Elevated C-Reactive Protein Levels Predictive of Later Cognitive Decline in Female Breast Cancer Survivors

Judith Carroll, PhD

Increases in C-reactive protein (CRP) may lead to cognitive complications in older breast cancer survivors, according to a findings from a recent study published in the Journal of Clinical Oncology. Therefore, testing for CRP may be a clinically useful component in breast cancer survivorship care, according to study authors.

Findings show that breast cancer survivors who had higher levels of In-CRP were more likely to experience a decline in participant-reported cognition over the course of follow-up; however, this same association was not identified in a control sample of non-breast cancer survivors (P = .008). This connection was not affected by depression or anxiety.

Ultimately, the Functional Assessment of Cancer Therapy-Cognitive Function scores held by survivors were 9.5 and 14.2 points lower than their control counterparts at 3.0 and 10.0 mg/L. Survivors also had poorer neuropsychological test performances compared with controls, and significant interactions with CRP were only evident for the trials B test.

“Longitudinal relationships between CRP and cognition in older breast cancer survivors suggest that chronic inflammation plays a mechanistic role in development of cognitive problems,” wrote Judith Carroll, PhD, associate professor of psychiatry and biobehavioral science at UCLA, and coinvestigators. “CRP testing could be clinically useful in survivorship care to identify survivors needing intervention to prevent and/or long-term surveillance for cognitive decline.”

For decades, investigators have known that many patients face cognitive problems following breast cancer. Nevertheless, the underlying mechanisms are not well understood. Some investigators hypothesize the inflammation is a driving factor for cognitive function decline and preclinical models have brought light to the possible connection between peripheral indicators of increased inflammation and the development of cognitive decline in cancer survivors.

CRP has been shown to signal risk for cardiovascular disease and mortality, as well as cognitive problems in patients with cancer. However, previous reports have centered on the effect on cognitive decline pre- and postchemotherapy, whereas this study set to understand how the peripheral indication may cause longer-term cognitive problems long after treatment.

Investigators recruited women over the age of 60 who had recently received a diagnosis of primary breast cancer (stage 0-II), alongside frequency-matched controls; women with dementia, neurologic disorders, or cancers besides breast cancer could not enroll. Four hundred survivors and 329 controls were enrolled between September 2010 and March 2020.

Most survivors had stage I disease (60.9%) and estrogen receptor-positive tumors were the most common disease subtype (87.6%). Notably, survivors had significantly higher adjusted mean In-CRP compared with non-survivors at baseline at baseline, as well as at the 12-,24-, and 60-month check-ins.

Cognitive assessments were conducted prior to systemic therapy, and annually thereafter, for up to 60 months post-treatment. Investigators used the Functional Assessment of Cancer Therapy-Cognitive Function and neuropsychological testing.

Investigators assessed 1,550 specimens (819 for survivors and 731 for controls) for CRP levels. At baseline, survivors were more likely than controls to have CRP values greater or equal to 3 mg/L (42.4% vs 6.1%, P < .001). Levels of CRP were also significantly higher at all other time points (P < .05).

Moreover, survivors who had higher In-CRP values reported statistically worse cognitive decline at each study visit compared with those with lower In-CRP levels (P = .040). This relationship was not observed in the control population (P = .795).

“Our data support the need for studies to test the hypothesis that behavioral and/or pharmacological interventions targeting inflammation may prevent or reduce cancer-related cognitive problems in older breast cancer survivors,” study authors concluded. “Potential interventions targeting inflammation include increasing physical activity, improving sleep, reducing stress, and administering drugs that block inflammatory pathways.”

Reference

Carroll JE, Nakamura ZM, Small BJ, et al. Elevated C-reactive protein and subsequent patient-reported cognitive problems in older breast cancer survivors: the thinking and living with cancer study. J Clin Oncol. Published online September 30, 2022. doi:10.1200/JCO.22.00406