An investigation into socio-demographic-, health-, and cancer-related factors associated with cortisol and C-reactive protein levels in breast cancer survivors: a longitudinal study



Breast cancer survivors (BCS) may exhibit dysregulated patterns of cortisol and C-reactive protein (CRP). The aims of this study were to describe BCS’ cortisol and CRP levels over a 1-year period after treatment, and assess how levels relate to socio-demographic- (age, education level, marital status), health- (body mass index [BMI] category, menopausal status), and cancer-related factors (cancer stage, chemotherapy exposure, time since diagnosis).


Participants (N = 201) provided data at 3 months post-treatment (T1) and again 3, 6, 9, and 12 months later (T2–T5). At T1, participants completed self-report questionnaires and had their weight and height measured by a trained technician. At T1–T5, they provided five saliva samples at awakening, 30 min after awakening, 2:00 pm, 4:00 pm, and before bedtime on two nonconsecutive days to measure diurnal cortisol, and provided capillary whole blood to measure CRP. Data were analyzed using repeated-measure analyses of variance (ANOVAs) and mixed-design ANOVAs.


Diurnal cortisol and CRP levels fluctuated over time. In univariate models, older age and post-menopausal status were associated with higher cortisol and CRP levels, higher cancer stage and chemotherapy were associated with lower cortisol levels, and higher BMI category was associated with higher CRP levels. In adjusted models, age was no longer associated with CRP levels and shorter time since diagnosis was significantly associated with higher CRP levels.


Socio-demographic-, health-, and cancer-related factors may help identify BCS at risk of physiological dysregulation who need intervention. Identifying modifiable factors associated with cortisol and CRP will inform cancer care interventions.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3


  1. 1.

    Selye H. Stress in Health and Disease. Butterworth-Heinemann; 2013.

  2. 2.

    Wiley JF, Bower JE, Petersen L, Ganz PA. Trajectories of C-reactive protein in the year after breast cancer treatment. Brain Behav Immun. 2017;66:e28–e2929.

    Article  Google Scholar 

  3. 3.

    Hsiao F-H, Jow G-M, Kuo W-H, Wang M-Y, Chang K-J, Lai Y-M, et al. A longitudinal study of diurnal cortisol patterns and associated factors in breast cancer patients from the transition stage of the end of active cancer treatment to post-treatment survivorship. The Breast. 2017;36:96–101.

    Article  Google Scholar 

  4. 4.

    Asegaonkar SB, Asegaonkar BN, Takalkar UV, Advani S, Thorat AP. C-reactive protein and breast cancer: new insights from old molecule. Int J Breast Cancer. 2015;2015:1–16.

    Article  Google Scholar 

  5. 5.

    Bower JE, Ganz PA, Aziz N. Altered cortisol response to psychologic stress in breast cancer survivors with persistent fatigue. Psychosom Med. 2005;67:277–80.

    Article  Google Scholar 

  6. 6.

    Xiao C, Miller AH, Felger J, Mister D, Liu T, Torres MA. Depressive symptoms and inflammation are independent risk factors of fatigue in breast cancer survivors. Psychol Med. 2017;47:1733–43.

    CAS  Article  Google Scholar 

  7. 7.

    Kirschbaum C, Prüssner JC, Stone AA, Federenko I, Gaab J, Lintz D, et al. Persistent high cortisol responses to repeated psychological stress in a subpopulation of healthy men. Psychosom Med. 1995;57:468–74.

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Miller GE, Chen E, Zhou ES. If it goes up, must it come down? Chronic stress and the hypothalamic-pituitary-adrenocortical axis in humans. Psychol Bull. 2007;133:25–45.

    Article  Google Scholar 

  9. 9.

    Heim C, Ehlert U, Hellhammer DH. The potential role of hypocortisolism in the pathophysiology of stress-related bodily disorders. Psychoneuroendocrinology. 2000;25:1–35.

    CAS  Article  Google Scholar 

  10. 10.

    McEwen BS. Stress, adaptation, and disease. Allostasis and allostatic load. Ann N Y Acad Sci. 1998;840:33–44.

    CAS  Article  Google Scholar 

  11. 11.

    Cubała WJ, Landowski J. C-reactive protein and cortisol in drug-naïve patients with short-illness-duration first episode major depressive disorder: Possible role of cortisol immunomodulatory action at early stage of the disease. J Affect Disord. 2014;152–154:534–7.

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Tolmay CM, Malan L, Van Rooyen JM. The relationship between cortisol, C-reactive protein and hypertension in African and Caucasian women: the POWIRS study. Cardiovasc J Afr. 2012;23:78–84.

    Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Slavish DC, Graham-Engeland JE, Smyth JM, Engeland CG. Salivary markers of inflammation in response to acute stress. Brain Behav Immun. 2015;44:253–69.

