Association of markers of tumor aggressivity and cognition in women with breast cancer before adjuvant treatment: The Thinking and Living with Cancer Study

Abstract

Purpose: Tumor features associated with aggressive cancers may affect cognition prior to systemic therapy. We evaluated associations of pre-treatment cognition and tumor aggressivity in older breast cancer patients.Methods: Women diagnosed with non-metastatic breast cancer (n=705) ages 60-98 were enrolled from August 2010-March 2020. Cognition was measured post-surgery, pre-systemic therapy using self-reported (FACT-Cog Perceived Cognitive Impairment [PCI]) and objective tests of attention, processing speed, and executive function (APE domain) and learning and memory [LM domain]. Linear regression tested associations of pre-treatment tumor features and cognition, adjusting for age, race, and study site. HER2 positivity and higher stage (II/III vs. 0/I) were a priori predictors of cognition; in secondary analyses we explored associations of other tumor features and cognitive impairment (i.e., PCI score <54 or having 2 tests <1.5 SD or 1 test <2 SD from the mean APE or LM domain score).Results: HER2 positivity and the hormone receptor negative/HER2+ molecular subtype were associated with lower adjusted mean self-reported cognition scores and higher impairment rates (p values <.05). Higher stage of disease was associated with lower objective performance in APE. Other tumor features were associated with cognition in unadjusted and adjusted models, including larger tumor size and lower PCI scores (p = 0.02). Tumor features were not related to LM.Conclusions: Pre-adjuvant therapy cognition was associated with HER2 positivity and higher stage of disease and other features of aggressive tumors. Additional research is needed to con rm these results and assess potential mechanisms and clinical management strategies.

The high burden of symptoms associated with cognitive impairment in lung cancer patients: A latent class analysis

“…A score less than 54 is indicative of cognitive impairment and can well distinguish between CRCI and non-CRCI. 24 , 25 The Cronbach's α coefficient of the CogPCI in this study was 0.947.…”

Plasma levels of interleukin‐6 mediate neurocognitive performance in older breast cancer survivors: The Thinking and Living With Cancer study

“…35 The presystemic therapy differences in IL-6 levels between survivors and controls also add to the body of evidence that cancer may have important effects on inflammation and cognition even before systemic therapy begins. 21,22,37,38 The finding that survivor-control differences in factors including comorbidity and obesity slightly attenuated IL-6 mediation effects on cognition suggests that a preexisting proinflammatory state may contribute to the risk of developing breast cancer and/or cognitive decline. 21 Prospective studies with assessments before and after cancer would be necessary to fully explore this possibility.…”

“…This will be important to examine further, because others have found that radiotherapy and/or chemotherapy induce cellular damage that increases peripheral inflammation and cognitive problems and that HER2-positive cancers are associated with cognitive problems even before treatment. 19,24,38 Fifth, because we added blood collection to an already established cohort, not all survivors had plasma data before systemic therapy.…”

“…Additionally, there is some evidence that IL‐6 receptors in the brain may contribute to neuroinflammation and microglia activation that arise from neurotoxicity 35 . The presystemic therapy differences in IL‐6 levels between survivors and controls also add to the body of evidence that cancer may have important effects on inflammation and cognition even before systemic therapy begins 21,22,37,38 . The finding that survivor–control differences in factors including comorbidity and obesity slightly attenuated IL‐6 mediation effects on cognition suggests that a preexisting proinflammatory state may contribute to the risk of developing breast cancer and/or cognitive decline 21 .…”

“…Fourth, we had an insufficient number of survivors with aggressive tumor markers or receiving chemotherapy and limited variability in the types of hormonal regimens to determine whether the mediation of the relationship between survivor/control group and cognition by IL‐6 markers varies by tumor type or specific treatment regimens. This will be important to examine further, because others have found that radiotherapy and/or chemotherapy induce cellular damage that increases peripheral inflammation and cognitive problems and that HER2‐positive cancers are associated with cognitive problems even before treatment 19,24,38 . Fifth, because we added blood collection to an already established cohort, not all survivors had plasma data before systemic therapy.…”