TY - JOUR
T1 - Screening for clonal hematopoiesis as a predictive marker for development of therapy-related myeloid neoplasia (t-MN) following neoadjuvant therapy for breast cancer
T2 - A Southwest Oncology Group study (S0012)
AU - Slovak, Marilyn L.
AU - Bedell, Victoria
AU - Lew, Danika
AU - Albain, Kathy S.
AU - Ellis, Georgiana K.
AU - Livingston, Robert B.
AU - Martino, Silvana
AU - Perez, Edith A.
AU - Hortobagyi, Gabriel N.
AU - Sher, Dorie
AU - Stock, Wendy
N1 - Funding Information:
Acknowledgments This investigation was supported in part by a grant from the Department of Defense, DOD # DAMD17-97-1-7088 and in part by the following PHS Cooperative Agreement grant numbers awarded by the National Cancer Institute, DHHS: CA32102, CA38926, CA58882, CA86780, CA14028, CA20319, CA52654, CA63845, CA379891, CA63844, CA22433, CA35431, CA76448, CA35176, CA58861, CA46441, CA35178, CA67575, CA45808, CA12644, CA11083, CA35192, CA76447, CA46282, CA45560, CA04919, CA45377, CA35090, CA74811, CA95860, CA35281, CA74647, CA76462, CA35128, CA76462, CA46136, and CA35119. The authors also thank Mr. Aaron Theisen for assistance in paper preparation.
PY - 2010/1
Y1 - 2010/1
N2 - A serious complication associated with breast cancer treatment is the increased risk for development of therapy-related myeloid neoplasms (t-MN). To determine whether dose-intensive adjuvant regimens for breast cancer induce genetic damage to hematopoietic stem cells, defined by the emergence of clonal hematopoiesis, and whether detection of clonal hematopoiesis could be used as an early marker for the subsequent development of t-MN, the Southwest Oncology Group designed a pilot clonality investigation to estimate the incidence of clonal hematopoiesis during and shortly after completion of the dose-intensive neoadjuvant regimens for high-risk breast cancer patients. Peripheral blood samples from 274 patients obtained prior to treatment, at time of surgery, and at 6 and 12 months post-surgery were examined by two different clonality assays: The HUMARA (HUMan Androgen Receptor) assay to estimate the incidence of early genetic damage by clonal proliferation, and microsatellite instability (MSI) testing to screen for LOH or defective DNA mismatch repair mechanisms. Clonal hematopoiesis was negative in 93.5% of the samples analyzed. Five patients showed a HUMARA-positive/MSI-negative pattern, and no patients showed a HUMARA-negative/MSI-positive pattern. With a median follow-up of 3.1 years, one patient in our study developed t-AML at 3 years 5 months after randomization. Our results indicate that clonal hematopoiesis assays performed within the 2 years following dose-intensive neoadjuvant therapy failed to identify an emerging clonal hematopoietic stem cell population. Longer clinical follow-up will be necessary to define better the positive predictive value of detecting clonal hematopoiesis in the HUMARA+/MSI- cases.
AB - A serious complication associated with breast cancer treatment is the increased risk for development of therapy-related myeloid neoplasms (t-MN). To determine whether dose-intensive adjuvant regimens for breast cancer induce genetic damage to hematopoietic stem cells, defined by the emergence of clonal hematopoiesis, and whether detection of clonal hematopoiesis could be used as an early marker for the subsequent development of t-MN, the Southwest Oncology Group designed a pilot clonality investigation to estimate the incidence of clonal hematopoiesis during and shortly after completion of the dose-intensive neoadjuvant regimens for high-risk breast cancer patients. Peripheral blood samples from 274 patients obtained prior to treatment, at time of surgery, and at 6 and 12 months post-surgery were examined by two different clonality assays: The HUMARA (HUMan Androgen Receptor) assay to estimate the incidence of early genetic damage by clonal proliferation, and microsatellite instability (MSI) testing to screen for LOH or defective DNA mismatch repair mechanisms. Clonal hematopoiesis was negative in 93.5% of the samples analyzed. Five patients showed a HUMARA-positive/MSI-negative pattern, and no patients showed a HUMARA-negative/MSI-positive pattern. With a median follow-up of 3.1 years, one patient in our study developed t-AML at 3 years 5 months after randomization. Our results indicate that clonal hematopoiesis assays performed within the 2 years following dose-intensive neoadjuvant therapy failed to identify an emerging clonal hematopoietic stem cell population. Longer clinical follow-up will be necessary to define better the positive predictive value of detecting clonal hematopoiesis in the HUMARA+/MSI- cases.
KW - Breast cancer
KW - Clonal hematopoiesis
KW - HUMARA
KW - MSI
KW - T-MN
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U2 - 10.1007/s10549-009-0597-5
DO - 10.1007/s10549-009-0597-5
M3 - Article
C2 - 19851858
AN - SCOPUS:75049085476
SN - 0167-6806
VL - 119
SP - 391
EP - 398
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 2
ER -