J Breast Cancer.  2017 Dec;20(4):356-360. 10.4048/jbc.2017.20.4.356.

Tamoxifen and the Risk of Parkinson's Disease in Female Patients with Breast Cancer in Asian People: A Nationwide Population-Based Study

• Hong CT
• Chan L
• Hu CJ
• Lin CM
• Hsu CY
• Lin MC

• KMID: 2398205
• DOI: http://doi.org/10.4048/jbc.2017.20.4.356

Abstract

PURPOSE
Whether tamoxifen affects the risk of neurodegenerative disease is controversial. This nationwide population-based study investigated the risk of Parkinson's disease (PD) associated with tamoxifen treatment in female patients with breast cancer using Taiwan's National Health Insurance Research Database.
METHODS
A total of 5,185 and 5,592 female patients with breast cancer who did and did not, respectively, receive tamoxifen treatment between 2000 and 2009 were included in the study. Patients who subsequently developed PD were identified. A Cox proportional hazards model was used to compare the risk of PD between the aforementioned groups.
RESULTS
Tamoxifen did not significantly increase the crude rate of developing PD in female patients with breast cancer (tamoxifen group, 16/5,169; non-tamoxifen group, 11/5,581; p=0.246). Tamoxifen did not significantly increase the adjusted hazard ratio (aHR) for subsequently developing PD (aHR, 1.310; 95% confidence interval [CI], 0.605-2.837; p=0.494). However, tamoxifen significantly increased the risk of PD among patients followed up for more than 6 years (aHR, 2.435; 95% CI, 1.008-5.882; p=0.048).
CONCLUSION
Tamoxifen treatment may increase the risk of PD in Taiwanese female patients with breast cancer more than 6 years after the initiation of treatment.

Keyword

Breast neoplasms; Parkinson disease; Tamoxifen

MeSH Terms

Asian Continental Ancestry Group*
Breast Neoplasms*
Breast*
Female*
Humans
National Health Programs
Neurodegenerative Diseases
Parkinson Disease*
Proportional Hazards Models
Tamoxifen*
Tamoxifen

Reference

1. Trimmer PA, Bennett JP Jr. The cybrid model of sporadic Parkinson's disease. Exp Neurol. 2009; 218:320–325. PMID: 19328199.

2. Kieburtz K, Wunderle KB. Parkinson's disease: evidence for environmental risk factors. Mov Disord. 2013; 28:8–13. PMID: 23097348.

3. Van Den Eeden SK, Tanner CM, Bernstein AL, Fross RD, Leimpeter A, Bloch DA, et al. Incidence of Parkinson's disease: variation by age, gender, and race/ethnicity. Am J Epidemiol. 2003; 157:1015–1022. PMID: 12777365.

4. Wooten GF, Currie LJ, Bovbjerg VE, Lee JK, Patrie J. Are men at greater risk for Parkinson's disease than women? J Neurol Neurosurg Psychiatry. 2004; 75:637–639. PMID: 15026515.

5. Currie LJ, Harrison MB, Trugman JM, Bennett JP, Wooten GF. Postmenopausal estrogen use affects risk for Parkinson disease. Arch Neurol. 2004; 61:886–888. PMID: 15210525.

6. Gatto NM, Deapen D, Stoyanoff S, Pinder R, Narayan S, Bordelon Y, et al. Lifetime exposure to estrogens and Parkinson's disease in California teachers. Parkinsonism Relat Disord. 2014; 20:1149–1156. PMID: 25179495.

7. Latourelle JC, Dybdahl M, Destefano AL, Myers RH, Lash TL. Risk of Parkinson's disease after tamoxifen treatment. BMC Neurol. 2010; 10:23. PMID: 20385012.

8. Lee ES, Yin Z, Milatovic D, Jiang H, Aschner M. Estrogen and tamoxifen protect against Mn-induced toxicity in rat cortical primary cultures of neurons and astrocytes. Toxicol Sci. 2009; 110:156–167. PMID: 19383943.

9. Mosquera L, Colón JM, Santiago JM, Torrado AI, Meléndez M, Segarra AC, et al. Tamoxifen and estradiol improved locomotor function and increased spared tissue in rats after spinal cord injury: their antioxidant effect and role of estrogen receptor alpha. Brain Res. 2014; 1561:11–22. PMID: 24637260.

10. Lin HL, Lin HC, Tseng YF, Chen SC, Hsu CY. Inverse association between cancer and dementia: a population-based registry study in Taiwan. Alzheimer Dis Assoc Disord. 2016; 30:118–122. PMID: 26523711.

