Endocrine Risk Factors of Endometrial Cancer: Polycystic Ovary Syndrome, Oral Contraceptives, Infertility, Tamoxifen

Atanas Ignatov, Olaf Ortmann, Atanas Ignatov, Olaf Ortmann

Abstract

Endometrial cancer is the most common gynecologic cancer and is predominantly endocrine-related. The role of unopposed estrogen in the development of endometrial cancer has been investigated in numerous studies. Different reproductive factors such as younger age at menarche, late age at menopause, infertility, nulliparity, age of birth of the first child, and long-term use of unopposed estrogens during hormone replacement therapy have been associated with an increased risk of endometrial cancer. In contrast, there is a growing body of evidence for a protective role of oral contraceptives. Most of the published data on the association between infertility and polycystic ovary syndrome are inconclusive, whereas the effect of tamoxifen on the risk of endometrial cancer has been well established. With this review, we aim to summarize the evidence on the association between infertility, polycystic ovary syndrome, oral contraceptives, and tamoxifen and the development of endometrial cancer.

Keywords: PCOS; endometrial cancer; infertility; oral contraceptives; tamoxifen.

Conflict of interest statement

The authors declare no conflict of interest.

References

    1. Colombo N., Creutzberg C., Amant F., Bosse T., Gonzalez-Martin A., Ledermann J., Marth C., Nout R., Querleu D., Mirza M.R., et al. Esmo-esgo-estro consensus conference on endometrial cancer: Diagnosis, treatment and follow-up. Ann. Oncol. 2016;27:16–41. doi: 10.1093/annonc/mdv484.
    1. Ali A.T. Reproductive factors and the risk of endometrial cancer. Int. J. Gynecol. Cancer. 2014;24:384–393. doi: 10.1097/IGC.0000000000000075.
    1. Yang H.P., Cook L.S., Weiderpass E., Adami H.O., Anderson K.E., Cai H., Cerhan J.R., Clendenen T.V., Felix A.S., Friedenreich C.M., et al. Infertility and incident endometrial cancer risk: A pooled analysis from the epidemiology of endometrial cancer consortium (e2c2) Br. J. Cancer. 2015;112:925–933. doi: 10.1038/bjc.2015.24.
    1. Skalkidou A., Sergentanis T.N., Gialamas S.P., Georgakis M.K., Psaltopoulou T., Trivella M., Siristatidis C.S., Evangelou E., Petridou E. Risk of endometrial cancer in women treated with ovary-stimulating drugs for subfertility. Cochrane Database Syst. Rev. 2017;3:CD010931. doi: 10.1002/14651858.CD010931.pub2.
    1. Reigstad M.M., Storeng R., Myklebust T.A., Oldereid N.B., Omland A.K., Robsahm T.E., Brinton L.A., Vangen S., Furu K., Larsen I.K. Cancer risk in women treated with fertility drugs according to parity status-a registry-based cohort study. Cancer Epidemiol. Biomarkers Prev. 2017;26:953–962. doi: 10.1158/1055-9965.EPI-16-0809.
    1. Lundberg F.E., Iliadou A.N., Rodriguez-Wallberg K., Gemzell-Danielsson K., Johansson A.L.V. The risk of breast and gynecological cancer in women with a diagnosis of infertility: A nationwide population-based study. Eur. J. Epidemiol. 2019;34:499–507. doi: 10.1007/s10654-018-0474-9.
    1. Murugappan G., Li S., Lathi R.B., Baker V.L., Eisenberg M.L. Risk of cancer in infertile women: Analysis of us claims data. Hum. Reprod. 2019;34:894–902. doi: 10.1093/humrep/dez018.
    1. Barry J.A., Azizia M.M., Hardiman P.J. Risk of endometrial, ovarian and breast cancer in women with polycystic ovary syndrome: A systematic review and meta-analysis. Hum. Reprod. Update. 2014;20:748–758. doi: 10.1093/humupd/dmu012.
