An Integrated Clinical, Omic, and Image Atlas of an Evolving Metastatic Breast Cancer

Abstract

Metastatic cancers often respond to treatment initially but almost universally escape therapeutic control through molecular mechanisms intrinsic to tumor cells, as well as extrinsic influences from immune cells, stroma, and structural microenvironments. We explore the extent to which we can learn these mechanisms and associated therapeutic vulnerabilities by linking comprehensive molecular and multiscale imaging analyses of tumor biopsies to detailed clinical information for a patient with metastatic breast cancer. Our analyses of three serial biopsies include DNA, RNA, and protein profiling, plus quantification of tumor microenvironment composition using multiplex immunostaining and electron microscopy. Features from these analyses are linked to treatments and treatment-response measurements, including CT and PET images, circulating tumor DNA and tumor protein levels in blood, and treatment-limiting readouts of blood counts and liver function. Importantly, the measurement modalities unique to this study complemented routine diagnostics to suggest actionable mechanisms of response and resistance for each treatment phase.