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

Funding

• Avon Foundation

• NCI U01 CA079778, U01 CA89008

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?

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

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

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

Results: Imaging

Process Utilities in Days

Screening Diagnostic

Mammogram US MRI Mammogram US

N=109 N=109 N=110 N=108 N=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)

Results: Biopsy

Process Utilities in DaysUS-Guided

CoreStereotactic

CoreMRI-guided

CoreExcisional

N=103 N=47 N=9 N=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)

Results: Patient Factors

• Procedures better tolerated by:

– Women with prior cancer

– Women over 50

– Post-menopausal women

ResultsBenefits /1000 women

vs. no screeningProcedures / 1000 women

Strategy Cancer Deaths Averted

Life-years gained

Mammograms Additional imaging

Negative Biopsies

Biennial 50-74

7.5 121 11,109 940 66

Biennial 40-69

6.1 120 13,865 1,250 88

Annual 50-69

7.3 132 17,759 1,350 95

Annual 50-74

9.5 156 21,357 1,570 110

Annual 40-69

8.3 164 27,583 2,250 158

Mandelblatt, Ann Intern Med, 2009

QOL toll (QALYs)

Mean Median

124.4 19.8

156.4 25.0

196.4 31.4

235.3 37.7

307.5 49.1

Limitations

• Generalizability– Elevated risk– Dense breasts– SES– Trial participants– MRI participation rate

• Methodologically– Timing of procedures

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