n Educational support from GE and Volpara n Reduce mortality n Healthy women will not be harmed

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1 Dense Breasts: What to Know and What to Do Wendie A. Berg, MD, PhD, FACR Professor of Radiology Magee-Womens Hospital of UPMC University of Pittsburgh School of Medicine Disclosures n I am a radiologist specializing in breast imaging n Hologic, General Electric Healthcare, Gamma Medica, Inc. provide equipment and research support to the institution n Unpaid Chief Scientific Advisor to DenseBreast-info.org n Educational support from GE and Volpara Basic Principles SCREENING n Early detection will alter the natural history n Reduce mortality n Earlier detection will allow more breast conservation, less harmful treatments n Healthy women will not be harmed n Test widely available, cost effective, well tolerated Survival by Invasive Tumor size at Detection Survival probability Time in years since diagnosis Mammo CBE 1-9 mm mm mm mm mm 50+ mm Tabar Rad Clin NA 2000;38: , via R. Edward Hendrick, PhD, U. Colorado 1

2 RCT Results in Women n Mammography is the only screening test for which randomized trials have been conducted n Mammography has been shown to reduce deaths due to breast cancer Randomized Trial Relative Risk 95% Confidence Interval HIP of NY Malmo Sw. 2 County Gothenburg Stockholm Edinburgh CNBSS Combined Combined results demonstrate a statistically significant 22% mortality reduction from invitation to screening RCT Results in Women Randomized Trial Relative Risk 95% Confidence Interval HIP of NY Malmo Sw. 2 County Gothenburg Stockholm Edinburgh CNBSS Age Trial (GB) Combined Nelson et al. meta-analysis released with the USPSTF guidelines demonstrated a statistically significant 15% mortality reduction Delay in Benefit of Screening Tabar L et al Lancet 2003;361: Life Expectancy 10-Year Horizon n Stop screening when life expectancy < 10 years n Healthiest quartile at age 85 n Comorbidities: Lowest quartile at age 70 n Applies to supplemental screening as well Walter LC and Covinsky KE. JAMA 2001;285:2570 2

3 Why isn t screening more effective at reducing mortality? n Nonparticipation n Diagnosed at young age before screening would have commenced n Cancer not detected n Cancer has already spread at time of detection Webb ML et al Cancer 2013 n Invasive breast cancers Partners Health dx , followed through 2007, median 12.5 yrs, 609 breast cancer deaths n Median age at dx of fatal cancer = 49 yrs n 118 (19.4%) deaths screen-detected ca n 60 (9.8%) from interval cancers (lumps) n 395 (64.9%) in women never screened n 36 (5.9%) in women screened > 2 yr prior n 71% of deaths in women without regular screening n Median age at diagnosis of fatal breast cancer is 49 Webb ML et al: Cancer 2013 epub n Women should participate in screening by age 40 n Improve efforts to identify high-risk women who may be diagnosed even earlier Supplemental Screening n At best, can reduce n 10% of breast cancer deaths due to interval cancers, palpable in the interval between screens n Another ~20% of deaths by earlier detection of screen-detected cancers Deaths n 34% of all deaths in women screened are due to interval cancers n 60% of deaths if dx < age 40 n 47% of deaths n 28% of deaths n 26% of deaths n 24% of deaths 70 or older Webb ML et al: Cancer 2013 epub

4 Reasons for Mammographic Nondetection n #1: Dense breasts n Benign appearing: seen and dismissed n Asymmetries n Benign-appearing mass n Stable calcifications n Overlooked n Calcifications, distortion n Rapidly growing cancer, not present on prior mammogram Reasons for Mammographic Nondetection n #1: Dense breasts Supplemental screen n Benign appearing: seen and dismissed n Asymmetries n Benign-appearing mass - Feedback n Stable calcifications n Overlooked CAD n Calcifications, distortion n Rapidly growing cancer, not present on prior mammogram Screen more often What is Breast Density? DENSE BREASTS n Dense tissue in a mammogram is comprised of ducts, glands and fibrous tissue from Courtesy Hologic Inc. Breast Density n Is determined on imaging: mammography or MRI, but also CT and ultrasound n Not related to the way the breast feels 4

