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Cancer Treatment and Pharmacology / HER2/EGFR in Cancer Research / Advanced Breast Cancer Therapies · Journal article
Biomolecules and Biomedicine · September 4, 2026
Encouraging direction, but not yet definitive.
This study develops and internally validates nomograms predicting 1-, 3-, and 5-year overall and breast cancer-specific survival in de novo stage IV HER2-positive breast cancer using contemporary SEER data (2018–2021). The models show good internal discrimination (C-index 0.74–0.76) and identify high-risk patients with markedly worse outcomes (hazard ratio ~5 for OS), but external validation and treatment-level data are required before clinical deployment.
Prognostic model development with internal hold-out validation cohort. Patients with de novo stage IV HER2-positive breast cancer diagnosed during 2018–2021 in SEER database. Intervention: Nomogram development for prognostic prediction based on clinical and demographic variables. n = 1,516. SEER database (US).
Concordance indices in validation cohort: 0.741 for OS and 0.736 for BCSS Areas under time-dependent ROC curves ranged from 0.73 to 0.82 High-risk patients had hazard ratio 5.07 (validation) for OS and 4.09 for BCSS, both p < 0.001
Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.
These nomograms may support individualized prognostic counselling and risk stratification once initial treatment information is available. However, clinicians should await external validation in treatment-annotated cohorts and should interpret 5-year estimates cautiously given the median follow-up of 27 months.
A methodologically sound single-centre internal validation study of prognostic nomograms with good discrimination (C-index 0.74–0.76) in a contemporary HER2-positive metastatic cohort, but limited by lack of specific treatment annotation and short median follow-up relative to the 5-year outcome estimates.
As stated by the source record.
Quoted from the source exactly as published.
These nomograms may support individualized prognostic counselling and risk stratification once initial treatment information is available. However, clinicians should await external validation in treatment-annotated cohorts and should interpret 5-year estimates cautiously given the median follow-up of 27 months.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
The widespread adoption of contemporary human epidermal growth factor receptor 2 (HER2)-targeted therapies has altered survival in HER2-positive metastatic breast cancer, potentially limiting the applicability of older prognostic models. We aimed to develop and internally validate nomograms for overall survival (OS) and breast cancer-specific survival (BCSS) in patients with de novo stage IV HER2-positive breast cancer diagnosed during 2018–2021. Using the Surveillance, Epidemiology, and End Results (SEER) database, 1,516 patients were randomly assigned to training (n = 1,061) and internal hold-out validation (n = 455) cohorts. Random Survival Forest analysis with a 98% out-of-bag concordance index criterion selected variables for multivariable Cox regression models predicting 1-, 3-, and 5-year survival. Discrimination, calibration, clinical utility, and risk stratification were assessed. Nine variables were retained for OS and seven for BCSS. Concordance indices in the training and validation cohorts were 0.764 and 0.741 for OS and 0.747 and 0.736 for BCSS, respectively. Areas under the time-dependent receiver operating characteristic curves (AUCs) ranged from 0.73 to 0.82. Calibration was generally acceptable, and decision curve analysis suggested potential net clinical benefit. High-risk patients had markedly poorer OS (hazard ratios, 5.05 in training and 5.07 in validation) and BCSS (4.32 and 4.09, respectively; all p < 0.001). Sensitivity analyses addressing the time-varying chemotherapy effect and competing risks broadly supported the primary findings. The nomograms showed good internal discrimination and may support individualized prognostic assessment once initial treatment information is available. However, SEER does not record specific HER2-targeted regimens; therefore, this cohort represents a contemporary calendar period rather than a treatment-confirmed dual-HER2-blockade population. External validation in treatment-annotated cohorts is required, and 5-year estimates should be interpreted cautiously given the median follow-up of 27 months.
Taken from the source record, never inferred. Follow any of these and new work involving them reaches your briefing.