Abstract
Ductal carcinoma in situ (DCIS) is the most commonly diagnosed precursor of invasive breast cancer (IBC), with variable propensity for progression. We have performed the first multiscale, integrated profiling of DCIS with clinical outcomes to identify predictors of subsequent ipsilateral breast events. We analyzed 677 DCIS samples from 481 patients with 7.1 years median follow-up from two independent cohorts. We made observations on DNA, RNA, and protein expression, and generated a de novo clustering scheme for DCIS that represents a fundamental transcriptomic organization at this early stage of breast neoplasia. Distinct DCIS stromal expression patterns and immune cell compositions were identified. We also found RNA expression patterns that correlate with later events in both cohorts. Our multiscale approach employed in situ methods to generate a spatially resolved atlas of breast precancers, where complementary modalities can be directly compared and correlated with conventional pathology findings, disease states, and clinical outcome.
Competing Interest Statement
CC serves on the Scientific Advisory Board and/or as a consultant for GRAIL, Deepcell, Ravel, Viosera, NanoString, Genetech and holds equity in GRAIL, Deepcell, Ravel. KP serves on the Scientific Advisory Board of Acrivon Therapeutics, Vividion Therapeutics, and Scorpion Therapeutics, holds equity in Scorpion Therapeutics and Vividion Therapeutics, is a consultant to Aria Pharmaceuticals, and received honorarium from Astra-Zeneca. RMA is an inventor on patent US20150287578A, and is a board member and shareholder in IonPath Inc. TR and RBW have consulted for IonPath Inc.