5 Tabar Classification Low Risk Gram IT et al Eur J Radiol 1997;24: High Risk BI-RADS Density n Visual n A. Almost entirely fatty n B. Scattered fibroglandular density n C. Heterogeneously dense which could obscure detection of small masses n D. Extremely dense, which lowers the sensitivity of mammography A B C D Volumetric Density vs. 2D Visual Relative Risk n Risk of developing breast cancer for women with that risk factor compared to risk for women without that risk factor n Usually stated as risk with extremely dense vs. fatty breasts 100 BIRADS 1, 2, 3 and 4 from University of Virginia, courtesy Volpara, Inc. 5

6 Boyd, 1995 via J. Harvey, UVA Interval Cancer n Cancer diagnosed because of clinical symptoms in the interval between recommended screenings n Worse prognosis and worse outcome Relative Risk! None <10 % % 25 50% % >75% n ~Half of deaths in screened women who are diagnosed in their 40 s are due to interval cancers Interval Cancers and Breast Density Increased Deaths Density Odds Ratio 95% CI* < 10% % 2.1 (0.9, 5.2) 25-49% 3.6 (1.5, 8.7) 50-74% 5.6 (2.1, 15.3) 75% 17.8 (4.8, 65.9) Adjusted for age, BMI, parity, menarche, #childbirths, menopausal status, HRT use *p<0.001 Boyd NF, et al. NEJM 2007;356: Chiu SY et al. Cancer Epidemiol Biomarkers Prev 2010;19: n 25 yr f/u Sweden 15,658 women n 12.7% had dense breasts n Increased breast cancer mortality in women with dense breasts n RR 1.91 (95%CI ) n Attributed to higher incidence n Shorter sojourn time Dense Breasts, 25 Yr F/U Density Decreases with Age RR 95% CI Incidence Tumors > 2 cm Node Grade 2-3 tumor Death Chiu SY et al. Cancer Epidemiol Biomarkers Prev 2010;19: Age 52 Age 54 Courtesy Wendie Berg, MD, PhD 6

7 Breast Density as Function of Age Dense Breasts n Heterogeneously or extremely dense n > 1/2 of women < age 50 n > 1/3 of women age 50 n Dense tissue itself a risk factor: 3-6 X compared to fatty breasts n Mammographic sensitivity reduced: Masking n 30 to 48% in densest breasts n Digital mammography slightly better than film Kerlikowske et al. JNCI 2007; 99: Harvey and Bovbjerg Radiology 2004;230:29-41 Boyd NF et al NEJM 2007;356: Hormones Increase Density Additive Risk of HT and Density n Combination estrogen (E) and progesterone (P) therapy increases breast density n Increases risk for breast cancer Kerlikowske K et al J Clin Oncol 2010; 28: Fatty Minimal Hetero Ext Dense Premenopausal Post, no HT Post, E use Post, E+P RR stage III or IV disease in post-menopausal nonusers 1.75 RR stage III or IV disease in post-menopausal HT users What is the referent standard? n Average woman has scattered fibroglandular density n Relative to average, extreme breast density only 1.5-2X risk Biennial vs. Annual Mammography, Extremely Dense Kerlikowske K et al JAMA Int Med 2013:173: Stage IIB, III, IV Tumor Size > 2 cm Node positive yrs no HT 1.89 ( ) 2.39 ( ) 1.34 ( ) 1.21 ( ) 1.10 ( ) 1.14 ( ) E+P 1.56 ( ) 1.59 ( ) 1.05 ( ) 7

8 Outcomes from Dense Breasts 48F screening n Cancer more often found as a lump n Clinically detected in interval between screens n Increased risk of recurrence (if no XRT) n More often stage IIb, III n More often multifocal, multicentric, mastectomy more often needed n May increase risk of death from breast cancer (requires very long term follow-up) Courtesy Dr. Wei Yang, MD Anderson n Stereotactic biopsy: High nuclear grade DCIS solid type with comedo necrosis, with microinvasion, ER, PR-, HER2 + n Skin-sparing mastectomy, 0/4 SLN RT CC MAG RT ML MAG Courtesy Dr. Wei Yang, MD Anderson BREAST DENSITY INFORM LAWS 24 states require notification: 67% of USA population 8