    1. Fearnley E.J., Marquart L., Spurdle A.B., Weinstein P., Webb P.M., Australian Ovarian Cancer Study Group. Australian National Endometrial Cancer Study Group Polycystic ovary syndrome increases the risk of endometrial cancer in women aged less than 50 years: An australian case-control study. Cancer Causes Control. 2010;21:2303–2308. doi: 10.1007/s10552-010-9658-7.
    1. Zucchetto A., Serraino D., Polesel J., Negri E., De Paoli A., Dal Maso L., Montella M., La Vecchia C., Franceschi S., Talamini R. Hormone-related factors and gynecological conditions in relation to endometrial cancer risk. Eur. J. Cancer Prev. 2009;18:316–321. doi: 10.1097/CEJ.0b013e328329d830.
    1. Ding D.C., Chen W., Wang J.H., Lin S.Z. Association between polycystic ovarian syndrome and endometrial, ovarian, and breast cancer: A population-based cohort study in taiwan. Medicine (Baltimore) 2018;97:e12608. doi: 10.1097/MD.0000000000012608.
    1. Fauser B.C., Tarlatzis B.C., Rebar R.W., Legro R.S., Balen A.H., Lobo R., Carmina E., Chang J., Yildiz B.O., Laven J.S., et al. Consensus on women’s health aspects of polycystic ovary syndrome (pcos): The amsterdam eshre/asrm-sponsored 3rd pcos consensus workshop group. Fertil. Steril. 2012;97:28–38.e25. doi: 10.1016/j.fertnstert.2011.09.024.
    1. Harris H.R., Terry K.L. Polycystic ovary syndrome and risk of endometrial, ovarian, and breast cancer: A systematic review. Fertil. Res. Pract. 2016;2:14. doi: 10.1186/s40738-016-0029-2.
    1. Gierisch J.M., Coeytaux R.R., Urrutia R.P., Havrilesky L.J., Moorman P.G., Lowery W.J., Dinan M., McBroom A.J., Hasselblad V., Sanders G.D., et al. Oral contraceptive use and risk of breast, cervical, colorectal, and endometrial cancers: A systematic review. Cancer Epidemiol. Biomarkers Prev. 2013;22:1931–1943. doi: 10.1158/1055-9965.EPI-13-0298.
    1. Collaborative Group on Epidemiological Studies on Endometrial Cancer Endometrial cancer and oral contraceptives: An individual participant meta-analysis of 27 276 women with endometrial cancer from 36 epidemiological studies. Lancet Oncol. 2015;16:1061–1070. doi: 10.1016/S1470-2045(15)00212-0.
    1. Iversen L., Sivasubramaniam S., Lee A.J., Fielding S., Hannaford P.C. Lifetime cancer risk and combined oral contraceptives: The royal college of general practitioners’ oral contraception study. Am. J. Obstet. Gynecol. 2017;216:580.e1–580.e9. doi: 10.1016/j.ajog.2017.02.002.
    1. Michels K.A., Pfeiffer R.M., Brinton L.A., Trabert B. Modification of the associations between duration of oral contraceptive use and ovarian, endometrial, breast, and colorectal cancers. JAMA Oncol. 2018;4:516–521. doi: 10.1001/jamaoncol.2017.4942.
    1. Onstad M.A., Schmandt R.E., Lu K.H. Addressing the role of obesity in endometrial cancer risk, prevention, and treatment. J. Clin. Oncol. 2016;34:4225–4230. doi: 10.1200/JCO.2016.69.4638.
    1. Schlesselman J.J. Risk of endometrial cancer in relation to use of combined oral contraceptives. A practitioner’s guide to meta-analysis. Hum. Reprod. 1997;12:1851–1863. doi: 10.1093/humrep/12.9.1851.
    1. Jareid M., Thalabard J.C., Aarflot M., Bovelstad H.M., Lund E., Braaten T. Levonorgestrel-releasing intrauterine system use is associated with a decreased risk of ovarian and endometrial cancer, without increased risk of breast cancer. Results from the nowac study. Gynecol. Oncol. 2018;149:127–132. doi: 10.1016/j.ygyno.2018.02.006.
    1. Dumesic D.A., Lobo R.A. Cancer risk and pcos. Steroids. 2013;78:782–785. doi: 10.1016/j.steroids.2013.04.004.
    1. Fleming C.A., Heneghan H.M., O’Brien D., McCartan D.P., McDermott E.W., Prichard R.S. Meta-analysis of the cumulative risk of endometrial malignancy and systematic review of endometrial surveillance in extended tamoxifen therapy. Br. J. Surg. 2018;105:1098–1106. doi: 10.1002/bjs.10899.
