title: PAM50 proliferation score as a predictor of weekly paclitaxel benefit in breast cancer.
abstract: To identify a group of patients who might benefit from the addition of weekly paclitaxel to conventional anthracycline-containing chemotherapy as adjuvant therapy of node-positive operable breast cancer. The predictive value of PAM50 subtypes and the 11-gene proliferation score contained within the PAM50 assay were evaluated in 820 patients from the GEICAM/9906 randomized phase III trial comparing adjuvant FEC to FEC followed by weekly paclitaxel (FEC-P). Multivariable Cox regression analyses of the secondary endpoint of overall survival (OS) were performed to determine the significance of the interaction between treatment and the (1) PAM50 subtypes, (2) PAM50 proliferation score, and (3) clinical and pathological variables. Similar OS analyses were performed in 222 patients treated with weekly paclitaxel versus paclitaxel every 3 weeks in the CALGB/9342 and 9840 metastatic clinical trials. In GEICAM/9906, with a median follow up of 8.7 years, OS of the FEC-P arm was significantly superior compared to the FEC arm (unadjusted HR = 0.693, p = 0.013). A benefit from paclitaxel was only observed in the group of patients with a low PAM50 proliferation score (unadjusted HR = 0.23, p < 0.001; and interaction test, p = 0.006). No significant interactions between treatment and the PAM50 subtypes or the various clinical-pathological variables, including Ki-67 and histologic grade, were identified. Finally, similar OS results were obtained in the CALGB data set, although the interaction test did not reach statistical significance (p = 0.109). The PAM50 proliferation score identifies a subset of patients with a low proliferation status that may derive a larger benefit from weekly paclitaxel.
authors: Department of Medical Oncology, Instituto de Investigación Sanitaria Hospital General Universitario Gregorio Marañón, Universidad Complutense, Madrid, Spain. mmartin@geicam.org
authors: Miguel
authors: M
authors: Martín
authors: Aleix
authors: A
authors: Prat
authors: Alvaro
authors: A
authors: Rodríguez-Lescure
authors: Rosalía
authors: R
authors: Caballero
authors: Mark T W
authors: MT
authors: Ebbert
authors: Blanca
authors: B
authors: Munárriz
authors: Manuel
authors: M
authors: Ruiz-Borrego
authors: Roy R L
authors: RR
authors: Bastien
authors: Carmen
authors: C
authors: Crespo
authors: Carole
authors: C
authors: Davis
authors: César A
authors: CA
authors: Rodríguez
authors: José M
authors: JM
authors: López-Vega
authors: Vicente
authors: V
authors: Furió
authors: Ana M
authors: AM
authors: García
authors: Maribel
authors: M
authors: Casas
authors: Matthew J
authors: MJ
authors: Ellis
authors: Donald A
authors: DA
authors: Berry
authors: Brandelyn N
authors: BN
authors: Pitcher
authors: Lyndsay
authors: L
authors: Harris
authors: Amparo
authors: A
authors: Ruiz
authors: Eric
authors: E
authors: Winer
authors: Clifford
authors: C
authors: Hudis
authors: Inge J
authors: IJ
authors: Stijleman
authors: David P
authors: DP
authors: Tuck
authors: Eva
authors: E
authors: Carrasco
authors: Charles M
authors: CM
authors: Perou
authors: Philip S
authors: PS
authors: Bernard
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D049109:Cell Proliferation; D017326:Clinical Trials, Phase III as Topic; D003520:Cyclophosphamide / Q000627:therapeutic use; D015251:Epirubicin / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D015999:Multivariate Analysis; D017239:Paclitaxel / Q000008:administration & dosage; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D019394:Ki-67 Antigen; D015251:Epirubicin; D003520:Cyclophosphamide; D017239:Paclitaxel; D005472:Fluorouracil