9 PA Act 86 PA 86 n Effective 1/30/14, each mammography report shall include written notification of breast density based on BI-RADS This notice contains the results of your recent mammogram, including information about breast density. If your mammogram shows that your breast tissue is dense, you should know that dense breast tissue is a common finding and is not abnormal. Statistics show many women could have dense or highly dense breasts. Dense breast tissue can make it harder to find cancer on a mammogram and may be associated with an increased risk of cancer. This information about the result of your mammogram is given to you to raise your awareness and to inform your conversations with your physician. Together, you can decide which screening options are right for you, based on your mammogram results, individual risk factors or physical examination. A report of your results was sent to your physician. Possible tests to add to mammography SUPPLEMENTAL SCREENING Modality vs. Mammography alone Absolute Cancer Detection per 1000 screens Clinical breast exam 0.3 Double Read 1 CAD 1 Tomosynthesis 1-2 Ultrasound 2-4 Molecular Breast 8 Imaging, CE-Mammo MRI 10 Summary Screening Results by Modality/Combination Berg WA, AJR 2009;192:390 n 36% cancers seen on mammography n 40% cancers seen on US n 64% cancers seen if both mammo+us n 81% cancers seen on MRI n 93% cancers seen if both mammo+mri How Do We Measure Impact of Supplemental Screening? n Reduction in interval cancer rate n Ideally fewer than 10% of all cancers n Reduction in # node-positive cancers n Reduction in stage II-IV disease 9

10 Standard Mammography Tube TOMOSYNTHESIS Compression paddle Detector Courtesy Rita Zuley, MD Digital close up Tomosynthesis close up Compression paddle Detector Invasive Ductal CA Courtesy Rita Zuley, MD Rafferty EA et al. Radiology 2013, 266: Tomo n 120 µm resolution vs. 70 µm 2D n 4 to 7 sec acquisition vs. 1-3 sec: greater potential for motion n Radiation dose to pt similar to single 2D digital mammogram: 2X dose if have both n FDA requires standard 2D mammogram in addition to tomo ( combo mode): can be created synthetically from projection images if facility has the software 40F with lump noted after fall on bicycle 10

11 Single slices from tomosynthesis Sagittal post-contrast MRI Multifocal grade 3 IDC (ER, PR, HER2 positive) Oslo Screening Trial: Interim Analysis Addition of 3D (Tomo) Added Cancers Detected Tomo Cancer Detection Rate False positive rate Time to interpret 2D alone 2D+3D Diff. P-value 6.1/ / / % 5.3% -0.8% < sec 91 sec +46 sec <.001 Skaane P et al Radiology, e-pub 1/7/2013 n 1.9 per 1000 n Nearly all invasive n 83% (19/23) with node staging N0 n 60% grade 1 n 68% spiculated masses or distortions n Same detection benefit for each category of breast density n Requires soft tissue contrast: Likely less effective if extremely dense Skaane P et al Radiology, e-pub 1/7/

12 Tomosynthesis Performance Study Design ICDR per 1000 Absolute Change in Recall Rate Skaane 2013 Prospective % Ciatto 2013 Prospective % Rose 2013 Historical control % Friedewald 2014 Historical control % Greenberg 2014 Historical control % Overall % Unanswered Questions Tomo Close up of 2D Synthetic 2D from 3D acquisition: C view n Yield from annual (incidence) screening n Interval cancer rate, esp. in dense breasts n Yield from US after tomo (do patients benefit from both) n Preliminary data suggest CDR of HHUS after tomo of ~2/1000 n Hooley RJ et al 12/5/13 RSNA SS Arie Crown MRI Screening High-Risk Women: MRI Women w/cancer Mammo (%) US (%) MRI (%) Hartman NP 1 (100) Warner (36) 7 (32) 17 (77) Kuhl (33) 17(40) 39 (91) Leach (40) NP 27 (77) Lehman (25) NP 4 (100) Kriege (31) NP 34 (76) Sardanelli (60) 9 (60) 13 (87) Lehman (33) 1 (17) 4 (67) Hagen (38) NP 16 (76) TOTAL (36) 34/86 (40) 155 (81) From Berg WA, AJR 2009;192:390 12

