1. Tolerability of Breast Cancer Screening, Diagnostic and Biopsy Procedures: An ACRIN 6666 Substudy Mark D. Schleinitz, MD, MS Dina DePalo Jeffrey Blume, PhD Jean Cormack, PhD Etta D. Pisano, MD Wendie A. Berg, MD, PhD

2. Funding Avon Foundation NCI U01 CA079778, U01 CA89008

3. Background In women at elevated risk with mammographically dense breasts the addition of US: –Improves cancer detection –Increases rates of additional imaging and biopsies What is the trade-off between improved cancer detection and increased healthcare utilization?

4. Objectives To estimate the tolerability of imaging and biopsies To compare these results across procedures To determine if patient factors affect tolerability To combine tolerability with survival

5. Methods: Process Utility Place test tolerability on same scale as benefits (survival) Waiting time trade-off –How long (in days) would you wait to get results and avoid procedure? –How do you feel about waiting? –Combined via multiplication Swan, Med Decis Making 2000, 2006

6. Methods: Combine with Survival CISNET models of mammography screening strategies –Survival gain –Procedures incurred Use our data to scale QOL impact of: –Screening –Additional imaging –Negative biopsies Mandelblatt, Ann Intern Med, 2009

7. Results: Imaging Process Utilities in Days ScreeningDiagnostic MammogramUSMRIMammogramUS N=109 N=110N=108 Median (IQR) 0.6 (0.1-1.6) 0.4 (0.03-1.0) 1.7 (0.6-4.4) 0.5 (0.1-2.2) 0.5 (0.05-1.4) Mean (SD) 3.6 (10.3) 2.4 (7.5) 4.9 (11.5) 5.4 (35.2) 1.0 (1.8)

8. Results: Biopsy Process Utilities in Days US-Guided Core Stereotactic Core MRI-guided Core Excisional N=103N=47N=9N=42 Median (IQR) 1.5 (0.4-4.6) 1.5 (0.4-3.7) 1.9 (0.4-3.8) 2.2 (0.6-3.8) Mean (SD) 7.9 (37.9) 4.9 (9.4) 6.6 (12.5) 10.3 (28.3)

9. Results: Patient Factors Procedures better tolerated by: –Women with prior cancer –Women over 50 –Post-menopausal women

10. Results Benefits /1000 women vs. no screening Procedures / 1000 women StrategyCancer Deaths Averted Life-years gained MammogramsAdditional imaging Negative Biopsies Biennial 50-74 7.512111,10994066 Biennial 40-69 6.112013,8651,25088 Annual 50-69 7.313217,7591,35095 Annual 50-74 9.515621,3571,570110 Annual 40-69 8.316427,5832,250158 Mandelblatt, Ann Intern Med, 2009 QOL toll (QALYs) MeanMedian 124.419.8 156.425.0 196.431.4 235.337.7 307.549.1

11. Limitations Generalizability –Elevated risk –Dense breasts –SES –Trial participants –MRI participation rate Methodologically –Timing of procedures

12. Conclusions US better tolerated than mammography MRI less well-tolerated still Tolerability, especially for induced procedures, should be considered in setting policy Variability high, policy may not apply to all