The goal of this clinical trial is to evaluate whether oral creatine supplementation can prevent chemotherapy-related cognitive impairment in patients with early-stage breast cancer undergoing neoadjuvant or adjuvant chemotherapy. The main questions it aims to answer are:

• Does creatine supplementation reduce the occurrence and severity of chemotherapy-related cognitive impairment, as measured by patient-reported cognitive function?
• Does creatine supplementation preserve objective cognitive performance compared with placebo during and after chemotherapy?

Researchers will compare creatine supplementation (5 g/day) with placebo to assess differences in cognitive outcomes, safety, and exploratory biological markers.

Participants will:

• Receive oral creatine or placebo starting 7 days before chemotherapy and continuing until 12 months after chemotherapy completion
• Complete patient-reported cognitive assessments and objective neuropsychological tests at predefined time points
• Undergo clinical follow-up for safety and oncologic outcomes
• Provide blood samples for biomarker analyses and stool samples for gut microbiota assessment
• Undergo brain magnetic resonance imaging at selected study visits

Inclusion Criteria:

• Age ≥18 years.
• Histologically confirmed invasive breast cancer (stages I-III).
• Indication for neoadjuvant or adjuvant chemotherapy containing an anthracycline or a taxane.
• Targeted therapies and hormone therapy are permitted according to clinical indication.
• Ability to provide informed consent and comply with study procedures.
• ECOG performance status 0-2.
• Ability to maintain adequate hydration.

Exclusion Criteria:

• Prior neurologic conditions that may impair cognitive assessment, including previous stroke, dementia, traumatic brain injury with neurologic sequelae, or other neurologic disorders affecting cognition.
• Uncorrected sensory impairments that preclude cognitive assessment and/or completion of study instruments.
• History of uncontrolled psychiatric disorders that may interfere with cognitive evaluation.
• Creatinine clearance <60 mL/min, calculated using the Cockcroft-Gault formula.
• Known liver disease.
• Pregnancy.
• Heart failure.
• Presence of ascites.
• Inflammatory bowel disease.
• Chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs).
• Lactation.
• Chronic use of immunosuppressive agents, including doses greater than 10 mg/day or equivalent.
• Prior chronic creatine supplementation within the last 3 months.
• Known allergy to any component of the supplement or placebo.

This is a double-blind study. Participants, investigators, study staff involved in clinical care, outcome assessment, cognitive testing, imaging analyses, laboratory analyses, and data analysis are masked to treatment allocation. Creatine and placebo are identical in appearance, taste, and packaging. Unblinding will occur only if required for participant safety, according to predefined protocol procedures.