Evaluating Clonal Hematopoiesis in Tumor-Infiltrating Leukocytes in Breast Cancer and Secondary Hematologic Malignancies
Abstract
Chemotherapy and radiation therapy are the foundations of adjuvant therapy for early-stage breast cancer. As a complication of cytotoxic regimens, breast cancer patients are at risk for therapy-related myeloid neoplasms (t-MNs). These t-MNs are commonly refractory to antileukemic therapies and result in poor patient outcomes. We previously demonstrated that somatic mutations in leukemia-related genes are present in the tumor-infiltrating leukocytes (TILeuks) of a subset of early breast cancers. Here, we performed genomic analysis of microdissected breast cancer tumor cells and TILeuks from seven breast cancer patients who subsequently developed leukemia. In four patients, mutations present in the leukemia were detected in breast cancer TILeuks. This finding suggests that TILeuks in the primary breast cancer may harbor the ancestor of the future leukemogenic clone. Additional research is warranted to ascertain whether infiltrating mutant TILeuks could constitute a biomarker for the development of t-MN and to determine the functional consequences of mutant TILeuks.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 27, 2019
- Source ID
- 10.1093/jnci/djz157
Entities
People
- Abigail Alon
- Britta Weigelt
- Corinne E Hill
- Elizabeth A Comen
- Felipe C. Geyer
- Fresia Pareja
- Guray Akturk
- Jorge S Reis-Filho
- Larry Norton
- Maria Kleppe
- Noushin R Farnoud
- Pier Selenica
- Robert L Bowman
- Ross L Levine
Organizations
- American Society of Hematology
- European Molecular Biology Organization
- Leukemia & Lymphoma Society
- Memorial Sloan Kettering Cancer Center
- National Cancer Institute
- National Institutes of Health
- The Breast Cancer Research Foundation
- United States Department of Defense