The Risk of Antihypertensive Drug among Breast Cancer Patient: A Systematic Review and Meta-analysis

Sinta Wiranata; Ida Ayu Widya Anjani; Putri Ayu  Wulandari; Anak Agung Bagus Putra  Indrakusuma; I Gede Krisna Arim  Sadeva; Ayu Dilia Febriani  Wisnawa; Jonny Karunia  Fajar; I Putu Yuda  Prabawa; Putu Anda Tusta  Adiputra; I Wayan  Sudarsa; Anak Agung Wiradewi  Lestari; Desak Made  Wihandani; I Gede Putu  Supadmanaba

doi:10.3889/oamjms.2021.6841

Authors

Sinta Wiranata Medical Student, Faculty of Medicine, Universitas Udayana, Denpasar, Bali, Indonesia https://orcid.org/0000-0001-5364-1969
Ida Ayu Widya Anjani Medical Student, Faculty of Medicine, Universitas Udayana, Denpasar, Bali, Indonesia
Putri Ayu Wulandari Medical Student, Faculty of Medicine, Universitas Udayana, Denpasar, Bali, Indonesia
Anak Agung Bagus Putra Indrakusuma Medical Student, Faculty of Medicine, Universitas Udayana, Denpasar, Bali, Indonesia
I Gede Krisna Arim Sadeva Medical Student, Faculty of Medicine, Universitas Udayana, Denpasar, Bali, Indonesia
Ayu Dilia Febriani Wisnawa Medical Student, Faculty of Medicine, Universitas Udayana, Denpasar, Bali, Indonesia
Jonny Karunia Fajar Department of Internal Medicine, Brawijaya Internal Medicine Research Center, Faculty of Medicine, Universitas Brawijaya, Malang, East Java, Indonesia
I Putu Yuda Prabawa Department of Clinical Pathology, Faculty of Medicine, Universitas Udayana, Sanglah General Hospital, Denpasar, Bali, Indonesia
Putu Anda Tusta Adiputra Department of Surgery, Division of Surgical Oncology, Faculty of Medicine, Universitas Udayana, Sanglah General Hospital, Denpasar, Bali, Indonesia
I Wayan Sudarsa Department of Surgery, Division of Surgical Oncology, Faculty of Medicine, Universitas Udayana, Sanglah General Hospital, Denpasar, Bali, Indonesia https://orcid.org/0000-0002-6581-7244
Anak Agung Wiradewi Lestari Department of Clinical Pathology, Faculty of Medicine, Universitas Udayana, Sanglah General Hospital, Denpasar, Bali, Indonesia
Desak Made Wihandani Department of Biochemistry, Faculty of Medicine, Universitas Udayana, Denpasar, Bali, Indonesia https://orcid.org/0000-0003-4270-8552
I Gede Putu Supadmanaba Department of Biochemistry, Faculty of Medicine, Universitas Udayana, Denpasar, Bali, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2021.6841

Keywords:

Breast cancer, Antihypertensive drugs, Risk factors

Abstract

BACKGROUNDS: Breast cancer or breast carcinoma is the most common type of malignancy in women globally. According to the previous studies that indicate the usage of antihypertensive drugs may become a risk factor of cancer (beta-blockers [BBs], calcium channel blockers [CCBs], and diuretics). Both angiotensin-converting enzymes inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), on the other hand, have been associated to an increased or decreased risk of breast cancer.

AIM: To compare each type of antihypertensive medicines as a risk factor for breast cancer, we did a systematic review and meta-analysis of current evidence.

METHODS: We utilized the terms “antihypertensive”, “anti-hypertensive”, “anti-hypertensive medications”, “breast cancer”, “risk”, “case control”, and “cohort” in PubMed, ScienceDirect, and Google Scholar databases.

