Inflammation ups risk of chemo-induced decline in frailty status in older women with breast cancer

Robust older women with early breast cancer who have high prechemotherapy levels of both interleukin-6 (IL-6) and C-reactive protein (CRP) are >3 times more likely to experience chemotherapy-induced decline in frailty status than their counterparts with low levels of these inflammatory markers, a prospective study has shown.

According to the investigators, these findings suggest that biologic measures of inflammation may facilitate individualized assessment of risk of chemotherapy-induced decline in frailty status at the time of diagnosis, which may help predict tolerability of cancer treatment and guide treatment decisions. [J Clin Oncol 2022;doi:10.1200/JCO.22.01217]

The study included 295 robust women aged ≥65 years with stage I–III breast cancer treated with adjuvant chemotherapy. At the time of starting chemotherapy, the patients were at a median age of 69 years, with a median BMI of 27.9 kg/m² and a median of 2.0 comorbidities. All patients were robust at baseline, with a Deficit Accumulation Index (DAI) score of 0 to >2.

Most patients (62.7 percent) in the study had stage II or III breast cancer. About half (46.8 percent) had HER2-negative/hormone receptor (HR)–positive disease, 31.2 percent had HER2-positive disease, while 22 percent had triple-negative disease. An anthracycline-containing regimen was used in 32.3 percent of patients, and 72.5 percent received primary granulocyte-colony stimulating factor prophylaxis.

Chemotherapy-induced decline in frailty status occurred in 76 patients (25.8 percent). This included 69 patients (23.4 percent) who became prefrail (DAI score, 0.2 to <0.35), and seven patients (2.4 percent) who became frail (DAI score, ≥0.35).

Applying median cut-offs of 2.5 pg/mL for IL-6 and 3.5 mg/L for CRP, patients who experienced chemotherapy-induced decline in frailty status were found to have higher baseline levels of IL-6 (median, 3.57 pg/mL vs 2.15 pg/mL; p=0.003) and CRP (median, 4.75 mg/L vs 3.06 mg/L; p=0.007) than those who remained clinically fit.

Among 76 patients who experienced chemotherapy-induced decline in frailty status, 65.8 percent had high IL-6 levels and 63.2 percent had high CRP levels before the start of chemotherapy. High prechemotherapy levels of both IL-6 and CRP were found in 46.1 percent of patients with chemotherapy-induced decline in frailty status, compared with only 25.6 percent of patients who remained clinically fit after chemotherapy.

In multivariable logistic regression analysis, patients with high levels of both IL-6 and CRP were found to be >3 times more likely to experience chemotherapy-induced decline in frailty status (odds ratio, 3.52; 95 percent confidence interval, 1.55–8.01; p=0.003) than those with low levels of these inflammatory markers, after adjusting for age, race/ethnicity, education, BMI, cancer stage, breast cancer surgery, use of anti-inflammatory medications, and number of comorbidities.

Although 37 percent of patients in the study were taking anti-inflammatory medications, the use of these medications was not significantly associated with IL-6 (median, 2.7 pg/mL among nonusers vs 2.3 pg/mL among users; p=0.28) or CRP (median, 3.4 mg/L among nonusers vs 3.6 mg/L among users; p=0.76).

“Our findings suggest that older patients with breast cancer with high IL-6 and CRP, especially those with both markers elevated, are vulnerable to experiencing a decline in physiologic reserve with chemotherapy, even if they appear to be robust or clinically fit,” the investigators commented.

“Inflammation may be a targetable biological pathway that can be leveraged to prevent and mitigate chemotherapy-induced clinical decline,” they added.