title: Chemotherapy-induced apoptosis and Bcl-2 levels correlate with breast cancer response to chemotherapy.
abstract: OBJECTIVE
  The relevance of apoptosis to breast cancer response to chemotherapy is unclear. We investigated whether changes in tumor cell apoptosis and Bcl-2 expression immediately after chemotherapy correlated with response to breast cancer treatment.
  
  
  METHODS
  Serial core biopsies of 25 breast cancer primary tumors were performed at either two or three time points: before treatment (N = 24) and approximately 24 hours (N = 22) and/or 48 hours (N = 19) after the initiation of the first cycle of chemotherapy. Apoptosis levels were quantified by use of a fluorescent terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) stain, and Bcl-2 and Bax were measured by semiquantitative immunohistochemical assays. All calculated P values were two sided.
  
  
  RESULTS
  The apoptosis level at 48 hours was significantly higher in the tumors with pathological complete response or < 1 cm of residual disease (median, 22%; range, 6%-51%) than in the tumors with > 1 cm residual disease (median, 7%; range, 1%-36%); Mann-Whitney test. This difference was also present in the subgroup of 16 tumors treated with docetaxel/doxorubicin chemotherapy (25% vs 4%, respectively). A decrease in Bcl2 expression after chemotherapy relative to the expression from the pretreatment sample also correlated with disease response. Specifically, three of the nine tumors with a decrease in Bcl-2 had a pathological complete response, compared with 0 of the 15 tumors with stable levels of Bcl-2 (Fisher's exact test). There was no relationship between serial measurements of Bax and response.
  
  
  CONCLUSIONS
  These data suggest that apoptosis may play an important role in determining breast cancer response to chemotherapy and that the level of treatment-induced apoptosis may have some value as a predictive marker.
authors.affiliation: Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. tbuchhol@mdanderson.org
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Buchholz
authors.forename: Darren W
authors.initials: DW
authors.lastname: Davis
authors.forename: David J
authors.initials: DJ
authors.lastname: McConkey
authors.forename: W Fraser
authors.initials: WF
authors.lastname: Symmans
authors.forename: Vicente
authors.initials: V
authors.lastname: Valero
authors.forename: Anuja
authors.initials: A
authors.lastname: Jhingran
authors.forename: Susan L
authors.initials: SL
authors.lastname: Tucker
authors.forename: Lajos
authors.initials: L
authors.lastname: Pusztai
authors.forename: Massimo
authors.initials: M
authors.lastname: Cristofanilli
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Esteva
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: Aysegul A
authors.initials: AA
authors.lastname: Sahin
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001706:Biopsy / Q000379:methods; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D000077143:Docetaxel; D004317:Doxorubicin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D043823:Taxoids; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D043823:Taxoids; D000077143:Docetaxel; D004317:Doxorubicin; D017239:Paclitaxel