Dataset Information

Toronto Workshop on Late Recurrence in Estrogen Receptor-Positive Breast Cancer: Part 2: Approaches to Predict and Identify Late Recurrence, Research Directions.

ABSTRACT: Late disease recurrence (more than 5?years after initial diagnosis) represents a clinical challenge in the treatment and management of estrogen receptor-positive breast cancer (BC). An international workshop was convened in Toronto, Canada, in February 2018 to review the current understanding of late recurrence and to identify critical issues that require future study. The underlying biological causes of late recurrence are complex, with the processes governing cancer cell dormancy, including immunosurveillance, cell proliferation, angiogenesis, and cellular stemness, being integral to disease progression. These critical processes are described herein as well as their role in influencing risk of recurrence. Moreover, observational and interventional clinical trials are proposed, with a focus on methods to identify patients at risk of recurrence and possible strategies to combat this in patients with estrogen receptor-positive BC. Because the problem of late BC recurrence of great importance, recent advances in disease detection and patient monitoring should be incorporated into novel clinical trials to evaluate approaches to enhance patient management. Indeed, future research on these issues is planned and will offer new options for effective late recurrence treatment and prevention strategies.

SUBMITTER: Dowling RJO

PROVIDER: S-EPMC7050024 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Toronto Workshop on Late Recurrence in Estrogen Receptor-Positive Breast Cancer: Part 2: Approaches to Predict and Identify Late Recurrence, Research Directions.

Dowling Ryan J O RJO Sparano Joseph A JA Goodwin Pamela J PJ Bidard Francois-Clement FC Cescon David W DW Chandarlapaty Sarat S Deasy Joseph O JO Dowsett Mitch M Gray Robert J RJ Henry N Lynn NL Meric-Bernstam Funda F Perlmutter Jane J Sledge George W GW Thorat Mangesh A MA Bratman Scott V SV Carey Lisa A LA Chang Martin C MC DeMichele Angela A Ennis Marguerite M Jerzak Katarzyna J KJ Korde Larissa A LA Lohmann Ana Elisa AE Mamounas Eleftherios P EP Parulekar Wendy R WR Regan Meredith M MM Schramek Daniel D Stambolic Vuk V Whelan Timothy J TJ Wolff Antonio C AC Woodgett Jim R JR Kalinsky Kevin K Hayes Daniel F DF

JNCI cancer spectrum 20190810 4

Late disease recurrence (more than 5 years after initial diagnosis) represents a clinical challenge in the treatment and management of estrogen receptor-positive breast cancer (BC). An international workshop was convened in Toronto, Canada, in February 2018 to review the current understanding of late recurrence and to identify critical issues that require future study. The underlying biological causes of late recurrence are complex, with the processes governing cancer cell dormancy, including im ...[more]

PMID: 32337478

Similar Datasets

Project description:The adverse effects of chemotherapy on normal cells of the body create substantial clinical problems for many cancer patients. However, relatively little is known about the effects, other than promotion of cell death, of such agents on the function of normal precursor cells critical in tissue homeostasis and repair. We have combined mathematical and experimental analyses to identify the effects of sublethal doses of chemotherapy on glial precursor cells of the central nervous system. We modeled the temporal development of a population of precursor and terminally differentiated cells exposed to sublethal doses of carmustine (BCNU), a classic alkylating chemotherapeutic agent used in treatment of gliomas and non-Hodgkin's lymphomas, as a multitype age-dependent branching process. We fitted our model to data from in vitro clonal experiments using the method of pseudo-likelihood. This approach identifies several novel drug effects, including modification of the cell cycle length, the time between division and differentiation, and alteration in the probability of undergoing self-renewal division in precursor cells. These changes of precursor cell function in the chemotherapy-exposed brain may have profound clinic implications.We applied our computational approach to analyze the effects of BCNU on clonal cultures of oligodendrocyte progenitor cells-one of the best-characterized neural progenitor cells in the mammalian brain. Our analysis reveals that transient exposures to BCNU increased the cell cycle length of progenitor cells and decreased their time to differentiation, while also decreasing the likelihood that they will undergo self-renewing divisions. By investigating the behavior of our mathematical model, we demonstrate that precursor cell populations should recover spontaneously from transient modifications of the timing of division and of differentiation, but such recovery will not happen after alteration of cell fate. These studies identify means by which precursor cell function can be critically compromised by transient exposure to chemotherapy with long-term consequences on the progenitor cell pool even in the absence of drug-induced apoptosis. These analyses also provide novel tools that apply broadly to identify effects of chemotherapeutic agents and other physiological stressors.

Dataset Information

Toronto Workshop on Late Recurrence in Estrogen Receptor-Positive Breast Cancer: Part 2: Approaches to Predict and Identify Late Recurrence, Research Directions.

Publications

Toronto Workshop on Late Recurrence in Estrogen Receptor-Positive Breast Cancer: Part 2: Approaches to Predict and Identify Late Recurrence, Research Directions.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets