Biomarkers in Breast Cancer Survivors: The Search for Predictors
Creators: name: Lambert, Maude
Publisher: name: Université d'Ottawa / University of Ottawa
Year: 2021
Subjects: Cancer survivors
Biomarkers
Cortisol
Immunoglobulin
Breast cancer
C-reactive protein

description: Receiving a breast cancer (BC) diagnosis generates significant physical and psychological stress that may persist months, years, or even decades beyond treatment completion. Such chronic stress can severely alter the biological systems of BC survivors (BCS). Yet, little is known about the impact and associated variables of these long-term physiological sequelae. Considering that the number of BCS continues to grow each year, it is imperative to assess the extent to which a BC experience impacts human physiological mechanisms by examining the secretion patterns of associated stress- and immune-related biomarkers and by exploring the behavioural, physical, and psychological variables implicated in these dysregulations. Such research is of particular importance in order to guide cancer survivorship care and develop interventions promoting optimal health outcomes in BCS. This research program sought to address this through three inter-related studies. Study One was a quasi-experimental design study examining both the diurnal and reactive concentration patterns of secretory immunoglobulin A (SIgA) in a sample of women with (n = 22) and without a prior history of BC (n = 26). SIgA concentration patterns were contrasted to concentration patterns of cortisol and salivary alpha-amylase (sAA) in the same individuals (complementary to two previously published studies). Participants supplied saliva samples at five time points on two consecutive typical days (for diurnal data) and at seven time points before, during, and after an acute laboratory stressor (for reactive data). Results reveled no evidence of uncharacteristic SIgA diurnal or reactive concentration patterns, suggesting a normal and well-functioning immunological SIgA system in BCS on average 4.6 years post-diagnosis. Study One acted as a summary article allowing readers to grasp the "big picture" of long-term physiological dysregulations in BCS as a whole. Building on this, Study Two, which used the same dataset as Study One, aimed to determine whether physical activity (PA) could mitigate the adverse physiological effects of a BC experience in BCS (n = 25), as indexed by their cortisol concentration patterns. Participants self-reported their PA frequency and engaged in the same cortisol assay protocol reported in Study One. Results indicated no statistically significant differences in diurnal and reactive cortisol patterns between low- and high-PA groups. A trend that PA might not have the same effect on women with and without a history of BC was noted. Important limitations to Study Two included the small sample size and the lack of sensitivity and objectivity of the PA measure. To address Study Two’s limitations and to consider a wider range of modifiable variables that could contribute to the physiological dysregulations observed in BCS, Study Three aimed to assess the predictive value of six behavioural, physical, and psychological variables on the physiological effects of a BC experience, as indexed by cortisol (n = 192) and C-reactive protein (CRP; n = 168) levels over the first 1.5 year post-treatment. CRP, a biomarker that had not been considered so far in this research program, allowed to assess systemic inflammation in BCS post-treatment. Study Three also aimed to describe naturally occurring changes in cortisol and CRP levels and assess whether they changed in tandem. Data were drawn from 201 BCS who provided capillary blood and saliva samples at approximately 3.5 months post-treatment and again 3, 6, 9, and 12 months later. At each time point, participants also completed self-report questionnaires and wore an accelerometer for seven consecutive days. Multilevel modeling analyses revealed no significant change over time for cortisol levels post-treatment and a non-linear trajectory of change for CRP levels which was not predicted by cortisol levels. Associations between cortisol and sedentary time as well as associations between CRP and PA, body mass index, and health- and cancer-related stress were found. Collectively, these three inter-related studies uniquely add to the literature by describing long-term physiological trajectories of stress- and immune-related biomarkers in BCS. This research program attempts to gain a better understanding of the underlying mechanisms that tie behavioural, physical, and psychological variables and biomarker secretion to a BC experience. It also offers opportunities to identify women at greater risk of physiological dysregulations following a BC experience. This represents an important step towards the development of tailored interventions targeting specific BCS that most warrant them. With the number of BCS climbing each year, cancer survivorship needs to be a priority in research and efforts to better understand, monitor, and mitigate the physiological consequences of a BC experience are critical.