Grant Number:	2R01CA248068-06 Interpret this number
Primary Investigator:	Sprague, Brian
Organization:	University Of Vermont & St Agric College
Project Title:	Evaluation of Risk-Based Supplemental Ultrasound and Mri Screening Strategies for Women with Dense Breasts
Fiscal Year:	2025

PROJECT SUMMARY Approximately 43% of women undergoing breast cancer screening have mammographically dense breast tissue that absorbs x-rays and makes cancers difficult to visualize. A new FDA rule effective September 2024 requires radiology facilities to inform women with dense breasts that they should consider other imaging tests, in addition to a screening mammogram, to help find cancers earlier. However, no consensus guidelines regarding supplemental screening for women with dense breasts exist. Ultrasound and MRI are clinically available screening modalities, but policymakers cite inadequate evidence regarding their effectiveness and studies to date suggest that supplemental ultrasound or MRI screening of all women with dense breasts have poor benefit-to-harm profiles. We propose a new conceptual framework tailoring supplemental screening of women with dense breasts based on a women’s risk of being diagnosed with an advanced cancer despite regular mammography screening, which offers the potential to realize the benefits of early detection while limiting the number of women experiencing harms due to false-positive results. This competitive renewal extends our current project to evaluate both supplemental ultrasound and MRI screening, evaluate outcomes by screening round and advanced cancer risk, compare the effectiveness of supplemental screening to mammography alone in an emulated randomized trial, and use simulation modeling to evaluate lifetime outcomes of population-level screening strategies targeting supplemental screening based on advanced cancer risk. Our comprehensive study leverages data on over 1.5 million screening exams in the Breast Cancer Surveillance Consortium, a large alliance of breast imaging registries including 64 healthcare facilities performing supplemental ultrasound or MRI screening. Using data from breast cancer screening of women with dense breasts in routine clinical practice, we will (Aim 1) characterize supplemental ultrasound and MRI screening performance by screening round and by advanced breast cancer risk; (Aim 2) use an emulated trial causal inference framework to estimate the effectiveness of supplemental screening versus mammography alone, overall and according to advanced cancer risk; and (Aim 3) use the validated University of Wisconsin CISNET breast cancer simulation model to estimate lifetime benefits and harms associated with population- level risk-based supplemental screening strategies (Aim 3). Our results will identify women with dense breasts for whom the benefit-to-harm tradeoffs for supplemental screening are favorable. In the coming year, more than 27 million U.S. women will receive letters informing them that they have dense breasts and should discuss screening options with their providers, without any established consensus recommendations to guide them. Our findings will provide the rigorous and generalizable evidence that is needed by women, healthcare providers, and policymakers considering breast cancer screening options for women with dense breasts.