Clonal Hematopoiesis as a Marker of Genetic Damage Following Adjuvant Chemotherapy for Breast Cancer: Pilot Study to Evaluate Incidence

Abstract

Dose intensive anthracycline-based adjuvant regimens improve disease-free survival in breast cancer patients; however, recent studies also show an increased risk for development of therapy-related hematologic malignancies. Models of leukemogenesis propose that clonal hematopoiesis may be an early marker of genetic damage, preceding the acquisition of critical, recurring genetic alterations associated with the development of therapy related myelodysplastic syndromes and acute leukemia. The goal of this study is to determine whether dose-intensive adjuvant regimens for breast cancer induce genetic damage to hematopoietic stem cells, defined by the emergence of clonal hematopoiesis in a subset of patients following dose-intensive adjuvant therapy for breast cancer. Clonal hematopoiesis will be evaluated using two different methods, the HUMARA clonality assay (based on a methylated X-linked polymorphism) and microsatellite instability assays. In year one, the following objectives were completed: (a) activation of the clonal hematopoiesis biological protocol (S9719), (b) introductory protocol presentations at the SWOG Fall 1997 and Spring 1998 meetings, (c) advertisements mailed to SWOG institutions including revisions of model consent form, (d) beginning of patient registration, (e) development of a centralized specimen collection/processing repository, (f) standardization of the HUMARA and microsatellite assays, and (g) addressing quality control and quality assurance issues.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Sep 01, 1998
Accession Number
ADA364724

Entities

People

  • Charles A. Coltman

Tags

DTIC Thesaurus Topics

  • Breast Cancer
  • Cells
  • Chemotherapy
  • Chromosomes
  • Diseases And Disorders
  • Drug Therapy
  • Genomic Instability
  • Health Services
  • Hematologic Diseases
  • Lymphatic Diseases
  • Lymphocytes
  • Medical Personnel
  • Neoplasms
  • Pilot Studies
  • Quality Control
  • Stem Cells
  • Therapy

Fields of Study

  • Medicine

Readers

  • Clinical Trial Research.
  • Molecular and genetic basis of cancer.

Technology Areas

  • Biotechnology