Fertility Treatment and Breast-cancer Incidence: Meta-analysis

Overview

Journal BJS Open

Publisher Oxford University Press

Specialty General Surgery

Date 2022 Feb 10

PMID 35143625

Authors

Carolyn Cullinane

Hannah Gillan

James Geraghty

Denis Evoy

Jane Rothwell

Damian McCartan

Enda W McDermott

Ruth S Prichard

Affiliations

Soon will be listed here.

Abstract

Background: The significance of exogenous hormone manipulation as part of fertility treatment and its relationship to the development of breast cancer remains uncertain. Several historical reviews have been performed with conflicting results. This study is an updated meta-analysis to determine whether there is a causal relationship between different fertility treatments and breast cancer.

Methods: The study report is based on the guidelines of PRISMA and Meta-Analysis of Observational Studies in Epidemiology. Studies published within the last 20 years were included to reflect up to date in vitro fertilization (IVF) practice. This study was prospectively registered on PROSPERO on 07/04/2021, registration identification CRD42021247706. The primary outcome of the study was to determine whether there is an increased incidence of breast cancer in women treated with hormonal fertility treatment. The secondary outcomes were to determine whether fertility treatments were individually associated with excess breast-cancer risk.

Results: Overall, 25 studies, including 617 479 participants, were eligible for inclusion. There was no significant breast-cancer risk association with fertility treatment (compared with general and subfertility reference groups). Summary odds ratio of all included studies was 0.97 (95 per cent c.i. 0.90 to 1.04). Women who received six or more IVF cycles did not have an increased risk of breast cancer. Similarly, there was no excess breast-cancer risk associated with clomiphene, human chorionic gonadotropin, gonadotropin analogues and progesterone when examined individually. Comparably, there was no significant association between fertility treatment and excess breast-cancer risk in patients with more than 10 years' follow-up. Summary odds ratio was 0.97 (95 per cent c.i. 0.85 to 1.12).

Conclusion: This meta-analysis did not find a significant association between fertility treatments and excess breast-cancer risk. Women considering IVF should be informed that it does not appear to increase breast-cancer risk.

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References

. Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence. Lancet. 2019; 394(10204):1159-1168. PMC: 6891893. DOI: 10.1016/S0140-6736(19)31709-X. View

Li L, Zhou J, Qian X, Chen Y . Meta-analysis on the possible association between in vitro fertilization and cancer risk. Int J Gynecol Cancer. 2012; 23(1):16-24. DOI: 10.1097/IGC.0b013e318277608b. View

Taheripanah R, Balash F, Anbiaee R, Mahmoodi M, Akbari Sene A . Breast Cancer and Ovulation Induction Treatments. Clin Breast Cancer. 2018; 18(5):395-399. DOI: 10.1016/j.clbc.2018.03.003. View

Gauthier E, Paoletti X, Clavel-Chapelon F . Breast cancer risk associated with being treated for infertility: results from the French E3N cohort study. Hum Reprod. 2004; 19(10):2216-21. DOI: 10.1093/humrep/deh422. View

. Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies. Lancet Oncol. 2012; 13(11):1141-51. PMC: 3488186. DOI: 10.1016/S1470-2045(12)70425-4. View

Fei C, DeRoo L, Sandler D, Weinberg C . Fertility drugs and young-onset breast cancer: results from the Two Sister Study. J Natl Cancer Inst. 2012; 104(13):1021-7. PMC: 3634553. DOI: 10.1093/jnci/djs255. View

Stewart L, Holman C, Hart R, Bulsara M, Preen D, Finn J . In vitro fertilization and breast cancer: is there cause for concern?. Fertil Steril. 2012; 98(2):334-40. DOI: 10.1016/j.fertnstert.2012.04.019. View

Brinton L, Scoccia B, Moghissi K, Westhoff C, Niwa S, Ruggieri D . Long-term relationship of ovulation-stimulating drugs to breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2014; 23(4):584-93. PMC: 3979528. DOI: 10.1158/1055-9965.EPI-13-0996. View

Terry K, Willett W, Rich-Edwards J, Michels K . A prospective study of infertility due to ovulatory disorders, ovulation induction, and incidence of breast cancer. Arch Intern Med. 2006; 166(22):2484-9. DOI: 10.1001/archinte.166.22.2484. View

10.

Song D, Shi Y, Zhong Y, Meng Q, Hou S, Li H . Efficiency of mild ovarian stimulation with clomiphene on poor ovarian responders during IVF\ICSI procedures: a meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2016; 204:36-43. DOI: 10.1016/j.ejogrb.2016.07.498. View

11.

Tsafrir A, Lerner-Geva L, Zaslavsky-Paltiel I, Laufer N, Simon A, Einav S . Cancer in IVF patients treated at age 40 years and older: long term follow-up. Reprod Biomed Online. 2020; 40(3):369-373. DOI: 10.1016/j.rbmo.2019.11.015. View

12.

Boivin J, Bunting L, Collins J, Nygren K . International estimates of infertility prevalence and treatment-seeking: potential need and demand for infertility medical care. Hum Reprod. 2007; 22(6):1506-12. DOI: 10.1093/humrep/dem046. View

13.

Guleria S, Kjaer S, Albieri V, Frederiksen K, Jensen A . A Cohort Study of Breast Cancer Risk after 20 Years of Follow-Up of Women Treated with Fertility Drugs. Cancer Epidemiol Biomarkers Prev. 2019; 28(12):1986-1992. DOI: 10.1158/1055-9965.EPI-19-0652. View

14.

Steiner A, Terplan M, Paulson R . Comparison of tamoxifen and clomiphene citrate for ovulation induction: a meta-analysis. Hum Reprod. 2005; 20(6):1511-5. DOI: 10.1093/humrep/deh840. View

15.

Joo B, Park S, An B, Kim K, Moon S, Moon H . Serum estradiol levels during controlled ovarian hyperstimulation influence the pregnancy outcome of in vitro fertilization in a concentration-dependent manner. Fertil Steril. 2009; 93(2):442-6. DOI: 10.1016/j.fertnstert.2009.02.066. View

16.

Lerner-Geva L, Geva E, Lessing J, Chetrit A, Modan B, Amit A . The possible association between in vitro fertilization treatments and cancer development. Int J Gynecol Cancer. 2003; 13(1):23-7. DOI: 10.1136/ijgc-00009577-200301000-00004. View

17.

Malina A, Blaszkiewicz A, Owczarz U . Psychosocial aspects of infertility and its treatment. Ginekol Pol. 2016; 87(7):527-31. DOI: 10.5603/GP.2016.0038. View

18.

Mains L, Zimmerman M, Blaine J, Stegmann B, Sparks A, Ansley T . Achievement test performance in children conceived by IVF. Hum Reprod. 2010; 25(10):2605-11. DOI: 10.1093/humrep/deq218. View

19.

Gennari A, Costa M, Puntoni M, Paleari L, De Censi A, Sormani M . Breast cancer incidence after hormonal treatments for infertility: systematic review and meta-analysis of population-based studies. Breast Cancer Res Treat. 2015; 150(2):405-13. DOI: 10.1007/s10549-015-3328-0. View

20.

Dor J, Lerner-Geva L, Rabinovici J, Chetrit A, Levran D, Lunenfeld B . Cancer incidence in a cohort of infertile women who underwent in vitro fertilization. Fertil Steril. 2002; 77(2):324-7. DOI: 10.1016/s0015-0282(01)02986-7. View