ENDO-BRAIN: Effects of Endocrine Adjuvant Therapy with Aromatase Inhibitors on the Cognitive Function of Breast Cancer Patients (ENDO-BRAIN)

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.

Study Overview

• Status: Recruiting
• Conditions: Hypoestrogenism; Cognitive Side Effects of Cancer Therapy
• Intervention / Treatment: Diagnostic test: validated questionnaires; Diagnostic test: functional MRI; Diagnostic test: Optical Coherent Tomography Angiography

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: Claudia Massarotti, Dr; Phone Number: 0039 + 0105555845; Email: claudia.massarotti@unige.it

Study Locations

• Italy
  • GE
    • Genova, GE, Italy, 16132
      • Recruiting
      • IRCCS Ospedale Policlinico San Martino
      • Contact: Claudia Massarotti, Dr; Phone Number: 0039 + 0105555845; Email: claudia.massarotti@unige.it
      • Contact: Claudia Massarotti, Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

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.

Description

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)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cases; Breast cancer patients undergoing endocrine adjuvant therapy with Aromatase Inhibitors (+ GnRH analogues if they are premenopausal)	Diagnostic test: validated questionnaires; Validated questionnaires for climacteric symptoms; Diagnostic test: functional MRI; functional MRI; Diagnostic test: Optical Coherent Tomography Angiography; OCT angiography, macular and peripapillary scans; Other Names: OCT angiography
Controls; Healthy age-matched women who are not using hormonal contraception or hormonal replacement therapy at the time of the study.	Diagnostic test: validated questionnaires; Validated questionnaires for climacteric symptoms; Diagnostic test: functional MRI; functional MRI; Diagnostic test: Optical Coherent Tomography Angiography; OCT angiography, macular and peripapillary scans; Other Names: OCT angiography

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cognitive assessment	The principal aim of this project is to investigate the cognitive function of breast cancer patients that use Aromatase Inhibitors, comparing it with age-matched healthy controls, utilizing cognitive assessment and fMRI.; neuropsychological battery composed of the i) prose recall test, ii) trail making test A and B, iii) digit span backward and forward and iv) the symbol digit modalities test; 3T MRI (Siemens Prisma): 3D sagittal T2-FLAIR; 3D MP2RAGE; T2* gradient echo-planar imaging under resting condition; twice-refocused spin echo echo-planar imaging sequence for multi-shell diffusion-weighted images	Once, at enrollment.

Collaborators and Investigators

• Sponsor: Ospedale Policlinico San Martino
• Collaborators: University of Genova

Publications and helpful links

General Publications

• Menning S, de Ruiter MB, Veltman DJ, Boogerd W, Oldenburg HS, Reneman L, Schagen SB. Changes in brain activation in breast cancer patients depend on cognitive domain and treatment type. PLoS One. 2017 Mar 7;12(3):e0171724. doi: 10.1371/journal.pone.0171724. eCollection 2017.
• Chen X, He X, Tao L, Li J, Wu J, Zhu C, Yu F, Zhang L, Zhang J, Qiu B, Yu Y, Wang K. The Working Memory and Dorsolateral Prefrontal-Hippocampal Functional Connectivity Changes in Long-Term Survival Breast Cancer Patients Treated with Tamoxifen. Int J Neuropsychopharmacol. 2017 May 1;20(5):374-382. doi: 10.1093/ijnp/pyx008.

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2024
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: September 12, 2024
• First Submitted That Met QC Criteria: September 18, 2024
• First Posted (Actual): September 23, 2024

Study Record Updates

• Last Update Posted (Actual): September 23, 2024
• Last Update Submitted That Met QC Criteria: September 18, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: breast cancer; aromatase inhibitor; cognitive side effects; ovarian function suppression; hypoestrogenism
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: ENDO-BRAIN; DB id 13624 (Other Identifier: regional IRB (CERLiguria))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No