Breast Density: Significance and Notification. Carol H. Lee Memorial Sloan-Kettering Cancer Center New York, NY

Transcription

1 Breast Density: Significance and Notification Carol H. Lee Memorial Sloan-Kettering Cancer Center New York, NY

2 Significance of Breast Density Association with increased risk for breast cancer Decreased sensitivity of mammography

3 Grass-roots movement for direct patient notification of breast density D.E.N.S.E. Density Education National Survivors Effort

4 "I was diagnosed with Stage 3c breast cancer two months after receiving a "normal" mammography report. Little did I know at the time that there was information about my health and my life that was being kept from me the patient and others like me. I call it the best-kept secret - but it WAS known in the medical community. I have dense breast tissue and women like me have less than a 48% chance of having breast cancer detected by a mammogram. Nancy M. Cappello, Ph.D.

5 It just might be the greatest cancer risk you ve never heard of. Five facts about dense breast tissue 1. 40% of women have dense breast tissue. 2. Breast density is one of the strongest predictors of the failure of mammography to detect cancer. 3. Mammography misses every other cancer in dense breasts.

6 It just might be the greatest cancer risk you ve never heard of. 4. Breast density is a well-established predictor of breast cancer risk. 5. High breast density is a greater risk factor than having two first degree relatives with breast cancer.

7 It just might be the greatest cancer risk you ve never heard of. Additional screening tests to mammography for women with dense breast tissue will nearly increase detection up to 100%. These invasive cancers, missed by mammography, are small, node negative and at an EARLY stage.

8 Density Notification Laws 24 States

9 Density Notification Laws As of April 2018 Alabama Arizona California Connecticut Delaware Hawaii Ohio Louisiana Maryland Massachusetts Michigan Minnesota Missouri Nevada New Jersey New York North Carolina Oregon Pennsylvania Rhode Island Tennessee Texas Virginia North Dakota

10 Density Notification Laws So far in 2016, bills have been introduced in an additional 10 state legislatures. FL, GA, IA, KY, MS, NH, SC, VT, WA, WV

11 CONNECTICUT LAW S.B. 458 Where applicable, such report shall include the following notice: "If your mammogram demonstrates that you have dense breast tissue, which could hide small abnormalities, you might benefit from supplementary screening tests, which can include a breast ultrasound screening or a breast MRI examination, or both, depending on your individual risk factors. You should contact your physician if you have any questions or concerns about this report."

12 The decision to withhold dense tissue composition from women is denying women the right to make an informed decision about their breast screening protocol. The medical community has failed to enact a standard that requires heath care providers to inform women that mammography can miss more cancer than it detects in women who have dense breasts.

13 As a result, women with dense breast tissue are being denied access to an Early Breast Cancer Diagnosis. A policy change by the government is necessary to ensure that patient safety becomes a high priority and that the communication of Breast Density to Women is standardized across the country.

14 The Breast Density and Mammography Reporting Act Senate bill S. 370 introduced by February 4, 2015, Diane Feinstein (D-CA) and Kelly Ayotte (R-NH). 17 co-sponsors. House bill H.R. 716 introduced by Rosa DeLauro (D-CT), Steve Israel (D-NY) and Mike Fitzpatrick (R-PA). 27 co-sponsors.

15 The Breast Density and Mammography Reporting Act The legislation would mandate that the patient summary required under MQSA convey the effect of breast density in masking the presence of breast cancer on mammography individuals with dense breasts should talk with their physicians about whether the patient might benefit from additional tests

16 The Breast Density and Mammography Reporting Act Bill would also direct HHS to study improved screening options for women with dense b reasts including research on cost effectiveness and research in support of clinical guidelines and best practices concerning use of mammograms and supplemental screening for women with dense breasts

17 Density Notification Laws Four states have mandatory insurance coverage for supplemental screening CT, IL, IN, NJ

18 Questions and Issues Surrounding Breast Density What is the best method for assessing breast density? What is the risk associated with high breast density Should all women with dense breasts have supplemental screening? Which supplemental screening modality is best?

