Inflammatory Biomarker C-Reactive Protein and Radiotherapy-Induced Early Adverse Skin Reactions in Patients with Breast Cancer

Abstract

Background Breast cancer is the most frequently diagnosed cancer and the second leading cause of cancer death in American women. Post-surgery adjuvant radiotherapy (RT) significantly reduced the local recurrence rate. However, many patients develop early adverse skin reactions (EASRs) that impact quality of life and treatment outcomes. Methods We evaluated an inflammatory biomarker, C-reactive protein (CRP) in predicting RT-induced EASRs in 159 breast cancer patients undergoing RT. In each patient, we measured pre- and post-RT plasma CRP levels using a highly-sensitive ELISA CRP assay. RT-induced EASRs were assessed at weeks 3 and 6 using the National Cancer Institute Common Toxicity Criteria (v3.0). Association between EASRs and CRP levels were assessed using logistic regression models after adjusting for potential confounders. Results RT-induced grade 2+ EASRs were observed in 8 (5%) and 80 (50%) patients at weeks 3 and 6 (end of RT), respectively. At the end of RT, significantly higher proportion of African Americans developed grade 3 EASRs (13.8% vs. 2.3% in others); grade 2+ EASRs were significantly associated with: change of CRP>1 mg/L (OR=2.51; 95%CI=1.06, 5.95, p=0.04), obesity (OR=2.08; 95%CI=1.03, 4.21, p=0.04), or combined both factors (OR=5.21; 95%CI=1.77, 15.38, p=0.003). Conclusion This is the first study to demonstrate that an inflammatory biomarker CRP is associated with RT-induced EASRs, particularly combined with obesity. Impact Future larger studies are warranted to validate our findings and facilitate the discovery and development of anti-inflammatory agents to protect normal tissue from RT-induced adverse effects and improve quality of life in breast cancer patients undergoing RT.

Prospective evaluation of radiation‐induced skin toxicity in a race/ethnically diverse breast cancer population

“…Our prospective analysis also includes collection of genomic DNA, serum, and urine specimens at the start and completion of RT, and we are optimistic that future studies may begin to elucidate molecular and genetic mechanisms . Indeed, our preliminary analysis has uncovered a relationship between C‐reactive protein and skin reaction . However, the relationships identified in this study must be interpreted cautiously, and are simply hypothesis‐generating at this time.…”

Characterization of risk factors for adjuvant radiotherapy-associated pain in a tri-racial/ethnic breast cancer population

“…Among the 11 comorbid conditions, diabetes, hypertension, or thyroid disease may increase pain intensity through modulating pain hypersensitivity/threshold, systemic inflammation, and/or radio-sensitivity [44]. Our previous study demonstrated that comorbid conditions increased inflammatory biomarker in radio-sensitivity and skin toxicity, particularly among obese breast cancer patients [35]. These comorbid conditions will need to be considered as part of the treatment decision making process and effective pain management strategies are needed to improve QOL in high-risk breast cancer patients with at least 2 comorbid conditions.…”

Biomarkers of radiation‐induced vascular injury

“…High-sensitivity CRP Acute phase protein synthesized during an inflammatory response; has been evaluated in head and neck cancers undergoing RT; maybe an indicator of persistent cardiac inflammation secondary to RT and ongoing remodeling; elevated CRP is predictive of decreased LVEF and diastolic dysfunction. 43…”