PAM50 proliferation score as a predictor of weekly paclitaxel benefit in breast cancer Journal Article
| Authors: | Martin, M.; Prat, A.; Rodríguez-Lescure, A.; Caballero, R.; Ebbert, M. T. W.; Munárriz, B.; Ruiz-Borrego, M.; Bastien, R. R. L.; Crespo, C.; Davis, C.; Rodríguez, C. A.; López-Vega, J. M.; Furió, V.; García, A. M.; Casas, M.; Ellis, M. J.; Berry, D. A.; Pitcher, B. N.; Harris, L.; Ruiz, A.; Winer, E.; Hudis, C.; Stijleman, I. J.; Tuck, D. P.; Carrasco, E.; Perou, C. M.; Bernard, P. S. |
| Article 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. © 2013 The Author(s). |
| Keywords: | adult; cancer chemotherapy; cancer survival; controlled study; treatment outcome; middle aged; survival rate; major clinical study; overall survival; histopathology; fluorouracil; dose response; paclitaxel; outcome assessment; follow up; cancer grading; prospective studies; ki 67 antigen; cell proliferation; ki-67 antigen; multiple cycle treatment; breast cancer; randomized controlled trial; antineoplastic combined chemotherapy protocols; proportional hazards models; randomized controlled trials as topic; cyclophosphamide; drug effect; breast neoplasms; survival time; clinical trials, phase iii as topic; dosage schedule comparison; multicenter study; scoring system; epirubicin; multivariate analysis; phase 3 clinical trial; multicenter studies as topic; predictive value; kaplan-meier estimate; comparative effectiveness; pam50 proliferation score; pam50 subtypes; prediction of paclitaxel efficacy |
| Journal Title: | Breast Cancer Research and Treatment |
| Volume: | 138 |
| Issue: | 2 |
| ISSN: | 0167-6806 |
| Publisher: | Springer |
| Date Published: | 2013-04-01 |
| Start Page: | 457 |
| End Page: | 466 |
| Language: | English |
| DOI: | 10.1007/s10549-013-2416-2 |
| PROVIDER: | scopus |
| PMCID: | PMC3608881 |
| PUBMED: | 23423445 |
| DOI/URL: | |
| Notes: | --- - Cited By (since 1996):2 - "Export Date: 1 August 2013" - "CODEN: BCTRD" - "Source: Scopus" |
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