Higher CRP Levels Tied to Cognitive Problems in Older Breast Cancer Survivors

Higher levels of C-reactive protein (CRP) were associated with cognitive problems in older breast cancer survivors, a longitudinal analysis showed.

Among participants of the Thinking and Living With Cancer study, breast cancer survivors with higher CRP levels than others reported statistically worse cognition (P=0.040) — a relationship that was not seen in women with no history of breast cancer, reported Judith E. Carroll, PhD, of the University of California Los Angeles, and colleagues.

Moreover, as CRP levels increased from 1.0 to 3.0 to 10.0 mg/L, adjusted Functional Assessment of Cancer Therapy-Cognitive Function scores were 5.2, 9.5, and 14.2 points lower, respectively, compared with controls, they noted in the Journal of Clinical Oncology.

“The results underscore the importance of asking about survivors’ perceptions of their cognitive function and suggest that CRP data may be useful to oncology providers to identify older breast cancer survivors at risk for cognitive problems,” Carroll and team wrote.

Inflammation driven by cellular damage occurring with cancer and its therapies could be an underlying mechanism, the researchers noted.

“It is important for clinicians to understand that there are a number of factors that can increase the risk of cognitive difficulties following treatment,” Carroll told MedPage Today. “CRP is one of these routine blood markers that are known to increase the risk for cardiovascular disease, so it is reasonable to check for elevated levels among women in general, as well as survivors of breast cancer. That’s just good clinical practice.”

“Both in the literature and in patient reports, cognitive challenges are common in survivorship,” she added. “It is one of the most concerning symptoms that they report.”

Although these results suggest a link between inflammation and cognition in breast cancer survivors, Carroll and colleagues also found that adjusted CRP levels were not predictive of overall neuropsychological test performance (attention, processing speed, executive function, and learning and memory).

“We think [CRP] is only one marker of inflammation,” Carroll noted. “There may be other factors going on.”

For example, she and her colleagues pointed out that 23.3% of survivors received chemotherapy, and previous research has shown declines in neuropsychological test performance in patients receiving chemotherapy.

As for future research, “in terms of whether or not lowering inflammation will improve cognitive function, we’d really like to test that out,” Carroll said. “If we could treat inflammation with pharmacological methods or behavioral modifications would that then have an impact on cognitive function long term in survivors? A really important next step is to try to lower inflammation and see if it improves outcomes.”

For this analysis, Carroll and colleagues used longitudinal data on 400 women with breast cancer from the Thinking and Living With Cancer study, and included 329 frequency-matched controls without cancer who were enrolled from September 2010 to March 2020.

Participants ranged in age from 60 to 90 years (average age 67.7 years), and were mostly white and well-educated. Other demographics were comparable between survivors and controls at enrollment. However, survivors were more likely to have more than two comorbidities and have obesity (with subsequent analyses controlled for these imbalances).

Most survivors had stage I disease (60.9%), with estrogen receptor-positive (87.6%) and HER2-negative (88.0%) tumors. CRP levels were obtained from 1,550 specimens (819 from survivors; 731 from controls). Survivors had significantly higher adjusted mean CRP levels versus controls at baseline and at 12-, 24-, and 60-month visits (all P<0.05).

Carroll and colleagues acknowledged several limitations to their study, including the fact that the study population was predominantly white and well-educated. “It will be critical to replicate our results in more diverse samples, especially groups with lifetime experiences associated with increased chronic inflammation,” they wrote.