An updated PREDICT breast cancer prognostication and treatment benefit prediction model with independent validation

BACKGROUND PREDICT is a breast cancer prognostic and treatment benefit model implemented online. The overall fit of the model has been good in multiple independent case series, but PREDICT has been shown to underestimate breast cancer specific mortality in women diagnosed under the age of 40. Ano...

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Main Authors: Candido Dos Reis, Francisco J., Wishart, Gordon C., Dicks, Ed M., Greenberg, David, Rashbass, Jem, Schmidt, Marjanka K., van den Broek, Alexandra J., Ellis, Ian O., Green, Andrew, Rakha, Emad, Maishman, Tom, Eccles, Diana M., Pharoah, Paul D.P.
Format: Article
Language:English
Published: BioMed Central 2017
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Online Access:https://eprints.nottingham.ac.uk/43221/
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author Candido Dos Reis, Francisco J.
Wishart, Gordon C.
Dicks, Ed M.
Greenberg, David
Rashbass, Jem
Schmidt, Marjanka K.
van den Broek, Alexandra J.
Ellis, Ian O.
Green, Andrew
Rakha, Emad
Maishman, Tom
Eccles, Diana M.
Pharoah, Paul D.P.
author_facet Candido Dos Reis, Francisco J.
Wishart, Gordon C.
Dicks, Ed M.
Greenberg, David
Rashbass, Jem
Schmidt, Marjanka K.
van den Broek, Alexandra J.
Ellis, Ian O.
Green, Andrew
Rakha, Emad
Maishman, Tom
Eccles, Diana M.
Pharoah, Paul D.P.
author_sort Candido Dos Reis, Francisco J.
building Nottingham Research Data Repository
collection Online Access
description BACKGROUND PREDICT is a breast cancer prognostic and treatment benefit model implemented online. The overall fit of the model has been good in multiple independent case series, but PREDICT has been shown to underestimate breast cancer specific mortality in women diagnosed under the age of 40. Another limitation is the use of discrete categories for tumour size and node status resulting in 'step' changes in risk estimates on moving between categories. We have refitted the PREDICT prognostic model using the original cohort of cases from East Anglia with updated survival time in order to take into account age at diagnosis and to smooth out the survival function for tumour size and node status. METHODS Multivariable Cox regression models were used to fit separate models for ER negative and ER positive disease. Continuous variables were fitted using fractional polynomials and a smoothed baseline hazard was obtained by regressing the baseline cumulative hazard for each patients against time using fractional polynomials. The fit of the prognostic models were then tested in three independent data sets that had also been used to validate the original version of PREDICT. RESULTS In the model fitting data, after adjusting for other prognostic variables, there is an increase in risk of breast cancer specific mortality in younger and older patients with ER positive disease, with a substantial increase in risk for women diagnosed before the age of 35. In ER negative disease the risk increases slightly with age. The association between breast cancer specific mortality and both tumour size and number of positive nodes was non-linear with a more marked increase in risk with increasing size and increasing number of nodes in ER positive disease. The overall calibration and discrimination of the new version of PREDICT (v2) was good and comparable to that of the previous version in both model development and validation data sets. However, the calibration of v2 improved over v1 in patients diagnosed under the age of 40. CONCLUSIONS The PREDICT v2 is an improved prognostication and treatment benefit model compared with v1. The online version should continue to aid clinical decision making in women with early breast cancer.
