S9719 Gene Damage Following Chemotherapy in Women With Stage II or Stage III Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Observational

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.
    

Detailed 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.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Must be enrolled in SWOG-9623 at time of registration to this study, but must not have
        started treatment Hormone receptor status: Not specified
      
Biospecimen description: 
      tissue and blood
    
Keywords: stage II breast cancer; stage III breast cancer