Increased pre-chemotherapy inflammatory biomarkers (IL-6 and CRP) correlated to increased risk of frailty post-chemotherapy in older breast cancer patients

1. 25.8% of patients receiving chemotherapy for breast cancer experienced worsening frailty status.

2. Patients with both biomarkers (IL-6 and CRP) elevated before chemotherapy had a significantly higher risk of decline in frailty status.

Evidence Rating Level: 2 (Good)

Study Rundown: Interleukin-6 (IL-6) and C-reactive protein (CRP) are two inflammatory biomarkers that have been associated with worse post-chemotherapy frailty in older patients diagnosed and treated for breast cancer. This study investigated whether there was worsening frailty status from baseline corresponding to inflammatory biomarkers after adjuvant chemotherapy in patients with breast cancer. Median cutoff levels were chosen based on previous studies and IL-6 was 2.5pg/mL and CRP was 3.5 mg/L. The primary outcome of this study was whether there was a post-chemotherapy decline in frailty status as measured by a Deficit Accumulation Index (DAI). In the baseline characteristics assessment, it was found that BMI or use of anti-inflammatory medication were not associated with biomarkers of inflammation (IL-6 and CRP). There was evidence of worsening frailty status in 25.8% of women as a result of chemotherapy treatment for their breast cancer. Patients who became frailer had significantly higher baseline levels of inflammatory biomarkers IL-6 and CRP. Limitations to this study include the short follow-up period which makes it difficult to apply conclusions to the long-term recovery of frailty status. Additionally, the study did not account for events that may have occurred during treatment, including hospitalizations or severe toxicities due to treatment. Overall, the results from this study reveal that high baseline levels of inflammatory biomarkers IL-6 and CRP are associated with increased frailty due to chemotherapy after treatment for breast cancer.

Click to read the study in the Journal of Clinical Oncology

Relevant Reading: Interleukin-6 and C-reactive protein, successful aging, and mortality: The PolSenior study.

In-Depth [prospective cohort]: This prospective cohort study was completed out of 16 healthcare centres in the United States. The study enrolled adult patients who were 65 years and older and who were diagnosed and treated for stage I, II, or III breast cancer. The final study cohort was comprised of 295 patients, 37.3% of whom had stage I and 62.7% who had either stage II or III cancer. Prior to receiving chemotherapy, 82% of patients received breast cancer surgery (48% received a mastectomy and 52% received a lumpectomy). Patients who had higher baseline levels of IL-6 (median 3.57 pg/mL) experienced a decline in their frailty status after receiving chemotherapy, as compared to those who did not experience a decline (median 2.15 pg/mL). The result was similar for baseline CRP levels (median 4.75 mg/L compared to 3.06 mg/L, respectively). The majority of the 76 patients who experienced a decline in their frailty status post-chemotherapy had high levels of biomarkers; 63.2% had high CRP, 65.8% had high IL-6 and almost half (46.1%) had high levels of both biomarkers. Chemotherapy-induced frailty was 2.2 times more likely in those with high IL-6 (odds ratio (OR) 2.21; 95% confidence interval (CI), 1.28-3.80) and was 2.1 times more likely in those with high CRP (OR, 2.1; 95% CI, 1.23-3.62). Patients who had increased levels of both biomarkers had a more than 3-fold increased odds of frailty after chemotherapy (OR, 3.61; 95% CI, 1.75-7.44). There was a clinically significant median change of 0.06 in the DAI pre- and post-chemotherapy overall. When comparing with patients whose frailty status was unaffected it was found that there was a greater change in DAI in those patients whose frailty status declined (median change in DAI 0.12 vs. 0.03).

Image: PD

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