Breast cancer incidence after hormonal treatment for infertility: A meta-analysis of population-based studies.

Objectives: To comprehensively understand the relationship between infertility medications and the risk of breast cancer (BC) in females.

Methods: Relevant literature search using different databases (PubMed, The Cochrane Library, Embase, Scopus, and Web of Sciences) following preferred reporting items for systematic reviews and meta-analyses guidelines was carried out from 2003-2023. Population-based studies comparing the incidence of BC after hormonal fertility treatment and a control group were included. In addition, random and fixed effect models were used to carry out meta-analyses.

Results: A total of 15 studies involving 92,555 women were included in this review. The pooled analysis using risk ratios (RRs) showed no evidence of increased BC risk associated with hormonal fertility medications (RR=1.00, 95% confidence interval [CI]: [0.97-1.02], p=0.83). The level of heterogeneity, as indicated by the I² statistic, was low (32%), and the Q test was not statistically significant. Sensitivity analysis using a random-effects model yielded consistent findings, suggesting no increased BC development risk with infertility medications. Among the 4 studies reporting hazard ratios (HRs), a significant protective effect on BC risk was observed (HR=0.91, 95% CI: [0.88-0.94], p<0.001). The heterogeneity was substantially high (I²=96%), and the Q test demonstrated statistical significance. Sensitivity analysis using a random-effects model showed that heterogeneity remained constant, suggesting that the heterogeneity was attributable to the methods utilized in the included studies rather than being a result of statistical heterogeneity. The overall effect, as determined by the HR, was 1.01 and was not statistically significant (p=0.94).

Conclusion: This meta-analysis found no evidence of increased risk of BC following hormonal infertility treatment. However, the results should be illustrated cautiously, given the heterogeneity between studies.PROSPERO No. ID: CRD42024569158.