Breast Cancer Patients' Cognitive Symptoms After Information About Chemotherapy-Related Cognitive Symptoms (CONTEXT)

Downsides of Being Well-Informed: Tracking and Preventing Chemotherapy-Related Cognitive Problems in Breast Cancer Patients

Previous cross-sectional studies have shown that informing cancer patients about potential chemotherapy-related cognitive symptoms may negatively affect perceived cognitive symptoms and verbal memory performance. A multicenter, randomized study in newly diagnosed breast cancer patients receiving (neo) adjuvant chemotherapy was performed to evaluate this Adverse Information Effect (AIE) over time and investigated whether inviting patients to self-affirm can reduce such AIEs on perceived cognitive symptoms and cognitive test performance.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Cognitive Decline; Cognitive Symptoms
• Intervention / Treatment: Other: Written information about potential chemotherapy-related cognitive symptoms without self-affirmation; Other: Written information about potential chemotherapy-related cognitive symptoms with self-affirmation

Detailed Description

Rationale:

Although information about their treatment and its side-effects is requested by cancer patients, is vital for informed decision making and can positively impact patients' health outcomes and illness perceptions, this kind of information can also adversely impact perceived cognitive symptoms and cognitive test performance. Previous studies have shown that informing cancer patients about potential chemotherapy-related cognitive symptoms may negatively affect perceived cognitive symptoms and verbal memory performance. A multicenter, randomized study in newly diagnosed breast cancer patients receiving (neo) adjuvant chemotherapy was performed to evaluate this Adverse Information Effect (AIE) over time and investigated whether inviting patients to self-affirm can reduce such AIEs on perceived cognitive symptoms and cognitive test performance.

Main objectives and hypotheses:

The overall aim of the study was to investigate the occurrence and duration of AIEs on the perceived frequency of cognitive symptoms, the perceived severity of cognitive symptoms and cognitive performance in breast cancer patients, and to examine ways to reduce such AIEs. First, evaluated the effect of providing breast cancer patients with additional factual written information about potential chemotherapy-related cognitive symptoms before chemotherapy-initiation on perceived cognitive symptoms and cognitive performance was evaluated, and the duration of such effects was assessed. Building on previous findings that breast cancer patients showed an increase in perceived cognitive symptoms and a decrease in verbal memory performance after receiving cognitive side-effect information, it was hypothesized that communicating about potential chemotherapy-related cognitive symptoms will result in AIEs, and it was explored to what extent these AIEs persist over time. Second, this study aimed to translate the beneficial effects of self-affirmation to the oncology domain, and examined the efficacy of a text-integrated self-affirmation intervention in reducing the impact of AIEs on perceived cognitive symptoms and cognitive performance in breast cancer patients when communicating about chemotherapy-related cognitive symptoms. It was hypothesized that a textual self-affirmation intervention would reduce AIEs in breast cancer patients, building on evidence from health promotion and stereotype threat research outside the oncology domain that individuals' self-concepts can be affirmed via text-integrated health messages and that allowing individuals the opportunity for self-affirmation can reduce stereotype threat effects.

The main research questions were:

1. Does written information about potential chemotherapy-related cognitive symptoms presented only once before treatment-initiation affect short- and longer-term perceived cognitive symptoms (the perceived frequency and severity of cognitive symptoms) and cognitive performance (verbal memory performance, information processing speed, executive functioning) in newly diagnosed breast cancer patients scheduled for (neo) adjuvant chemotherapy?
2. Does providing newly diagnosed breast cancer patients with a text integrated self-affirmation intervention after being informed about potential chemotherapy-related cognitive symptoms reduce AIEs on short- and longer-term perceived cognitive symptoms and cognitive performance?