13 MRI Recommended for High-Risk Women n Of 192 women with cancer, 158 (82%) were invasive, 24 of those (15%) node positive n Across series: 2 cancers only on US in 1037 women vs. 31 only on MRI n No need for screening US if patient is having MRI From Berg WA, AJR 2009;192:390 Annual MRI in addition to mammography n BRCA mutation carrier n First degree relative of BRCA carrier but untested n Lifetime risk of 20-25% or greater as estimated by risk model (e.g. Claus, BRCAPRO, Tyrer- Cuzick, BOADICEA) n Prior chest radiation age Saslow et al. Ca Cancer J Clin 2007;57:75 When to Start Screening Women at Increased Risk n When risk is equivalent to a woman at age yr Probability (%) of Breast Cancer Age Relatives with Breast Cancer BRCA 1 None One 1º Two 1º carrier BRCA 2 carrier Unknown Unknown Berg WA; AJR 2009;192: When to Start Screening n BRCA-1 carriers: begin at age 25 n BRCA-2 carriers: start by age 30 n Radiation risk of mammography highest at young age, prevalence of dz lowest n Avoid mammography before age 30 n Annual MRI only for BRCA carriers under 30 Efficacy MRI Ellen Warner et al. JCO 2011;29: n Women with pathogenic BRCA mutations n Not all women can have MRI n 445 in MRI group n 830 controls matched for age and mutation n Mean 3.2 yr follow-up NCCN Genetic/Familial High Risk Assessment: Breast and Ovarian Updated 2/28/

14 Stage Distribution of Cancers MRI Cohort N=41 Controls N=77 Mean Age DCIS 24% 12% Invasive, mean 0.9 cm 1.8 cm 1 cm 74% 35% > 2 cm 3% 29% Node + 13% 40% Warner, E. et al. JCO 2011;29: Cumulative Incidence MRI Group (%) Control Group (%) P- value DCIS or 13.8 (9.1 to 18.5) 7.2 (4.5 to 9.9).01 Stage I Stage II to IV 1.9 (0.2 to 3.7) 6.6 (3.8 to 9.3).02 Hazard ratio for development of stage II-IV breast cancer associated with MRI screening was 0.30 (0.12 to 0.72, p=.008) Approximately 2% more women dx with cancer in the MRI group Warner E et al JCO 2011;29: Interval Cancers: MR Screening Benchmarks Screening MRI BRCA1 BRCA2 Women Women-Yrs Cancers Interval 8 2 Cancers Interval Ca 3.6/ /1000 Rate % Interval Ca 10.9% 3.9% Heijnsdijk EAM et al Cancer Epidemiol Biomarkers Prev2012;21: UK, Dutch, Canadian trials combined n Cancer detection rate 10/1000 n Percent node-negative >80% n Minimal cancer ( 1 cm or DCIS) >50% n Recall rate 10-15% n PPV3 (of biopsy) 20-50% n Sensitivity >80% n Specificity 85-90% Morris EA et al BI-RADS: MRI (ACR, Reston), 2013 Insufficient Evidence for or Against MRI n Lifetime risk of 15-20% by risk model n LCIS/ALH (LIN) or ADH n Personal history of breast cancer n Dense breasts Saslow et al. Ca Cancer J Clin 2007;57:75 Worse Outcomes with PHBC? Houssami NH et al JAMA 2011;305: Interval Ca Rate per 1000 Node Positive interval ca Interval Ca Stage IIB* PHBC No PHBC P-value 3.6 ( ) 1.4 ( ) < % 29.0% 21.4% 17.9% *% advanced stage after excluding cases with missing stage 14

15 PHBC Mammography Outcomes Berg W et al JAMA 2012;307: n More interval cancers and lower sensitivity of mammography in women with PHBC n But, no difference in rates of node positive or advanced stage disease n ACRIN 6666: 612 women had MRI after 3 rounds of screening mammo+us n Overall yield 15/1000 of MR n 7.3 per 1000 in women with PHBC n 26.7 per 1000 in women without PHBC n Supplemental MRI less likely to prompt unnecessary recall or biopsy for PHBC n Sensitivity and specificity > for PHBC vs. those with other risk factors 607 women with PHBC, negative mammogram, screening MR n 18.1 cancers per 1000 n Sensitivity of MR 91.7% n Specificity of MR 82.2% n Modeling suggests all women treated with BCT and dx age 50 meet the 20% LTR threshold for screening MR (assuming at least 10-yr life expectancy) Gweon et al. Radiology 2014;272: MRI Screening Average Risk Women Schrading S et al SABCS Dec n 1705 MRI exams (mix of prevalent and incident screens), no personal or family hx of breast or ovarian cancer or dx of atypia, normal mammograms; 89% had US (-) n 54/1705 (3.2%) suspicious findings biopsied n 18/54 (33%) malignant n ICDR 10.6 per 1000 n 11/18 (61%) invasive, median size 10 mm, N0 51F with no known risk factors MRI Screen-Detected Courtesy Dr. Simone Schrading Courtesy Dr. Simone Schrading 15