11. You CW, Rau HH, Chang YC, Chen LF, Hung JF, Lin YA, et al. Design a service model with cloud computing architecture for value-added applications of health data. J Taiwan Assoc Med Inform. 2015; 24:33–41.

12. Lee YC, Lin CH, Wu RM, Lin MS, Lin JW, Chang CH, et al. Discontinuation of statin therapy associates with Parkinson disease: a population-based study. Neurology. 2013; 81:410–416. PMID: 23884037.

13. De Vera M, Rahman MM, Rankin J, Kopec J, Gao X, Choi H. Gout and the risk of Parkinson's disease: a cohort study. Arthritis Rheum. 2008; 59:1549–1554. PMID: 18975349.

14. Alonso A, Rodríguez LA, Logroscino G, Hernán MA. Gout and risk of Parkinson disease: a prospective study. Neurology. 2007; 69:1696–1700. PMID: 17954784.

15. Sun Y, Chang YH, Chen HF, Su YH, Su HF, Li CY. Risk of Parkinson disease onset in patients with diabetes: a 9-year population-based cohort study with age and sex stratifications. Diabetes Care. 2012; 35:1047–1049. PMID: 22432112.

16. 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; 40:373–383. PMID: 3558716.

17. Bourque M, Liu B, Dluzen DE, Di Paolo T. Tamoxifen protects male mice nigrostriatal dopamine against methamphetamine-induced toxicity. Biochem Pharmacol. 2007; 74:1413–1423. PMID: 17825264.

18. Mickley KR, Dluzen DE. Dose-response effects of estrogen and tamoxifen upon methamphetamine-induced behavioral responses and neurotoxicity of the nigrostriatal dopaminergic system in female mice. Neuroendocrinology. 2004; 79:305–316. PMID: 15256808.

19. Gao X, Dluzen DE. Tamoxifen abolishes estrogen's neuroprotective effect upon methamphetamine neurotoxicity of the nigrostriatal dopaminergic system. Neuroscience. 2001; 103:385–394. PMID: 11246153.

20. Bower JH, Maraganore DM, McDonnell SK, Rocca WA. Incidence and distribution of parkinsonism in Olmsted County, Minnesota, 1976-1990. Neurology. 1999; 52:1214–1220. PMID: 10214746.

21. Kuopio AM, Marttila RJ, Helenius H, Rinne UK. Changing epidemiology of Parkinson's disease in southwestern Finland. Neurology. 1999; 52:302–308. PMID: 9932948.

22. Chen RC, Chang SF, Su CL, Chen TH, Yen MF, Wu HM, et al. Prevalence, incidence, and mortality of PD: a door-to-door survey in Ilan county, Taiwan. Neurology. 2001; 57:1679–1686. PMID: 11706111.

23. Wang YS, Shi YM, Wu ZY, He YX, Zhang BZ. Coordinational Group of Neuroepidemiology, PLA. Parkinson's disease in China. Chin Med J(Engl). 1991; 104:960–964. PMID: 1800040.

24. Liu B, Dluzen DE. Oestrogen and nigrostriatal dopaminergic neurodegeneration: animal models and clinical reports of Parkinson's disease. Clin Exp Pharmacol Physiol. 2007; 34:555–565. PMID: 17581209.

25. Graham CD, Kaza N, Klocke BJ, Gillespie GY, Shevde LA, Carroll SL, et al. Tamoxifen induces cytotoxic autophagy in glioblastoma. J Neuropathol Exp Neurol. 2016; 75:946–954. PMID: 27516117.

26. Ribeiro MP, Santos AE, Custódio JB. Mitochondria: the gateway for tamoxifen-induced liver injury. Toxicology. 2014; 323:10–18. PMID: 24881593.

27. Tsai YW, Tsai TI, Yang CL, Kuo KN. Gender differences in smoking behaviors in an Asian population. J Womens Health (Larchmt). 2008; 17:971–978. PMID: 18681817.

28. Vollenweider-Zerargui L, Barrelet L, Wong Y, Lemarchand-Béraud T, Gómez F. The predictive value of estrogen and progesterone receptors' concentrations on the clinical behavior of breast cancer in women. Clinical correlation on 547 patients. Cancer. 1986; 57:1171–1180. PMID: 3943040.

29. Hähnel R, Woodings T, Vivian AB. Prognostic value of estrogen receptors in primary breast cancer. Cancer. 1979; 44:671–675. PMID: 476576.

30. Senkus E, Kyriakides S, Ohno S, Penault-Llorca F, Poortmans P, Rutgers E, et al. Primary breast cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015; 26(Suppl 5):v8–v30. PMID: 26314782.