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Background: Current prediction tools for breast cancer outcomes are not tailored to the older patient, in whom competing risk strongly influences treatment effects. We aimed to develop and validate a prediction tool for 5-year recurrence, overall mortality, and other-cause mortality for older patients (aged ≥65 years) with early invasive breast cancer and to estimate individualised expected benefits of adjuvant systemic treatment.
Methods: We selected surgically treated patients with early invasive breast cancer (stage I-III) aged 65 years or older from the population-based FOCUS cohort in the Netherlands. We developed prediction models for 5-year recurrence, overall mortality, and other-cause mortality using cause-specific Cox proportional hazard models. External validation was performed in a Dutch Cancer registry cohort. Performance was evaluated with discrimination accuracy and calibration plots.
Findings: We included 2744 female patients in the development cohort and 13631 female patients in the validation cohort. Median age was 74·8 years (range 65-98) in the development cohort and 76·0 years (70-101) in the validation cohort. 5-year follow-up was complete for more than 99% of all patients. We observed 343 and 1462 recurrences, and 831 and 3594 deaths, of which 586 and 2565 were without recurrence, in the development and validation cohort, respectively. The area under the receiver-operating-characteristic curve at 5 years in the external dataset was 0·76 (95% CI 0·75-0·76) for overall mortality, 0·76 (0·76-0·77) for recurrence, and 0·75 (0·74-0·75) for other-cause mortality.
Interpretation: The PORTRET tool can accurately predict 5-year recurrence, overall mortality, and other-cause mortality in older patients with breast cancer. The tool can support shared decision making, especially since it provides individualised estimated benefits of adjuvant treatment.
Funding: Dutch Cancer Foundation and ZonMw.
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http://dx.doi.org/10.1016/S2666-7568(21)00229-4 | DOI Listing |
Mol Cancer Ther
September 2025
Case Western Reserve University School of Medicine, Cleveland, OH, United States.
The estrogen receptor (ER or ERα) remains the primary therapeutic target for luminal breast cancer, with current treatments centered on competitive antagonists, receptor down-regulators, and aromatase inhibitors. Despite these options, resistance frequently emerges, highlighting the need for alternative targeting strategies. We discovered a novel mechanism of ER inhibition that targets the previously unexplored interface between the DNA-binding domain (DBD) and ligand-binding domain (LBD) of the receptor.
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Department of Natural Products and Medicinal Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
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Paris Cité University, INSERM UMR-S 970, Paris Cardiovascular Research Centre, Paris, France.
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View Article and Find Full Text PDFAnn Surg Oncol
September 2025
Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.