19 Methods for Determining Breast Density Visual inspection No additional cost or equipment Subjective Intra- and Inter-observer variability Semi-automated computerized programs Fully-automated software programs Reproducible Requires additional software Not validated

20 BI-RADS Breast Density Categories Almost entirely fatty 0% - 25% 2. Scattered areas of fibrogl. density 25% - 50% 3. Heterogeneously dense 50% - 75% 4. Extremely dense 75% - 100%

21 Predominately fatty Scattered fibroglandular Heterogeneously dense Extremely dense 10% of women 40% of women 40% of women 10% of women

22 BI-RADS Breast Density Categories 2013 A. Almost entirely fatty B. Scattered areas of fibroglandular density C. Heterogeneously dense D. Extremely dense

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26 Kappa Statistic Landis, Koch Biometrics 1977;33:159 κ Strength of Agreement Slight Fair Moderate Substantial Almost perfect

27 Interobserver Variability in Breast Density Assignment Study Kappa Berg et al Ciatto et al Ooms et al Redondo et al

28 Interobserver Variability in Breast Density Assignment Study Kappa for heterogeneously dense Berg et al Ciatto Ooms et al

29 Raza et al JACR 2016;13: radiologists reading 200 mammograms Density assigned before and after training video Density assignment compared to expert and quantitative assignment Agreement improved from 65% to 72% Improvement for categories A and D Decreased accuracy for categories B and C

30 Gur et al Acad Radiol 2015;22: radiologists surveyed as to effect of density notification law on their density assessments Actual density assessments soon after law passed and compared to pre-law assessments 56% not in favor of law 13% in favor of law 31% neutral

31 Gur et al Acad Radiol 2015;22:679 After law, how often will density be assessed as scattered fibroglandular rather than heterogenously dense More often 8/16 (50%) Same 7/16 (44%) Less often 1/16 ( 6%)

32 Gur et al Acad Radiol 2015;22:679 44% of radiologists performed differently than their answer 14/16 (87.5%) assessed SFG more often 7/14 statistically significant Conclusion:Radiologists reporting patterns changed, at least for a short duration, after the new density reporting law and for some of the radiologists in an unexpected way.

33 Breast Density and Parenchymal Patterns as Markers of Breast Cancer Risk: A Meta-analysis McCormack et al Cancer Epidemiol Biomarkers Prev 2006;15:1159 % DENSITY RELATIVE RISK (COMPARED TO < 5%) >

34 Approximate Relative Risk Heterogeneously dense vs scattered 1.2 Extremely dense vs scattered 2 Fam Hx breast cancer: Mother dx > Proliferative benign breast biopsy Fam Hx breast cancer: Mother dx <50 3 Fam Hx breast cancer: two 1 st degree 3-4 Extremely dense vs fatty 3-5 Atypia on bx 4-5 BRCA 1 or

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38 Background Parenchymal Enhancement at Breast MR Imaging and Breast Cancer Risk King V et al. Radiology 2011;260: Women Odds ratio for breast cancer moderate or marked BPE Odds ratio for breast cancer increased fibroglandular tissue

39 del Carmen et al. AJR 2007;188:1147 Race Asian 1% 16% 56% 27% White 7% 27% 54% 12% African American 8% 31% 51% 9% Other 9% 29% 52% 9%

40 Breast Cancer Risk Race and ethnicity Lifetime risk of breast cancer (up to age 80) White 13% African-American 11% Hispanic (may include other ethnic groups) 10% American Indian or Alaska Native 8% Asian-American or Pacific Islander 10%

41 Breast Cancer Incidence in U.S. Women by Race and Ethnicity

42 Sensitivity of Mammography in dense breasts STUDY Fatty Extremely Dense Carney et al 87% 63% Kerlikowske 86% 68% Kavanaugh 85% 55%

43 SENSITIVITY OF SCREENING MAMMOGRAPHY Rosenberg et al, Radiology 209:511, ,134 Women Age Sensitivity (%) Not dense Dense >

44 Kerlikowske et al. Ann Internal Med 2011;155:493 Data from Breast Cancer Screening Consortium (BCSC) participating facilities 869,286 mammograms 231,034 digital 638,252 film 4046 cancers

