DOI QR코드

DOI QR Code

Impact of beta blockers on survival outcomes in ovarian cancer: a nationwide population-based cohort study

  • Baek, Min-Hyun (Department of Obstetrics and Gynecology, Hallym University Sacred Heart Hospital) ;
  • Kim, Dae-Yeon (Department of Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Kim, Seon Ok (Department of Biostatistics, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Kim, Ye-Jee (Department of Biostatistics, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Park, Young-Han (Department of Obstetrics and Gynecology, Hallym University Sacred Heart Hospital)
  • Received : 2018.01.04
  • Accepted : 2018.07.04
  • Published : 2018.11.10

Abstract

Objective: The impact of beta blockers (BBs) on survival outcomes in ovarian cancer was investigated. Methods: By using Korean National Health Insurance Service Data, Cox proportional hazards regression was performed to analyze hazard ratios (HRs) with 95% confidence intervals (CIs) adjusting for confounding factors. Results: Among 866 eligible patients, 206 (23.8%) were BB users and 660 (76.2%) were non-users. Among the 206 BB users, 151 (73.3%) were non-selective beta blocker (NSBB) users and 105 (51.0%) were selective beta blocker (SBB) users. BB use in patients aged ${\geq}60$ years, longer duration use (${\geq}1$ year), in patients with Charlson Comorbidity Index (CCI) ${\geq}3$, and in cardiovascular disease including hypertension was associated with better survival outcome. These findings were observed in both NSBB and SBB. When duration of medication was analyzed based on number of days, NSBB (${\geq}180$ days) was associated with improved overall survival (OS) with a relatively shorter period of use compared to SBB (${\geq}720$ days). In multivariate Cox proportional hazards model, longer duration of BB medication (${\geq}1$ year) was an independent favorable prognostic factor for both OS and disease-specific survival in ovarian cancer patients. Conclusion: In our nationwide population-based cohort study, BB use was associated with better survival outcomes in ovarian cancer in cases of long term duration of use, in older patients, and in cardiovascular and/or other underlying disease (CCI ${\geq}3$).

