title: Topoisomerase II alpha and TLE3 as predictive markers of response to anthracycline and taxane-containing regimens for neoadjuvant chemotherapy in breast cancer.
abstract: OBJECTIVE
  Anthracyclines and taxanes are considered the standard for neoadjuvant chemotherapy of breast cancer, although they are often associated with serious side effects and wide variability of individual response. In this study, we analyzed the value of topoisomerase II alpha (TOP2A) and transducin-like enhancer of split 3 (TLE3) as predictive markers of response to therapy with anthracyclines and taxanes.
  
  
  METHODS
  TOP2A and TLE3 protein expressions were evaluated using immunohistochemistry on 28 samples, obtained by core needle biopsy in patients with locally advanced breast carcinoma, subsequently subjected to epirubicin- and paclitaxel-based neoadjuvant chemotherapy. The immunohistochemical staining was correlated with the clinical response measured by the tumor size reduction evaluated by breast magnetic resonance imaging, prior and after chemotherapy, and by pathologic evaluation of the surgical specimen.
  
  
  RESULTS
  Neoadjuvant chemotherapy achieved a size reduction in 26/28 tumors (92.9%), with an average percentage decrease of 45.6%. A downstaging was achieved in 71.4% of the cases of locally advanced carcinoma. TOP2A positivity was correlated with a greater reduction in tumor diameter (P=0.06); negative staining for TLE3 was predictive of a better response to neoadjuvant chemotherapy (P=0.07). A higher reduction in tumor diameter (P=0.03) was also found for tumors that were concurrently TLE3-negative and TOP2A-positive.
  
  
  CONCLUSIONS
  TOP2A and TLE3 showed a correlation with response to neoadjuvant chemotherapy. While TOP2A is a well-known marker of response to anthracyclines-based chemotherapy, TLE3 is a new putative predictor of response to taxanes. Data from the current study suggest that TOP2A and TLE3 warrant further investigation in a larger series as predictors of response to neoadjuvant chemotherapy for locally advanced breast carcinoma.
authors.affiliation: Department of Health Science, Gynecology Section, University of Florence, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Susini
authors.affiliation: Department of Health Science, Gynecology Section, University of Florence, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Berti
authors.affiliation: Department of Health Science, Gynecology Section, University of Florence, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Carriero
authors.affiliation: Department of Health Science, Chemotherapy Section, University of Florence, Italy.
authors.forename: Ketty
authors.initials: K
authors.lastname: Tavella
authors.affiliation: Diagnostic Senology Unit, Azienda Ospedaliera-Universitaria Careggi, Florence, Italy.
authors.forename: Jacopo
authors.initials: J
authors.lastname: Nori
authors.affiliation: Diagnostic Senology Unit, Azienda Ospedaliera-Universitaria Careggi, Florence, Italy.
authors.forename: Ermanno
authors.initials: E
authors.lastname: Vanzi
authors.affiliation: Department of Health Science, Gynecology Section, University of Florence, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Molino
authors.affiliation: Department of Health Science, Gynecology Section, University of Florence, Italy.
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Di Tommaso
authors.affiliation: Department of Health Science, Gynecology Section, University of Florence, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Santini
authors.affiliation: Department of Surgery and Translational Medicine, Pathology Unit, University of Florence, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Saladino
authors.affiliation: Department of Surgery and Translational Medicine, Pathology Unit, University of Florence, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Bianchi
keywords: advanced stage disease; breast carcinoma; immunohistochemical markers