Levonorgestrel-releasing intrauterine system and breast cancer risk: A systematic review and meta-analysis

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48
Tipo de produção
article
Data de publicação
2020
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ISSN da Revista
Título do Volume
Editora
WILEY
Autores
CONZ, Livia
BAHAMONDES, Luis
DORIA, Maira Teixeira
DERCHAIN, Sophie Francoise Mauricette
RIEIRA, Rachel
SARIAN, Luis Otavio
Citação
ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA, v.99, n.8, p.970-982, 2020
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Resumo
Introduction Epidemiological studies have shown that some hormonal contraceptive methods are associated with increased breast cancer risk, especially if used over long periods. Our objective was to conduct a systematic review and meta-analysis of the literature on the risk of breast cancer development in women using the 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS). Material and methods We performed a thorough review of peer-reviewed publications from 10 January 1999, through 31 July 2019, using combinations of search terms for breast cancer risk and LNG-IUS in the Medline, EMBASE, LILACS (Latin American and Caribbean Health Sciences Literature), and Scielo databases. This review was registered in PROSPERO (CRD42017059076). Studies reporting breast cancer risk estimates among healthy users of LNG-IUS were included according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis) criteria. Two authors performed data extraction, and a third author resolved disagreements. The quality of evidence was evaluated using the Downs and Black instrument. A funnel plot was generated, and a linear regression test of funnel plot asymmetry was used to assess publication bias. Finally, we performed a random-effects model (owing to high study heterogeneity) meta-analysis of 7 suitable studies, stratified by the age distribution of patients (<50 years, >= 50 years, and mixed). Results We identified 96 studies and manually cross-referenced and excluded duplicate articles. Seventy articles were excluded on the basis of the inclusion and exclusion criteria, resulting in the assessment of 26 full-text articles. Eight articles were considered adequate for inclusion in this systematic review, and 7 studies were included in the meta-analysis. Three publications were case-control studies and 5 were cohort studies. According to the Downs and Black instrument, 5 studies were rated as ""good"" and 3 studies were deemed ""fair"". Our meta-analysis results indicated increased breast cancer risk in LNG-IUS users: for all women, odds ratio (OR) = 1.16 (95% CI 1.06-1.28, I-2 = 78%, P < .01); for women aged <50 years, OR = 1.12 (95% CI 1.02-1.22, I-2 = 66%, P = .02); and for women aged >= 50 years, OR = 1.52 (95% CI 1.34-1.72, I-2 = 0%, P = .84). Conclusions Current evidence suggests that LNG-IUS users have an increased breast cancer risk regardless of age and indication. The effect of LNG-IUS on breast cancer risk seems to be larger in older users. However, our systematic review detected methodological issues across the available studies, and confounding factors may be responsible for at least a fraction of the risk effects associated with LNG-IUS use. Nevertheless, users of LNG-IUS should be aware of these trends. We believe that caution is needed, and risks should be balanced against proven health benefits (eg effective treatment of heavy menstrual bleeding and avoidance of surgical interventions), when prescribing LNG-IUS for long periods of use, especially in women with other known breast cancer risk factors such as old age, obesity, and familial predisposition.
Palavras-chave
breast cancer, contraception, dysmenorrhea, levonorgestrel, levonorgestrel-releasing intrauterine system, menopause
Referências
  1. Backman T, 2005, OBSTET GYNECOL, V106, P813, DOI 10.1097/01.AOG.0000178754.88912.b9
  2. Backman T, 2001, EUR J CONTRACEP REPR, V6, P23, DOI 10.3109/ejc.6.s1.23.26
  3. Banks E, 2003, LANCET, V362, P419, DOI 10.1016/s0140-6736(03)14065-2
  4. Beral V, 1997, LANCET, V350, P1047, DOI 10.1016/s0140-6736(97)08233-0
  5. Chlebowski RT, 2012, JNCI-J NATL CANCER I, V104, P517, DOI 10.1093/jnci/djs014
  6. Clemons M, 2001, NEW ENGL J MED, V344, P276, DOI 10.1056/NEJM200101253440407
  7. Collaborative Grp Hormonal Factors, 2019, LANCET, V394, P1159, DOI 10.1016/S0140-6736(19)31709-X
  8. Dinger J, 2011, CONTRACEPTION, V83, P211, DOI 10.1016/j.contraception.2010.11.009
  9. Downs SH, 1998, J EPIDEMIOL COMMUN H, V52, P377, DOI 10.1136/jech.52.6.377
  10. Eden J, 2003, AM J OBSTET GYNECOL, V188, P1123, DOI 10.1067/mob.2003.201
  11. Egger M, 1997, BMJ-BRIT MED J, V315, P629, DOI 10.1136/bmj.315.7109.629
  12. Graham JD, 1997, ENDOCR REV, V18, P502, DOI 10.1210/er.18.4.502
  13. Heikkinen S, 2016, CANCER CAUSE CONTROL, V27, P249, DOI 10.1007/s10552-015-0702-5
  14. Inumaru LE, 2011, CAD SAUDE PUBLICA, V27, P1259, DOI 10.1590/S0102-311X2011000700002
  15. Jareid M, 2018, GYNECOL ONCOL, V149, P127, DOI 10.1016/j.ygyno.2018.02.006
  16. Jones ME, 2016, BRIT J CANCER, V115, P1
  17. Lyytinen HK, 2010, INT J CANCER, V126, P483, DOI 10.1002/ijc.24738
  18. Morch LS, 2017, NEW ENGL J MED, V377, P2228, DOI 10.1056/NEJMoa1700732
  19. MUSGROVE EA, 1991, MOL CELL BIOL, V11, P5032, DOI 10.1128/MCB.11.10.5032
  20. NILSSON CG, 1982, CLIN ENDOCRINOL, V17, P529, DOI 10.1111/j.1365-2265.1982.tb01625.x
  21. Okobia M N, 2005, Niger J Clin Pract, V8, P35
  22. Samson M, 2016, BREAST CANCER RES TR, V155, P3, DOI 10.1007/s10549-015-3663-1
  23. Siegelmann-Danieli N, 2018, BREAST CANCER RES TR, V167, P257, DOI 10.1007/s10549-017-4491-2
  24. Soini T, 2016, ACTA ONCOL, V55, P188, DOI 10.3109/0284186X.2015.1062538
  25. VANLEEUWEN FF, 1991, ACTA ENDOCRINOL-COP, V125, P13
  26. Wiseman M, 2008, P NUTR SOC, V67, P253, DOI 10.1017/S002966510800712X