Keywords

Acknowledgement

Supported by : Hallym University

References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin 2017;67:7-30. https://doi.org/10.3322/caac.21387
  2. Jung KW, Won YJ, Oh CM, Kong HJ, Lee DH, Lee KH. Prediction of cancer incidence and mortality in Korea, 2017. Cancer Res Treat 2017;49:306-12. https://doi.org/10.4143/crt.2017.130
  3. Lim MC, Moon EK, Shin A, Jung KW, Won YJ, Seo SS, et al. Incidence of cervical, endometrial, and ovarian cancer in Korea, 1999-2010. J Gynecol Oncol 2013;24:298-302. https://doi.org/10.3802/jgo.2013.24.4.298
  4. Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 2011;365:2473-83. https://doi.org/10.1056/NEJMoa1104390
  5. du Bois A, Reuss A, Pujade-Lauraine E, Harter P, Ray-Coquard I, Pfisterer J. Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: a combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials: by the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and the Groupe d'Investigateurs Nationaux Pour les Etudes des Cancers de l'Ovaire (GINECO). Cancer 2009;115:1234-44. https://doi.org/10.1002/cncr.24149
  6. Chong CR, Sullivan DJ Jr. New uses for old drugs. Nature 2007;448:645-6. https://doi.org/10.1038/448645a
  7. Rains SL, Amaya CN, Bryan BA. Beta-adrenergic receptors are expressed across diverse cancers. Oncoscience 2017;4:95-105.
  8. Armaiz-Pena GN, Allen JK, Cruz A, Stone RL, Nick AM, Lin YG, et al. Src activation by ${\beta}$-adrenoreceptors is a key switch for tumour metastasis. Nat Commun 2013;4:1403. https://doi.org/10.1038/ncomms2413
  9. Lutgendorf SK, Cole S, Costanzo E, Bradley S, Coffin J, Jabbari S, et al. Stress-related mediators stimulate vascular endothelial growth factor secretion by two ovarian cancer cell lines. Clin Cancer Res 2003;9:4514-21.
  10. Bunch KP, Annunziata CM. Are beta-blockers on the therapeutic horizon for ovarian cancer treatment? Cancer 2015;121:3380-3. https://doi.org/10.1002/cncr.29394
  11. Sood AK, Bhatty R, Kamat AA, Landen CN, Han L, Thaker PH, et al. Stress hormone-mediated invasion of ovarian cancer cells. Clin Cancer Res 2006;12:369-75. https://doi.org/10.1158/1078-0432.CCR-05-1698
  12. Lee JW, Shahzad MM, Lin YG, Armaiz-Pena G, Mangala LS, Han HD, et al. Surgical stress promotes tumor growth in ovarian carcinoma. Clin Cancer Res 2009;15:2695-702. https://doi.org/10.1158/1078-0432.CCR-08-2966
  13. Thaker PH, Han LY, Kamat AA, Arevalo JM, Takahashi R, Lu C, et al. Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma. Nat Med 2006;12:939-44. https://doi.org/10.1038/nm1447
  14. Hefner J, Csef H. The clinical relevance of beta blockers in ovarian carcinoma: a systematic review. Geburtshilfe Frauenheilkd 2016;76:1050-6. https://doi.org/10.1055/s-0042-115016
  15. Diaz ES, Karlan BY, Li AJ. Impact of beta blockers on epithelial ovarian cancer survival. Gynecol Oncol 2012;127:375-8. https://doi.org/10.1016/j.ygyno.2012.07.102
  16. Heitz F, du Bois A, Harter P, Lubbe D, Kurzeder C, Vergote I, et al. Impact of beta blocker medication in patients with platinum sensitive recurrent ovarian cancer-a combined analysis of 2 prospective multicenter trials by the AGO Study Group, NCIC-CTG and EORTC-GCG. Gynecol Oncol 2013;129:463-6. https://doi.org/10.1016/j.ygyno.2013.03.007
  17. Watkins JL, Thaker PH, Nick AM, Ramondetta LM, Kumar S, Urbauer DL, et al. Clinical impact of selective and nonselective beta-blockers on survival in patients with ovarian cancer. Cancer 2015;121:3444-51. https://doi.org/10.1002/cncr.29392
  18. Johannesdottir SA, Schmidt M, Phillips G, Glaser R, Yang EV, Blumenfeld M, et al. Use of ${\beta}$-blockers and mortality following ovarian cancer diagnosis: a population-based cohort study. BMC Cancer 2013;13:85. https://doi.org/10.1186/1471-2407-13-85
  19. Minlikeeva AN, Freudenheim JL, Cannioto RA, Szender JB, Eng KH, Modugno F, et al. History of hypertension, heart disease, and diabetes and ovarian cancer patient survival: evidence from the ovarian cancer association consortium. Cancer Causes Control 2017;28:469-86. https://doi.org/10.1007/s10552-017-0867-1
  20. Heitz F, Hengsbach A, Harter P, Traut A, Ataseven B, Schneider S, et al. Intake of selective beta blockers has no impact on survival in patients with epithelial ovarian cancer. Gynecol Oncol 2017;144:181-6. https://doi.org/10.1016/j.ygyno.2016.11.012
  21. Al-Niaimi A, Dickson EL, Albertin C, Karnowski J, Niemi C, Spencer R, et al. The impact of perioperative ${\beta}$ blocker use on patient outcomes after primary cytoreductive surgery in high-grade epithelial ovarian carcinoma. Gynecol Oncol 2016;143:521-5. https://doi.org/10.1016/j.ygyno.2016.09.019
  22. Lee J, Lee JS, Park SH, Shin SA, Kim K. Cohort profile: the National Health Insurance Service-National Sample Cohort (NHIS-NSC), South Korea. Int J Epidemiol 2017;46:e15.
  23. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987;40:373-83. https://doi.org/10.1016/0021-9681(87)90171-8
  24. Charmandari E, Tsigos C, Chrousos G. Endocrinology of the stress response. Annu Rev Physiol 2005;67:259-84. https://doi.org/10.1146/annurev.physiol.67.040403.120816
  25. Glaser R, Kiecolt-Glaser JK. Stress-induced immune dysfunction: implications for health. Nat Rev Immunol 2005;5:243-51. https://doi.org/10.1038/nri1571
  26. Jang HI, Lim SH, Lee YY, Kim TJ, Choi CH, Lee JW, et al. Perioperative administration of propranolol to women undergoing ovarian cancer surgery: a pilot study. Obstet Gynecol Sci 2017;60:170-7. https://doi.org/10.5468/ogs.2017.60.2.170

Cited by

  1. Stress and cancer. Part II: Therapeutic implications for oncology vol.346, pp.None, 2018, https://doi.org/10.1016/j.jneuroim.2020.577312
  2. Reactivation of dormant tumor cells by modified lipids derived from stress-activated neutrophils vol.12, pp.572, 2018, https://doi.org/10.1126/scitranslmed.abb5817
  3. Use of beta blockers is associated with survival outcome of multiple myeloma patients treated with pomalidomide vol.106, pp.3, 2018, https://doi.org/10.1111/ejh.13559
  4. Signaling Pathways That Control Apoptosis in Prostate Cancer vol.13, pp.5, 2018, https://doi.org/10.3390/cancers13050937
  5. Antihypertensive Drug Use and the Risk of Ovarian Cancer Death among Finnish Ovarian Cancer Patients-A Nationwide Cohort Study vol.13, pp.9, 2018, https://doi.org/10.3390/cancers13092087
  6. lncRNA LOC102724169 plus cisplatin exhibit the synergistic anti-tumor effect in ovarian cancer with chronic stress vol.24, pp.None, 2018, https://doi.org/10.1016/j.omtn.2021.03.001
  7. Neurobiology of Cancer: Introduction of New Drugs in the Treatment and Prevention of Cancer vol.22, pp.11, 2018, https://doi.org/10.3390/ijms22116115