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Background: Using the large nationwide French, national, multicenter, prospective cancer and toxicities (CANTO) cohort, we assessed cognitive functioning change after cancer treatments in a subgroup of breast cancer (BC) patients., Methods: We included patients with newly diagnosed invasive stage I-III BC enrolled in the CANTO substudy focused on cognitive evaluation and healthy control women matched for age and education. Episodic and working memory, executive functions, processing speed, attention, self-report cognitive difficulties (SRCD), fatigue, anxiety and depression were assessed with neuropsychological tests and self-report questionnaires before treatment (baseline) and approximately 1 (year 1) and 2 years (year 2) after diagnosis. We used linear mixed models to study changes in cognition and tested the effect of adjuvant chemotherapy., Results: We studied 276 localized BC patients (62% chemotherapy) compared with 135 healthy controls (HC). After adjustment, patients had lower baseline working memory, processing speed, and attention scores than HC (P ≤ .001), and the difference remained statistically significant over follow-up for working memory and processing speed. Executive function scores were similar between groups at baseline but decreased at year 1 among patients compared with HC (Pchange = .006). This decrease in chemotherapy patients was statistically significant compared with HC scores (Pchange < .001). After adjustment, SRCD were similar between BC patients and HC at baseline but increased in patients after treatment at year 1 (Pchange = .002)., Conclusions: Cognitive difficulties are an important concern in BC patients, starting at diagnosis. Cancer treatments induce executive function decline and SRCD, which decrease over follow-up., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)