PURPOSE: Prognostication of breast cancer using clinicopathologic variables, although useful, remains imperfect. Many reports suggest that gene expression profiling can refine the current approach. Alternatively, it has been shown that panels of proteins assessed by immunohistochemistry might also be useful in this regard. We evaluate the prognostic potential of a panel of markers by immunohistochemistry in a large case series to establish if either a single marker or a panel could improve the prognostic power of the Nottingham Prognostic Index (NPI). We validated the results in an independent series. EXPERIMENTAL DESIGN AND RESULTS: The expression of 13 biomarkers was evaluated in 930 breast cancers on a tissue microarray. Eight markers [estrogen receptor (ER), progesterone receptor (PR), Bcl-2, cyclin E, p53, MIB-1, cytokeratin 5/6, and HER2] showed a significant association with survival at 10 years on univariate analysis. On multivariate analysis that included these eight markers and the NPI, only the NPI [hazard ratio (HR), 1.35; 95% confidence interval (95% CI), 1.16-1.56; P = 0.0005], ER (HR, 0.59; 95% CI, 0.39-0.88; P = 0.011), and Bcl-2 (HR, 0.68; 95% CI, 0.46-0.99; P = 0.055) were significant. In a subsequent multivariate analysis that included the NPI, ER, and Bcl-2, only Bcl-2 (HR, 0.62; 95% CI, 0.44-0.87; P = 0.006) remained independent of NPI (HR, 1.50; 95% CI, 1.16-1.56; P = 0.004). In addition, Bcl-2, used as a single marker, was more powerful than the use of a panel of markers. Based on these results, an independent series was used to validate the prognostic significance of Bcl-2. ER and PR were also evaluated in this validation series. Bcl-2 (HR, 0.83; 95% CI, 0.71-0.96; P = 0.018) retained prognostic significance independent of the NPI (HR, 2.04; 95% CI, 1.67-2.51; P < 0.001) with an effect that was maximal in the first 5 years. CONCLUSION: Bcl-2 is an independent predictor of breast cancer outcome and seems to be useful as a prognostic adjunct to the NPI, particularly in the first 5 years after diagnosis.
PURPOSE: Prognostication of breast cancer using clinicopathologic variables, although useful, remains imperfect. Many reports suggest that gene expression profiling can refine the current approach. Alternatively, it has been shown that panels of proteins assessed by immunohistochemistry might also be useful in this regard. We evaluate the prognostic potential of a panel of markers by immunohistochemistry in a large case series to establish if either a single marker or a panel could improve the prognostic power of the Nottingham Prognostic Index (NPI). We validated the results in an independent series. EXPERIMENTAL DESIGN AND RESULTS: The expression of 13 biomarkers was evaluated in 930 breast cancers on a tissue microarray. Eight markers [estrogen receptor (ER), progesterone receptor (PR), Bcl-2, cyclin E, p53, MIB-1, cytokeratin 5/6, and HER2] showed a significant association with survival at 10 years on univariate analysis. On multivariate analysis that included these eight markers and the NPI, only the NPI [hazard ratio (HR), 1.35; 95% confidence interval (95% CI), 1.16-1.56; P = 0.0005], ER (HR, 0.59; 95% CI, 0.39-0.88; P = 0.011), and Bcl-2 (HR, 0.68; 95% CI, 0.46-0.99; P = 0.055) were significant. In a subsequent multivariate analysis that included the NPI, ER, and Bcl-2, only Bcl-2 (HR, 0.62; 95% CI, 0.44-0.87; P = 0.006) remained independent of NPI (HR, 1.50; 95% CI, 1.16-1.56; P = 0.004). In addition, Bcl-2, used as a single marker, was more powerful than the use of a panel of markers. Based on these results, an independent series was used to validate the prognostic significance of Bcl-2. ER and PR were also evaluated in this validation series. Bcl-2 (HR, 0.83; 95% CI, 0.71-0.96; P = 0.018) retained prognostic significance independent of the NPI (HR, 2.04; 95% CI, 1.67-2.51; P < 0.001) with an effect that was maximal in the first 5 years. CONCLUSION:Bcl-2 is an independent predictor of breast cancer outcome and seems to be useful as a prognostic adjunct to the NPI, particularly in the first 5 years after diagnosis.
Authors: Fiona M Blows; Kristy E Driver; Marjanka K Schmidt; Annegien Broeks; Flora E van Leeuwen; Jelle Wesseling; Maggie C Cheang; Karen Gelmon; Torsten O Nielsen; Carl Blomqvist; Päivi Heikkilä; Tuomas Heikkinen; Heli Nevanlinna; Lars A Akslen; Louis R Bégin; William D Foulkes; Fergus J Couch; Xianshu Wang; Vicky Cafourek; Janet E Olson; Laura Baglietto; Graham G Giles; Gianluca Severi; Catriona A McLean; Melissa C Southey; Emad Rakha; Andrew R Green; Ian O Ellis; Mark E Sherman; Jolanta Lissowska; William F Anderson; Angela Cox; Simon S Cross; Malcolm W R Reed; Elena Provenzano; Sarah-Jane Dawson; Alison M Dunning; Manjeet Humphreys; Douglas F Easton; Montserrat García-Closas; Carlos Caldas; Paul D Pharoah; David Huntsman Journal: PLoS Med Date: 2010-05-25 Impact factor: 11.069
Authors: Christopher I van de Wetering; Mitchell C Coleman; Douglas R Spitz; Brian J Smith; C Michael Knudson Journal: Free Radic Biol Med Date: 2008-02-07 Impact factor: 7.376
Authors: Julie A Vendrell; Katherine E Robertson; Patrice Ravel; Susan E Bray; Agathe Bajard; Colin A Purdie; Catherine Nguyen; Sirwan M Hadad; Ivan Bieche; Sylvie Chabaud; Thomas Bachelot; Alastair M Thompson; Pascale A Cohen Journal: Breast Cancer Res Date: 2008-10-17 Impact factor: 6.466
Authors: E K A Millar; L R Anderson; C M McNeil; S A O'Toole; M Pinese; P Crea; A L Morey; A V Biankin; S M Henshall; E A Musgrove; R L Sutherland; A J Butt Journal: Br J Cancer Date: 2008-12-09 Impact factor: 7.640
Authors: S J Dawson; S W Duffy; F M Blows; K E Driver; E Provenzano; J LeQuesne; D C Greenberg; P Pharoah; C Caldas; G C Wishart Journal: Br J Cancer Date: 2009-09-22 Impact factor: 7.640