Predicting the risk of locoregional recurrence after early breast cancer: an external validation of the Dutch INFLUENCE-nomogram with clinical cancer registry data from Germany

J Cancer Res Clin Oncol. 2019 Jul;145(7):1823-1833. doi: 10.1007/s00432-019-02904-4. Epub 2019 Mar 29.

Abstract

Purpose: Follow-up after breast cancer treatment aims for an early detection of locoregional breast cancer recurrences (LRR) to improve the patients' outcome. By estimating individual's 5-year recurrence-risks, the Dutch INFLUENCE-nomogram can assist health professionals and patients in developing personalized risk-based follow-up pathways. The objective of this study is to validate the prediction tool on non-Dutch patients.

Material and methods: Data for this external validation derive from a large clinical cancer registry in southern Germany, covering a population of 1.1 million. Patients with curative resection of early-stage breast cancer, diagnosed between 2000 and 2012, were included in the analysis (n = 6520). For each of them, an individual LRR-risk was estimated by the INFLUENCE-nomogram. Its predictive ability was tested by comparing estimated and observed LRR-probabilities using the Hosmer-Lemeshow goodness-of-fit test and C-statistics.

Results: In the German validation-cohort, 2.8% of the patients developed an LRR within 5 years after primary surgery (n = 184). While the INFLUENCE-nomogram generally underestimates the actual LRR-risk of the German patients (p < 0.001), its discriminative ability is comparable to the one observed in the original Dutch modeling-cohort (C-statistic German validation-cohort: 0.73, CI 0.69-0.77 vs. C-statistic Dutch modeling-cohort: 0.71, CI 0.69-0.73). Similar results were obtained in most of the subgroup analyses stratified by age, type of surgery and intrinsic biological subtypes.

Conclusion: The outcomes of this external validation underline the generalizability of the INFLUENCE-nomogram beyond the Dutch population. The model performance could be enhanced in future by incorporating additional risk factors for LRR.

Keywords: Cancer registry; Follow-up; Health services research; Mamma carcinoma; Personalized care; Tertiary prevention.

MeSH terms

  • Aged
  • Breast Neoplasms / epidemiology*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / surgery
  • Cohort Studies
  • Female
  • Germany / epidemiology
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local / diagnosis
  • Neoplasm Recurrence, Local / enzymology*
  • Neoplasm Recurrence, Local / pathology
  • Netherlands / epidemiology
  • Nomograms*
  • Registries
  • Reproducibility of Results