16 n Why isn t screening MRI offered to everyone? n Cost n Availability of equipment/personnel n Injection of contrast n Renal function n Pacemaker, some other metal implants Courtesy Dr. Simone Schrading FAST MR FAST MR Performance FAST MR Full Diagnostic Protocol MIP MIP Single post-contrast sequence One pre- and three postcontrast sequences STIR/T2W 3 min table time 17 min table time 30 sec reading time 90 sec reading time FAST MR FULL PROTOCOL Sensitivity 11/11 (100) 11/11 (100) Specificity 561/595 (94.3) 559/595 (93.9) Recall rate 45/606 (7.4) 47/606 (7.8) PPV of recall 11/45 (24.4) 11/47 (23.4) BI-RADS 3 rate 53/606 (8.7) 33/606 (5.4) Kuhl CK et al JCO 2014;32: Kuhl CK et al JCO 2014;32: n 7/11 (64%) cancers invasive; all invasive cancers T1N0 n 10/11 not seen prospectively on US n 1/11 not seen on targeted US after MR n None were grade 1 n No interval cancers n Abbreviated MR protocol requires further validation n Prospective trial in development (ACRIN/ ECOG) Kuhl CK et al JCO 2014;32:

17 Unable to Tolerate MRI Supplemental US n 18.5% (1 in 5.4) (95% CI 16.4 to 20.8%) of high-risk women who had completed 3 years of annual screening with US and mammography were unable to undergo an MRI n Physician Performed n Technologist Performed n Automated Berg WA et al. Radiology 2010;254:79-87 Handheld US n High-frequency transducer, MHz linear array n Survey scanning transverse and sagittal n Document 1 image per quadrant, 1 behind nipple for negative exam n Lesions (all studies to date): Orthogonal views ± calipers; optional color or power Doppler image n Positive test: BI-RADS 3 or higher assessment, or recommendation for further imaging (BI- RADS 0) Physician Performed US: Multicenter Results Author N screens ICDR per 1000 Recall Rate (%) Bx Rate (% women) PPV3 Bx Performed Corsetti NS 449 (4.9) 50/623 (8.0) Berg yr (15.1) 207 (7.8) 14/264 (5.3) Berg (7.4) 242 (5.0) 21/276 (7.6) yr2-3 TOTAL 16, % 898 (5.4) 85/1163 (7.3) 4.9% of women had biopsies for benign findings Tech-Performed US (USA): Prevalent Screens Is the ICDR Lower for Technologist- Performed US? Author N ICDR per 1000 Recall Rate (%) Bx Rate (%) PPV3 Bx Performed Kaplan, , (9.5) 97 (5.2) 6/96 (6.3) Hooley, * (23.8) 46 (7.1) 3/58 (5.2) Weigert, , ,196 (13.8) 429 (5.0) 25/418 (6.7) Parris, , (12.3) 185 (3.3) 10/181 (5.5) Overall 16, ,206 (13.2) 757 (4.5) 47/753 (6.2) n Direct prospective comparison of technologistand physician-performed HHUS has not been performed n 2.5 vs. 4.3 per 1000 on prevalent screens (p<. 0067) n Likely due to differences in disease prevalence with broader populations screened *analysis presented for women with negative screening mammograms Berg WA and Mendelson EB. Radiology 2014;272:

18 Disease Prevalence Affects Yield Node-Negative Invasive Cancers Kolb 2002 Crystal 2003 Moderate Risk* No Known Risks P-value 14/2914 (4.8 per 1000) 14/7901 (1.8 per 1000).011 4/318 (12.5 per 1000) 3/1199 (2.5 per 1000) <.04 n Across 10 series, 475 cancers seen only on US, 415 (87.4%) invasive n 273/303 (90.1%) with staging were node negative n 22/91 (24%) ILC Overall 18/3232 (5.6 per 1000) 17/9100 (1.9 per 1000) *Personal hx of breast cancer or first-degree relative with breast cancer vs. no risks Types of Cancers Found with Screening US Bae MS et al Cancer Sci 2011;102: (Korea) US Mammo P-value N Age (mean, yrs) <.0001 BCT 84.4% 68.4% <.0001 Invasive 81.2% 73.5% <.0001 Mean invasive size 1.3 cm 1.7 cm <.0001 N <.0001 More likely US detected: < 1 cm (RR 2.2); luminal A vs. Her-2+; 3.7x more likely to have dense breasts; 89% of US-detected cancers were in dense breasts (vs. 65% of mammo-detected) By Participant, Yield/1000, ACRIN 6666 Year M+US M Supp. Yield, 95% CI P-value (2.1, 8.4) (0.9, 6.4) (0.9, 6.8).004 Supplemental yield of US is significant each year and similar for incidence and prevalence screens Berg WA et al JAMA 2012;307: Radial Antiradial 60F, 5-yr risk 2.5%, 24-mo US: 12 mm grade 1 IDC-DCIS, N0 70F personal hx rt mastectomy, BRCA-1 mutation carrier 24 mo screen US+ 19 mm grade 3 IDC-DCIS, N0 Courtesy WP Evans, III, MD Courtesy Dr. Mary Mahoney, U Cincinnati 18

