Breast Cancer Screening and Diagnosis

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1 Breast Cancer Screening and Diagnosis Priya Thomas, MD Assistant Professor Clinical Cancer Prevention and Breast Medical Oncology University of Texas MD Anderson Cancer Center

2 Disclosures Dr. Thomas has disclosed that she has no actual or potential conflict of interest in relation to this topic.

3 Educational Objectives By the end of this activity, the participant should be better able to: Outline risk-based breast cancer screening recommendations. Discuss diagnostic evaluation of a breast mass/thickening. Discuss diagnostic evaluation of nipple discharge and skin changes.

4 Breast Cancer Screening Guidelines Age to Start Mammograms USPSTF American Cancer Society (ACS) (individual choice 40-44) Interval 2 years Annual 45-54; 1-2 years 55+ Age to Stop Mammograms 74 Life Expectancy < 10 years National Comprehensive Cancer Network (NCCN) 40 Annual Upper age limit not established

5 Screening Mammography

6 2016 U.S. Preventive Services Task Force Recommendations The decision to start screening mammography in women prior to age 50 should be an individual one. Women who place a higher value on the potential benefit than the potential harms may choose to begin biennial screening between the ages years. (Grade C Recommendation) Siu AL et al. Annals Int Med 2016;164:

7 Harms of Screening Mammography False positives Associated anxiety and distress Over diagnosis Radiation exposure US Preventive Services Task Force, Ann Intern Med, 2009; 151(10):

8 Evaluation of False Positives ~10% of women screened will be recalled for additional evaluation >80% will be normal/benign after dx evaluation May include: add l mmg views, u/s 15% recalled will be recommended for biopsy Associated anxiety and distress Several studies show that anxiety related to a false positive test results does not result in a decrease in future screening participation Brewer Ann Intern Med 146 (7): , 2007.

9 Another Perspective. As many as 70% of breast cancers seen in women in their 40 s occur in women with no risk factors >40% of years of life lost to breast cancer are due to women diagnosed in their 40s Many women place a very high value on the benefits and very little weight on the harms of mammographic screening Differs from perspective of USPSTF Kopans, J Am Coll Radiol, 2010 Smith RA et al. CA Cancer J Clin, 2010

10 2016 U.S. Preventive Services Task Force Recommendations Recommends biennial screening mammography for women aged (Grade B Recommendation) Siu AL et al. Annals Int Med 2016;164:

11 2016 U.S. Preventive Services Task Force Recommendations The current evidence is insufficient to assess the balance of benefits and harms of screening mammography in women aged 75 years or older. (Grade I Recommendation) Siu AL et al. Annals Int Med 2016;164:

12 Rationale for USPSTF Recommendation Screening biennially 81% of the benefit of annual screening Almost half the number of false-positives However.. CISNET models show 71% fewer deaths with annual screening mammography compared to biennial Annual mammographic screening from ages would save 99,829 more lives than USPSTF recommended biennial screening Mandelblatt JS, et al, Ann Intern Med, 2009; 151(10): Hendrick MA, Am J Roentgenology 2011.

13 ACS Breast Cancer Screening Recommendations Women at average risk of breast cancer should undergo regular screening mammography starting at age 45 (Strong rec) Women aged years should be screened annually (Qualified rec) Women 55 years and older should transition to biennial screening or have the opportunity to continue screening annually (Qualified rec) Women should have the opportunity to begin annual screening between the ages of years (Qualified rec) Women should continue screening mammography as long as their overall health is good and they have a life expectancy of 10 years or longer (Qualified rec) The ACS does not recommend clinical breast exam for breast cancer screening among average-risk women at any age (Qualified rec) Oeffinger KC et al JAMA 2015;314(15):

14 M. D. Anderson Risk-based Breast Cancer Screening Guidelines

15 Breast Awareness Paradigm shift from Breast Self-examination to Breast Awareness: Evidence shows there is no right or wrong way for women to identify a breast abnormality. Women know their breasts better than anyone else and do not have to be instructed in how to do this. Most lumps are found during routine, daily activities such as bathing and dressing. Instead of using a specific technique to examine their breasts, women should simply be aware of their breasts and promptly report any changes

16 Breast Screening Considerations Upper age limit for breast cancer screening is not yet established Breast cancer screening may continue for as long as: A woman has a 10-year life expectancy No co-morbidities that would limit the diagnostic evaluation or treatment of any identified problem Women should be counseled about the benefits, risks and limitations of breast screening

17 Average Risk Women Age years Clinical Breast Exam every 1-3 years Breast Awareness Age 40 years and over Annual CBE Annual Mammogram Breast Awareness

