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 confirm these results and assess potential mechanisms and clinical management strategies.