    1. Cohen I., Perel E., Flex D., Tepper R., Altaras M.M., Cordoba M., Beyth Y. Endometrial pathology in postmenopausal tamoxifen treatment: Comparison between gynaecologically symptomatic and asymptomatic breast cancer patients. J. Clin. Pathol. 1999;52:278–282. doi: 10.1136/jcp.52.4.278.
    1. Runowicz C.D., Costantino J.P., Wickerham D.L., Cecchini R.S., Cronin W.M., Ford L.G., Vogel V.G., Wolmark N. Gynecologic conditions in participants in the nsabp breast cancer prevention study of tamoxifen and raloxifene (star) Am. J. Obstet. Gynecol. 2011;205:535.e1–535.e5. doi: 10.1016/j.ajog.2011.06.067.
    1. Committee opinion no. 601: Tamoxifen and uterine cancer. Obstet. Gynecol. 2014;123:1394–1397. doi: 10.1097/.
    1. Fisher B., Costantino J.P., Wickerham D.L., Redmond C.K., Kavanah M., Cronin W.M., Vogel V., Robidoux A., Dimitrov N., Atkins J., et al. Tamoxifen for prevention of breast cancer: Report of the national surgical adjuvant breast and bowel project p-1 study. J. Natl. Cancer Inst. 1998;90:1371–1388. doi: 10.1093/jnci/90.18.1371.
    1. Fisher B., Costantino J.P., Wickerham D.L., Cecchini R.S., Cronin W.M., Robidoux A., Bevers T.B., Kavanah M.T., Atkins J.N., Margolese R.G., et al. Tamoxifen for the prevention of breast cancer: Current status of the national surgical adjuvant breast and bowel project p-1 study. J. Natl. Cancer Inst. 2005;97:1652–1662. doi: 10.1093/jnci/dji372.
    1. Iqbal J., Ginsburg O.M., Wijeratne T.D., Howell A., Evans G., Sestak I., Narod S.A. Endometrial cancer and venous thromboembolism in women under age 50 who take tamoxifen for prevention of breast cancer: A systematic review. Cancer Treat. Rev. 2012;38:318–328. doi: 10.1016/j.ctrv.2011.06.009.
    1. Davies C., Pan H., Godwin J., Gray R., Arriagada R., Raina V., Abraham M., Medeiros Alencar V.H., Badran A., Bonfill X., et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: Atlas, a randomised trial. Lancet. 2013;381:805–816. doi: 10.1016/S0140-6736(12)61963-1.
    1. Markovitch O., Tepper R., Fishman A., Aviram R., Cohen I. Long-term follow-up of postmenopausal breast cancer patients following discontinuation of tamoxifen therapy. Maturitas. 2008;59:387–393. doi: 10.1016/j.maturitas.2008.04.001.
    1. Curtis R.E., Freedman D.M., Sherman M.E., Fraumeni J.F., Jr. Risk of malignant mixed mullerian tumors after tamoxifen therapy for breast cancer. J. Natl. Cancer Inst. 2004;96:70–74. doi: 10.1093/jnci/djh007.
    1. Magriples U., Naftolin F., Schwartz P.E., Carcangiu M.L. High-grade endometrial carcinoma in tamoxifen-treated breast cancer patients. J. Clin. Oncol. 1993;11:485–490. doi: 10.1200/JCO.1993.11.3.485.
    1. Hu R., Hilakivi-Clarke L., Clarke R. Molecular mechanisms of tamoxifen-associated endometrial cancer (review) Oncol. Lett. 2015;9:1495–1501. doi: 10.3892/ol.2015.2962.
    1. Lin S.L., Yan L.Y., Zhang X.T., Yuan J., Li M., Qiao J., Wang Z.Y., Sun Q.Y. Er-alpha36, a variant of er-alpha, promotes tamoxifen agonist action in endometrial cancer cells via the mapk/erk and pi3k/akt pathways. PLoS ONE. 2010;5:e9013.
    1. Ignatov T., Claus M., Nass N., Haybaeck J., Seifert B., Kalinski T., Ortmann O., Ignatov A. G-protein-coupled estrogen receptor gper-1 expression in hormone receptor-positive breast cancer is associated with poor benefit of tamoxifen. Breast Cancer Res. Treat. 2019;174:121–127. doi: 10.1007/s10549-018-5064-8.
    1. Ignatov T., Eggemann H., Semczuk A., Smith B., Bischoff J., Roessner A., Costa S.D., Kalinski T., Ignatov A. Role of gpr30 in endometrial pathology after tamoxifen for breast cancer. Am. J. Obstet. Gynecol. 2010;203:595.e9–595.e16. doi: 10.1016/j.ajog.2010.07.034.

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera