Advertisement

Breast Cancer Research and Treatment

, Volume 150, Issue 1, pp 219–229 | Cite as

Antihypertensive medication use and incident breast cancer in women

  • Elizabeth E. Devore
  • Sung Kim
  • Cody A. Ramin
  • Lani R. Wegrzyn
  • Jennifer Massa
  • Michelle D. Holmes
  • Karin B. Michels
  • Rulla M. Tamimi
  • John P. Forman
  • Eva S. Schernhammer
Epidemiology

Abstract

The purpose of this study was to evaluate whether antihypertensive medication use, including long-term use, is associated with increased breast cancer incidence in women. We studied 210,641 U.S. registered nurses participating in the Nurses’ Health Study (NHS) and Nurses’ Health Study II (NHS II). Information on antihypertensive medication use was collected on biennial questionnaires in both cohorts, and breast cancer cases were ascertained during this period. Multivariable-adjusted Cox proportional hazard models were used to estimate relative risks of invasive breast cancer over follow-up (1988–2012 in NHS, 1989–2011 in NHS II) across categories of overall antihypertensive medication use and use of specific classes (diuretics, beta blockers, calcium channel blockers, and angiotensin-converting enzyme inhibitors). During follow-up, 10,012 cases of invasive breast cancer developed (6718 cases in NHS and 3294 in the NHS II). Overall, current use of any antihypertensive medication was not associated with breast cancer risk compared with past/never use in NHS (multivariable-adjusted relative risk = 1.00, 95 % CI = 0.95–1.06) or NHS II (multivariable-adjusted relative risk = 0.94, 95 % CI = 0.86–1.03). Furthermore, no specific class of antihypertensive medication was consistently associated with breast cancer risk. Results were similar when we considered hypertensive women only, and when we evaluated consistency and duration of medication use over time. Overall, antihypertensive medication use was largely unrelated to the risk of invasive breast cancer among women in the NHS cohorts.

Keywords

Antihypertensive medication Breast cancer Cohort study Epidemiology 

Abbreviations

ACE

Angiotensin-converting enzyme

CI

Confidence interval

ER

Estrogen receptor

MV

Multivariable

NHS

Nurses’ Health Study

NHS II

Nurses’ Health Study II

RR

Relative risk

Notes

Acknowledgments

We would like to thank the participants and staff of the Nurses’ Health Study and Nurses’ Health Study II for their valuable contributions, as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. We also want to acknowledge the contribution of Dr. Steven Lockley, Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women’s Hospital. He provided the initial impetus for examining associations between beta blocker use and breast cancer risk in women, based on his interest in the melatonin-modulating effects of beta blockers. Dr. Lockley did not receive any compensation for his contribution.

Funding

The National Cancer Institute funds the Nurses’ Health Study (P01 CA87969) and Nurses’ Health Study II (UM1 CA176726). L.R.W. received partial support from a National Institutes of Health training grant (R25 CA098566) during the time that she contributed to this paper.

Conflict of interest

The authors declare that they have no conflict of interest.

Statement on research involving human participants and/or animals

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. This article does not contain any studies with animals performed by any of the authors.

Informed consent

Implied informed consent, indicated by voluntary return of the cohort questionnaires, was obtained from all individual participants included in the study.

Supplementary material

10549_2015_3311_MOESM1_ESM.pdf (68 kb)
(PDF 68 kb)
10549_2015_3311_MOESM2_ESM.pdf (79 kb)
(PDF 79 kb)