RESULTS: Our data calculation found that the risk of antihypertensive drugs was significantly different in overall analysis (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.42–0.83, p = 0.003). Five studies with 39.503 breast cancer patients and 372.037 controls were included in the ARBs user sub-group. Our results found significant different of antihypertensive drugs among breast cancer patient (OR = 1.47, 95% CI = 1.02–2.11 p = 0.04). Our data calculation also confirmed no significant different in antihypertensive drugs among breast cancer patient (OR = 1.07, 95% CI = 0.99–1.16, p = 0.09) in diuretics user, (OR = 1.08, 95% CI = 0.99–1.18, p = 0.08) in CCBs user, (OR = 1.11, 95% CI = 0.98–1.26, p = 0.09) in BBs user, and (OR = 1.27, 95% CI = 0.64–2.50, p = 0.50) in ACEIs user.

CONCLUSIONS: Although, the finding reveal that antihypertensive drugs (diuretics, CCBs, BBs, and ACEIs) in overall are significant for the risk of breast cancer and also found that ARBs have a low potential in the risk of breast cancer.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Biggar RJ, Andersen EW, Wohlfahrt J, Melbye M. Spironolactone use and the risk of breast and gynecologic cancers. Cancer Epidemiol. 2013;37(6):870-5. https://doi.org/10.1016/j.canep.2013.10.004 PMid:24189467

Chang CH, Chiang CH, Yen CJ, Wu LC, Lin JW, Lai MS. Antihypertensive agents and the risk of breast cancer in women aged 55 years and older: A nested case-control study. J Hypertens. 2016;34(3):558-66. https://doi.org/10.1097/hjh.0000000000000813 PMid:26818924

Largent JA, McEligot AJ, Ziogas A, Reid C, Hess J, Leighton N, et al. Hypertension, diuretics and breast cancer risk. J Hum Hypertens. 2006;20(10):727-32. https://doi.org/10.1038/sj.jhh.1002075 PMid:16885996

Li CI, Malone KE, Weiss NS, Boudreau DM, Cushing-Haugen KL, Daling JR. Relation between use of antihypertensive medications and risk of breast carcinoma among women ages 65-79 years. Cancer. 2003;98(7):1504-13. https://doi.org/10.1002/cncr.11663 PMid:14508839

World Health Organization. A Global Brief on Hypertension: Silent Killer, Global Public Health Crisis. Geneva: World Health Organization; 2013.

Li CI, Daling JR, Tang MT, Haugen KL, Porter PL, Malone KE. Use of antihypertensive medications and breast cancer risk among women aged 55 to 74 years. JAMA Intern Med. 2013;173(17):1629-37. https://doi.org/10.1001/jamainternmed.2013.9071 PMid:23921840

Oster JR, Materson BJ, Perez-Stable E. Antihypertensive medications. South Med J. 1984;77(5):621-30. https://doi.org/10.1097/00007611-198405000-00020

Jackson RE, Bellamy MC. Antihypertensive drugs. BJA Educ. 2015;15(6):280-5.

Battistoni A, Volpe M. Recent warnings about antihypertensive drugs and cancer risk: Where do they come from? Eur Cardiol. 2020;15:e21. https://doi.org/10.15420/ecr.2019.21 PMid:32419852

Chen L, Chubak J, Boudreau DM, Barlow WE, Weiss NS, Li CI. Use of antihypertensive medications and risk of adverse breast cancer outcomes in a SEER-medicare population. Cancer Epidemiol Biomarkers Prev. 2017;26(11):1603-10. https://doi.org/10.1158/1055-9965.epi-17-0346 PMid:28807926

Watkins EJ. Overview of breast cancer. JAAPA. 2019;32(10):13-7. PMid:31513033

American Cancer Society. Cancer Facts and Figures 2020. United States: American Cancer Society; 2020.

Kim H, Choi DH, Park W, Huh SJ, Nam SJ, Lee JE, et al. Prognostic factors for survivals from first relapse in breast cancer patients: Analysis of deceased patients. Radiat Oncol J. 2013;31(4):222-7. https://doi.org/10.3857/roj.2013.31.4.222 PMid:24501710

Devore EE, Kim S, Ramin CA, Wegrzyn LR, Massa J, Holmes MD, et al. Antihypertensive medication use and incident breast cancer in women. Breast Cancer Res Treat. 2015;150(1):219-29. https://doi.org/10.1007/s10549-015-3311-9 PMid:25701121

