Functional Magnetic Resonance Imaging in Assessing Affect Reactivity and Regulation in Patients With Stage 0-III Breast Cancer

• ClinicalTrials.gov Identifier: NCT03050463
• Recruitment Status: Active, not recruiting
• First Posted: February 13, 2017
• Last Update Posted: April 22, 2020
• Sponsor: Stanford University
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Stanford University

Study Description

Brief Summary:

The investigators hope to gain a better understanding of the influence of affect reactivity and regulation on the decision of newly diagnosed breast cancer patients to choose bilateral mastectomy. The information gained can help develop an intervention to enable management of cancer-related anxiety by non-surgical means.

Condition or disease	Intervention/treatment
Healthy Subject; Stage 0 Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer	Procedure: Biospecimen Collection; Procedure: Functional Magnetic Resonance Imaging; Other: Questionnaire Administration

Detailed Description:

PRIMARY OBJECTIVES:

I. Examine affect reactivity and regulation among women with a recent diagnosis of breast cancer in comparison to healthy controls.

II. Relate affect reactivity and regulation to choice of bilateral mastectomy (BLM).

SECONDARY OBJECTIVES:

I. Assess long term functioning correlates of BLM decision and affect reactivity and regulation.

OUTLINE: Study plans to recruit total of 170 women. Participants will be assigned to 3 arms. For women diagnosed with breast cancer (total of 130) 65 with BLM as part of their cancer treatment and 65 non-BLM. The 3rd arm being 40 women with no cancer diagnosis as controls.

Study protocol will be the same for all 170 Study participants. Active participation by each participant will be approximately 8 hours at baseline and 2 hours at 6, 12, and 18-month follow-ups. Baseline assessment involve completing a set of questionnaires, participating in various tasks while undergoing an MRI scan of the head, providing saliva samples and I tube of blood. Follow-up assessments involve completing a set of questionnaires and saliva collection, all can be done at home.

Study Design

• Study Type: Observational
• Actual Enrollment: 178 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: Impact of Affect Reactivity and Regulation on Breast Cancer Treatment Decisions
• Actual Study Start Date: August 2016
• Actual Primary Completion Date: September 23, 2019
• Estimated Study Completion Date: March 2021

Groups and Cohorts

Group/Cohort	Intervention/treatment
breast cancer with bilateral mastectomy; This group has patients with breast cancer who have chosen to have a bilateral mastectomy. Patients complete questionnaires over 1 hour, undergo fMRI related tasks over 2-2.5 hours, and blood/saliva sample collection upon awakening, 30 minutes after awakening, and at 9 pm in the evening for 3 consecutive days.	Procedure: Biospecimen Collection; Undergo blood and saliva sample collection; Procedure: Functional Magnetic Resonance Imaging; Undergo fMRI related tasks; Other Names: fMRI; FUNCTIONAL MRI; Other: Questionnaire Administration; Ancillary studies
breast cancer without bilateral mastectomy; This group has patients diagnosed with breast cancer who have chosen not to have bilateral mastectomy (e.g. they may have unilateral mastectomy, lumpectomy, radiation, etc. but not bilateral mastectomy). Patients complete questionnaires over 1 hour, undergo fMRI related tasks over 2-2.5 hours, and blood/saliva sample collection upon awakening, 30 minutes after awakening, and at 9 pm in the evening for 3 consecutive days.	Procedure: Biospecimen Collection; Undergo blood and saliva sample collection; Procedure: Functional Magnetic Resonance Imaging; Undergo fMRI related tasks; Other Names: fMRI; FUNCTIONAL MRI; Other: Questionnaire Administration; Ancillary studies
healthy subjects; Patients complete questionnaires over 1 hour, undergo fMRI related tasks over 2-2.5 hours, and blood/saliva sample collection upon awakening, 30 minutes after awakening, and at 9 pm in the evening for 3 consecutive days.	Procedure: Biospecimen Collection; Undergo blood and saliva sample collection; Procedure: Functional Magnetic Resonance Imaging; Undergo fMRI related tasks; Other Names: fMRI; FUNCTIONAL MRI; Other: Questionnaire Administration; Ancillary studies

Outcome Measures

Primary Outcome Measures :

1. Explicit Affect Reactivity and Regulation Measured Using functional MRI (fMRI) Reactivity Probes [ Time Frame: Up to 18 months ]
   Multivariate regression analysis will be used to examine affect reactivity among women with a recent diagnosis of breast cancer in comparison to healthy controls at baseline. Functional data will be collected on the explicit affect regulation task (20 minutes) and explicit cancer related affect regulation task (8 minutes). Affect reactivity and cancer-related affect reactivity will be defined by WATCH negative minus WATCH neutral and by WATCH cancer-related negative and WATCH neutral contrast. The larger this value, the greater the affect reactivity. Explicit affect regulation will defined by WATCH negative minus REAPPRAISE negative, and by WATCH negative minus REAPPRAISE cancer-related negative contrasts. The greater this value, the less successful explicit regulation is.
2. Implicit Affect Reactivity and Regulation Measured Using fMRI Reactivity Probes [ Time Frame: Up to 18 months ]
   Multivariate regression analysis will be used to examine affect reactivity among women with a recent diagnosis of breast cancer in comparison to healthy controls at baseline. Functional data will be collected on the implicit affect regulation task (13 minutes) and implicit cancer-related affect regulation task (13 minutes). Affect reactivity and cancer-related affect reactivity will be defined by incongruent minus congruent trials and incongruent cancer minus congruent cancer-related trials. The greater this value, the more affect reactivity there is. Implicit affect regulation for general affective content will be calculated by post-congruent incongruent trials minus post-incongruent incongruent trials. Similarly, implicit affect regulation for cancer related content will be calculated from the post-congruent incongruent trials minus post-incongruent incongruent trials in the cancer-related adaptation of the task. The greater this value, the less successful implicit regulation is.

