Clinical trial NCT06346457: Breast Cancer & Antiestrogenic Therapy & Brain
Official title: The Impact of Anti-estrogenic Therapy in Breast Cancer Patients on Brain Architecture, Psychosexual Health, and Quality of Life
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Breast Cancer Female
Healthy Female
Menopause
Anti-estrogenic Therapy
Keywords: Women´s mental health
Breast cancer
Anti-estrogenic therapy
Neuroimaging(fMRI)
Estrogen
Menopause
Reward processing
Psychosexual health
Quality of life (QoL)
MRI
Lead sponsor: International Research Training Group 2804
Sponsor class: OTHER
Collaborators: name: German Research Foundation
name: University Hospital Tuebingen
name: Uppsala University
First posted: 2024-04-04
Enrollment: 180
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_CONTROL
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population (breast cancer patients and healthy control) will mainly consist of residents of Tübingen and surrounding areas.

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.

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

Additional exclusion criteria for MRI:

* 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

Primary outcomes:
measure: Correlations between antiestrogen hormone therapy and brain function & structure
timeFrame: Measured twice 2-3 weeks apart; approx. 32 minutes each time
measure: Correlations between antiestrogen hormone therapy and reward processing in both behavioral and neural aspects
timeFrame: Measured twice 2-3 weeks apart; approx. 17 minutes each time
measure: Brain Disparities: Contrasting Breast Cancer Patients with Healthy Controls
timeFrame: Measured twice 2-3 weeks apart; approx. 32 minutes each time
measure: Reward Processing Disparities: Contrasting Breast Cancer Patients with Healthy Controls
timeFrame: Measured twice 2-3 weeks apart; approx. 17 minutes each time
measure: Brain Disparities: Contrasting Breast Cancer Patients with Healthy Controls
timeFrame: Measured twice 2-3 weeks apart; approx. 32 minutes each time, with fMRI, Anatomical Scan and Diffusion tensor imagingDiffisuin
Secondary outcomes:
measure: Correlation between antiestrogen hormone therapy and psychosexual health
timeFrame: Measured three times: before treatment, within 2-3 weeks after treatment and 6 months after treatment; approx 60 minutes each time
measure: Correlation between antiestrogen hormone therapy and quality of life
timeFrame: Measured with questionnaires three times: before treatment, within 2-3 weeks after treatment and 6 months after treatment; approx 60 minutes each time
measure: Psychosexual Health Disparities: Contrasting Breast Cancer Patients with Healthy Controls
timeFrame: Measured two times: before treatment and within 2-3 weeks after treatment; approx 60 minutes each time
measure: Psychosexual Health Disparities: Contrasting Breast Cancer Patients with Healthy Controls
timeFrame: Measured two times: before treatment and within 2-3 weeks after treatment; approx 60 minutes each time
measure: Correlation between antiestrogen hormone therapy and cognitive changes
timeFrame: Measured for 2-3 weeks: Patients performing both tasks for 2-3 weeks.
measure: Quality of Life Disparities: Contrasting Breast Cancer Patients with Healthy Controls
timeFrame: Measured two times: before treatment, within 2-3 weeks after treatment; approx 60 minutes each time
Other outcomes:
Locations:
city: Tuebingen
country: Germany
facility: University of Tuebingen; Department of Psychiatry & Psychotherapy Tuebingen
state: BW
Study officials:
affiliation: Department of Psychiatry & Psychotherapy, University of Tuebingen
name: Birgit Derntl, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Women's Health University Women's Clinic
name: Sara Brucker, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Women's Health University Women's Clinic
name: Markus Hahn, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Women's and Children's Health, Reproductive Health
name: Anna Wikman, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Psychiatry & Psychotherapy, University of Tuebingen
name: Ann Christin Kimmig, Dr
role: PRINCIPAL_INVESTIGATOR
References: