The principal aim of this prospective observational study is to investigate the cognitive function of breast cancer patients that use AI, comparing it with age-matched healthy controls, utilizing cognitive assessments and functional magnetic resonance imaging (fMRI). Additionally, the project seeks to establish correlations between cognitive function and other estrogen deprivation symptoms, including vasomotor symptoms, and to evaluate a possible correlation with endothelial damage studied through Angio Optical Coherent Tomography (angio OCT).

Patients will be recruited during follow up visits at the iatrogenic menopause outpatient clinic. After informed consent, the will be asked for detailed demographic data, medical, oncological and gynecological history. Hypoestrogenism symptoms will be collected through validated questionnaires. The cognitive assessment will be performed on the same day, by trained staff. The fMRI and angioOCT will be booked and performed depending on patient and clinic availability.

Inclusion Criteria:

• Breast cancer patients undergoing endocrine adjuvant therapy with AI, with or without GnRH agonists, depending on menopause status at diagnosis (cases only)
• At least 18 years old
• Good comprehension of oral and written Italian language

Exclusion Criteria:

• incomplete ovarian suppression (cases)
• previous neoplastic diseases other than the presently treated breast cancer for cases
• known neurological or psychiatric disorders
• use of hormonal contraception or hormonal replacement therapy (controls)

This is a monocentric study, taking place in an university hospital, which is a referral point for both oncology and neurology.

Cases are recruited from the iatrogenic menopause outpatient clinic. This is a dedicated outpatient clinic for the gynecological follow up of cancer survivors, including breast cancer patients undergoing adjuvant endocrine therapy. It is part of the oncofertility pathway of the institution, it is run by doctors with specific expertise in reproductive endocrinology, fertility and menopause. The clinic is accessed by all patients, not only the symptomatic ones, for yearly follow ups. Healthy controls are recruited from the gynecological, neurological or ophthalmological outpatient clinics.