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spelling nottingham-432212017-10-13T00:20:24Z https://eprints.nottingham.ac.uk/43221/ An updated PREDICT breast cancer prognostication and treatment benefit prediction model with independent validation Candido Dos Reis, Francisco J. Wishart, Gordon C. Dicks, Ed M. Greenberg, David Rashbass, Jem Schmidt, Marjanka K. van den Broek, Alexandra J. Ellis, Ian O. Green, Andrew Rakha, Emad Maishman, Tom Eccles, Diana M. Pharoah, Paul D.P. BACKGROUND PREDICT is a breast cancer prognostic and treatment benefit model implemented online. The overall fit of the model has been good in multiple independent case series, but PREDICT has been shown to underestimate breast cancer specific mortality in women diagnosed under the age of 40. Another limitation is the use of discrete categories for tumour size and node status resulting in 'step' changes in risk estimates on moving between categories. We have refitted the PREDICT prognostic model using the original cohort of cases from East Anglia with updated survival time in order to take into account age at diagnosis and to smooth out the survival function for tumour size and node status. METHODS Multivariable Cox regression models were used to fit separate models for ER negative and ER positive disease. Continuous variables were fitted using fractional polynomials and a smoothed baseline hazard was obtained by regressing the baseline cumulative hazard for each patients against time using fractional polynomials. The fit of the prognostic models were then tested in three independent data sets that had also been used to validate the original version of PREDICT. RESULTS In the model fitting data, after adjusting for other prognostic variables, there is an increase in risk of breast cancer specific mortality in younger and older patients with ER positive disease, with a substantial increase in risk for women diagnosed before the age of 35. In ER negative disease the risk increases slightly with age. The association between breast cancer specific mortality and both tumour size and number of positive nodes was non-linear with a more marked increase in risk with increasing size and increasing number of nodes in ER positive disease. The overall calibration and discrimination of the new version of PREDICT (v2) was good and comparable to that of the previous version in both model development and validation data sets. However, the calibration of v2 improved over v1 in patients diagnosed under the age of 40. CONCLUSIONS The PREDICT v2 is an improved prognostication and treatment benefit model compared with v1. The online version should continue to aid clinical decision making in women with early breast cancer. BioMed Central 2017-05-22 Article PeerReviewed application/pdf en cc_by https://eprints.nottingham.ac.uk/43221/1/art%253A10.1186%252Fs13058-017-0852-3.pdf Candido Dos Reis, Francisco J., Wishart, Gordon C., Dicks, Ed M., Greenberg, David, Rashbass, Jem, Schmidt, Marjanka K., van den Broek, Alexandra J., Ellis, Ian O., Green, Andrew, Rakha, Emad, Maishman, Tom, Eccles, Diana M. and Pharoah, Paul D.P. (2017) An updated PREDICT breast cancer prognostication and treatment benefit prediction model with independent validation. Breast Cancer Research, 19 (1). 58/1-58/13. ISSN 1465-542X Breast cancer; Prognosis https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-017-0852-3 doi:10.1186/s13058-017-0852-3 doi:10.1186/s13058-017-0852-3
spellingShingle Breast cancer; Prognosis
Candido Dos Reis, Francisco J.
Wishart, Gordon C.
Dicks, Ed M.
Greenberg, David
Rashbass, Jem
Schmidt, Marjanka K.
van den Broek, Alexandra J.
Ellis, Ian O.
Green, Andrew
Rakha, Emad
Maishman, Tom
Eccles, Diana M.
Pharoah, Paul D.P.
An updated PREDICT breast cancer prognostication and treatment benefit prediction model with independent validation
title An updated PREDICT breast cancer prognostication and treatment benefit prediction model with independent validation
title_full An updated PREDICT breast cancer prognostication and treatment benefit prediction model with independent validation
title_fullStr An updated PREDICT breast cancer prognostication and treatment benefit prediction model with independent validation
title_full_unstemmed An updated PREDICT breast cancer prognostication and treatment benefit prediction model with independent validation
title_short An updated PREDICT breast cancer prognostication and treatment benefit prediction model with independent validation
title_sort updated predict breast cancer prognostication and treatment benefit prediction model with independent validation
topic Breast cancer; Prognosis
url https://eprints.nottingham.ac.uk/43221/
https://eprints.nottingham.ac.uk/43221/
https://eprints.nottingham.ac.uk/43221/