References

  1. 1.
    Carson AP, Howard G, Burke GL, Shea S, Levitan EB, Muntner P (2011) Ethnic differences in hypertension incidence among middle-aged and older adults: the multi-ethnic study of atherosclerosis. Hypertension 57(6):1101–1107. doi: 10.1161/HYPERTENSIONAHA.110.168005 CrossRefPubMedCentralPubMedGoogle Scholar
  2. 2.
    Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ (2003) The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA 289(19):2560–2572. doi: 10.1001/jama.289.19.2560 CrossRefPubMedGoogle Scholar
  3. 3.
    Group USCSW (2013) United States Cancer Statistics: 1999-2010 Incidence and mortality web-based report. Atlanta, GAGoogle Scholar
  4. 4.
    Pahor M, Guralnik JM, Ferrucci L, Corti MC, Salive ME, Cerhan JR, Wallace RB, Havlik RJ (1996) Calcium-channel blockade and incidence of cancer in aged populations. Lancet 348(9026):493–497. doi: 10.1016/S0140-6736(96)04277-8 CrossRefPubMedGoogle Scholar
  5. 5.
    Jick H, Jick SS, Myers MW, Vasilakis C (1997) Third-generation oral contraceptives and venous thrombosis. Lancet 349(9053):731–732; author reply 732–733. doi: 10.1016/S0140-6736(05)60173-0
  6. 6.
    Olsen JH, Sorensen HT, Friis S, McLaughlin JK, Steffensen FH, Nielsen GL, Andersen M, Fraumeni JF Jr, Olsen J (1997) Cancer risk in users of calcium channel blockers. Hypertension 29(5):1091–1094CrossRefPubMedGoogle Scholar
  7. 7.
    Rosenberg L, Rao RS, Palmer JR, Strom BL, Stolley PD, Zauber AG, Warshauer ME, Shapiro S (1998) Calcium channel blockers and the risk of cancer. JAMA 279(13):1000–1004CrossRefPubMedGoogle Scholar
  8. 8.
    Michels KB, Rosner BA, Walker AM, Stampfer MJ, Manson JE, Colditz GA, Hennekens CH, Willett WC (1998) Calcium channel blockers, cancer incidence, and cancer mortality in a cohort of U.S. women: the nurses’ health study. Cancer 83(9):2003–2007CrossRefPubMedGoogle Scholar
  9. 9.
    Sorensen HT, Olsen JH, Mellemkjaer L, Marie A, Steffensen FH, McLaughlin JK, Baron JA (2000) Cancer risk and mortality in users of calcium channel blockers. A cohort study. Cancer 89(1):165–170CrossRefPubMedGoogle Scholar
  10. 10.
    Meier CR, Derby LE, Jick SS, Jick H (2000) Angiotensin-converting enzyme inhibitors, calcium channel blockers, and breast cancer. Arch Intern Med 160(3):349–353CrossRefPubMedGoogle Scholar
  11. 11.
    Friis S, Sorensen HT, Mellemkjaer L, McLaughlin JK, Nielsen GL, Blot WJ, Olsen JH (2001) Angiotensin-converting enzyme inhibitors and the risk of cancer: a population-based cohort study in Denmark. Cancer 92(9):2462–2470CrossRefPubMedGoogle Scholar
  12. 12.
    Gonzalez-Perez A, Ronquist G, Garcia Rodriguez LA (2004) Breast cancer incidence and use of antihypertensive medication in women. Pharmacoepidemiol Drug Saf 13(8):581–585. doi: 10.1002/pds.910 CrossRefPubMedGoogle Scholar
  13. 13.
    Fryzek JP, Ye W, Nyren O, Tarone RE, Lipworth L, McLaughlin JK (2006) A nationwide epidemiologic study of breast cancer incidence following breast reduction surgery in a large cohort of Swedish women. Breast Cancer Res Treat 97(2):131–134. doi: 10.1007/s10549-005-9099-2 CrossRefPubMedGoogle Scholar
  14. 14.
    Coogan PF, Strom BL, Rosenberg L (2009) Diuretic use and the risk of breast cancer. J Hum Hypertens 23(3):216–218. doi: 10.1038/jhh.2008.131 CrossRefPubMedGoogle Scholar
  15. 15.
    Bergman GJ, Khan S, Danielsson B, Borg N (2014) Breast cancer risk and use of calcium channel blockers using Swedish population registries. JAMA Intern Med. doi: 10.1001/jamainternmed.2014.3867 PubMedGoogle Scholar
  16. 16.
    Fitzpatrick AL, Daling JR, Furberg CD, Kronmal RA, Weissfeld JL (1997) Use of calcium channel blockers and breast carcinoma risk in postmenopausal women. Cancer 80(8):1438–1447CrossRefPubMedGoogle Scholar
  17. 17.
    Lever AF, Hole DJ, Gillis CR, McCallum IR, McInnes GT, MacKinnon PL, Meredith PA, Murray LS, Reid JL, Robertson JW (1998) Do inhibitors of angiotensin-I-converting enzyme protect against risk of cancer? Lancet 352(9123):179–184. doi: 10.1016/S0140-6736(98)03228-0 CrossRefPubMedGoogle Scholar
  18. 18.
    Li CI, Malone KE, Weiss NS, Boudreau DM, Cushing-Haugen KL, Daling JR (2003) Relation between use of antihypertensive medications and risk of breast carcinoma among women ages 65–79 years. Cancer 98(7):1504–1513. doi: 10.1002/cncr.11663 CrossRefPubMedGoogle Scholar
  19. 19.
    Largent JA, McEligot AJ, Ziogas A, Reid C, Hess J, Leighton N, Peel D, Anton-Culver H (2006) Hypertension, diuretics and breast cancer risk. J Hum Hypertens 20(10):727–732. doi: 10.1038/sj.jhh.1002075 CrossRefPubMedGoogle Scholar
  20. 20.
