Role of Chronic Psychological Stress Biomarkers in Triple-Negative Breast Cancer Progression
DOI:
https://doi.org/10.61919/47vgv538Keywords:
Breast Neoplasms; C-Reactive Protein; Cortisol; Disease Progression; Psychoneuroimmunology; Stress, Psychological; Triple Negative Breast NeoplasmsAbstract
Background: Triple-negative breast cancer (TNBC) is an aggressive subtype with limited therapeutic targets and variable disease progression. Emerging evidence suggests that chronic psychological stress and its biological correlates, particularly cortisol and inflammatory markers, may influence tumor behavior through psychoneuroimmunological pathways. Objective: To evaluate the association between chronic psychological stress, serum cortisol, C-reactive protein (CRP), and disease severity in patients with TNBC. Methods: A cross-sectional study was conducted over four months in the Islamabad–Rawalpindi region, including 72 histopathologically confirmed TNBC patients. Participants were categorized into early-stage (I–II) and advanced-stage (III–IV) groups. Serum cortisol was measured using enzyme-linked immunosorbent assay, and CRP levels were assessed via high-sensitivity assays. Psychological stress was evaluated using the Perceived Stress Scale (PSS-10). Statistical analysis included independent t-tests and Pearson correlation, with significance set at p < 0.05. Results: The mean age of participants was 48.6 ± 10.2 years. Advanced-stage patients exhibited significantly higher cortisol (21.3 ± 5.2 µg/dL vs. 15.4 ± 4.1 µg/dL, p < 0.001) and CRP levels (8.2 ± 2.9 mg/L vs. 5.1 ± 2.4 mg/L, p < 0.001) compared to early-stage patients. Psychological stress scores were also elevated in advanced disease (24.1 ± 5.7 vs. 17.9 ± 4.8, p < 0.001). Positive correlations were observed between stress scores and cortisol (r = 0.52, p < 0.001), stress scores and CRP (r = 0.47, p < 0.001), and cortisol with CRP (r = 0.44, p < 0.01). Conclusion: Chronic psychological stress and its associated biomarkers were significantly associated with advanced TNBC, suggesting a potential role of psychoneuroimmunological mechanisms in disease progression. Integrating stress assessment into cancer care may provide additional clinical value
References
1. La Marca A, Volpe A. Anti-Müllerian hormone (AMH) in female reproduction: is measurement useful? Clin Endocrinol (Oxf). 2006;64(6):603-610. doi:10.1111/j.1365-2265.2006.02530.x
2. Pigny P, Merlen E, Robert Y, Cortet-Rudelli C, Decanter C, Jonard S, et al. Elevated serum level of anti-Müllerian hormone in patients with polycystic ovary syndrome: relationship to the ovarian follicle excess and to the follicular arrest. J Clin Endocrinol Metab. 2003;88(12):5957-5962. doi:10.1210/jc.2003-030222
3. Toulis KA, Iliodromiti S, Venetis CA, Tsametis C, Tarlatzis BC, Papadimas I, et al. Serum anti-Müllerian hormone levels in polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update. 2011;17(3):300-313. doi:10.1093/humupd/dmq047
4. Knochenhauer ES, Key TJ, Kahsar-Miller M, Waggoner W, Boots LR, Azziz R. Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study. Fertil Steril. 1998;70(1):52-57. doi:10.1016/S0015-0282(98)00111-3
5. Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 2004;89(6):2745-2749. doi:10.1210/jc.2003-032046
6. Franks S. Polycystic ovary syndrome. N Engl J Med. 1995;333(13):853-861. doi:10.1056/NEJM199509283331307
7. Legro RS, Arslanian SA, Ehrmann DA, Hoeger KM, Murad MH, Pasquali R, et al. Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2013;98(12):4565-4592. doi:10.1210/jc.2013-2350
8. Eldar-Geva T, Ben-Chetrit A, Spitz IM, Rabinowitz R, Markowitz E, Mimoni T, et al. Serum anti-Müllerian hormone levels during controlled ovarian hyperstimulation for in vitro fertilization: relation to ovarian response and pregnancy outcome. Hum Reprod. 2005;20(7):1829-1835. doi:10.1093/humrep/dei016
