Abstract PL03-02: When to intervene along the breast cancer continuum?

Abstract

Abstract Advances in epidemiology and cancer biology have clearly established that the group of diseases currently deemed “cancers” in fact encompasses many conditions with enormous variation in biologic behavior. Decades of cancer screening have preferentially diagnosed early, asymptomatic, indolent lesions. This trend will only increase as screening technologies become ever more sensitive, leading to an epidemic of overtreatment in completely asymptomatic individuals. The treatment of many of these conditions often has uncertain benefit on cancer mortality, while coming at the clear cost of treatment-related morbidity. Multi-omic testing plays a role in refining treatment recommendations based upon risk of progression. Genomic profiling of accurately annotated longitudinal case control datasets have provided insights into breast lesions termed “ductal carcinoma in situ” (DCIS), which are thought to be precursors to invasion and metastases. Both transcriptomics as well spatially resolved proteomic characterization of DCIS have uncovered novel biology of the epithelial cells that make up DCIS, as well as the heterogeneous precancer ecosystems which can be either permissive or inhibitory for invasion. Recent work has uncovered a clonal evolution pathway characterized by multiclonal invasion, and has helped to build risk stratification tools to refine treatment recommendations. In addition to molecular characterization, risk modeling may yield insights about which patients derive greatest benefit from intervention. For asymptomatic tumors at low risk of cancer progression, there may be little to no benefit to treatment, whereas for more high-risk lesions, progression to invasion and metastasis may be rapid and deadly. Given the lead-time between the development of precancer and progression to invasive disease, there may also be a case for tailoring intervention of screen detected cancer by age and the presence of competing comorbidities. The decision of whether and when to intervene for screen-detected cancers will require a multidisciplinary effort including expertise in cancer biology, mathematical modeling, psychology, health policy, decision science and communication, as well as thoughtful engagement from patients and health care providers to identify the optimal time to intervene along the cancer progression continuum. Citation Format: E. Shelley Hwang. When to intervene along the breast cancer continuum?. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr PL03-02.