Implications for surveillance for breast cancer patients based on the internally and externally validated BRENDA-metastatic recurrence score.

Purpose: Although the incidence of distant relapse is decreasing, 20-30% of patients with early breast cancer die of metastasis. The aim of this study is to characterize patients with metastasis-free survival(MFS) less than 5 years, to analyze the most probable site of metastases according to the internally and externally validated BRENDA-score. The BRENDA-score is a combination of the biological subtype and clinical staging.

Method: 3832 patients with primary diagnosis of breast cancer and either distant metastatic recurrence within 5 years or MFS ≥ 5 years were assigned to this study. Patients were classified for metastatic recurrence according to the BRENDA-score. 1765 patients were in a validation set. Statistical methods were Kaplan-Meier curves, Cox regression analysis, Exhausted CHAID, likelihood-ratio tests and the Nearest Neighbor Estimation method.

Results: There was a significant(p < 0.001) difference between the Kaplan-Meier MFS-functions of M0-patients stratified by BRENDA-score. The BRENDA score outperforms intrinsic subtypes and the Nottingham prognostic score. It fits the original data and the validation set equally well (p = 0.179).There was a significant(p < 0.001) difference between mean BRENDA-Index for patients with MFS < 5y(21.0 ± 9.0) and patients with MFS ≥ 5y(mean BRENDA-Index 11.7 ± 8.2). 55.6% of the very high risk patients(BRENDA-Index ≥ 27) had metastases within 5 years. The most likely primary metastatic site was bone(30%) followed by liver(19%) and lung(18%). The discriminatory ability(areas under the time dependent ROC curve) of the BRENDA score is good to acceptable for the first 5 years. In the very low/low risk (intermediate, high/very high) risk group 50% of all metastases were diagnosed within 26 months. Guideline adherence had a highly significant influence on outcome independent of the risk group.

Conclusion: The evaluation showed that the BRENDA-Score is a robust predictive tool for breast cancer recurrence and site of metastases in the first five years after diagnosis. It outperforms intrinsic subtypes and the Nottingham prognostic score. The BRENDA-score could be a tool for a risk orientated and targeted follow up.