    Largent JA, Bernstein L, Horn-Ross PL, Marshall SF, Neuhausen S, Reynolds P, Ursin G, Zell JA, Ziogas A, Anton-Culver H (2010) Hypertension, antihypertensive medication use, and breast cancer risk in the California Teachers Study cohort. Cancer Causes Control 21(10):1615–1624. doi: 10.1007/s10552-010-9590-x CrossRefPubMedCentralPubMedGoogle Scholar
  21. 21.
    Saltzman BS, Weiss NS, Sieh W, Fitzpatrick AL, McTiernan A, Daling JR, Li CI (2013) Use of antihypertensive medications and breast cancer risk. Cancer Causes Control 24(2):365–371. doi: 10.1007/s10552-012-0122-8 CrossRefPubMedGoogle Scholar
  22. 22.
    Li CI, Daling JR, Tang MT, Haugen KL, Porter PL, Malone KE (2013) Use of antihypertensive medications and breast cancer risk among women aged 55 to 74 years. JAMA Intern Med 173(17):1629–1637. doi: 10.1001/jamainternmed.2013.9071 CrossRefPubMedCentralPubMedGoogle Scholar
  23. 23.
    Colditz GA (1995) The nurses’ health study: a cohort of US women followed since 1976. J Am Med Women’s Assoc 50(2):40–44Google Scholar
  24. 24.
    Rich-Edwards JW, Goldman MB, Willett WC, Hunter DJ, Stampfer MJ, Colditz GA, Manson JE (1994) Adolescent body mass index and infertility caused by ovulatory disorder. Am J Obstet Gynecol 171(1):171–177CrossRefPubMedGoogle Scholar
  25. 25.
    Wang J, Eliassen AH, Spiegelman D, Willett WC, Hankinson SE (2014) Plasma free 25-hydroxyvitamin D, vitamin D binding protein, and risk of breast cancer in the Nurses’ Health Study II. Cancer Causes Control. doi: 10.1007/s10552-014-0383-5 Google Scholar
  26. 26.
    Fung TT, Chiuve SE, Willett WC, Hankinson SE, Hu FB, Holmes MD (2013) Intake of specific fruits and vegetables in relation to risk of estrogen receptor-negative breast cancer among postmenopausal women. Breast Cancer Res Treat 138(3):925–930. doi: 10.1007/s10549-013-2484-3 CrossRefPubMedCentralPubMedGoogle Scholar
  27. 27.
    Baer HJ, Rich-Edwards JW, Colditz GA, Hunter DJ, Willett WC, Michels KB (2006) Adult height, age at attained height, and incidence of breast cancer in premenopausal women. Int J Cancer 119(9):2231–2235. doi: 10.1002/ijc.22096 CrossRefPubMedGoogle Scholar
  28. 28.
    Holmes MD, Hankinson SE, Feskanich D, Chen WY (2013) Beta blockers and angiotensin-converting enzyme inhibitors’ purported benefit on breast cancer survival may be explained by aspirin use. Breast Cancer Res Treat 139(2):507–513. doi: 10.1007/s10549-013-2553-7 CrossRefPubMedCentralPubMedGoogle Scholar
  29. 29.
    Stoschitzky K, Sakotnik A, Lercher P, Zweiker R, Maier R, Liebmann P, Lindner W (1999) Influence of beta-blockers on melatonin release. Eur J Clin Pharmacol 55(2):111–115CrossRefPubMedGoogle Scholar
  30. 30.
    Schernhammer ES, Hankinson SE (2005) Urinary melatonin levels and breast cancer risk. J Natl Cancer Inst 97(14):1084–1087. doi: 10.1093/jnci/dji190 CrossRefPubMedGoogle Scholar
  31. 31.
    Schernhammer ES, Hankinson SE (2009) Urinary melatonin levels and postmenopausal breast cancer risk in the Nurses’ Health Study cohort. Cancer Epidemiol Biomark Prev 18(1):74–79. doi: 10.1158/1055-9965.EPI-08-0637 CrossRefGoogle Scholar
  32. 32.
    Colditz GA, Martin P, Stampfer MJ, Willett WC, Sampson L, Rosner B, Hennekens CH, Speizer FE (1986) Validation of questionnaire information on risk factors and disease outcomes in a prospective cohort study of women. Am J Epidemiol 123(5):894–900PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Elizabeth E. Devore
    • 1
    • 9
  • Sung Kim
    • 2
  • Cody A. Ramin
    • 1
    • 3
  • Lani R. Wegrzyn
    • 4
  • Jennifer Massa
    • 5
  • Michelle D. Holmes
    • 1
    • 4
  • Karin B. Michels
    • 1
    • 4
    • 6
  • Rulla M. Tamimi
    • 1
    • 4
  • John P. Forman
    • 7
  • Eva S. Schernhammer
    • 1
    • 4
    • 8
  1. 1.Channing Division of Network Medicine, Department of MedicineBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA
  2. 2.Massachusetts College of Pharmacy and Health SciencesBostonUSA
  3. 3.Department of EpidemiologyJohns Hopkins Bloomberg School of Public Health, BaltimoreBaltimoreUSA
  4. 4.Department of EpidemiologyHarvard School of Public HeathBostonUSA
  5. 5.Department of NutritionHarvard School of Public HealthBostonUSA
  6. 6.Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics, Gynecology and Reproductive BiologyBrigham and Women’s Hospital, Harvard Medical SchoolBostonUSA
  7. 7.Renal DivisionBrigham and Women’s HospitalBostonUSA
  8. 8.Applied Cancer Research-Institution for Translational Research Vienna (ACR-ITR VIEnna)ViennaAustria
  9. 9.BostonUSA

Personalised recommendations