9. Seifer DB, MacLaughlin DT, Christian BP, Feng B, Shelden RM. Early follicular serum Müllerian-inhibiting substance levels are associated with ovarian response during assisted reproductive technologies. Fertil Steril. 2002;77(3):468-471. doi:10.1016/S0015-0282(01)03269-9
10. Escobar-Morreale HF, Villuendas G, Botella-Carretero JI, Alvarez-Blasco F, Sancho J, San Millán JL. Serum anti-Müllerian hormone levels in women with hyperandrogenism and oligomenorrhea: effects of adiposity and insulin resistance. J Clin Endocrinol Metab. 2005;90(10):5718-5723. doi:10.1210/jc.2005-0603
11. Sahmay S, Aydin Y, Oncul M, Senturk LM. Basal serum anti-Müllerian hormone level is associated with the severity of ovarian disease in polycystic ovary syndrome. Fertil Steril. 2014;101(3):790-796. doi:10.1016/j.fertnstert.2013.11.024
12. Rosenfield RL. The diagnosis of polycystic ovary syndrome in adolescents. Pediatrics. 2015;136(6):1154-1165. doi:10.1542/peds.2015-1434
13. Dewailly D, Andersen CY, Balen A, Broekmans F, Dilaver N, Fanchin R, et al. The physiology and clinical utility of anti-Müllerian hormone in women. Hum Reprod Update. 2014;20(3):370-385. doi:10.1093/humupd/dmt062
14. Karaer A, et al. The predictive value of AMH and LH/FSH ratio for ovulation induction in patients with PCOS. Gynecol Endocrinol. 2019;35(4):345-349. doi:10.1080/09513590.2018.1523511
15. Li R, et al. Anti-Müllerian hormone: a marker for ovarian function in women with and without polycystic ovary syndrome. Maturitas. 2015;81(1):23-27. doi:10.1016/j.maturitas.2015.02.287
16. Prapas Y, et al. Can basal AMH levels and LH/FSH ratio predict ovarian response and pregnancy in women with PCOS? Arch Gynecol Obstet. 2010;282(3):289-295. doi:10.1007/s00404-010-1417-9
17. Balen AH, Conway GS, Kaltsas G, Techatrasak K, Manning PJ, West C, et al. Polycystic ovary syndrome: the spectrum of the disorder in 1741 patients. Hum Reprod. 1995;10(8):2107-2111. doi:10.1093/oxfordjournals.humrep.a135553
18. Almog B, et al. Serum anti-Müllerian hormone levels in women with PCOS compared with normally ovulating women. Am J Obstet Gynecol. 2011;204(2):143.e1-143.e6. doi:10.1016/j.ajog.2010.09.019
19. Schildkraut JM, et al. The relationship between AMH and polycystic ovaries on ultrasound. Fertil Steril. 2019;112(4):723-729. doi:10.1016/j.fertnstert.2019.07.005
20. Liu H, et al. Elevated LH/FSH ratio and its association with metabolic outcomes in PCOS: a systematic review. J Endocrinol Invest. 2018;41(9):1033-1042. doi:10.1007/s40618-018-0899-x
21. Farquhar C, et al. Anti-Müllerian hormone (AMH) for predicting age at menopause and age at premature ovarian failure. Cochrane Database Syst Rev. 2020;3:CD012701. doi:10.1002/14651858.CD012701.pub2
22. Risal S, et al. The role of anti-Müllerian hormone in diagnosis and prediction of PCOS. J Clin Med. 2020;9(11):3520. doi:10.3390/jcm9113520
23. Teede HJ, et al. Recommendations for assessment and management of PCOS: executive summary. Hum Reprod. 2018;33(9):1602-1618. doi:10.1093/humrep/dey256
24. Gebril OA, et al. Serum AMH as a predictor of ovarian reserve and menstrual regularity in PCOS. Reprod Biomed Online. 2019;38(1):143-150. doi:10.1016/j.rbmo.2018.09.010
25. Valgeirsdottir R, et al. LH/FSH ratio in PCOS: correlation with ovarian morphology and reproductive outcomes. Fertil Steril. 2017;108(4):635-642. doi:10.1016/j.fertnstert.2017.07.005
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Sajida Memon, Fareeha F Khan, Zainab Tanveer, Ayesha Khalid, Asad Hassnain, Amir Ali, Dua Jabbar (Author)
This work is licensed under a Creative Commons Attribution 4.0 International License.
© The Authors. This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
.png)