19 ACRIN 6666: Breast Density Density n Yield per % P-value 26-40% % % >80% Berg WA, et al., RSNA 2009 Berg W et al JAMA 2012;307: Mammo Combined Mammo+ US Difference CDR per 1000 PHBC No PHBC Sensitivity PHBC 55.9% 84.7% 28.8% No PHBC 50% 78.8% 28.8% Specificity PHBC 91.4% 83.1% -8.3% No PHBC 89.4% 77.8% -11.6% Recall rate PHBC 9.3% 17.9% 8.6% No PHBC 11.1% 23.0% 11.9% Bx Rate PHBC No PHBC PPV3 PHBC No PHBC Berg W et al JAMA 2012;307: Interval Cancer Rate: ACRIN 6666 n Supplemental yield and sensitivity of US same in women with PHBC as without n Supplemental US less likely to cause unnecessary recall or biopsy in women with PHBC than those without n Study supports the use of annual supplemental screening with ultrasound in addition to mammography Yr N Interval N Cancers (%) All Interval Ca Rate: 9/7473 screens = 1.2 per % of all cancers Berg WA et al JAMA 2012;307: Interval Cancer Rate Italy Benchmarks HH Screening US Corsetti V et al Cancer 2011;47: n Interval cancer rate in fatty breasts n 1.0 per 1000 n Interval cancer rate in dense breasts after adding screening US n 1.1 per 1000 n Cancer detection rate 3-4/1000 n Percent node negative 85% n Minimal cancer ( 1 cm or DCIS) 50% n Recall rate 8-15% n PPV3 10% n Sensitivity? n Specificity 85-90% 19

20 Semi-Automated US Automated Arm Results A Tower B Y-axis Gantry & Transducer Carrier C X-axis Gantry D Ultrasound Machine Monitor E Touch Screen / Monitor F Transducer Holster G Patient Bed Kelly KM et al Eur Radiol 2010; 20: n 4419 women, 6425 exams, 8 facilities n 40% women at intermediate risk n 23 cancers mammography n 46 cancers M+US n Supplemental yield 3.6 per 1000 (95% CI 2.3 to 5.4) n 10% recall rate n 23/75 (31%) biopsies prompted only by ABUS showed cancer Automated Breast US n 12 MHz n 15 cm footprint n 3 acquisitions in ~15 minutes n 3D dataset n Transverse n Created coronal and sagittal displays ABUS Results Three-Step Implementation Brem RF et al RSNA 2012; Tabar L et al Radiology 2015 n 15,000 women BI-RADS 1 or 2 mammo, dense breasts, automated whole breast US n 30 (2/1000) cancers only by ABUS n 25 detailed: 23 (92%) invasive, mean size 13 mm, 18 (78%) of those N0 n 20/23 (87%) ER+ n 3/22 (14%) stage IIB or higher n 13% absolute increase in recall rate n 1) Does the woman have at least 10-yr life expectancy? n No, then CBE only, with mammography only if warranted by symptoms 20

21 n 2) Is the patient at high risk for breast cancer and under age 60-70? n Yes, then MRI annually beginning: n When ascertained to be high risk n Age 25 if BRCA1/2 or other pathogenic mutation n 8yr prior to chest XRT n If unable to tolerate MRI, then US n 3) Dense? n Yes: Option to supplement annual mammography with US beginning at age 40 n No: Tomosynthesis beginning at age 40 Get Smart About Being Dense Iceland-Bargmundsson 21