BRENDA-score, a highly significant, internally and externally validated prognostic marker for metastatic recurrence: analysis of 10,449 primary breast cancer patients
Creators: name: Wischnewsky, Manfred
name: Schwentner, Lukas
name: Diessner, Joachim Diessner
name: De Gregorio, Amelie
name: Joukhadar, Ralf
name: Davut, Dayan
name: Salmen, Jessica
name: Bekes, Inga
name: Kiesel, Matthias
name: Müller-Reiter, Max
name: Blettner, Maria
name: Wolters, Regine
name: Janni, Wolfgang
name: Kreienberg, Rolf
name: Wöckel, Achim
name: Ebner, Florian
Publisher: name: Universität Ulm
Year: 2021
Subjects: subject: breast cancer
subject: risk
subject: prediction
subject: BRENDA
subject: score
subject: follow up
subject: DDC 610 / Medicine &amp; health
subject: Survival rate
subject: Breast neoplasms
subject: Biomarkers, Tumor
subject: Prognosis
subject: Brustkrebs
subject: Tumormarker
subject: Prognose

description: Background Current research in breast cancer focuses on individualization of local and systemic therapies with adequate escalation or de-escalation strategies. As a result, about two-thirds of breast cancer patients can be cured, but up to one-third eventually develop metastatic disease, which is considered incurable with currently available treatment options. This underscores the importance to develop a metastatic recurrence score to escalate or de-escalate treatment strategies. Patients and methods Data from 10,499 patients were available from 17 clinical cancer registries (BRENDA-project. In total, 8566 were used to develop the BRENDA-Index. This index was calculated from the regression coefficients of a Cox regression model for metastasis-free survival (MFS). Based on this index, patients were categorized into very high, high, intermediate, low, and very low risk groups forming the BRENDA-Score. Bootstrapping was used for internal validation and an independent dataset of 1883 patients for external validation. The predictive accuracy was checked by Harrell’s c-index. In addition, the BRENDA-Score was analyzed as a marker for overall survival (OS) and compared to the Nottingham prognostic score (NPS). Results: Intrinsic subtypes, tumour size, grading, and nodal status were identified as statistically significant prognostic factors in the multivariate analysis. The five prognostic groups of the BRENDA-Score showed highly significant (p &lt; 0.001) differences regarding MFS:low risk: hazard ratio (HR) = 2.4, 95%CI (1.7–3.3); intermediate risk: HR = 5.0, 95%CI.(3.6–6.9); high risk: HR = 10.3, 95%CI (7.4–14.3) and very high risk: HR = 18.1, 95%CI (13.2–24.9). The external validation showed congruent results. A multivariate Cox regression model for OS with BRENDA-Score and NPS as covariates showed that of these two scores only the BRENDA-Score is significant (BRENDA-Score p &lt; 0.001; NPS p = 0.447). Therefore, the BRENDA-Score is also a good prognostic marker for OS. Conclusion: The BRENDA-Score is an internally and externally validated robust predictive tool for metastatic recurrence in breast cancer patients. It is based on routine parameters easily accessible in daily clinical care. In addition, the BRENDA-Score is a good prognostic marker for overall survival. Highlights: The BRENDA-Score is a highly significant predictive tool for metastatic recurrence of breast cancer patients. The BRENDA-Score is stable for at least the first five years after primary diagnosis, i.e., the sensitivities and specificities of this predicting system is rather similar to the NPI with AUCs between 0.76 and 0.81 the BRENDA-Score is a good prognostic marker for overall survival.