Development and Validation of a Risk Tool for Predicting Severe Toxicity in Older Adults Receiving Chemotherapy for Early-Stage Breast Cancer

Abstract

PURPOSE Limited tools exist to predict the risk of chemotherapy toxicity in older adults with early-stage breast cancer. METHODS 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. RESULTS In 473 patients (283 in development and 190 in validation cohort), 46% developed grade 3-5 chemotherapy toxicities. Eight independent predictors were identified (each assigned weighted points): anthracycline use (1 point), stage II or III (3 points), planned treatment duration > 3 months (4 points), abnormal liver function (3 points), low hemoglobin (3 points), falls (4 points), limited walking (3 points), and lack of social support (3 points). We calculated risk scores for each patient and defined three risk groups: low (0-5 points), intermediate (6-11 points), or high (≥ 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 < .01). In the validation cohort, the corresponding toxicity rates were 27%, 45%, and 76%. The AUC was 0.75 (95% 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 hospitalizations and reduced dose intensity ( P < .01). CONCLUSION The Cancer and Aging Research Group-Breast Cancer (CARG-BC) score was developed and validated to predict grade 3-5 chemotherapy toxicity in older adults with early-stage breast cancer.

Mucinous carcinoma in an octogenarian: Treatment and management of breast cancer in the elderly

“…Though the benefits and tolerability of endocrine therapy does not depend on age, research has shown chemotherapy tolerability decreases with age [ 28 , 29 ]. The recent 2021 Cancer and Aging Research Group-Breast Cancer (CARG-BC) score has been developed as a risk calculation tool to predict chemotherapy toxicity in treatment of early stage breast cancer in the elderly; the goal is to make chemotherapy a safer and more accessible treatment option in this group [30] .…”

“…Elderly women with breast cancer have significantly better overall and cancer-specific survival when they received surgery, and surgery is the most important factor associated with better survival, moreso than age, stage, and ER/PR/HER2 status [29] . Despite this, research has shown that the elderly are less likely to undergo surgery for breast cancer [ 30 , 31 ].…”

Adjuvant Trastuzumab Without Chemotherapy For Treating Early HER2-Positive Breast Cancer In Older Patients: A Cohort Study Accompanying With The RESPECT Trial

“…Comprehensive geriatric-assessment (CGA) screening tools for older patients can be useful for predicting severe AE [27], and it is important to intensify supportive care and develop modi ed treatment regimens in vulnerable patients who may subsequently experience greater toxicity [28]. For the RCT group, we developed a CGA screening tool at baseline and at each point to analyze the relationship between AEs and DFS.…”

Personalising therapy for early-stage oestrogen receptor-positive breast cancer in older women

“…Notably, the Cancer and Aging Research Group-Breast Cancer score was validated to predict grade 3–5 chemotherapy toxicity in older adults with early-stage breast cancer. 95 Among the eight predictors of toxicity, limited mobility and insufficient social support were both identified as important parameters. These findings further highlight that, in the setting of escalating therapy to include chemotherapy, clinicians should consider a comprehensive geriatric assessment before starting treatment.…”