Breast Cancer & Antiestrogenic Therapy & Brain

The Impact of Anti-estrogenic Therapy in Breast Cancer Patients on Brain Architecture, Psychosexual Health, and Quality of Life

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Menopause; Breast Cancer Female; Healthy Female; Anti-estrogenic Therapy
• Intervention / Treatment: Drug: Tamoxifen; Drug: Letrozole; Drug: Letrozole + GnRH

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.

• Study Type: Observational
• Enrollment (Estimated): 180

Contacts and Locations

• Study Contact: Name: Birgit Derntl, Prof.; Phone Number: 0049 07071 2985437; Email: birgit.derntl@med.uni-tuebingen.de
• Study Contact Backup: Name: Serenay Yazici Sarikaya, M.Sc.; Phone Number: 0049 07071 2962492; Email: serenay.yazici.sarikaya@med.uni-tuebingen.de

Study Locations

• Germany
  • BW
    • Tuebingen, BW, Germany, 72076
      • University of Tuebingen; Department of Psychiatry & Psychotherapy Tuebingen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• 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.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
premenopausal women diagnosed with breast cancer; receiving anti-estrogenic therapy	Drug: Tamoxifen; 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	Drug: Letrozole; Letrozole (Aromatase inhibitor) is 2,5 mg once daily for two to three weeks.; Drug: Letrozole + GnRH; When they take Letrozole + GnRh, the GnRh is an injection once a month.
premenopausal healthy women; before menopause
postmenopausal healthy women with/out previous hormonal replacement therapy; after menopause

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlations between antiestrogen hormone therapy and brain function & structure	Possible effects of antiestrogen hormone therapy on brain function (functional activation based on BOLD effect) and structure in pre- and postmenopausal women diagnosed with breast cancer. Anatomical scan, Resting state and Diffusion Tensor Imaging will be assessed	Measured twice 2-3 weeks apart; approx. 32 minutes each time
Correlations between antiestrogen hormone therapy and reward processing in both behavioral and neural aspects	Possible effects of antiestrogen hormone therapy on reward processing in pre- and postmenopausal women diagnosed with breast cancer. Effort Allocation Task will be applied.	Measured twice 2-3 weeks apart; approx. 17 minutes each time
Brain Disparities: Contrasting Breast Cancer Patients with Healthy Controls	Any differences in brain Function (functional activation based on BOLD effect) between Breast Cancer Patients and Healthy control	Measured twice 2-3 weeks apart; approx. 32 minutes each time
Reward Processing Disparities: Contrasting Breast Cancer Patients with Healthy Controls	Differences in reward processing between Breast Cancer Patients and Healthy control. Effort Allocation Task will be applied.	Measured twice 2-3 weeks apart; approx. 17 minutes each time
Brain Disparities: Contrasting Breast Cancer Patients with Healthy Controls	Any differences in brain structure between Breast Cancer Patients and Healthy control.	Measured twice 2-3 weeks apart; approx. 32 minutes each time, with fMRI, Anatomical Scan and Diffusion tensor imagingDiffisuin

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between antiestrogen hormone therapy and psychosexual health	Possible effects of antiestrogen hormone therapy on psychosexual health in pre- and postmenopausal women diagnosed with breast cancer. Questionnaires: Body Image Scale, Female Sexual Function Index	Measured three times: before treatment, within 2-3 weeks after treatment and 6 months after treatment; approx 60 minutes each time
Correlation between antiestrogen hormone therapy and quality of life	Possible effects of antiestrogen hormone therapy on quality of life in pre- and postmenopausal women diagnosed with breast cancer. Questionnaires:European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire, Positive and Negative Affect Schedule	Measured with questionnaires three times: before treatment, within 2-3 weeks after treatment and 6 months after treatment; approx 60 minutes each time
Psychosexual Health Disparities: Contrasting Breast Cancer Patients with Healthy Controls	Differences in Psychosexual health between Breast Cancer Patients and Healthy control. Questionnaires: Female Sexual Function Index	Measured two times: before treatment and within 2-3 weeks after treatment; approx 60 minutes each time
Psychosexual Health Disparities: Contrasting Breast Cancer Patients with Healthy Controls	Differences in Psychosexual health between Breast Cancer Patients and Healthy control. Questionnaires: Body Image Scale	Measured two times: before treatment and within 2-3 weeks after treatment; approx 60 minutes each time
Correlation between antiestrogen hormone therapy and cognitive changes	Possible effects of antiestrogen hormone therapy on cognitive changes in pre- and postmenopausal women diagnosed with breast cancer. It has two different behavioral tasks measured by home battery testing: a reinforcement-learning risk sensitivity task and a Pavlovian go/no-go task.	Measured for 2-3 weeks: Patients performing both tasks for 2-3 weeks.
Quality of Life Disparities: Contrasting Breast Cancer Patients with Healthy Controls	Differences in quality of life between Breast Cancer Patients and Healthy control. It measured with questionnaires.	Measured two times: before treatment, within 2-3 weeks after treatment; approx 60 minutes each time

Collaborators and Investigators

• Sponsor: International Research Training Group 2804
• Collaborators: German Research Foundation; Uppsala University; University Hospital Tuebingen
• Investigators: Principal Investigator: Birgit Derntl, Prof, Department of Psychiatry & Psychotherapy, University of Tuebingen; Principal Investigator: Sara Brucker, Prof, Department of Women's Health University Women's Clinic; Principal Investigator: Markus Hahn, Prof, Department of Women's Health University Women's Clinic; Principal Investigator: Anna Wikman, Prof, Department of Women's and Children's Health, Reproductive Health; Principal Investigator: Ann Christin Kimmig, Dr, Department of Psychiatry & Psychotherapy, University of Tuebingen

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: February 14, 2024
• First Submitted That Met QC Criteria: March 28, 2024
• First Posted (Actual): April 4, 2024

Study Record Updates

• Last Update Posted (Actual): April 4, 2024
• Last Update Submitted That Met QC Criteria: March 28, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: MRI; Breast cancer; Menopause; Estrogen; Reward processing; Quality of life (QoL); Women´s mental health; Anti-estrogenic therapy; Neuroimaging(fMRI); Psychosexual health
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Bone Density Conservation Agents; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Letrozole; Tamoxifen
• Other Study ID Numbers: IRTG_P08

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No