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

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 (Ն20 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 Ն4 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.

Use of fertility medications and cancer risk: a review and update

“…Most recent studies have not shown an association between breast cancer and fertility medication use when comparing women undergoing fertility treatment to both a general population and infertile controls [33] [12] [34] [35] [36]. Although two recent studies found an association of fertility treatment with breast cancer, the increased risk was modest [37] [38].…”

“…A recent cohort study of 19,158 IVF patients and 5,950 nonIVF-related patients receiving fertility treatment compared breast cancer risk to the general population with a median follow-up of 21.1 years. No increased risk of breast cancer occurred in IVF patients compared to either the general population (SIR: 1.01, 95% CI 0.93–1.09) or nonIVF-related patients receiving fertility treatment (HR: 1.01, 95% CI 0.86–1.19) [33]. These data agree with a recent meta-analysis of 8 cohort studies that comprised 1,554,332 women and 14,961 breast cancer cases and demonstrated no increased risk of breast cancer in IVF patients versus the general (RR: 0.91, 95% CI 0.74–1.11) or infertile female population (RR: 1.02, 95% CI 0.88–1.18) [37].…”

How many oocytes are optimal to achieve multiple live births with one stimulation cycle? The one-and-done approach

“…In addition, clinicians have been wary of potential complications with increasing doses of gonadotropins, particularly OHSS (11,12). There is also concern about the potential association between the use of ovarian stimulants and cancer (13)(14)(15), although, reassuringly, a recent large Dutch study did not find an association between breast cancer and IVF (16).…”

Long-term breast cancer risk following ovarian stimulation in young egg donors: a call for follow-up, research and informed consent

“…Two of the three studies found significant increases in breast cancer risk among certain subpopulations, such as those who took clomiphene or those who remained nulligravid (Brinton et al, 2014) or only in those who had IVF at a young age (Stewart et al, 2012). A recent study by Van den Belt-Dusebout et al (2016), however, found no significant increase in breast cancer risk. In this study, among women undergoing fertility treatment in the Netherlands between 1983 and 1995, IVF treatment compared with non-IVF treatment was not associated with increased risk of breast cancer after a median followup of 21 years.…”