ABSTRACT: Breast cancer in Uganda presents a pressing public health challenge, characterized by late-stage diagnoses and high mortality rates, particularly among women residing in rural and semi-urban areas. This proposal addresses this critical issue by optimizing, validating, and deploying a point-of-care diagnostic kit, tailored for primary care clinics in Uganda, where most women access care. The proposed diagnostic kit combines (1) an FDA-cleared automated AI-enabled whole breast ultrasound and (2) a smartphone- enabled AI-powered device that performs brightfield imaging of basic cytology preparations and incorporates a self-contained immunodiagnostic chip to quantify breast tumor biomarkers. Our approach involves a two-fold validation strategy. First, we will validate the diagnostic performance of the proposed diagnostic kit in a U.S. clinical setting, comparing it to standard-of-care methods such as ultrasound, mammography, tissue sampling, and pathology (aim 1). Utilizing quality improvement cycles and feedback from end-users, we will refine the kit's performance and usability. Next, we will validate the kit at the Uganda Cancer Institute, tailoring it to Uganda's healthcare landscape, considering factors like infrastructure, health workers’ expertise, and accessibility (aim 2). Following validation, and guided by a Ugandan Community Advisory Board, we will implement a cluster randomized controlled trial involving eight community health centers (CHCs) across two health districts in Uganda (aim 3). A mobile breast cancer detection clinic will deliver the diagnostic kit to CHCs during bi-monthly Breast Health Days for N=1000 patients referred for diagnostic evaluation, at 4 CHCs. We will compare the effectiveness of the diagnostic kit with women receiving care at control CHCs, who will be referred for standard-of-care ultrasound at Regional Hospitals (N=1000). Our collaboration draws upon expertise in engineering and biomedical device development, breast cancer research, and global health, positioning us to significantly impact breast cancer outcomes in Uganda. This initiative aligns with the RFA-CA-24-005 mission to develop cancer-relevant technologies suitable for use in low- and middle-income countries. By validating and deploying a practical, cost-effective, and user-friendly detection and diagnostic technology, we aim to empower healthcare providers in Uganda and, ultimately, improve patient outcomes. If successful, this innovation stands to enhance access to timely breast cancer detection and diagnosis in resource- constrained settings.

PROJECT NARRATIVE Women with suspected breast cancer in low- and middle-income countries often face delayed diagnosis due to systemic barriers, leading to worse outcomes compared to developed countries. To fill this gap, we will determine whether a portable diagnostic kit for breast cancer that merges point-of-care technologies in both ultrasound imaging and molecular/cellular pathology can mitigate these barriers to timely diagnosis. The portable diagnostic kit will be deployed in clinical settings for women with breast cancer —first in U.S.-based settings, then in the intended population in Uganda— and evaluated against gold standard methods for the ability to visualize breast tumors and characterize their cellular/molecular pathology to guide treatment.