18 Breast Cancer Risk Categories Prior thoracic radiotherapy ages Gail Model 5 year risk >1.7% Lifetime risk > 20% defined by models dependent on family history Genetic predisposition LCIS

19 MD Anderson Breast Cancer Screening Guidelines

20 Screening Mammography Randomized controlled trials assessing effectiveness of mammographic screening Health insurance plan, US-1963 Edinburgh, UK-1978 Canadian national breast screening trial-1980 Study 1-age Study 2-age Swedish Two County Ostergotland, Sweden Kopparbreg, Sweden Malmo, Sweden-1976 Stockholm, Sweden-1981 Goteborg, Sweden-1982 Age-2006 Different ages of enrollment and screening frequency in each trial

21 Meta-Analysis of Case Control Studies (10): Breast Cancer Mortality 49% Mortality Reduction Cancer Epidemiol Biomarkers Prev 2012;21:

22 Meta-Analysis of Modeling Studies (7): Breast Cancer Mortality CISNET models demonstrate a 46% mortality reduction Suggests that observational studies may be a better estimate of mortality reduction associated with modern screening mammography

23 False positives Harms of Screening Mammography Associated anxiety and distress Has not been shown to affect intent to obtain future screening mammograms Additional diagnostic evaluation Overdiagnosis Breast Cancer does not spontaneously regress Of 479 breast cancer detected on screening mammography that was not treated within 10 years, none decreased in size or regressed. Some of the cancers, as expected, progressed. Delaying initiation of screening from age 40 to age 50 or increasing the screening interval from annual to biennial would not reduce over-diagnosis of breast cancer Arleo, J. Am Coll Radiol, 2017 US Preventive Services Task Force, Ann Intern Med, 2009; 151(10): Bleyer A, NEJM (21):

24 Breast MRI Studies have shown that MRI in addition to mammography in high risk women identifies breast cancers not seen on mammography More sensitive than mammography MRI=77-100% Mammography=16-40% Lord SJ, et al. Eur J Cancer 2007;43: Saslow D, et al. CA Cancer J Clin 2007;57(2):75-89.

Breast MRI The Limitations Not very specific False positives common Not as sensitive as mammography in detecting low-grade DCIS Studies only in high risk women Gene mutation carriers Women

25 Breast MRI The Limitations Not very specific False positives common Not as sensitive as mammography in detecting low-grade DCIS Studies only in high risk women Gene mutation carriers Women with a significant family history No benefit on breast cancer mortality has yet been demonstrated Lord SJ, et al. Eur J Cancer 2007;43: Saslow D, et al. CA Cancer J Clin 2007;57(2):75-89.

26 MRI Findings Most breast MRI studies will reveal one or more enhancing lesions Problem: Which are clinically significant?

27 Kinetic Description Initial Delayed SI fast medium slow Persistent (benign) plateau Washout (malignant) Initial slope within 2 minutes or when curve starts to change Delayed slope after 2 minutes or after curve starts to change

28 Breast MRI Facilities Facility doing breast MRI should have capability to do MRI-guided biopsy Issues encountered when changing facilities after a MRIguided biopsy has been recommended Software compatibility issues can limit ability to assess kinetics Difficulty obtaining reimbursement for a 2 nd MRI

29 What about Open MRI? Claustrophobia is an issue for many women Unfortunately, open MRI s do not provide satisfactory image resolution

30 ACS Recommendations: Screening Breast MRI Recommend Annual Screening Breast MRI for women with: Gene mutation (BRCA 1 or 2; Li-Fraumeni syndrome; Cowden syndrome; Bannayan-Riley-Ruvalcaba syndrome) First-degree relative with one of these mutations (if the woman has not yet been tested) History of radiation therapy to the chest between ages 10 and 30 Lifetime risk > 20% as defined by BRCAPRO or other models that are largely dependent on family history Saslow D, et al. CA Cancer J Clin 2007;57(2):75-89

31 ACS Recommendations: Screening Breast MRI Insufficient evidence to recommend for or against Screening Breast MRI for women with: Lifetime risk 15-20% LCIS or atypical hyperplasia Dense breasts Personal h/o breast cancer Saslow D, et al. CA Cancer J Clin 2007;57(2):75-89

32 ACS Recommendations: Screening Breast MRI Recommend against breast MRI screening for women with: Lifetime risk < 15% (i.e., average risk women) Saslow D, et al. CA Cancer J Clin 2007;57(2):75-89

