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

A substantial group of breast cancer patients report cognitive complaints after
chemotherapy. Information on chemotherapy side effects like cognitive problems
is increasingly accessible for patients, for instance on the Internet. But what
are the effects of informing patients about chemotherapy treatment side
effects?
Studies show that although treatment-related information may help patients make
an informed decision, and take away worries and doubts, it also may have
downsides. Research of our own group showed that merely informing (ex) breast
cancer patients about the association between chemotherapy and cognitive
deficits prior to completing a memory test and questionnaires, resulted in
reduced memory ability and increased complaint reporting. An explanation for
this mere information effect is derived from social psychological research on
stereotype threat and priming and literature on Nocebo effects. Activation of
the *chemotherapy-causes-cognitive problems-schema or stereotype* just before
patients complete a memory test can thus affect the performance on this test.
Now that research shows that (short term) information-effects are also present
in a clinical setting, and can affect life after breast cancer treatment, it is
important to investigate: 1.) What is the severity and duration of these
negative effects of information or stereotype priming effects on cognitive
deficits after chemotherapy? 2.) What are effective psychological interventions
to diminish stereotype priming effects?

Previous studies have found evidence for short term priming effects in a
clinical setting, but literature shows us that there is also reason to believe
that priming effects are long lasting and can increase over time. In addition,
empirical support has been found for promising, feasible and cost-effective
interventions regarding stereotype priming. This leads to the expectation that
similar interventions will be effective in reducing stereotype-threat effects
in a breast cancer population. This project will address both issues. The main
research hypotheses are that:
H1). Priming (activation of the *chemotherapy-causes-cognitive
problems-schema*) patients with information about the relationship between
chemotherapy and cognitive complaints prior to completing the questionnaires,
will increase the reporting of cognitive complaints and decrease cognitive
performance, compared with patients who did not receive this information;
H2). Patients in the intervention condition will report less cognitive
complaints and increased cognitive performance than patients in the priming
condition.
In addition, effects of potential moderating processes, mediating variables and
effects of covariates will be explored. It is expected that priming especially
affects respondents for whom the information is relevant. Priming is expected
to operate via various mechanisms, such as increased worry and motivation. This
study will also examine severity and duration of the stereotype priming
effects.

The objective of this study is to investigate effects of different forms of
patient information on chemotherapy side effects, in particular, assessing the
severity and duration of the negative effects of information on
chemotherapy-associated cognitive problems in breast cancer patients. The
second goal of this project is to assess potential interventions to diminish
the negative effects of informing patients on chemotherapy-associated cognitive
problems.

This multicentre, randomized controlled trial assesses the severity and
duration of stereotype threat effects (RQ1) and the effects of a psychological,
information-based intervention in routine clinical practice (RQ2). The duration
of the study will be three years and is a joint venture of the department of
Psychosocial Research and Epidemiology of the NKI, the department of Medical
Oncology of the AVL and the department of Business Communication Studies
(Persuasive Communication) of the Raboud University Nijmegen.

At T0, Patients will be invited by their treating physician to take part in an
online study *on experiences before, during and after cancer treatment* (in
Dutch: *Ervaringen vóór, tijdens en na de behandeling voor kanker: een
onderzoek naar patiënteninformatie*). This written introduction provided by the
physician will be held constant and will be neutral with respect to specific
information regarding cognitive problems following chemotherapy in order to
prevent priming effects. However, we only ask health professionals to hold
constant the information about the goals of this study, to prevent activation
of the concept of cognitive difficulties after chemotherapy in relation to this
study for all patients. We want to stress that the usual care and information
on (chemotherapy) treatment side effects will be offered to all patients in
this study.

In the online environment, participants will be randomly assigned to one of
three experimental conditions; one third of the patients receive the
introduction prior to the questionnaires and neuropsychological tests that
*some patients treated with chemotherapy experience cognitive problems* (the
experimental condition). One third of the patients will receive the same
introduction, with the addition of reassuring information for example: *By far
not all patients will experience these complaints. It is known that patients
with cognitive complaints still can perform well on cognitive
tests* (intervention condition). One third of the patients will receive a
neutral introduction prior to the questionnaires, lacking the association
between cognitive problems and chemotherapy (control condition). These
experimental materials extend previous studies in this domain. Short-term,
medium-term and longer-term priming and intervention effects will be assessed
by asking patients to fill out several questionnaires and tests at T0 (before
chemotherapy), T1 (six months after chemotherapy treatment), and T2 (twelve
months after chemotherapy treatment). Each online assessment will take
approximately 40 minutes to complete.

Patients will be randomly assigned to one of three experimental conditions: the
experimental condition, the intervention condition and the control condition.
These groups will receive different information formats regarding side effects
of chemotherapy prior to completing the questionnaires and neuropsychological
tests. The experimental group will receive an introduction before completing
the questionnaires stating that: *some patients treated with chemotherapy
experience cognitive problems*. The intervention group will receive a
comparable introduction, with the addition of reassuring and positively framed
information including the following sentence: *By far not all patients will
experience these complaints. It is known that patients with cognitive
complaints still can perform well on cognitive tests*. This text also contains
linguistic variations. The third group of patients will receive a neutral
introduction to the questionnaires and tests, which does not refer to the
association between cognitive problems and chemotherapy (control condition).
These experimental materials extend previous studies in this domain.

We want to stress that this study does not interfere with clinical care as
usual: information on treatment and treatment side effects is offered to all
patients by their physician in the usual manner. Only the study specific
information that is given to patients just prior to the completion of the
questionnaires and neuropsychological tests varies between groups. This extra
information on cognitive problems following chemotherapy provided to patients
prior to the questionnaires is correct and based on the current knowledge and
research outcomes regarding chemotherapy-associated cognitive problems. Conform
the informed consent procedures in daily practice, information on
(chemotherapy) treatment side effects, including cognitive problems, will be
given by the physician in the usual manner.

This study does not include invasive procedures, will not harm patients and
does not interfere with clinical care as usual: information on treatment and
treatment side effects is offered to all patients by their physician in the
usual manner. Only the study specific information that is given to patients
just prior to the completion of the questionnaires and neuropsychological tests
varies between groups. This extra information on cognitive problems following
chemotherapy provided to patients prior to the questionnaires is correct and
based on the current knowledge and research outcomes regarding
chemotherapy-associated cognitive problems. Conform the informed consent
procedures in daily practice, information on (chemotherapy) treatment side
effects, including cognitive problems, will be given by the physician in the
usual manner.

All participants will be asked to complete the online questionnaire (40
minutes) three times. Overall, completing online questionnaires is expected to
be not too burdensome.

It is important to study late effects of chemotherapy in breast cancer patients
from a descriptive and preventive standpoint, as people with (a history of)
breast cancer constitute an increasingly large group in our community and the
number of breast cancer survivors is growing. Cognitive complaints after
chemotherapy are common in (ex) breast cancer patients.