Assisted Reproductive Technologies (ART) and breast cancer risk: hormonal treatments under the spotlight

Assisted Reproductive Technologies (ART) have become nowadays a cornerstone in the management of infertility. While these treatments are generally considered safe, concerns have been raised regarding their potential influence on breast cancer (BC) risk, particularly in specific subgroups of women.

This narrative review aims to evaluate the most relevant past and current literature on the association between ART-related hormonal treatments and breast cancer risk, highlighting potential biological mechanisms, epidemiological evidence, and clinical implications.

A literature search was conducted through PubMed, focusing on medium-to-large cohort and case-control studies, meta-analyses, and guidelines published to date. Evidence was synthesized by distinguishing overall ART/IVF risk estimates from drug-specific findings and subgroup-specific risk modifiers. Particular attention was given to the most recent or most comprehensive reports when multiple publications were derived from the same cohort.

To date, current evidence does not support a real and consistent overall increase in breast cancer risk following ART-related hormonal treatments. Large population-based studies and recent meta-analyses are generally reassuring, particularly when ART-treated women are compared with infertile untreated women rather than with the general population. Some studies report modest risk elevations in selected subgroups, including nulliparous or nulligravid women, women undergoing repeated or high-dose stimulation cycles, and women with hereditary BC predisposition; however, these findings are inconsistent and often limited by residual confounding, small subgroup numbers, and incomplete dose information. Progesterone supplementation appears safe in the context of ART, with no consistent evidence of increased BC risk. Gonadotropins, including hMG, may transiently increase estrogen exposure, but large-scale studies and meta-analyses generally do not confirm a long-term increase in breast cancer incidence.