Secondary Outcome Measures :

1. Diurnal Slope of Cortisol [ Time Frame: Up to 18 months ]
   Affect management is associated with the diurnal slope of cortisol. The stress of a breast cancer diagnosis and subsequent treatment choices is bound to affect hormonal stress response systems, such as the hypothalamic-pituitary-adrenal axis (HPA). Cortisol levels, measured reliably in saliva, are a meaningful and accessible way of assessing physiological stress response. Salient to this study of affect regulation, the investigators have found that flatter diurnal cortisol slope is associated with higher repressive-defensiveness and less sustained expression of primary negative affect in a group setting.
2. BLM decision and affective distress [ Time Frame: Up to 18 months ]
   Longitudinal trajectories of affective distress are examined. For this, The Contralateral Prophylactic Mastectomy (CPM) survey consists of 23 items related to decision making, knowledge, risk perceptions, and worry about breast cancer. It was developed based on expert knowledge measuring decision making, risk perceptions, and knowledge outcomes in patients with breast cancer. It showed in a recent study that choice of CPM is related to significant anxiety about cancer coupled with overestimation of the risk of recurrence and therefore of the benefit of the procedure. This will be used to study the link between affect reactivity and regulation and cognitive distortion about risks and benefits.
3. Functional status as a predictor of longitudinal progression [ Time Frame: Up to 18 months ]
   Functional status is assessed through self-report measures. The "Ways of Coping Checklist" was developed to assess eight fundamental dimensions of the coping process: confrontation, distancing, self-control, seeking social support, accepting responsibility, escape/avoidance, planful problem solving, and positive reappraisal. These dimensions measure two general functions of coping, problem-focused coping and emotion-focused coping. Problem-focused coping is aimed at doing something to change the stressful situation for the better, whereas emotion- focused coping is aimed at regulating emotional distress

Other Outcome Measures:

1. Choice of BLM and reliance on information from nonmedical sources assessed using the Rosenberg questionnaire [ Time Frame: Up to 18 months ]
   As an exploratory analysis, using logistic regression analysis, an examination of whether women who choose BLM report more reliance on information from nonmedical sources such as media and the internet than on medical professionals and family/friends (Rosenberg Questionnaire (29), question 23) will be conducted.

Biospecimen Retention:   Samples With DNA

blood and saliva

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

patients with stage 0-III breast cancer at Stanford Cancer Center, as well as healthy subjects

Criteria

Inclusion Criteria:

Women Diagnosed with breast cancer

• Female
• Age 18 or older
• Agree to suspend treatments containing Benzodiazepines and steroids up to 2 weeks pre and during cortisol sampling (based on PI's clinical judgement)
• Agree to taking saliva samples and having fMRI scan
• No contraindications to MRI imaging (like ferromagnetic metal in their body)
• Proficiency in English sufficient to complete questionnaires and follow instructions during the fMRI assessments
• US Citizen or resident able to receive payment legally
• Documented stage 0-III breast cancer
• Unilateral breast tumors

Controls

• Female
• Age 18 or older
• Agree to suspend treatments containing Benzodiazepines and steroids up to 2 weeks pre and during cortisol sampling (based on PI's clinical judgement)
• Agree to having saliva samples and fMRI scan
• No contraindications to MRI imaging (like ferromagnetic metal in their body)
• Proficiency in English sufficient to complete questionnaires and follow instructions during the fMRI assessments
• US Citizen or resident able to receive payment legally

Exclusion Criteria:

Women Diagnosed with breast cancer

• Other active cancers within the past 10 years other than squamous cell carcinoma of the skin
• Pregnant
• Any significant neurologic disease, such as dementia, multi-infarct dementia, Parkinson's or Huntington's disease, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, stroke, or traumatic brain injury
• Hearing impaired
• Current untreated psychosis, or bipolar disorder, or substance/alcohol abuse/dependence
• Current use of psychotropic (based on PI's clinical judgement) medication 5 or more days a week

Controls

• Cancer diagnosis, current or past
• Pregnant
• Any significant neurologic disease, such as dementia, multi-infarct dementia, Parkinson's or Huntington's disease, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, stroke, or traumatic brain injury
• Hearing impaired
• Current untreated psychosis, or bipolar disorder, or substance/alcohol abuse/dependence
• Current use of psychotropic (based on PI's clinical judgement) medication 5 or more days a week
• Breast cancer diagnosis in 1 first degree relative or 2 or more second degree relatives
• Ovarian cancer diagnosis in 1 first or second degree relative

Contacts and Locations

Locations

United States, California

Stanford University, School of Medicine

Palo Alto, California, United States, 94304

Sponsors and Collaborators

Stanford University

National Cancer Institute (NCI)

Investigators

• Principal Investigator: David Spiegel; Stanford University

More Information

• Responsible Party: Stanford University
• ClinicalTrials.gov Identifier: NCT03050463
• Other Study ID Numbers: BRSADJ0030; NCI-2016-01547 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); BRSADJ0030 ( Other Identifier: Stanford Cancer Institute ); U01CA197282 ( U.S. NIH Grant/Contract )
• First Posted: February 13, 2017
• Last Update Posted: April 22, 2020
• Last Verified: April 2020

Additional relevant MeSH terms:

Breast Neoplasms; Breast Carcinoma In Situ; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Carcinoma in Situ; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type