33 Breast MRI is an adjunct to mammography and should not be used as stand alone screening test No mortality reduction has yet been shown with screening breast MRI

34 New Screening Modalities

35 Digital Mammography Electronic image generated that allows for computer storage and manipulation Study of 49,528 women receiving both film screen and digital mammography No difference in overall accuracy was seen Digital mammography significantly more accurate in younger women with dense breasts Study of women aged years randomly assigned to film or digital mammography Digital mammography resulted in higher rate of cancer detection Pisano ED, et al. Radiology 2008;246: Skaane P, et al. Radiology 2007;244:

approximately the same as one 2D mammogram Projection images are reconstructed into

36 Tomosynthesis: Principle of Operation X-ray tube moves in an arc across the breast A series of low dose images are acquired from different angles Total dose approximately the same as one 2D mammogram Projection images are reconstructed into 1 mm slices Reconstructed Slices { Arc of motion of x-ray tube, showing individual exposures

37 Breast Tomosynthesis (3D Mammography) Reconstructed slices eliminates tissue superimposition Improved visibility of mass lesions Decreases recall rates

38 Breast Tomosynthesis

39 Tomosynthesis: Clinical Performance Analysis of 281,187 digital mmg (DM) and 173,663 DM + tomo Lower recall rate DM 107/1000 (95% CI, ) DM + tomo 91/1000 (95% CI, ) Increase in invasive cancer detection rate DM 2.9/1000 (95% CI, ) DM + tomo 4.1/1000 (95% CI, ) No difference in the in situ cancer detection rate Adding tomosynthesis increased PPV Recall: 4.3% to 6.4% (diff.=2.1%; 95% CI, 1.7%-2.5%; P<.001) Biopsy: 24.2% to 29.2% (diff=5.0%;95% CI,3.0%-7.0%;P<.001) Friedewald SM. JAMA 2014;311(24):

40 Breast Ultrasound Increased detection of breast cancer (Cancers/1000 women screened) MMG only: 7.6 MMG + U/S: 11.8 Supplemental yield: 4.2 Increased false positives MMG only: 4.4% MMG + U/S: 10.4% Median scan time=19 min (+ 2 min spent with patient) Berg W, et al. JAMA 2008;299:

41 Screening Breast Ultrasound Ultrasound may be considered as supplemental screening in women at increased risk with dense breasts when breast MRI screening is not recommended or not possible LCIS or atypical hyperplasia Lifetime risk >20-25% that is not largely based on family history Women eligible for breast MRI who are claustrophobic or whose insurance does not cover breast MRI (note: Medicare does not cover screening breast ultrasound) There is insufficient evidence to support routine supplemental screening in women with dense breasts and no other risk factors Berg W, et al. JAMA 2008;299:

42 Molecular Breast Imaging

43 Positron Emission Mammography (PEM)

44 Breast Screening Summary Breast cancer screening is no longer one size fits all Recommendations personalized based on level of risk

45 Breast Cancer Screening Guidelines USPSTF American Cancer Society (ACS) National Comprehensive Cancer Network (NCCN) Age to Start Mammograms (individual choice 40-44) Interval 2 years Annual 45-54; 1-2 years 55+ Age to Stop Mammograms 74 Life Expectancy < 10 years 40 Annual Upper age limit not established

46 Workup of Common Breast Complaints

47 Breast Mass Differential Diagnosis Benign cyst Complex Cystic and Solid Mass Intraductal Papilloma Fibroadenoma Breast Cancer Imaging Diagnostic Mammogram and Breast Ultrasound if age >30 Breast Ultrasound if age <30 NCCN Breast Cancer Screening and Diagnosis Guidelines

48 Clinical Presentation Nipple Discharge - Spontaneous or Non-spontaneous - Color of discharge - Unilateral or Bilateral - Single duct or multiple duct Types of Nipple Discharge Milky Clear/Serosanguinous Bloody

49 Nipple Discharge Differential Diagnosis Physiological Drugs Intraductal papilloma Breast Cancer Imaging Diagnostic Mammogram and Breast Ultrasound Consider MRI Breast and/or ductogram

Suspicion of Paget s Disease Nipple Excoriation Scaling, eczema Skin

50 Clinical Presentation Skin Changes Clinical Suspicion of Inflammatory Breast Cancer Peau d orange Skin Thickening Edema Erythema Clinical Suspicion of Paget s Disease Nipple Excoriation Scaling, eczema Skin Ulceration NCCN Breast Cancer Screening and Diagnosis Guidelines

51 Questions?

Untangling the Confusion: Multiple Breast Cancer Screening Guidelines and the Ones We Should Follow

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