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. 2016 Jul 19;316(3):300-12.
doi: 10.1001/jama.2016.9389.

Ovarian Stimulation for In Vitro Fertilization and Long-term Risk of Breast Cancer

Alexandra W van den Belt-Dusebout  1 , Mandy Spaan  1 , Cornelis B Lambalk  2 , Marian Kortman  3 , Joop S E Laven  4 , Evert J P van Santbrink  5 , Lucette A J van der Westerlaken  6 , Ben J Cohlen  7 , Didi D M Braat  8 , Jesper M J Smeenk  9 , Jolande A Land  10 , Mariëtte Goddijn  11 , Ron J T van Golde  12 , Minouche M van Rumste  13 , Roel Schats  2 , Katarzyna Józwiak  1 , Michael Hauptmann  1 , Matti A Rookus  1 , Curt W Burger  4 , Flora E van Leeuwen  1
Affiliations

Ovarian Stimulation for In Vitro Fertilization and Long-term Risk of Breast Cancer

Alexandra W van den Belt-Dusebout et al. JAMA. .

Abstract

Importance: Previous studies of breast cancer risk after in vitro fertilization (IVF) treatment were inconclusive due to limited follow-up.

Objective: To assess long-term risk of breast cancer after ovarian stimulation for IVF.

Design, setting, and participants: 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.

Exposures: Information on ovarian stimulation for IVF, other fertility treatments, and potential confounders was collected from medical records and through mailed questionnaires.

Main outcomes and measures: 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]).

Results: 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).

Conclusions and relevance: 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.

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