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Gouin J-P, Glaser R, Malarkey WB, Beversdorf D, Kiecolt-Glaser J. Chronic stress, daily stressors, and circulating inflammatory markers. Health Psychol. 2012;31:264–8.

    Article  PubMed  Google Scholar 

  15. 15.

    Johnson TV, Abbasi A, Master VA. Systematic review of the evidence of a relationship between chronic psychosocial stress and C-reactive protein. Mol Diagn Ther. 2013;17:147–64.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Villasenor A, Flatt SW, Marinac C, Natarajan L, Pierce JP, Patterson RE. Postdiagnosis C-reactive protein and breast cancer survivorship: findings from the WHEL study. Cancer Epidemiol Biomarkers Prev. 2014;23:189–99.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Allin KH, Nordestgaard BG. Elevated C-reactive protein in the diagnosis, prognosis, and cause of cancer. Crit Rev Clin Lab Sci. 2011;48:155–70.

    CAS  Article  Google Scholar 

  18. 18.

    Seruga B, Zhang H, Bernstein LJ, Tannock IF. Cytokines and their relationship to the symptoms and outcome of cancer. Nat Rev Cancer. 2008;8:887–99.

    CAS  Article  Google Scholar 

  19. 19.

    Caparević Z, Kostić N. The influence of age and the beginning of menopause on the lipid status, LDL oxidation, and CRP in healthy women. Srp Arh Celok Lek. 2007;135:280–5.

    Article  Google Scholar 

  20. 20.

    Chin B, Murphy MLM, Janicki-Deverts D, Cohen S. Marital status as a predictor of diurnal salivary cortisol levels and slopes in a community sample of healthy adults. Psychoneuroendocrinology. 2017;78:68–75.

    CAS  Article  Google Scholar 

  21. 21.

    Babaei Z, Moslemi D, Parsian H, Khafri S, Pouramir M, Mosapour A. Relationship of obesity with serum concentrations of leptin, CRP and IL-6 in breast cancer survivors. J Egypt Natl Canc Inst. 2015;27:223–9.

    Article  Google Scholar 

  22. 22.

    Limberaki E, Eleftheriou P, Gasparis G, Karalekos E, Kostoglou V, Petrou C. Cortisol levels and serum antioxidant status following chemotherapy. Health. 2011;03:512.

    CAS  Article  Google Scholar 

  23. 23.

    Sabiston CM, Wrosch C, Fong AJ, Brunet J, Gaudreau P, O’Loughlin J, et al. Life after breast cancer: moving on, sitting down or standing still? A prospective study of Canadian breast cancer survivors. BMJ Open. 2018;8:e021770.

    Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Kirschbaum C, Hellhammer DH. Encyclopedia of stress: salivary cortisol. San Diego: Academic Press; 2000.

    Google Scholar 

  25. 25.

    Pruessner JC, Kirschbaum C, Meinlschmid G, Hellhammer DH. Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change. Psychoneuroendocrinology. 2003;28:916–31.

    CAS  Article  Google Scholar 

  26. 26.

    McDade TW. Measuring immune function: markers of cell-mediated immunity and inflammation in dried blood sports. Measuring stress in humans: a practical guide for the field. Cambridge: Cambridge University Press; 2007. p. 181–208.

    Google Scholar 

  27. 27.

    World Health Organization. Global Database on Body Mass Index 2019. Accessed Mar 24 2020.

  28. 28.

    Enders CK. Multiple imputation as a flexible tool for missing data handling in clinical research. Behav Res Ther. 2017;98:4–18.

    Article  Google Scholar 

  29. 29.

    Tabachnick BG, Fidell LS. Using multivariate statistics. 6th ed. Upper Saddle River: Pearson Education; 2013.

    Google Scholar 

  30. 30.

    Kober KM, Olshen A, Conley YP, Schumacher M, Topp K, Smoot B, et al. Expression of mitochondrial dysfunction-related genes and pathways in paclitaxel-induced peripheral neuropathy in breast cancer survivors. Mol Pain. 2018;14:1744806918816462.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Bower JE, Ganz PA, Aziz N, Olmstead R, Irwin MR, Cole SW. Inflammatory responses to psychological stress in fatigued breast cancer survivors: relationship to glucocorticoids. Brain Behav Immun. 2007;21:251–8.

    CAS  Article  Google Scholar 

  32. 32.

    Allen J, Savadatti S, Levy A. The transition from breast cancer “patient” to ’survivor. Psycho-Oncol. 2008;18:71–8.

    Article  Google Scholar 

  33. 33.

    Herriot H, Wrosch C, Gouin J-P, Miller GE. Intra-individual cortisol variability and low-grade inflammation over 10 years in older adults. Psychoneuroendocrinology. 2017;77:141–9.

