A framework for understanding the complexity of
cancer development was established by Hanahan and Weinberg in their definition of the hallmarks of
cancer. In this review, we consider the evidence that
parabens can enable development in human breast epithelial cells of four of six of the basic hallmarks, one of two of the emerging hallmarks and one of two of the enabling characteristics. In Hallmark 1,
parabens have been measured as present in 99% of human breast tissue samples, possess oestrogenic activity and can stimulate sustained proliferation of human
breast cancer cells at concentrations measurable in the breast. In Hallmark 2,
parabens can inhibit the suppression of
breast cancer cell growth by
hydroxytamoxifen, and through binding to the oestrogen-related receptor gamma may prevent its deactivation by
growth inhibitors. In Hallmark 3, in the 10 nm-1 μm range,
parabens give a dose-dependent evasion of apoptosis in high-risk donor breast epithelial cells. In Hallmark 4, long-term exposure (>20 weeks) to
parabens leads to increased migratory and invasive activity in human
breast cancer cells, properties that are linked to the metastatic process. As an emerging hallmark
methylparaben has been shown in human breast epithelial cells to increase mTOR, a key regulator of energy metabolism. As an enabling characteristic
parabens can cause DNA damage at high concentrations in the short term but more work is needed to investigate long-term, low-dose mixtures. The ability of
parabens to enable multiple
cancer hallmarks in human breast epithelial cells provides grounds for regulatory review of the implications of the presence of
parabens in human breast tissue.