title: Chromosomal abnormalities in women with breast cancer after autologous stem cell transplantation are infrequent and may not predict development of therapy-related leukemia or myelodysplastic syndrome.
abstract: We determined prospectively the incidence of chromosomal abnormalities in patients with high-risk breast cancer (HRBC) after high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT), and correlated the cytogenetic abnormalities with the development of post-transplant myelodysplastic syndrome or acute myeloid leukemia (MDS/AML). From 1990 to 1999, 229 women with HRBC underwent ASCT. Cytogenetic analysis of bone marrow (BM) cells was performed 12-59 months after ASCT in 60 consecutive women uniformly treated with six courses of FAC/FEC followed by HDCT and ASCT. With a median follow-up of 36 months after ASCT, there were no cases of MDS/AML among the 229 patients. In the selected cohort of 60 patients, three (5%) showed clonal chromosomal abnormalities (two single trisomy X and one t(1;6)), whereas two additional patients showed non-clonal reciprocal translocations. Two of the patients with clonal aberrations had blood cytopenias as well as subtle dysplastic pictures in BM which were not classifiable as MDS according to the FAB criteria. Similar dysplastic features were also observed in four patients with normal karyotypes. All cytogenetic aberrations were transient and disappeared, except a +X detected by FISH in a residual cell population in one of the patients. Retrospective cytogenetic and FISH studies of samples obtained after six cycles of FAC/FEC and before transplant demonstrated no chromosomal abnormalities in any of the five patients with post-ASCT karyotypic changes. Early changes in karyotype detected in breast cancer patients following ASCT are transient and do not correlate with or predict development of MDS/AML. As these aberrations were not present before ASCT, they may be related to the HDCT regimen or transplant procedure rather than to the prior adjuvant therapy. Our results suggest that ASCT may be less likely to cause MDS or AML in breast cancer patients as compared to other malignancies. Bone Marrow Transplantation (2000) 25, 1203-1208.
authors.affiliation: Department of Hematology and Medical Oncology, Hospital Clinico Universitario, University of Valencia, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: Martínez-Climent
authors.forename: A M
authors.initials: AM
authors.lastname: Comes
authors.forename: E
authors.initials: E
authors.lastname: Vizcarra
authors.forename: I
authors.initials: I
authors.lastname: Benet
authors.forename: C
authors.initials: C
authors.lastname: Arbona
authors.forename: F
authors.initials: F
authors.lastname: Prósper
authors.forename: C
authors.initials: C
authors.lastname: Solano
authors.forename: B
authors.initials: B
authors.lastname: García Clavel
authors.forename: I
authors.initials: I
authors.lastname: Marugán
authors.forename: A
authors.initials: A
authors.lastname: Lluch
authors.forename: J
authors.initials: J
authors.lastname: García-Conde
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001853:Bone Marrow / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D002869:Chromosome Aberrations; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007938:Leukemia / Q000209:etiology*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000209:etiology*; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary / Q000209:etiology*; D017698:Postmenopause; D011237:Predictive Value of Tests; D017697:Premenopause; D014182:Transplantation, Autologous
chemical_list: D015251:Epirubicin; D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil