Prognostication and treatment predictions for estrogen receptor positive early-stage breast cancer: incorporating the 70-gene signature into the PREDICT prognostication model

The 70-gene signature (70-GS) has been shown to identify women at low-risk of distant recurrence who can safely forgo adjuvant chemotherapy. Incorporating this GS into the well-validated and widely used PREDICT breast cancer model could improve the model's ability to estimate breast cancer prog...

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Bibliographic Details
Published in:Breast (Edinburgh) Vol. 83; p. 104542
Main Authors: Engelhardt, Ellen G., Binuya, Mary Ann E., Pharoah, Paul D.P., Poncet, Coralie, Rutgers, Emiel J.T., Piccart, Martine, Cardoso, Fatima, van ‘t Veer, Laura J., Steyerberg, Ewout W., Linn, Sabine C., Schmidt, Marjanka K.
Format: Journal Article
Language:English
Published: Netherlands Elsevier Ltd 01.10.2025
Elsevier
Subjects:
70-Gene signature
Adult
Aged
Breast Neoplasms - drug therapy
Breast Neoplasms - genetics
Breast Neoplasms - mortality
Breast Neoplasms - pathology
Breast Neoplasms - therapy
Chemotherapy, Adjuvant
Female
Gene Expression Profiling
Hematology, Oncology, and Palliative Medicine
Humans
Middle Aged
Model extension
Neoplasm Recurrence, Local - genetics
Neoplasm Staging
Netherlands
Original
PREDICT for breast cancer model
Predictive Value of Tests
Prognosis
Prognostication
Receptors, Estrogen - metabolism
Registries
Risk Assessment - methods
Transcriptome
Validation
Netherlands
Validation
70-Gene signature
Prognostication
Model extension
PREDICT for breast cancer model
ISSN:0960-9776, 1532-3080, 1532-3080
Online Access:Get full text
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Summary:The 70-gene signature (70-GS) has been shown to identify women at low-risk of distant recurrence who can safely forgo adjuvant chemotherapy. Incorporating this GS into the well-validated and widely used PREDICT breast cancer model could improve the model's ability to estimate breast cancer prognosis, and thereby further reduce overtreatment and its long-term impact on patients' quality of life. We incorporated the 70-GS into PREDICT-v2.3 and assessed the new PREDICT-GS model's ability to predict 5-year risk of breast cancer death. Data from the MINDACT trial (N = 5920) was used to estimate the 70-GS's prognostic effect (coefficient = 0.70), which was then incorporated into PREDICT-v2.3. Netherlands Cancer Registry (NCR) data (N = 3323) was used to assess PREDICT-GS's discrimination (area under curve (AUC)), calibration and clinical utility. Compared to PREDICT-v2.3 (AUC: 0.71 (95 % CI: 0.63–0.79)), PREDICT-GS (AUC: 0.76 (95 % CI: 0.69–0.83)) had better discrimination. Both models tended to overestimate the 5-year risk of breast cancer death in the NCR cohort, but the absolute overestimation was smaller for PREDICT-GS. Regarding clinical utility, only at the 10 % decision threshold did we find modest improvement: four extra patients per 1000 tests were correctly classified as not needing chemotherapy by PREDICT-GS compared to PREDICT-v2.3. Extending PREDICT-v2.3 with 70-GS led to modest improvement in its ability to predict 5-year risk of breast cancer death. Future research should focus on assessing the added value of the 70-GS for longer-term prediction of recurrence and death with the incorporation of quality of life in risk prediction tools. •70-gene signature (GS) could improve PREDICT 5-year breast cancer death predictions.•PREDICT-GS (AUC:0.76) had slightly better discrimination than PREDICT (AUC:0.71).•Smaller overestimation of 5-year mortality by PREDICT-GS in population-based cohort.•Modest improvement in clinical utility of PREDICT-GS vs. PREDICT.
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Authors contributed equally.
ISSN:0960-9776
1532-3080
1532-3080
DOI:10.1016/j.breast.2025.104542