Cytogenetic outcomes of adjuvant chemotherapy in non-target cells of breast cancer patients.
Spontaneous and chemotherapy-induced sister chromatid exchanges (SCES) and lymphocyte proliferation rate index (PRI) in cultured peripheral lymphocytes were evaluated in 30 patients with diagnosed breast cancer before and after adjuvant chemotherapy and in 30 healthy women with no known familial history of breast cancer. Before chemotherapy, the breast cancer patients had a significantly increased background level of SCE, and lowered PRI as compared with the healthy women. Marked inter-individual variations were observed in both endpoints among the patients. Significantly elevated frequency of SCE and depressed PRI were recorded in blood samples collected after the first cycle of chemotherapy, with high inter-individual variations in the responses to the chemotherapy. FAC (5-fluorouracil, adriamycin and cyclophosphamide) protocol was the most genotoxic of the protocols studied, but also AC (adriamycin, cyclophosphamide) and CMF (cyclophosphamide, methotrexate and 5-fluorouracil) clearly increased SCE. All protocols significantly retarded lymphocyte proliferation in vitro. Our findings indicate that both SCE and PRI may serve as sensitive biomarkers for the routine detection of critical lesions produced by the administration of antineoplastic drugs in the clinical setting, as well as for possible screening of high-risk individuals among patients who have successfully completed chemotherapy.
Kopjar
Nevenka
N
Institute for Medical Research and Occupational Health, Ksaverska c.2, HR-10000 Zagreb, Croatia. nkopjar@imi.hr
Milas
Ivan
I
Garaj-Vrhovac
Verica
V
Gamulin
Marija
M
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000601:surgery; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D020732:Cytogenetic Analysis; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D007700:Kinetics; D008197:Lymph Node Excision; D008214:Lymphocytes / Q000187:drug effects*; D008408:Mastectomy; D008875:Middle Aged; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D016896:Treatment Outcome