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Inflammatory biomarkers, comorbidity, and neurocognition in women with newly diagnosed breast cancer

Sunita K. Patel, Andrew L. Wong, F. Lennie Wong, Elizabeth Crabb Breen, Arti Hurria, Mackenzie Smith, Christine Kinjo, I. Benjamin Paz, Laura Kruper, George Somlo, Joanne E. Mortimer, Melanie R. Palomares, Michael R. Irwin, Smita Bhatia

Journal of the National Cancer Institute (2015) 107(8): djv131

Selected and commented by Dr. Florian Scotté

Cognitive disorders remain an unmet need in cancer survivors, while they are linked to impaired quality of life and may also have a significant social impact through disrupted self-perception and by the others.Optimizing performance and cognitive status are key to a successful return to work.

In the article of this month, Sunita Patel and colleagues identify biomarkers of cognitive disorders in a postmenopausal breast cancer population prior to treatment initiation. Social, neurocognitive, functional (Brief Symptom Inventory BSI-18) and blood tests (cytokines IL1, IL6 and TNF) were performed.

At enrolment, cohorts were different in cognitive functions and mood status (altered in breast cancer population). After adjustment for a number of covariates (age, education, BMI, race, mood, fatigue, and comorbidities), high levels of cytokines were statistically related to cognitive disorders (p=0.01). High TNF blood levels appeared to be a predictive factor for memory troubles. Vascular disorders and hippocampus reduction were interestingly shown to be morphological predictive factors for a cognitive impairment.

These observations may explain the problems patients experience before they start an anti-cancer treatment. They need time to discuss and understand the goals of care as well as the treatment impact. Physicians have to make sure their patients are involved. Patients are not stupid; instead they are experiencing clinical disorders and a disease that has an impact on their intellectual functions. It is crucial to conduct an initial assessment of the memory troubles to educate, accompany and help cancer patients during their fight against the disease and also during survivorship.

Physicians must treat, they should also care for the patients’ limits from diagnosis to the «after cancer» phase. Then, survivor care and rehabilitation may be possible.

Abstract
 

Background: Neurocognitive dysfunction is reported in women with breast cancer even prior to receipt of adjuvant therapy; however, there is little understanding of underlying mechanisms. We tested the hypothesis that pretreatment neurocognitive dysfunction in newly diagnosed patients is related to immunological activation, as indexed by pro-inflammatory cytokines.

Methods: One hundred seventy-four postmenopausal patients with newly diagnosed breast cancer underwent a comprehensive neuropsychological evaluation (assessment of cognitive function, mood, and fatigue) and measurement of key cytokine levels prior to surgery. Age-matched control participants without cancer were evaluated concurrently. Multivariable regression analyses examined the contribution of circulating Interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1ra), and soluble TNF receptor type two (sTNF-RII) in predicting neurocognitive performance in patients after controlling for key factors thought to impact functioning. All tests of statistical significance were two-sided.

Results: Memory performance was statistically significantly reduced, in patients compared with controls (P = .02). Of the three cytokines measured, only IL-1ra was statistically significantly elevated in cancer patients when compared with control participants (mean ± SD, 375 ± 239 pg/mL vs 291 ± 169 pg/mL, P = .007). After controlling for age, education, race, mood, fatigue, body mass index, and comorbidity, cytokines independently explained 6.0% of the total variance in memory performance (P = .01) in cancer patients but not control participants, with higher sTNF-RII associated with worse functioning. Exploratory analyses found that comorbidity statistically significantly explained variance in processing speed and executive functioning (P = .03 and P = .03, respectively).

Conclusion: An association of TNF with memory, previously reported in patients after exposure to chemotherapy, was found prior to initiation of any treatment, including surgery. This association requires further investigation as sTNF-RII was not higher in cancer patients relative to control participants.

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