Breast Cancer & Antiestrogenic Therapy & Brain

NCT ID: NCT06346457

Last Updated: 2024-04-04

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Total Enrollment: 180 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-04-01
• Study Completion Date: 2026-04-01

Brief Summary

The study aims to investigate the effect of anti-estrogenic therapy in breast cancer patients on neural reward processing, psychosexual health, and quality of life, in reproductive vs. menopausal women. The investigators are directly comparing four groups 1) premenopausal women diagnosed with breast cancer receiving anti-estrogenic therapy, 2) postmenopausal women diagnosed with breast cancer with and without previous hormonal replacement therapy, receiving anti-estrogenic therapy, 3) premenopausal healthy women, and 4) postmenopausal healthy women. Furthermore, via assessment and integration of various data including subjective/self-report data via questionnaires and a standardized interview, physiological/endocrine (via blood sample), psychological and neural data (including anatomical scans, Diffusion tensor imaging (DTI), resting state, and a reward processing paradigm), this project will shed light on the connection between the brain, anti-estrogenic therapy, and psychosexual health.

Detailed Description

If participants qualify for the current study, the investigators will invite them to the laboratory (T0), where participants will provide written, informed consent. Subsequently, the investigators will conduct a standardized clinical interview to screen for mental disorders (SCID-5-CV). Participants will also be informed about the study procedure. After the interview, participants will receive a password-protected link by email to access an online survey that measures, among other things, depressive symptoms, personality traits, gender identity and norms, relationship quality, sexual health, state and trait anxiety, and verbal intelligence.

All fMRI measurements (T1 and T2) will precede the hormonal and surgical components of the breast cancer treatment. Biopsy and analysis of tumor tissue will be performed in the pathology department of the University of Tuebingen Women's Clinic. Similarly, clinical routine procedures and adjuvant systemic treatment will be administered at the University of Tuebingen Women's Clinic.

Following the first interview, participants will undergo the first MRI session (T1) before starting anti-estrogenic therapy. The second MRI session (T2) will be scheduled two- three weeks after commencing anti-estrogenic therapy and before the surgery.

For controls, premenopausal women and postmenopausal women who have stopped or never used hormone replacement therapy will be included. At the start of the MRI sessions, a 30ml blood draw will be performed by medically trained personnel. The investigators anticipate hormonal changes between T1 and T2 due to breast cancer treatment (anti-estrogenic therapy).

After the second measurement (T2), women diagnosed with breast cancer will be invited to the third online session (T3) to assess possible related changes in psychosexual health, body image, and quality of life through questionnaires.

The investigators have meticulously planned the sequence of our MRI measurements to ensure a comprehensive exploration of various aspects of brain structure and function. The protocol is structured as follows:

1. Anatomical Scan: The session begins with an anatomical scan, aiming to provide detailed insights into the structural aspects of the brain. This foundational step allows for a precise understanding of the anatomical features before delving into functional assessments.

2. Resting State: Following the anatomical scan, participants will engage in a resting-state session lasting approximately 10 minutes. During this period, participants will watch a video to capture diverse facets of brain function and physiological states during rest. Resting-state measurements provide valuable information about intrinsic brain activity in the absence of a specific task.

3. Effort Allocation Task (EAT): Subsequent to the resting-state session, participants will undertake the effort allocation task (EAT). This task is strategically designed to explore the trade-off between the benefits of effort and the associated costs. Participants will be involved in a task where monetary points are at stake, requiring physical effort by manipulating a grip-force measuring device. The payoff will be proportional to the duration of their invested effort. The EAT is anticipated to last up to 17 minutes.

4. Diffusion Tensor Imaging (DTI): Following the EAT, participants will undergo Diffusion Tensor Imaging (DTI) to examine and map the white matter tracts in the brain. DTI is a sophisticated imaging technique that provides insights into the microstructural organization of white matter pathways, offering valuable information about connectivity.

This sequential approach from anatomical scanning to resting state, effort allocation task, and DTI is designed to systematically investigate both the structural and functional aspects of the brain in our study participants. The combination of these different imaging modalities enables a comprehensive understanding of the neural dynamics associated with anatomical structures, intrinsic brain activity at rest, responses to effortful tasks, and the organization of white matter tracts.

To comprehensively investigate self-report changes, the investigators will administer several questionnaires designed to assess various aspects. These questionnaires will focus on body image, psychosexual health, cancer-related quality of life changes, dyadic adjustment scale, well-being, and positive and negative affect changes. The data will be collected and managed through Redcap, providing a systematic and secure platform for organizing and analyzing participant responses. This approach ensures a thorough exploration of subjective experiences and enables a nuanced understanding of the psychological and emotional impact of the variables under investigation.

