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In older patients with breast cancer, the risk of dying from other causes than breast cancer strongly increases after the age of 70. The aim of this study was to assess contributions of breast cancer mortality versus other-cause mortality after locoregional or distant recurrence in a population-based cohort of older patients analysed by multi-state models. Surgically treated patients ≥70 years diagnosed with stage I-III breast cancer in 2003–2009 were selected from the Netherlands Cancer Registry. A novel multi-state model with locoregional and distant recurrence that incorporates relative survival was fitted. Other-cause and breast cancer mortality were indicated as population and excess mortality. Overall, 18,419 patients were included. Ten-year cumulative incidences of locoregional and distant recurrence were 2.8% (95%CI 2.6–3.1%) and 12.5% (95%CI 11.9–13.1%). Other-cause mortality increased from 23.9% (95%CI 23.7–24.2%) in patients 70–74 years to 73.8% (95%CI 72.2–75.4%) in those ≥80 years. Ten-year probabilities of locoregional or distant recurrence with subsequent breast cancer death were 0.4–1.3% and 10.2–14.6%, respectively. For patients with a distant recurrence in the first two years after diagnosis, breast cancer death probabilities were 95.3% (95%CI 94.2–96.4%), 93.1% (95%CI 91.6–94.6%), and 88.6% (95%CI 86.5–90.8%) in patients 70–74, 75–79, and ≥80 years. In older patients without recurrence, prognosis is driven by other-cause mortality. Although locoregional recurrence is a predictor for worse outcome, given its low incidence it contributes little to breast cancer mortality after diagnosis. For patients who develop a distant recurrence, breast cancer remains the dominant cause of death, even at old age. • Older patients with breast cancer often die from competing causes. • Competing mortality after recurrence has not been extensively studied so far. • Novel multi-state models were used including time after recurrence. • These models can be applied to different datasets as input for clinical decision tools. [ABSTRACT FROM AUTHOR]

Simple Summary: Selecting older patients for adjuvant breast cancer treatments is challenging as its benefits can be diminished by shorter life expectancies. In addition to age, comorbidity increases the risk of dying from other causes than breast cancer. Available prediction tools have either not adjusted for individual comorbidities or have shown inaccurate predictions when a higher number of comorbidities are present. Up to now, an optimal comorbidity score to be used in prediction tools has not been established. Therefore, this study aimed to assess the predictive value of the Charlson comorbidity index for other-cause mortality and to compare these predictions with using a simple comorbidity count. We found that the Charlson index performed similarly as comorbidity count. The use of comorbidity count in the development of new prediction tools for older patients with breast cancer is recommended as its simplicity enhances the tool's applicability in clinical practice. Background: Individualized treatment in older patients with breast cancer can be improved by including comorbidity and other-cause mortality in prediction tools, as the other-cause mortality risk strongly increases with age. However, no optimal comorbidity score is established for this purpose. Therefore, this study aimed to compare the predictive value of the Charlson comorbidity index for other-cause mortality with the use of a simple comorbidity count and to assess the impact of frequently occurring comorbidities. Methods: Surgically treated patients with stages I-III breast cancer aged ≥70 years diagnosed between 2003 and 2009 were selected from the Netherlands Cancer Registry. Competing risk analysis was performed to associate 5-year other-cause mortality with the Charlson index, comorbidity count, and specific comorbidities. Discrimination and calibration were assessed. Results: Overall, 7511 patients were included. Twenty-nine percent had no comorbidities, and 59% had a Charlson score of 0. After five years, in 1974, patients had died (26%), of which 1450 patients without a distant recurrence (19%). Besides comorbidities included in the Charlson index, the psychiatric disease was strongly associated with other-cause mortality (sHR 2.44 (95%-CI 1.70–3.50)). The c-statistics of the Charlson index and comorbidity count were similar (0.65 (95%-CI 0.64–0.65) and 0.64 (95%-CI 0.64–0.65)). Conclusions: The predictive value of the Charlson index for 5-year other-cause mortality was similar to using comorbidity count. As it is easier to use in clinical practice, our findings indicate that comorbidity count can aid in improving individualizing treatment in older patients with breast cancer. Future studies should elicit whether geriatric parameters could improve prediction. [ABSTRACT FROM AUTHOR]

