S9719 Gene Damage Following Chemotherapy in Women With Stage II or Stage III Breast Cancer

Breast Cancer Clinical Trial

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

Status Completed

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy for breast cancer may damage the genes of cells. This may lead to the development of secondary cancers.

PURPOSE: Pilot study to evaluate the degree of gene damage following chemotherapy in women with stage II or stage III breast cancer involving four to nine axillary lymph nodes.

Clinical Trial Description

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. ;

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

• NCT number: NCT00003095
• Study type: Observational
• Source: Southwest Oncology Group
• Status: Completed
• Phase: N/A
• Start date: November 1997
• Completion date: February 2001