To thoroughly investigate cognitive changes, the investigators will use a home-testing battery. Participants will perform two online tasks: a reinforcement-learning risk sensitivity task and a gamified Pavlovian go/no-go task with varied bandits. Both tasks will be conducted weekly for three weeks, totaling approximately 1 hour. Data will be stored at the Quantitative Biology Center (QBiC) at the University of Tuebingen.

Conditions

Breast Cancer Female; Healthy Female; Menopause; Anti-estrogenic Therapy

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: OTHER

Study Groups

premenopausal women diagnosed with breast cancer

receiving anti-estrogenic therapy

Tamoxifen

Intervention Type: DRUG

Tamoxifen is 20 mg once daily for two to three weeks.

postmenopausal women diagnosed with breast cancer, with/out previous hormonal replacement therapy

receiving anti-estrogenic therapy

Letrozole

Intervention Type: DRUG

Letrozole (Aromatase inhibitor) is 2,5 mg once daily for two to three weeks.

Letrozole + GnRH

Intervention Type: DRUG

When they take Letrozole + GnRh, the GnRh is an injection once a month.

premenopausal healthy women

before menopause

No interventions assigned to this group

postmenopausal healthy women with/out previous hormonal replacement therapy

after menopause

No interventions assigned to this group

Interventions

Tamoxifen

Tamoxifen is 20 mg once daily for two to three weeks.

Intervention Type: DRUG

Letrozole

Letrozole (Aromatase inhibitor) is 2,5 mg once daily for two to three weeks.

Intervention Type: DRUG

Letrozole + GnRH

When they take Letrozole + GnRh, the GnRh is an injection once a month.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Women before or after menopause
• With/without a diagnosis of breast cancer
• Between 18 and 70 years old
• Body mass index 18-35 kg/m²
• Fluent in written and spoken German
• At least an intermediate school leaving certificate

Exclusion Criteria

• Any neurological or mental disease based on standardized diagnoses confirmed via the structured clinical interview for DSM-5, Clinical Version (SCID-5-CV)
• Women who gave birth or were breastfeeding within the last year
• Participants with a history of sexual trauma or abuse
• Participants taking any medication interfering with brain activation
• Participants taking oral contraceptives
• Male breast cancer patients
• Patients with alcohol or substance abuse
• Patients if the origin of the cancer is not in the breast cells
• Patients have any other physical severe diseases (stroke, diabetes, heart attack, etc.)
• Patients currently ongoing chemotherapy
• Participants who did not consent

• People with non-removable metal objects on or in the body
• Tattoos (if MRI-incompatible according to expert guidelines)
• Pathological hearing or increased sensitivity to loud noises
• Claustrophobia
• Surgery less than three months ago
• Moderate or severe head injury

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

German Research Foundation

OTHER

Sponsor Role: collaborator

University Hospital Tuebingen

OTHER

Sponsor Role: collaborator

Uppsala University

OTHER

Sponsor Role: collaborator

International Research Training Group 2804

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Birgit Derntl, Prof

Role: PRINCIPAL_INVESTIGATOR

Department of Psychiatry & Psychotherapy, University of Tuebingen

Sara Brucker, Prof

Role: PRINCIPAL_INVESTIGATOR

Department of Women's Health University Women's Clinic

Markus Hahn, Prof

Role: PRINCIPAL_INVESTIGATOR

Department of Women's Health University Women's Clinic

Anna Wikman, Prof

Role: PRINCIPAL_INVESTIGATOR

Department of Women's and Children's Health, Reproductive Health

Ann Christin Kimmig, Dr

Role: PRINCIPAL_INVESTIGATOR

Department of Psychiatry & Psychotherapy, University of Tuebingen

Locations

University of Tuebingen; Department of Psychiatry & Psychotherapy Tuebingen

Tübingen, Baden-Wurttemberg, Germany

Countries

Germany

Central Contacts

Birgit Derntl, Prof.

Role: CONTACT

birgit.derntl@med.uni-tuebingen.de

0049 07071 2985437

Serenay Yazici Sarikaya, M.Sc.

Role: CONTACT

serenay.yazici.sarikaya@med.uni-tuebingen.de

0049 07071 2962492

Other Identifiers

IRTG_P08

Identifier Type: -

Identifier Source: org_study_id