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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.

Authors

Francisco J. Candido Dos Reis

Gordon C. Wishart

Ed M. Dicks

David Greenberg

Jem Rashbass

Marjanka K. Schmidt

Alexandra J. van den Broek

Andrew Green

Emad Rakha

Tom Maishman

Diana M. Eccles

Paul D.P. Pharoah



Abstract

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.

Journal Article Type Article
Publication Date May 22, 2017
Journal Breast Cancer Research
Print ISSN 1465-5411
Electronic ISSN 1465-542X
Publisher BMC
Peer Reviewed Peer Reviewed
Volume 19
Issue 1
Article Number 58
APA6 Citation Candido Dos Reis, F. J., Wishart, G. C., Dicks, E. M., Greenberg, D., Rashbass, J., Schmidt, M. K., …Pharoah, P. D. (2017). An updated PREDICT breast cancer prognostication and treatment benefit prediction model with independent validation. Breast Cancer Research, 19(1), doi:10.1186/s13058-017-0852-3
DOI https://doi.org/10.1186/s13058-017-0852-3
Keywords Breast cancer; Prognosis
Publisher URL https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-017-0852-3
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0
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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0







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