Association between the CARG-BC score and clinical decline after adjuvant chemotherapy in fit older adults with breast cancer: Results from the Hurria Older PatiEnts (HOPE) Prospective Study

Background: We previously developed and validated a risk prediction model for grade 3-5 chemotherapy toxicity in patients age ≥65 with early breast cancer, known as the Cancer and Aging Research Group-Breast Cancer (CARG-BC) score. The CARG-BC score is calculated by combining eight clinical variables that classify patients as low, intermediate, and high risk for grade 3-5 chemotherapy toxicity. However, whether this score can also identify individuals most likely to experience a clinical decline after chemotherapy remains unknown. Here, we evaluated the association between the CARG-BC score and decline in health status.

Methods: This is a pre-specified secondary analysis of the Hurria Older PatiEnts (HOPE) with Breast Cancer Study (NCT01472094). This multicenter, prospective cohort study gathered biological and clinical data from women ≥65 with stage I-III breast cancer scheduled to receive neo/adjuvant chemotherapy. Health status was measured pre- (≤14 days) and post-chemotherapy (≤30 days) using a Deficit Accumulation Index (DAI), derived from geriatric assessment data (Cohen et al Cancer 2017). The DAI categorized patients as robust (0.0< 0.2), prefrail (0.2< 0.35), or frail (≥0.35). Baseline clinical characteristics, blood biomarkers of inflammation (interleukin-6 [IL-6] and C-reactive protein [CRP]), and CARG-BC scores (classified as low [0-5], intermediate [6-11] or high [≥12]) were collected pre-chemotherapy. The population of interest was older women who were clinically fit (defined as robust per the DAI) pre-chemotherapy. The primary outcome was chemotherapy-induced decline in health status, a dichotomized (yes/no) variable defined as a decline in DAI from robust pre-chemotherapy to pre-frail or frail post-chemotherapy. Multivariable logistic regression was used to examine the association between baseline CARG-BC score and chemotherapy-induced decline in health status.

Results: Of 392 women included in this analysis, 316 (80.6%) were clinically fit based on DAI assessment pre-chemotherapy. The median age was 70 (range 65-86), 61.7% had stage II or III disease, 31% had HR+/HER2+ disease, 22% had HR-/HER2- disease, 36% received an anthracycline, and 74% received prophylactic WBC growth factors. At baseline, 38.7% had low, 53.4% had intermediate, and 7.9% had high CARG-BC scores. Among the 316 clinically fit patients, 80 (25.3%) experienced a decline in health status at the end of chemotherapy. In univariate analysis, we observed that patients with high IL-6 (odds ratio [OR]=2.24, 95% CI: 1.32-3.79, p=0.003), high CRP (OR=1.84, 95%: CI 1.10-3.09, p=0.02), and intermediate (OR=3.29, 95% CI 1.72-6.29, p< 0.001) or high (OR=6.29, 95% CI 2.36-16.71, p< 0.001) CARG-BC scores were more likely to experience chemotherapy-induced decline in health status. After adjusting for IL-6 and CRP, patients with both intermediate (OR=3.25, 95% CI 1.68-6.27, p< 0.001) and high (OR=5.17, 95% CI 1.90-14.02, p=0.001) CARG-BC scores had significantly higher odds of experiencing chemotherapy-induced clinical decline as compared to patients with low CARG-BC scores.

Conclusions: In this cohort of older women with early breast cancer who were clinically fit pre-chemotherapy, 25% experienced a decline in health status after neo/adjuvant chemotherapy. Women with an intermediate/high CARG-BC score prior to chemotherapy had 3-5-fold increased odds of experiencing chemotherapy-induced decline in health status independent of baseline clinical characteristics and biomarkers of inflammation. These findings may be useful to clinicians for predicting individual probability of chemotherapy-induced clinical decline and informing treatment decisions in older adults with early breast cancer.

Table 1.

Univariate and multivariable association of the CARG-BC score with chemotherapy-induced decline in health status.

Univariate and multivariable association of the CARG-BC score with chemotherapy-induced decline in health status.
Univariate and multivariable association of the CARG-BC score with chemotherapy-induced decline in health status.

Multivariable analysis adjusted for baseline demographic, clinical, and inflammatory levels (IL-6 and CRP); *CARG-BC score is calculated using 8 independent predictors (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). The total CARG-BC risk score is the sum of each point derived from these 8 predictors. Each patient’s total CARG-BC score can then be classified into three risk groups: low (0-5 points), intermediate (6-11 points), or high (≥ 12 points).

Citation Format: Jingran Ji, Canlan Sun, Hyman B. Muss, Harvey J. Cohen, Mina S. Sedrak. PD6-01 Association between the CARG-BC score and clinical decline after adjuvant chemotherapy in fit older adults with breast cancer: Results from the Hurria Older PatiEnts (HOPE) Prospective Study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD6-01.