Trial Information

S9719: Clonal Hematopoiesis as a Marker of Genetic Damage Following Adjuvant Chemotherapy for Breast Cancer: Pilot Study to Evaluate Incidence. Ancillary to S9623

OBJECTIVES: I. Estimate the incidence of early genetic damage, defined by the presence of
clonal hematopoiesis using the human androgen receptor assay (HUMARA), in pretreatment blood
and bone marrow, apheresis, and two sequential post-treatment specimens from women with
stage II/III breast cancer enrolled in SWOG-S9623. II. Detect genetic damage following
dose-intensive adjuvant regimens for breast cancer by screening for the presence of
defective DNA mismatch repair mechanisms and loss of heterozygosity using microsatellite
instability assays. III. Estimate the incidence of myeloid lymphoid leukemia gene fusion
transcripts in cases where either the HUMARA or microsatellite repeat assays are positive
for clonal hematopoiesis. IV. Determine the frequency of RAS gene mutations (H-, K-, and
N-RAS) following dose-intensive adjuvant regimens for breast cancer.

OUTLINE: Prior to beginning treatment on SWOG-9623, blood samples and bone marrow aspirates
(when available) are collected from each patient. Patients randomized to autologous
peripheral stem cell transplant have specimens collected again at 3 months (apheresis
aliquot and blood). At 3 and 12 months after completing chemotherapy, blood samples are
collected from all patients. Samples are collected again from any patient presenting with a
second malignancy in the future. DNA is collected from blood or bone marrow samples.
Clonality at the HUMARA locus is examined. Microsatellite instability is assessed at
multiple chromosomal loci: 7q31, 5q31, 17p12, 8p22, 11q23, and the BAT loci. If the HUMARA
or microsatellite repeat assays are positive for clonal hematopoiesis, then specimens are
examined for myeloid lymphoid leukemia fusion transcripts commonly reported in acute myeloid
leukemia with 11q23 abnormalities. Specimens are also examined for RAS mutations (H-, K-,
N-RAS). Patients do not receive the results of the genetic testing and the results do not
influence the type or duration of treatment.

PROJECTED ACCRUAL: This study will accrue 100 patients for each arm of SWOG-9623, for a
total of 200 patients.