Study procedure and outcome measures:

Before (neo) adjuvant chemotherapy, 160 newly diagnosed breast cancer patients were randomly allocated to receive either standard information on side-effects (control condition), or standard information with additional information about chemotherapy-related cognitive symptoms (information condition), or standard and additional information with a subsequent self-affirmative text (information+SA condition; SA=self-affirmation). Online-questionnaires were completed before chemotherapy (baseline, T0), 6-months (T1) and 12-months (T2) later to measure the perceived frequency (MOS-cog) and severity (MDASI-cog) of cognitive symptoms. Patients also completed two online neuro-psychological tests (Trail Making Test; TMT, and 15 Words test) to measure verbal memory performance, information processing speed and executive functioning. Additionally, several potential underlying mechanisms and risk factors of AIEs were examined, such as cancer related distress and performance worries. Baseline-to-follow-up analyses were performed using a mixed-effects modeling approach to compare groups over time.

• Study Type: Interventional
• Enrollment (Actual): 148
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Primary breast cancer diagnosis stage I-III
• Scheduled to receive (neo) adjuvant chemotherapy
• 18 years or older
• Sufficient command of the Dutch language
• Internet access

Exclusion Criteria:

• A history of neurological and psychiatric symptoms that influence cognitive functioning
• Previous cancer diagnosis
• Using drugs
• Drinking more than three alcoholic drinks a day

