Associations between pathologic tumor features and preadjuvant therapy cognitive performance in women diagnosed with breast cancer

Intertumor heterogeneity has been proposed as a potential mechanism to account for variability in cognitive performance in women diagnosed with breast cancer. The purpose of this study was to explore associations between variation in pathologic tumor features (PTFs) and variability in preadjuvant therapy cognitive performance in postmenopausal women newly diagnosed with early‐stage breast cancer. Participants (N = 329) completed a comprehensive battery of neuropsychological tests to evaluate cognitive performance after primary surgery but prior to initiation of adjuvant anastrozole±chemotherapy. PTF data were abstracted from medical records. Robust multiple linear regression models were fit to estimate associations between individual PTFs and the cognitive function composite domain scores. All models controlled for age, estimated intelligence, and levels of depressive symptoms, anxiety, fatigue, and pain. Diagnosis of a HER2‐positive tumor contributed to poorer verbal (b = −0.287, P = 0.018), visual (b = −0.270, P = 0.001), and visual working (b = −0.490, P < 0.001) memory performance compared to diagnosis of a HER2‐negative tumor. Similarly, as HER2 immunohistochemistry classification score increased, verbal (b = −0.072, P = 0.093), visual (b = −0.081, P = 0.003), and visual working (b = −0.170, P < 0.001) memory performance score decreased. Associations with performance were also noted between location, focality/centricity, hormone receptor expression, cellular proliferation (i.e., Ki67), and Oncotype DX (®) Breast Cancer Assay Recurrence Score(®).) Our results suggest that certain PTFs related to more aggressive tumor phenotypes or inferior breast cancer prognosis may be implicated in poorer preadjuvant therapy cognitive performance. Follow‐up studies that include a cognitive assessment before primary surgery should be conducted to further delineate the role of intertumor heterogeneity on cognitive performance.