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- Title
Ovarian Stimulation for In Vitro Fertilization and Long-term Risk of Breast Cancer.
- Authors
van den Belt-Dusebout, Alexandra W.; Spaan, Mandy; Lambalk, Cornelis B.; Kortman, Marian; Laven, Joop S. E.; van Santbrink, Evert J. P.; van der Westerlaken, Lucette A. J.; Cohlen, Ben J.; Braat, Didi D. M.; Smeenk, Jesper M. J.; Land, Jolande A.; Goddijn, Mariëtte; van Golde, Ron J. T.; van Rumste, Minouche M.; Schats, Roel; Jóźwiak, Katarzyna; Hauptmann, Michael; Rookus, Matti A.; Burger, Curt W.; van Leeuwen, Flora E.
- Abstract
<bold>Importance: </bold>Previous studies of breast cancer risk after in vitro fertilization (IVF) treatment were inconclusive due to limited follow-up.<bold>Objective: </bold>To assess long-term risk of breast cancer after ovarian stimulation for IVF.<bold>Design, Setting, and Participants: </bold>Historical cohort (OMEGA study) with complete follow-up through December 2013 for 96% of the cohort. The cohort included 19,158 women who started IVF treatment between 1983 and 1995 (IVF group) and 5950 women starting other fertility treatments between 1980 and 1995 (non-IVF group) from all 12 IVF clinics in the Netherlands. The median age at end of follow-up was 53.8 years for the IVF group and 55.3 years for the non-IVF group.<bold>Exposures: </bold>Information on ovarian stimulation for IVF, other fertility treatments, and potential confounders was collected from medical records and through mailed questionnaires.<bold>Main Outcomes and Measures: </bold>Incidence of invasive and in situ breast cancers in women who underwent fertility treatments was obtained through linkage with the Netherlands Cancer Registry (1989-2013). Breast cancer risk in the IVF group was compared with risks in the general population (standardized incidence ratios [SIRs]) and the non-IVF group (hazard ratios [HRs]).<bold>Results: </bold>Among 25,108 women (mean age at baseline, 32.8 years; mean number of IVF cycles, 3.6), 839 cases of invasive breast cancer and 109 cases of in situ breast cancer occurred after a median follow-up of 21.1 years. Breast cancer risk in IVF-treated women was not significantly different from that in the general population (SIR, 1.01 [95% CI, 0.93-1.09]) and from the risk in the non-IVF group (HR, 1.01 [95% CI, 0.86-1.19]). The cumulative incidences of breast cancer at age 55 were 3.0% for the IVF group and 2.9% for the non-IVF group (P = .85). The SIR did not increase with longer time since treatment (≥20 years) in the IVF group (0.92 [95% CI, 0.73-1.15]) or in the non-IVF group (1.03 [95% CI, 0.82-1.29]). Risk was significantly lower for those who underwent 7 or more IVF cycles (HR, 0.55 [95% CI, 0.39-0.77]) vs 1 to 2 IVF cycles and after poor response to the first IVF cycle (HR, 0.77 [95% CI, 0.61-0.96] for <4 vs ≥4 collected oocytes).<bold>Conclusions and Relevance: </bold>Among women undergoing fertility treatment in the Netherlands between 1980 and 1995, IVF treatment compared with non-IVF treatment was not associated with increased risk of breast cancer after a median follow-up of 21 years. Breast cancer risk among IVF-treated women was also not significantly different from that in the general population. These findings are consistent with absence of a significant increase in long-term risk of breast cancer among IVF-treated women.
- Subjects
NETHERLANDS; HUMAN in vitro fertilization; BREAST cancer risk factors; INDUCED ovulation; INFERTILITY treatment; CANCER risk factors; BREAST tumors; FERTILIZATION in vitro; LONGITUDINAL method; QUESTIONNAIRES; DISEASE incidence; ACQUISITION of data
- Publication
JAMA: Journal of the American Medical Association, 2016, Vol 316, Issue 3, p300
- ISSN
0098-7484
- Publication type
journal article
- DOI
10.1001/jama.2016.9389