Study Finds Association Between C-reactive Protein and Radiotherapy-Related Pain in Breast Cancer Patients

Among American women, breast cancer is the second leading cause of cancer death and the most often diagnosed type of cancer. When compared to breast-conserving surgery (BCS), an operation that removes cancer while leaving as much normal breast as possible, adjuvant radiotherapy (RT) has significantly reduced recurrences in the area. RT is often used after primary treatments, such as surgeries like BCS, to decrease the likelihood of a relapse.

RT is recommended because even if all the visible cancer is removed during surgery, microscopic bits of cancer can remain. There are five types of therapies that treat the remaining cancer cells, which include chemotherapy, hormone therapy, radiation therapy, immunotherapy, and targeted therapy.

While RT reduces reoccurrences, it does have adverse responses that negatively affect the overall quality of life of patients. Patients have developed breast erythema, pain, retraction at the tumor-bed site, fibrosis, cardiac morbidity, lymphedema, and telangiectasia.

“Pain is one of the most common symptoms and is an important quality of life issue in breast cancer survivors,” said Jennifer Hu, Ph.D., professor of public health at the Miller School, who was one of the co-authors in the study. 

Pain is associated with inflammation, which can be measured as C-reactive protein (CRP). CRP is a protein made by the liver and is circulating in the bloodstream in response to inflammation, which usually protects human tissue when someone has been injured, has an infection, an autoimmune disorder and/or chronic disease. Aside from pain, swelling and redness also occur.

While identifying a biomarker can predict treatment-related symptoms and is an important research question in the field of radiation oncology, there are few studies that examine biomarkers for RT-related pain.

To help guide the decision of RT, as well as with the development of targeted interventions to improve the quality of life patients, a pilot study, published in Breast Cancer Research, examined CRP and its association with pain before and after RT.

“We evaluated whether the inflammatory biomarker, CRP, was associated with RT-related pain as it has been widely used as a robust inflammatory biomarker for many health conditions in both clinical and research settings. Our prior studies have shown a positive correlation between plasma CRP levels and RT-induced skin toxicity in breast cancer patients,” said Dr. Hu.

From 2008 to 2014, researchers evaluated pain levels before and after the RT treatment of breast cancer patients. Their CRP levels were also measured using the CRP ELISA Kit, which is a quick, but an accurate research tool. To assess levels of pain, researchers used scores from the Brief Pain Inventory, which provides a means of measuring pain intensity. Levels include pain at its worst, least, average and low. Scores of four to 10 were considered clinically relevant pain. To determine the association between CRP and RT-related pain, researchers used multivariable logistic regression analyses.

They found that in 366 breast cancer patients, of which 235 were Hispanic whites, 73 were black/African Americans, and 59 were non-Hispanic whites, 17 to 30 percent of patients reported having pain before and after RT, respectively. There were 23 percent of patients with RT-related pain. After conducting the analysis, pain levels differed significantly by race and ethnicity.

“Overall, patients reported a significantly higher pain score at post-RT compared to pre-RT. In general, African American and Hispanic White patients had significantly higher pre-RT and post-RT pain scores compared to those in non-Hispanic White patients,” said Dr. Hu. 

RT-related pain was also significantly associated with detections of high CRP levels before RT alone or combined with obesity after adjustment for age and race and ethnicity.

As this study is the first to examine CRP in RT-related pain, particularly in obese patients, future studies are necessary to validate its findings.

Dr. Hu is currently working on a validation study with 1,000 patients recruited nationwide as reported in a publication in the Journal of Clinical Oncology in 2018 entitled “Association Between Inflammatory Biomarker C-Reactive Protein and Radiotherapy-Induced Early Adverse Skin Reactions in a Multiracial/Ethnic Breast Cancer Population. If validated, these results pave the way for testing anti-inflammatory agents in reducing RT-related pain.

This study was co-authored by researchers at the University of Miami Miller School of Medicine’s Department of Public Health Sciences, Sylvester Comprehensive Cancer Center, and Department of Radiation Oncology, the University of Central Florida’s Department of Health Sciences, as well as by researcher at Johns Hopkins University’s Department of Radiation Oncology.

Previously, Dr. Hu collaborated with the Wake Forest University Community Clinical Oncology Program Research Base, funded by the Wake Forest National Cancer Institute, to conduct a validation study of the association between RT-induced skin toxicity and an increase in plasma CRP levels. The results suggested a potential relationship between inflammatory responses and RT-induced skin toxicities as another source of RT-related pain for patients with breast cancer.

“With a large sample size, this research base study will be used as an external validation study of our current findings that CRP is associated with RT-related pain in breast cancer,” Dr. Hu said.

Written by Amanda Torres

Published on October 1, 2019