Previous studies have shown that survival outcomes for older patients with breast cancer vary substantially across Europe, with worse survival reported in the United Kingdom. It has been hypothesised that these differences in survival outcomes could be related to treatment variation. We aimed to compare patient and tumour characteristics, treatment selection and survival outcomes between two large prospective cohorts of older patients with operable breast cancer from the United Kingdom (UK) and The Netherlands. Women diagnosed with operable breast cancer aged ≥70 years were included. A baseline comprehensive geriatric assessment was performed in both cohorts, with data collected on age, comorbidities, cognition, nutritional and functional status. Baseline tumour characteristics and treatment type were collected. Univariable and multivariable Cox regression models were used to compare overall survival between the cohorts. 3262 patients from the UK Age Gap cohort and 618 patients from the Dutch Climb cohort were included, with median ages of 77.0 (IQR: 72.0–81.0) and 75.0 (IQR: 72.0–81.0) years, respectively. The cohorts were generally comparable, with slight differences in rates of comorbidity and frailty. Median follow-up for overall survival was 4.1 years (IQR 2.9–5.4) in Age Gap and 4.3 years (IQR 2.9–5.5) in Climb. In Age Gap, both the rates of primary endocrine therapy and adjuvant hormonal therapy after surgery were approximately twice those in Climb (16.6% versus 7.3%, p < 0.001 for primary endocrine therapy, and 62.2% versus 38.8%, p < 0.001 for adjuvant hormonal therapy). There was no evidence of a difference in overall survival between the cohorts (adjusted HR 0.94, 95% CI 0.74–1.17, p = 0.568). In contrast to previous studies, this comparison of two large national prospective longitudinal multi-centre cohort studies demonstrated comparable survival outcomes between older patients with breast cancer treated in the UK and The Netherlands, despite differences in treatment allocation. • No survival difference between UK and Netherlands for older breast cancer patients. • Similar patient and tumour characteristics seen in both cohorts. • Higher rates of mastectomy for older breast cancer patients in Netherlands. • Higher rates of adjuvant therapies for older breast cancer patients in UK. [ABSTRACT FROM AUTHOR]

Background: Studies have demonstrated worse breast cancer-specific mortality with older age, despite an increasing risk of dying from other causes due to comorbidity (competing mortality). However, findings on the association between older age and recurrence risk are inconsistent. The aim of this study was to assess incidences of locoregional and distant recurrence by age, taking competing mortality into account., Materials and Methods: Patients surgically treated for nonmetastasized breast cancer between 2003 and 2009 were selected from The Netherlands Cancer Registry. Cumulative incidences of recurrence were calculated considering death without distant recurrence as competing event. Fine and Gray analyses were performed to characterize the impact of age (70-74 [reference group], 75-79, and ≥80 years) on recurrence risk., Results: A total of 18,419 patients were included. Nine-year cumulative incidences of locoregional recurrence were 2.5%, 3.1%, and 2.9% in patients aged 70-74, 75-79, and ≥80 years, and 9-year cumulative incidences of distant recurrence were 10.9%, 15.9%, and 12.7%, respectively. After adjustment for tumor and treatment characteristics, age was not associated with locoregional recurrence risk. For distant recurrence, patients aged 75-79 years remained at higher risk after adjustment for tumor and treatment characteristics (75-79 years subdistribution hazard ratio [sHR], 1.25; 95% confidence interval [CI], 1.11-1.41; ≥80 years sHR, 1.03; 95% CI, 0.91-1.17)., Conclusion: Patients aged 75-79 years had a higher risk of distant recurrence than patients aged 70-74 years, despite the higher competing mortality. Individualizing treatment by using prediction tools that include competing mortality could improve outcome for older patients with breast cancer., Implications for Practice: In this population-based study of 18,419 surgically treated patients aged 70 years or older, patients aged 75-79 years were at higher risk of distant recurrence than were patients aged 70-74 years. This finding suggests that patients in this age category are undertreated. In contrast, it was also demonstrated that the risk of dying without a recurrence strongly increases with age, and patients with a high competing mortality risk are easily overtreated. To identify older patients who may benefit from more treatment, clinicians should therefore take competing mortality risk into account. Prediction tools could facilitate this and thereby improve treatment strategy., (© AlphaMed Press 2019.)