Abstract S5-08: Breast cancer incidence after hormonal infertility treatments: Systematic review and meta-analysis of population based studies
Authors: Gennari A , Costa M , Paleari L , Puntoni M , Sormani MP , Decensi A , Bruzzi P 
Published: August 2014

Abstract
Background: With the increasing practice of hormonal infertility treatments in infertile women, both for ovulation induction in anovulatory women and for ovarian hyperstimulation in assisted reproductive technologies, concerns have been raised about the long-term effects of such practice on the subsequent risk of breast cancer. Sterility itself is an independent risk factor, though its effect is not yet clear. In the past years, a number of population-based studies has addressed the possible association between breast cancer incidence and infertility treatments, with inconsistent results. With these premises, we performed a systematic review and pooled analysis of the association between infertility treatments by any kind of hormonal manipulation and breast cancer incidence, based on published data.
Methods: Population cohort studies, evaluating the association between BC incidence and hormonal infertility treatments were identified by literature search. Standardised Incidence Ratios (SIRs) were pooled across the studies by inverse variance weighting. Subgroup analyses were performed according to the following covariates: length of follow up (&lt; 10 yrs vs &gt; 10 yrs), type of hormonal therapy (clomiphene vs gonadotropins) and type of control group (population based on internal control, ie infertile women). All statistical tests were two-sided.
Results: Seventeen eligible studies were identified and retrieved. Data on breast cancer incidence and type of fertility treatments were available for all studies. Overall hormonal infertility treatments were associated with a 11% increase in BC incidence as compared with untreated women (SIR SIR 1.11, 95%CI 0,91-1,30). BC risk was slightly higher in clomiphene treated women (SIR 1.04; 95%CI 0.76-1.32) than in gonadotropins users (SIR 0.83; 95%CI 0.60-1.07), p for interaction &lt; 0.0001. The increase in BC incidence seems to be dependent on follow up duration (SIR 0.94; 95%CI 0.8-1.08 for &lt;10 yrs vs 1.23; 95%CI 0.86-1.6 for &gt; 10yrs, p for interaction &lt; 0.0001). In the subset of cohort studies using population based estimates as controls, hormonal infertility treatment was associated with an increase in breast cancer risk (SIR 1.13, 95% CI 0.86-1.41); in studies with internal controls, i.e. cohorts of untreated infertile women, a similar breast cancer risk was observed (SIR 1.00; 95%CI 0.73-1.26; p for interaction &lt;0.001).
Conclusions: Overall hormonal infertility treatments do not appear to be consistently associated with a significant increase in breast cancer incidence. Subset analyses suggest a possible increase in BC incidence with longer FU (&gt;10 yrs) whereas the use of gonadotropins might exert a protective effect.
Finally, subset analyses according to type of controls suggest that the observed increased risk reported by several studies may be attributable to the infertility condition itself.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr S5-08.