Allison Magnuson of the University of Rochester in Rochester, NY, US and colleagues reported on 14 January 2021 in the Journal of Clinical Oncology that the Cancer and Aging Research Group-Breast Cancer score, which they derived by combining eight clinical and geriatric variables, was developed to classify elderly patients with early breast cancer into low, intermediate, and high risk for developing grade 3-5 chemotherapy toxicity. The score was externally validated and demonstrated that better predicts toxicity compared with prior models and physician-rated performance status. It was also strongly associated with dose reductions, dose delays, early treatment discontinuation, reduced dose intensity, and hospitalisations.

The authors commented in the study background that limited tools exist to predict the risk of chemotherapy toxicity in elderly patients with early breast cancer. Karnofsky performance status or Eastern Cooperative Oncology Group performance status, were developed and validated in younger patients but do not reliably assess the fitness of older patients. Existing toxicity prediction models were developed and validated in a heterogeneous elderly population with various cancer subtypes, stages, and chemotherapy regimens. They underlined that a tool that accounts for specific disease and treatment variables that are relevant for elderly patients with early breast cancer may provide more accurate risk estimates.

The authors conducted a multicentre, prospective cohort study of elderly patients with early breast cancer who were initiating adjuvant or neoadjuvant chemotherapy. The main objective was to develop and validate a model to predict grade 3-5 chemotherapy toxicity in elderly patients with early breast cancer.

Patients of age ≥65 years with stage I-III breast cancer from 16 institutions treated with neoadjuvant or adjuvant chemotherapy were prospectively evaluated for geriatric and clinical features predictive of grade 3-5 chemotherapy toxicity. Logistic regression with best-subsets selection was used to identify and incorporate independent predictors of toxicity into a model with weighted variable scoring. Model performance was evaluated using area under the ROC curve (AUC) and goodness-of-fit statistics. The model was internally and externally validated.

In 473 patients of whom 283 in development and 190 in validation cohort, 46% developed grade 3-5 chemotherapy toxicities. Eight independent predictors were identified and each assigned weighted points: 1 point  for anthracycline use, 3 points for stage II or III, 4 points for planned treatment duration >3 months, 3 points for abnormal liver function, 3 points for low haemoglobin, 4 points for falls, 3 points for limited walking, and 3 points for lack of social support.

The study team calculated risk scores for each patient and defined three risk groups: low in case of 0-5 points, intermediate in case of 6-11 points, or high in case of ≥12 points. In the development cohort, the rates of grade 3-5 chemotherapy toxicity for these three groups were 19%, 54%, and 87%, respectively (p < 0.01). In the validation cohort, the corresponding toxicity rates were 27%, 45%, and 76%. The AUC was 0.75 (95% confidence interval [CI] 0.70 to 0.81) in the development cohort and 0.69 (95% CI 0.62 to 0.77) in the validation cohort.

Risk groups were also associated with hospitalisations and reduced dose intensity (p < 0.01).

The authors commented that their findings may be useful to clinicians for predicting individual probability of chemotherapy toxicity and directing therapy in elderly patients with early breast cancer. Intensifying supportive care and developing modified treatment regimens may be appropriate for subgroups identified as being vulnerable to greater toxicity. 


Magnuson A, Sedrak MS, Gross CP, et al. Development and Validation of a Risk Tool for Predicting Severe Toxicity in Older Adults Receiving Chemotherapy for Early-Stage Breast Cancer. Journal of Clinical Oncology; Published online 14 January 2021. DOI: 10.1200/JCO.20.02063.