title: Systemic chemotherapy induces microsatellite instability in the peripheral blood mononuclear cells of breast cancer patients.
abstract: BACKGROUND
  Systemic chemotherapy is an important part of treatment for breast cancer. We conducted the present study to evaluate whether systemic chemotherapy could produce microsatellite instability (MSI) in the peripheral blood mononuclear cell fraction of breast cancer patients.
  
  
  METHODS
  We studied 119 sequential blood samples from 30 previously untreated breast cancer patients before, during and after chemotherapy. For comparison, we also evaluated 20 women who had no relevant medical history (control group).
  
  
  RESULTS
  In 27 out of 30 patients we observed MSI in at least one sample, and six patients had loss of heterozygosity. We found a significant correlation between the number of MSI events per sample and chemotherapy with alkylating agents (P < 0.0001). We also observed an inverse correlation between the percentage of cells positive for hMSH2 and the number of MSI events per sample (P = 0.00019) and use of alkylating agents (P = 0.019).
  
  
  CONCLUSIONS
  We conclude that systemic chemotherapy may induce MSI and loss of heterozygosity in peripheral blood mononuclear cells from breast cancer patients receiving alkylating agents, possibly mediated by a chemotherapy-induced decrease in the expression of hMSH2. These effects may be related to the generation of secondary leukaemia in some patients, and may also intensify the genetic instability of tumours and increase resistance to treatment.
authors.affiliation: ABC Foundation School of Medicine, Hematology and Oncology, Santo Andre, São Paulo, Brazil. ge.fonseca@uol.com.br
authors.forename: Fernando L A
authors.initials: FL
authors.lastname: Fonseca
authors.forename: Aleksandra V L
authors.initials: AV
authors.lastname: Sant Ana
authors.forename: Israel
authors.initials: I
authors.lastname: Bendit
authors.forename: Vitor
authors.initials: V
authors.lastname: Arias
authors.forename: Luciano J
authors.initials: LJ
authors.lastname: Costa
authors.forename: Aparecida A
authors.initials: AA
authors.lastname: Pinhal
authors.forename: Auro
authors.initials: A
authors.lastname: del Giglio
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D042822:Genomic Instability; D006801:Humans; D007150:Immunohistochemistry; D007963:Leukocytes, Mononuclear / Q000502:physiology; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D008875:Middle Aged
chemical_list: D018906:Antineoplastic Agents, Alkylating