45 Kerlikowske et al. Ann Internal Med 2011;155:493 Sensitivity Digital Film- Screen P-value Predominately fatty Scattered fibroglandular Heterogeneously dense Extremely dense *

46 Ciatto et al Br J Cancer 2004;90:393

47 Prevalence of Mammographically Dense Breasts in the United States Sprague et al. JNCI 2014; ,507 women > 40 years old 43% with heterogeneously or extremely dense breasts 27.6 million women aged in United States have dense breasts

48 ACOG Statement on Screening Women with Dense Breasts Women with dense breasts have a modestly increased risk of breast cancer and experience reduced sensitivity of mammography to detect breast cancer. However, evidence is lacking to advocate for additional testing until there are clinically validated data that indicate improved screening outcomes. Currently, screening mammography remains the most useful tool for breast cancer detection and has consistently demonstrated a reduction in breast cancer mortality. The American College of Obstetricians and Gynecologists does not recommend routine use of alternative or adjunctive tests to screening mammography in women with dense breasts who are asymptomatic and have no additional risk factors. The American College of Obstetricians and Gynecologists recommends that health care providers comply with state laws that may require disclosure to women of their breast density as recorded in a mammogram report.

49 CBDIG Recommendations for Supplemental Screening Benefits vs. drawbacks most favorable for women at increased risk beyond density Individualized risk-based approach Use of validated models to determine risk Supplemental screening (preferably MRI) for high risk after formal risk assessment

50 Kerlikowske et al Ann Int Med 2015;162: ,455 mammograms women Breast density, 5 yr risk, interval cancers determined High interval cancer rate: > 1 per 1000 mammos

51 Kerlikowske et al Ann Int Med 2015;162:673 High Interval Cancer Rate Extremely dense and 5 year risk > 1.67% Heterogeneously dense and 5 year risk > 2.50%

52 Kerlikowske et al Ann Int Med 2015;162:673 Low to Average 5 Year Risk 51% women with heterogeneously dense Interval cancer rate / % women with extremely dense Interval cancer rate /1000

53 Kerlikowske et al Ann Int Med 2015;162:673 Conclusion: Breast density should not be the sole criterion for deciding whether supplemental imaging is justified because not all women with dense breasts have high interval cancer rates.

54 Risk Assessment Models

55 Risk Model Summary FACTOR CONSIDERED? GAIL CLAUS BRCAPRO IBIS BOADICEA BCSC Family history YES YES YES YES YES YES BRCA1, BRCA2 mutations NO NO YES YES YES NO Intermediate-high risk NO NO NO NO YES NO mutations (CHEK2, PALB2, ATM) Mammographic density NO NO NO NO NO YES Hormonal/reproductive, YES NO NO YES NO NO lifestyle Other cancers than breast NO NO YES NO YES NO Second breast cancer risks NO NO NO NO YES NO

56 Which Risk Model to Use? Clinical Implications of the ACS MRI Screening Guidelines Ozanne et al Cancer Epidemiol Biomarkers Prev 2012;22: women undergoing screening mammography at a community hospital 342 (5.8%) lifetime risk of > 20% by one of the models Tyrer-Cusick (5.6%) BRCAPRO - 25 (0.4%) Claus - 54 (0.9%) Only 18 women at high risk in all 3 models

57 Supplemental Screening Modalities Tomosynthesis Low supplemental cancer yield Ultrasound High false positive rate, low PPV MRI Expensive, not everyone is candidate, intravenous contrast MBI Long acquisition time, relatively high radiation dose

58 Breast Density and Notification: Conclusions National mandate probably inevitable Provide information for providers and patients on significance of density Decide on a consistent policy of how to manage, what to recommend for women with dense breasts Tomo for all? Ultrasound for all? Defer to clinician?

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61 What Not to Do BI-RADS 0: Additional Imaging Evaluation Needed

62 Future Directions Incorporation of density into risk models Automated whole breast ultrasound Improvements in specificity of ultrasound Elastography Abbreviated MR protocol Contrast enhanced digital mammography