Hallas J, Christensen R, Andersen M, Friis S, Bjerrum L. Long term use of drugs affecting the renin-angiotensin system and the risk of cancer: A population-based case-control study. Br J Clin Pharmacol. 2012;74(1):180-8. https://doi.org/10.1111/j.1365-2125.2012.04170.x PMid:22243442

Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: Explanation and elaboration. BMJ. 2009;339:b2700. https://doi.org/10.1136/bmj.b2700 PMid:19622552

González-Pérez A, Ronquist G, García Rodríguez LA. Breast cancer incidence and use of antihypertensive medication in women. Pharmacoepidemiol Drug Saf. 2004;13(8):581-5. https://doi.org/10.1002/pds.910 PMid:15317040

Coogan PF, Strom BL, Rosenberg L. Diuretic use and the risk of breast cancer. J Hum Hypertens. 2009;23(3):216-8. https://doi.org/10.1038/jhh.2008.131 PMid:18971940

Leung HW, Hung LL, Chan AL, Mou CH. Long-term use of antihypertensive agents and risk of breast cancer: A populationbased case-control study. Cardiol Ther. 2015;4(1):65-76. https://doi.org/10.1007/s40119-015-0035-1 PMid:25657096

Chen L, Malone KE, Li CI. Use of antihypertensive medications not associated with risk of contralateral breast cancer among women diagnosed with estrogen receptor-positive invasive breast cancer. Cancer Epidemiol Biomarkers Prev. 2015;24(9):1423-6. https://doi.org/10.1158/1055-9965.epi-15-0547 PMid:26084603

Gómez-Acebo I, Dierssen-Sotos T, Palazuelos C, Pérez-Gómez B, Lope V, Tusquets I, et al. The use of antihypertensive medication and the risk of breast cancer in a case-control study in a Spanish population: The MCC-spain study. PLoS One. 2016;11(8):e0159672. https://doi.org/10.1371/journal.pone.0159672 PMid:27508297

Meier CR, Derby LE, Jick SS, Jick H. Angiotensin-converting enzyme inhibitors, calcium channel blockers, and breast cancer. Arch Intern Med. 2000;160(3):349-53. https://doi.org/10.1001/archinte.160.3.349 PMid:10668837

Davis S, Mirick DK. Medication use and the risk of breast cancer. Eur J Epidemiol. 2007;22(5):319-25. PMid:17487555

Botteri E, Munzone E, Rotmensz N, Cipolla C, de Giorgi V, Santillo B, et al. Therapeutic effect of β-blockers in triplenegative breast cancer postmenopausal women. Breast Cancer Res Treat. 2013;140(3):567-75. https://doi.org/10.1007/s10549-013-2654-3 PMid:23912960

Yancik R, Wesley MN, Ries LA, Havlik RJ, Edwards BK, Yates JW. Effect of age and comorbidity in postmenopausal breast cancer patients aged 55 years and older. JAMA. 2001;285(7):885-92. https://doi.org/10.1001/jama.285.7.885 PMid:11180731

Bangalore S, Kumar S, Kjeldsen SE, Makani H, Grossman E, Wetterslev J, et al. Antihypertensive drugs and risk of cancer: Network meta-analyses and trial sequential analyses of 324, 168 participants from randomised trials. Lancet Oncol. 2011;12(1):65-82. https://doi.org/10.1016/s1470-2045(10)70260-6 PMid:21123111

Chen Q, Zhang Q, Zhong F, Guo S, Jin Z, Shi W, et al. Association between calcium channel blockers and breast cancer: A metaanalysis of observational studies. Pharmacoepidemiol Drug Saf. 2014;23(7):711-8. https://doi.org/10.1002/pds.3645 PMid:24829113

Li W, Shi Q, Wang W, Liu J, Li Q, Hou F. Calcium channel blockers and risk of breast cancer: A meta-analysis of 17 observational studies. PLoS One. 2014;9(9):e0198220. https://doi.org/10.1371/journal.pone.0105801 PMid:29791500

Li C, Li T, Tang R, Yuan S, Zhang W. β-blocker use is not associated with improved clinical outcomes in women with breast cancer: A meta-analysis. Biosci Rep. 2020;40(6):BSR20200721. https://doi.org/10.1042/bsr20200721 PMid:32436935