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; Participants in the control group received standard information on treatment side-effects.
Experimental: Information without self-affirmation; Before completing the study's online baseline survey (pre-chemotherapy), participants in the information group received standard information with additional written information about potential chemotherapy-related cognitive symptoms.	Other: Written information about potential chemotherapy-related cognitive symptoms without self-affirmation; Other Names: Information
Experimental: Information with self-affirmation; Before completing the study's online baseline survey (pre-chemotherapy), participants in the information+SA group (SA=self-affirmation) received standard and additional written information about potential chemotherapy-related cognitive symptoms with a subsequent self-affirmative text.	Other: Written information about potential chemotherapy-related cognitive symptoms with self-affirmation; Other Names: Information+SA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Between-group differences in mean change in the perceived frequency of cognitive symptoms from baseline to T1, and from baseline to T2.	Six items of the revised Medical Outcomes Study - cognitive functioning subscale (MOS-cog; Stewart & Ware, 1992) to measure the perceived frequency of cognitive symptoms. Participants indicated the frequency of experiencing a range of day-to-day problems in six aspects of cognitive functioning during the past week (including today). Higher mean scores indicate better perceived cognitive functioning (range 0-100).	Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later
Between-group differences in mean change in the perceived severity of cognitive symptoms from baseline to T1, and from baseline to T2.	Two items of the M.D. Anderson Symptom Inventory Multiple Myeloma module (MDASI-MM part 1; Cleeland et al., 2000; Jones et al., 2013) to measure the perceived severity of cognitive symptoms. Patients reported the severity of two cognitive symptoms at their worst in the last 24 hours on a 0-10 scale, with 0 being 'not present' and 10 being 'as bad as you can imagine': difficulty remembering and difficulty paying attention (concentrating). Higher mean scores indicate more severe symptoms.	Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later
Between-group differences in mean change in verbal memory performance from baseline to T1, and from baseline to T2.	Online, adapted version of the Groningen Fifteen Words Test (Rey, 1964) measuring immediate recall (range 0-45), delayed recall (range 0-15) and recognition (range 0-30). Higher scores indicate better performance.	Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later
Between-group differences in mean change in information processing speed and executive functioning from baseline to T1, and from baseline to T2.	Online version of the Trail Making Test (TMT; Reitan & Wolfson, 1985) part A and B (and TMT-B to TMT-A ratio B/A) to measure the speed of information processing and executive functioning. The score on each part represents the amount of time in seconds required to complete the task. Higher scores indicate worse information processing and executive functioning.	Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Between-group differences in mean change in the levels of anxiety from baseline to T1, and from baseline to T2.	Dutch version of the Hospital Anxiety and Depression Scale (HADS; Spinhoven et al., 1997; Zigmond & Snaith, 1983) to measure levels of anxiety. Higher sum scores (range 0-21) indicate higher levels of anxiety.	Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later
Between-group differences in mean change in the levels of depression from baseline to T1, and from baseline to T2.	Dutch version of the Hospital Anxiety and Depression Scale (HADS; Spinhoven et al., 1997; Zigmond & Snaith, 1983) to measure levels of depression. Higher sum scores (range 0-21) indicate higher levels of depression.	Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later
Between-group differences in mean change in the perceived severity of other cancer-related symptoms from baseline to T1, and from baseline to T2.	Twelve items of the thirteen-item core M. D. Anderson Symptom Inventory (MDASI; part 1; Cleeland et al., 2000) to measure the perceived severity of other cancer-related symptoms. Participants reported the severity of twelve symptoms at their worst in the last 24 hours hours on a 0-10 scale, with 0 being 'not present' and 10 being 'as bad as you can imagine.' Difficulty remembering was excluded. Higher mean scores indicate more severe symptoms.	Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later
Between-group differences in pre-existing knowledge (prior to the experiment) about the potential cognitive symptoms of cancer treatment measured at twelve months follow-up (T2).	Participants indicated on one item (range 1-5) at the end of the T2 survey whether they had knowledge about the potential cognitive side-effects of cancer treatment prior to the experiment to measure pre-existing knowledge. Higher scores indicate more pre-existing knowledge.	Measured at twelve months follow-up (T2)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Between-group differences in mean change in the levels of the expected severity of cognitive symptoms from baseline to T1, and from baseline to T2.	An adapted version of two items of the M. D. Anderson Symptom Inventory Multiple Myeloma module (MDASI-MM; part 1; Cleeland et al., 2000; Jones et al., 2013) to measure the expected severity of cognitive symptoms during the next weeks (range 0-10). Higher scores indicate expectations of more severe cognitive symptoms.	Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later
Between-group differences in mean change in the levels of the expected severity of other cancer-related symptoms from baseline to T1, and from baseline to T2.	An adapted version of four items of the M. D. Anderson Symptom Inventory Multiple Myeloma module (MDASI-MM; part 1; Cleeland et al., 2000; Jones et al., 2013) to measure the expected severity of other cancer-related symptoms during the next weeks (range 0-10). Higher scores indicate expectations of more severe other cancer-related symptoms.	Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later
Between-group differences in mean change in the levels of motivation from baseline to T1, and from baseline to T2.	Five modified and translated items from the effort subscale of the Intrinsic Motivation Inventory (IMI; Ryan, 1982; Ryan & Deci, 2000) to measure the levels of motivation during the neuropsychological tasks (range 1-5). Higher mean scores indicate higher levels of motivation.	Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later
Between-group differences in mean change in the levels of worrying about cognitive test performance from baseline to T1, and from baseline to T2.	Four modified and translated items derived from the test anxiety subscale of the Motivated Strategies for learning Questionnaire (Pintrich & De Groot, 1990) to measure the levels of worrying about cognitive test performance (range 1-5). Higher mean scores denote higher levels of worries.	Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later
Low cancer-specific distress versus high cancer-specific distress subgroup analysis.	Seven items of the intrusion subscale of the Dutch version of the Impact of Events Scale (Horowitz, Wilner, & Alvarez, 1979; Van der Ploeg et al., 2004) to assess the levels of intrusion of cancer related stressful thoughts (range 0-28). Higher sum scores indicate higher intrusion when confronted with the stressful experience of being treated for cancer.	Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later
Low stigma consciousness versus high stigma consciousness subgroup analysis.	Eight translated and adapted items derived from the 10-item Stigma Consciousness Questionnaire to measure the extent to which patients expect to be stereotyped by others (Brown & Pinel, 2003; cf. Jacobs, Das, & Schagen, 2017; range 1-5). Higher mean scores indicate higher levels of stigma consciousness.	Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later
Low domain identification versus high domain identification subgroup analysis.	Three adapted and translated items from the math identification subscale of the Social Identities and Attitudes Scale (SIAS; Picho & Brown, 2011), to measure the extent to which participants identify with the domain of 'cognition' and the level of importance of their cognition (range 1-5). Higher mean scores indicate higher levels of domain identification.	Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later
Low group identification versus high group identification subgroup analysis.	Two newly developed items and four items derived and adapted from Doosje and colleagues (Doosje, Ellemers, & Spears, 1995), Spears and colleagues (Spears, Doosje, & Ellemers, 1997), and Quayle (2011) to measure the level of group identification, that is to what extent participants identify with other (ex) cancer patients (range 1-5). Higher mean scores indicate higher levels of group identification.	Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later
Low information monitoring versus high information monitoring subgroup analysis.	Information monitoring was measured by one item that asked patients how often during the past weeks they searched for health- and cancer related information (range 0-4). Higher scores indicate higher levels of information monitoring.	Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later
Between-group differences in changes in information source from baseline to T1, and from baseline to T2.	One item to indicate which information sources participants used (twelve options; for example information leaflets yes/no).	Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later
Between-group differences in changes in information content from baseline to T1, and from baseline to T2.	One item to assess what information content participants looked for (six options; for example information about chemotherapy side-effects yes/no).	Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later
Between-group differences in stereotype self-relevance measured at twelve months follow-up (T2).	At twelve months follow-up (T2), stereotype self-relevance was measured using one item that assessed perceived self-relevance of the chemotherapy-impairs-cognition stereotype: 'To what extent does the phenomena 'Chemo brain' apply to you?' (range 1-5). Higher scores indicate higher levels of self-relevance.	Measured at twelve months follow-up (T2)
Between-group differences in the extent to which participants attributed their own and others' cognitive symptoms to chemotherapy measured at twelve months follow-up (T2).	At twelve months follow-up (T2), two items asked participants to indicate the extent to which they attributed their own and others' cognitive symptoms to chemotherapy (range 1-5). Higher scores indicate higher levels of attribution of cognitive symptoms to chemotherapy.	Measured at twelve months follow-up (T2)