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Oktem O, Oktay K. Quantitative assessment of the impact of chemotherapy on ovarian follicle reserve and stromal function. Cancer. 2007;110:2222–9.

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Edwards KM, Mills PJ. Effects of estrogen versus estrogen and progesterone on cortisol and interleukin-6. Maturitas. 2008;61:330–3.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Liu Z, Sahli Z, Wang Y, Wolff A, Cope L, Umbricht C. Young age at diagnosis is associated with worse prognosis in the Luminal A breast cancer subtype: a retrospective institutional cohort study. Breast Cancer Res Treat. 2018;172:689–702.

    Article  Google Scholar 

  37. 37.

    Partridge AH, Hughes M, Warner E, Ottesen R, Wong Y-N, Edge S, et al. Subtype-dependent relationship between young age at diagnosis and breast cancer survival. J Clin Oncol. 2016;34:3308–14.

    Article  Google Scholar 

  38. 38.

    Lavretsky H, Newhouse PA. Stress, inflammation and aging. Am J Geriatr Psychiatry. 2012;20:729–33.

    Article  Google Scholar 

  39. 39.

    Azim HA, Partridge AH. Biology of breast cancer in young women. Breast Cancer Res. 2014;16:427.

    Article  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Anastasiadi Z, Lianos GD, Ignatiadou E, Harissis HV, Mitsis M. Breast cancer in young women: an overview. Updates Surg. 2017;69:313–7.

    Article  PubMed  Google Scholar 

  41. 41.

    Waks AG, Winer EP. Breast cancer treatment. JAMA. 2019;321:316.

    Article  PubMed  Google Scholar 

  42. 42.

    McEwen BS. Central effects of stress hormones in health and disease: Understanding the protective and damaging effects of stress and stress mediators. Eur J Pharmacol. 2008;583:174–85.

    CAS  Article  Google Scholar 

  43. 43.

    Mills RC. Breast Cancer Survivors, Common Markers of Inflammation, and Exercise: A Narrative Review. Breast Cancer (Auckl). 2017;11:1178223417743976.

    PubMed  PubMed Central  Google Scholar 

  44. 44.

    Porter LS, Mishel M, Neelon V, Belyea M, Pisano E, Soo MS. Cortisol levels and responses to mammography screening in breast cancer survivors: a pilot study. Psychosom Med. 2003;65:842–8.

    CAS  Article  Google Scholar 

  45. 45.

    Cirulli F, Capoccia S, Berry A, Raggi C, Vomero MA, Ortona E, et al. Increased cortisol secretion, immune activation and mood changes in breast cancer patients following surgery and adjuvant chemotherapy. Eur Psychiatry. 2015;30:1510.

    Article  Google Scholar 

  46. 46.

    Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140:883–99.

    CAS  Article  Google Scholar 

  47. 47.

    Timpson NJ, Nordestgaard BG, Harbord RM, Zacho J, Frayling TM, Tybjærg-Hansen A, et al. C-reactive protein levels and body mass index: elucidating direction of causation through reciprocal Mendelian randomization. Int J Obes (Lond). 2011;35:300–8.

    CAS  Article  Google Scholar 

  48. 48.

    Goldberg JE, Schwertfeger KL. Proinflammatory cytokines in breast cancer: mechanisms of action and potential targets for therapeutics. Curr Drug Targets. 2010;11:1133–46.

    CAS  Article  Google Scholar 

  49. 49.

    Rock CL, Doyle C, Demark-Wahnefried W, Meyerhardt J, Courneya KS, Schwartz AL, et al. Nutrition and physical activity guidelines for cancer survivors. CA Cancer J Clin. 2012;62:243–74.

    Article  PubMed  Google Scholar 

  50. 50.

    Lee J, Vicil F. Effects of an evidence-based exercise intervention on clinical outcomes in breast cancer survivors: a randomized controlled trial. Asian J Kinesiol. 2020;22:1–8.

    CAS  Article  Google Scholar 

Download references


We gratefully acknowledge the women who participated in this study, without whom our research could not be conducted.


This research was supported by a Canadian Institutes of Health Research grant (Grant no. 123358). CMS is supported by the Canada Research Chairs program.

Author information



Corresponding author

Correspondence to J. Brunet.

Ethics declarations

Conflict of interest

All authors certify no potential conflict of interest to disclose.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in this study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Verify currency and authenticity via CrossMark

Cite this article

Lambert, M., Sabiston, C.M., Wrosch, C. et al. An investigation into socio-demographic-, health-, and cancer-related factors associated with cortisol and C-reactive protein levels in breast cancer survivors: a longitudinal study. Breast Cancer (2020).

Download citation


  • Breast cancer survivors
  • Cortisol
  • C-reactive protein
  • Correlates