Zhao Y, Wang Q, Zhao X, Meng H, Yu J. Effect of antihypertensive drugs on breast cancer risk in female hypertensive patients: Evidence from observational studies. Clin Exp Hypertens. 2018;40(1):22-7. https://doi.org/10.1080/10641963.2017.1288736 PMid:29115847

Pahor M, Guralnik JM, Ferrucci L, Corti MC, Salive ME, Cerhan JR, et al. Calcium-channel blockade and incidence of cancer in aged populations. Lancet. 1996;348(9026):493-7. https://doi.org/10.1016/s0140-6736(96)04277-8 PMid:8757150

Whitfield JF. Calcium signals and cancer. Crit Rev Oncog. 1992;3(1-2):55-90. PMid:1550862

Reynolds JE, Li J, Craig RW, Eastman A. BCL-2 and MCL-1 expression in Chinese hamster ovary cells inhibits intracellular acidification and apoptosis induced by staurosporine. Exp Cell Res. 1996;225(2):430-6. https://doi.org/10.1006/excr.1996.0194 PMid:8660932

Rodriguez-Tarduchy G, Malde P, Lopez-Rivas A, Collins MK. Inhibition of apoptosis by calcium ionophores in IL-3-dependent bone marrow cells is dependent upon production of IL-4+. J Immunol. 1992;148(5):1416-22. PMid:1538126

Whyte MK, Hardwick SJ, Meagher LC, Savill JS, Haslett C. Transient elevations of cytosolic free calcium retard subsequent apoptosis in neutrophils in vitro. J Clin Invest. 1993;92(1):446-55. https://doi.org/10.1172/jci116587 PMid:8392090

Mason RP. Calcium channel blockers, apoptosis and cancer: Is there a biologic relationship? J Am Coll Cardiol. 1999;34(7):1857-66. PMid:10588195

Barron TI, Sharp L, Visvanathan K. Beta-adrenergic blocking drugs in breast cancer: A perspective review. Ther Adv Med Oncol. 2012;4(3):113-25. https://doi.org/10.1177/1758834012439738 PMid:22590485

Peixoto R, de Lourdes Pereira M, Oliveira M. Beta-blockers and cancer: Where are we? Pharmaceuticals (Basel). 2020;13(6):105. https://doi.org/10.3390/ph13060105 PMid:32466499

Park SY, Kang JH, Jeong KJ, Lee J, Han JW, Choi WS, et al. Norepinephrine induces VEGF expression and angiogenesis by a hypoxia-inducible factor-1α protein-dependent mechanism. Int J Cancer. 2011;128(10):2306-16. https://doi.org/10.1002/ijc.25589 PMid:20715173

Avraham R, Benish M, Inbar S, Bartal I, Rosenne E, Ben-Eliyahu S. Synergism between immunostimulation and prevention of surgery-induced immune suppression: An approach to reduce post-operative tumor progression. Brain Behav Immun. 2010;24(6):952-8. https://doi.org/10.1016/j.bbi.2010.03.010 PMid:20362661

Madden KS, Szpunar MJ, Brown EB. β-Adrenergic receptors (β-AR) regulate VEGF and IL-6 production by divergent pathways in high β-AR-expressing breast cancer cell lines. Breast Cancer Res Treat. 2011;130(3):747-58. https://doi.org/10.1007/s10549-011-1348-y PMid:21234673

Choy C, Raytis JL, Smith DD, Duenas M, Neman J, Jandial R, et al. Inhibition of β2-adrenergic receptor reduces triplenegative breast cancer brain metastases: The potential benefit of perioperative β-blockade. Oncol Rep. 2016;35(6):3135-42. https://doi.org/10.3892/or.2016.4710 PMid:27035124

Parada-Huerta E, Alvarez-Dominguez TP, Uribe-Escamilla R, Rodriguez-Joya J, Ponce-Medrano JD, Padron-Lucio S, et al. Metastasis risk reduction related with beta-blocker treatment in Mexican women with breast cancer. Asian Pacific J Cancer Prev. 2016;17(6):2953-7. PMid:27356717