidoux, MD

79 CC Tomosynthesis MLO Case 4 Screening digital mammogram

80 CC Tomosynthesis MLO DBT Case 4

81 Tomosynthesis MLO DBT slice Case 4

82 Tomosynthesis Case 5 Palpable lump

83 Tomosynthesis DBT DBT

84 Tomosynthesis DBT slices

85

86 Benefits Tomosynthesis Decrease overlapping tissue Increased sensitivity Decrease size of cancer detected Decreased recall rate Uses mammographic technology Helvie MA Digital Mammography Imaging: breast Tomosynthesis and Advanced Imaging Radiol Clin N Amer 48(

87 Benefits Tomosynthesis Decrease overlapping tissue Increased sensitivity Decrease size of cancer detected Decreased recall rate Uses mammographic technology Helvie MA Digital Mammography Imaging: breast Tomosynthesis and Advanced Imaging Radiol Clin N Amer 48(

88 Tomosynthesis Skaane April ,631 exams Digital Mammography and Tomosynthesis

89 Results Tomosynthesis 27% increase in cancer detection rate when Tomo added (p=.001) 15% decrease in recall rates from screening(p<.001) PPV of biopsy- same for M alone vs M+Tomo

90 Results Tomosynthesis Interpretation time doubled when tomo added (45 vs 91 seconds p<.001)

91 Molecular Breast Imaging Positron Emission Mammography (PEM) 18F-fluorodeoxyglucose High resolution PET scanner Breast Specific Gamma Imaging (BSGI) Tc99m Sestamibi

92 Molecular Breast Imaging Whole body exposure to ionizing radiation Not indicated for annual use. Current trials underway to decrease dose to allow for screening use.

93 Are you DENSE? Pink: Enacted law Red: Endorsed Bill Blue: Working on Bill White: No Action * : Insurance Coverage Bill CT and IL mandate insurance coverage for Screening US , Are You Dense Advocacy, Inc.. All rights reserved. Site designed and hosted by WORX Branding & Advertising.. the webmaster. Accessed

94 MICHIGAN Bill: patient notification "THE PHYSICIAN INTERPRETING YOUR MAMMOGRAPHY EXAMINATION HAS DETERMINED THAT YOU HAVE DENSE BREAST TISSUE. MAMMOGRAPHY HAS KNOWN LIMITATIONS AND, IN A PATIENT WHO HAS DENSE BREAST TISSUE, SOME ABNORMALITIES MAY NOT APPEAR. IF YOU WERE REFERRED TO US BY A PHYSICIAN, A WRITTEN REPORT OF THE RESULTS OF YOUR MAMMOGRAPHY EXAMINATION, INCLUDING INFORMATION ABOUT YOUR BREAST DENSITY, HAS BEEN SENT TO YOUR PHYSICIAN. THIS NOTICE IS INTENDED TO RAISE YOUR AWARENESS AND PROMOTE DISCUSSION BETWEEN YOU AND YOUR PHYSICIAN REGARDING THE RESULTS OF YOUR MAMMOGRAPHY EXAMINATION. DEPENDING UPON YOUR INDIVIDUAL RISK FACTORS, YOUR PHYSICIAN MAY RECOMMEND ADDITIONAL TESTS INCLUDING AN ULTRASOUND OR MAGNETIC RESONANCE IMAGING. YOU SHOULD CONTACT YOUR PHYSICIAN IF YOU HAVE ANY QUESTIONS OR CONCERNS REGARDING THE RESULTS OF YOUR MAMMOGRAPHY EXAMINATION.".

95 Are you Dense Legislation? The GOOD: Increased clinician and patient awareness Strengths and shortcomings of Mammography Risk factors Increase discussion with their clinicians Can address other risk factors

96 Are you Dense Legislation? The Bad: Patient anxiety Only 10% of screening population is extremely dense Significant risk seems to be directed at this group High false positives of supplemental studies Technology has not caught up- Measuring breast density-limited Moderate reliability of description Computerized models very limited use now

97 The Ugly: Are you Dense? Will this discourage women and clinicians from routine mammography? Who is going to pay for supplemental studies?

98 Recommendations Support education of public Data supports density as a risk factor Continue Annual Mammography Support Insurance coverage as a necessary part of legislation to ensure parity Consider limiting recommendation to Extremely Dense breasts

99 Thank you