@article{WischnewskySchwentnerDiessneretal.2021,
  author    = {Wischnewsky, Manfred and Schwentner, Lukas and Diessner, Joachim and De Gregorio, Amelie and Joukhadar, Ralf and Davut, Dayan and Salmen, Jessica and Bekes, Inga and Kiesel, Matthias and M{\"u}ller-Reiter, Max and Blettner, Maria and Wolters, Regine and Janni, Wolfgang and Kreienberg, Rolf and W{\"o}ckel, Achim and Ebner, Florian},
  title     = {BRENDA-Score, a hghly significant, internally and externally validated prognostic marker for metastatic recurrence: analysis of 10,449 primary breast cancer patients},
  series = {Cancers},
  volume    = {13},
  journal   = {Cancers},
  number    = {13},
  issn      = {2072-6694},
  doi       = {10.3390/cancers13133121},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241064},
  year      = {2021},
  abstract  = {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 < 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 < 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.},
  language  = {en}
}
@article{EbnerWoeckelSchwentneretal.2019,
  author    = {Ebner, Florian and W{\"o}ckel, Achim and Schwentner, Lukas and Blettner, Maria and Janni, Wolfgang and Kreienberg, Rolf and Wischnewsky, Manfred},
  title     = {Does the number of removed axillary lymphnodes in high risk breast cancer patients influence the survival?},
  series = {BMC Cancer},
  volume    = {19},
  journal   = {BMC Cancer},
  doi       = {10.1186/s12885-019-5292-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226445},
  year      = {2019},
  abstract  = {Background The decision making process for axillary dissection has changed in recent years for patients with early breast cancer and positive sentinel lymph nodes (LN). The question now arises, what is the optimal surgical treatment for patients with positive axillary LN (pN+). This article tries to answer the following questions: (1) Is there a survival benefit for breast cancer patients with 3 or more positive LN (pN3+) and with more than 10 removed LN? (2) Is there a survival benefit for high risk breast cancer patients (triple negative or Her2 + breast cancer) and with 3 or more positive LN (pN3+) with more than 10 removed LN? (3) In pN + patients is the prognostic value of the lymph node ratio (LNR) of pN+/pN removed impaired if 10 or less LN are removed? Methods A retrospective database analysis of the multi center cohort database BRENDA (breast cancer under evidence based guidelines) with data from 9625 patients from 17 breast centers was carried out. Guideline adherence was defined by the 2008 German National consensus guidelines. Results 2992 out of 9625 patients had histological confirmed positive lymph nodes. The most important factors for survival were intrinsic sub types, tumor size and guideline adherent chemo- and hormonal treatment (and age at diagnosis for overall survival (OAS)). Uni-and multivariable analyses for recurrence free survival (RFS) and OAS showed no significant survival benefit when removing more than 10 lymph nodes even for high-risk patients. The mean and median of LNR were significantly higher in the pN+ patients with ≤10 excised LN compared to patients with > 10 excised LN. LNR was in both, uni-and multivariable, analysis a highly significant prognostic factor for RFS and OAS in both subgroups of pN + patients with less respective more than 10 excised LN. Multivariable COX regression analysis was adjusted by age, tumor size, intrinsic sub types and guideline adherent adjuvant systemic therapy. Conclusion The removal of more than 10 LN did not result in a significant survival benefit even in high risk pN + breast cancer patients.},
  language  = {en}
}