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: UMC Utrecht; St. Antonius Hospital; The Netherlands Cancer Institute; Franciscus Gasthuis; Rijnstate Hospital; Deventer Ziekenhuis; Isala; Ziekenhuisgroep Twente; Meander Medical Center; St Jansdal Hospital
• Investigators: Principal Investigator: Enny Das, PhD, Radboud University Medical Center; Principal Investigator: Sanne B Schagen, PhD, The Netherlands Cancer Institute; Principal Investigator: Gabe S Sonke, PhD, MD, The Netherlands Cancer Institute

Publications and helpful links

General Publications

• Jacobs W, Schagen SB, Brouwer SM, Kieffer JM, Baas IO, Los M, Sonke GS, Das E. The Effects of Being Informed About Chemotherapy-Related Cognitive Symptoms With And Without Self-Affirmation on Perceived Cognitive Symptoms of Breast Cancer Patients: A Randomized Prospective, Longitudinal Study. Clin Breast Cancer. 2022 Jul;22(5):439-454. doi: 10.1016/j.clbc.2022.03.001. Epub 2022 Mar 26.

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2014
• Primary Completion (Actual): September 23, 2016
• Study Completion (Actual): September 23, 2016

Study Registration Dates

• First Submitted: March 17, 2021
• First Submitted That Met QC Criteria: March 21, 2021
• First Posted (Actual): March 24, 2021

Study Record Updates

• Last Update Posted (Actual): March 24, 2021
• Last Update Submitted That Met QC Criteria: March 21, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Breast cancer; Chemotherapy; Health communication; Cognitive symptoms; Nocebo; Self-affirmation; Stereotype threat
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Neurologic Manifestations; Neurocognitive Disorders; Breast Diseases; Cognition Disorders; Breast Neoplasms; Cognitive Dysfunction; Neurobehavioral Manifestations
• Other Study ID Numbers: M13WEL; 2016-8178 (Other Grant/Funding Number: KWF Kankerbestrijding Nederland); 2011.WO34.C123 (Other Grant/Funding Number: Pink Ribbon Nederland); NL43939.031.13 (Registry Identifier: Registry ID: CCMO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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