Bcl-2 is a prognostic marker in breast cancer independently of the Nottingham prognostic index

Grace M. Callagy; Paul D. Pharoah; Sarah E. Pinder; Forrest D. Hsu; Torsten O. Nielsen; Joseph Ragaz; Ian O. Ellis; David Huntsman; Carlos Caldas

doi:10.1158/1078-0432.CCR-05-2719

Bcl-2 is a prognostic marker in breast cancer independently of the Nottingham prognostic index

Grace M. Callagy
, Paul D. Pharoah
, Sarah E. Pinder
, Forrest D. Hsu
, Torsten O. Nielsen
, Joseph Ragaz
, Ian O. Ellis
, David Huntsman
, Carlos Caldas

Pathology

University of Cambridge
Strangeways Research Centre
Addenbrookes Hospital
University of British Columbia
McGill University
Nottingham City Hospital

Research output: Contribution to a Journal (Peer & Non Peer) › Article › peer-review

200 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	2468-2475
Number of pages	8
Journal	Clinical Cancer Research
Volume	12
Issue number	8
DOIs	https://doi.org/10.1158/1078-0432.CCR-05-2719
Publication status	Published - 15 Apr 2006

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Authors (Note for portal: view the doc link for the full list of authors)

Authors
Callagy, GM,Pharoah, PD,Pinder, SE,Hsu, FD,Nielsen, TO,Ragaz, J,Ellis, IO,Huntsman, D,Caldas, C

Access to Document

10.1158/1078-0432.CCR-05-2719

Cite this

@article{4cdfa08d0d394ee180e881a47adba48d,

title = "Bcl-2 is a prognostic marker in breast cancer independently of the Nottingham prognostic index",

abstract = "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.",

author = "Callagy, \{Grace M.\} and Pharoah, \{Paul D.\} and Pinder, \{Sarah E.\} and Hsu, \{Forrest D.\} and Nielsen, \{Torsten O.\} and Joseph Ragaz and Ellis, \{Ian O.\} and David Huntsman and Carlos Caldas",

year = "2006",

month = apr,

day = "15",

doi = "10.1158/1078-0432.CCR-05-2719",

language = "English",

volume = "12",

pages = "2468--2475",

journal = "Clinical Cancer Research",

issn = "1078-0432",

publisher = "American Association for Cancer Research Inc.",

number = "8",

}

TY - JOUR

T1 - Bcl-2 is a prognostic marker in breast cancer independently of the Nottingham prognostic index

AU - Callagy, Grace M.

AU - Pharoah, Paul D.

AU - Pinder, Sarah E.

AU - Hsu, Forrest D.

AU - Nielsen, Torsten O.

AU - Ragaz, Joseph

AU - Ellis, Ian O.

AU - Huntsman, David

AU - Caldas, Carlos

PY - 2006/4/15

Y1 - 2006/4/15

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/33646417913

U2 - 10.1158/1078-0432.CCR-05-2719

DO - 10.1158/1078-0432.CCR-05-2719

M3 - Article

SN - 1078-0432

VL - 12

SP - 2468

EP - 2475

JO - Clinical Cancer Research

JF - Clinical Cancer Research

IS - 8

ER -

Bcl-2 is a prognostic marker in breast cancer independently of the Nottingham prognostic index

Abstract

UN SDGs

Authors (Note for portal: view the doc link for the full list of authors)

Access to Document

Other files and links

Fingerprint

Cite this