Protocol for a Pilot Trial to Implement Diagnostics for Clonal Hematopoiesis of Indeterminate Potential into Routine Clinical Care of Older Patients with Breast Cancer

Nina Rosa Neuendorff; Ann-Kathrin Bittner; Sara Flossdorf; Tessy Mauer; Florian Schmitz; Nils von Neuhoff; Johannes Köster; Felix Mölder; Amin T Turki; Rainer Kimmig; Hans Christian Reinhardt; Oliver Hoffmann; Bastian von Tresckow

doi:10.37155/2972-4759-2023-01-01-4

Authors

Nina Rosa Neuendorff University Hospital Essen
Ann-Kathrin Bittner Department for Gynaecology and Obstetrics, Breast Cancer Center, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, D-45147 Essen
Sara Flossdorf Institute for Medical Informatics, Biometry, and Epidemiology (IMIBE), University Hospital Essen, University of Duisburg-Essen, Zweigertstr. 37, D-45130 Essen
Tessy Mauer Department for Hematology and Stem Cell Transplantation, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, D-45147 Essen
Florian Schmitz Department of Psychology, University of Duisburg-Essen, Universitätsstraße 2, D-45141 Essen
Nils von Neuhoff Clinic for Pediatrics III, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, D-45147 Essen
Johannes Köster Institute of Human Genetics, University of Duisburg-Essen, University of Duisburg-Essen, Hufelandstraße 55, D-45147 Essen
Felix Mölder Institute of Human Genetics, University of Duisburg-Essen, University of Duisburg-Essen, Hufelandstraße 55, D-45147 Essen
Amin T Turki Department for Hematology and Stem Cell Transplantation, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, D-45147 Essen
Rainer Kimmig Department for Gynaecology and Obstetrics, Breast Cancer Center, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, D-45147 Essen
Hans Christian Reinhardt Department for Hematology and Stem Cell Transplantation, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, D-45147 Essen
Oliver Hoffmann Department for Gynaecology and Obstetrics, Breast Cancer Center, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, D-45147 Essen
Bastian von Tresckow Department for Hematology and Stem Cell Transplantation, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, D-45147 Essen

DOI:

https://doi.org/10.37155/2972-4759-2023-01-01-4

Keywords:

clonal haematopoiesis of indeterminate potential (CHIP), breast cancer, older adults, cardiovascular risk factors, survivorship

Abstract

Clonal hematopoiesis of indeterminate potential (CHIP) refers to the presence of a hematopoietic clone with a common leukemia driver mutation without diagnosis of an underlying hematopoietic disease. The prevalence of CHIP is increasing with age and is associated with pro-inflammatory states, higher risk of cardiovascular diseases (CVD) and therapy-induced leukemia. However, these CHIP-associated risks overlap with treatment-related toxicities of breast cancer therapy, which potentially supports the integration of CHIP into treatment- and survivorship plans. However, so far no data on the feasibility and acceptance of a CHIP-based aftercare are available.

In this pilot trial, the feasibility to integrate pre-treatment CHIP diagnostics into the routine care of breast cancer patients is evaluated. Early-stage breast cancer is common among older women and has an excellent long-term outcome. Thus, 80-100 patients with limited stage breast cancer aged ≥ 60 years without known hematological disease will be included. CHIP is assessed by targeted next generation sequencing from peripheral blood samples. The primary outcome measures the estimation of willingness to participate. Secondary outcome measures include evaluation of patient acceptance of the study process, potential fears in relation to CHIP-positivity, and cardiovascular risk profile of CHIP-positive versus CHIP-negative patients.

In case this study meets its primary endpoint, the results are used to design a larger cohort study that integrates an intensified CHIP-tailored survivorship program, in order to minimize late treatment-related toxicities and improve long-term outcomes of older breast-cancer patients.

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