Parabens are widely used as preservatives in cosmetics and personal care products, as well as in pharmaceuticals and processed food. They extend shelf life by preventing microbial and fungal growth. Parabens are suspected of contributing to breast cancer risk since they are xenoestrogens, man-made compounds that bind to and activate estrogen receptors. Significant paraben levels have been found in the breast tissue of women with breast cancer. Now a new study has reported that parabens may be more potent at sharply lower doses than previous studies have suggested in estrogen receptor positive HER2/neu overexpressing (ER+/PR+/HER2+) breast cancer cells.
Parabens and breast cancer
Parabens are absorbed into circulation through the skin. In other words, parabens can penetrate human skin intact and be absorbed systemically. The most common parabens used in consumer products are methylparaben, ethylparaben, propylparaben, butylparaben and isobutylparaben. Despite some published claims that parabens have short half lives, they appear to be fairly stable molecules, which enables them to accumulate in breast tissue. Parabens were found in 99% of breast tissue samples of breast cancer patients in one study.
Affected industry groups have vigorously defended the use of parabens in their products, for example, by maintaining that parabens are 10,000 to 100,000 times less active than phytoestrogens consumed in plant foods or estrogens produced in the human body. However, parabens at concentrations found in breast cancer patients have been shown to be capable of initiating breast cancer development in the laboratory. In addition, paraben levels in breast tissue are often high enough to stimulate breast cancer cell proliferation and increase migratory activity. Finally, parabens can interfere with the treatment effects of tamoxifen in estrogen receptor positive (ER+) breast cancer cells.
Latest research finds paraben can promote cancer progression at lower levels
The study referenced at the beginning of this news article was designed to investigate the interaction between parabens and estrogen receptor positive HER2+ breast cancer (ER+/PR+/HER2+). Previous studies did not take into account the signaling cross-talk between estrogen receptor (ER) and the HER family. The authors hypothesized that the potency of parabens can be amplified with HER ligands, such as heregulin (HRG). HRG is a growth factor naturally produced in cells that binds to the erbB family of receptors, thereby contributing to breast cancer progression in tumors overexpressing the receptors.
To conduct the study, the authors examined the effects of HRG on butylparaben activation of c-Myc expression and cell proliferation in ER+/PR+/HER2+ BT-474 breast cancer cells. The protein encoded by the c-Myc gene is involved in cell cycle progression, programmed cell death, and cellular transformation. Butylparaben and HRG together were found to produce a synergistic increase in c-Myc mRNA and protein levels in the cells. Estrogen receptor antagonists blocked this increase in c-Myc protein. Butylparaben was able to stimulate breast cancer cell growth at concentrations 100 times lower than in cells that were deprived of HRG. HRG produced a synergistic increase in ER recruitment to the c-Myc gene. The authors conclude that HER ligands enhance the potency of butylparaben to stimulate oncogene expression and breast cancer cell proliferation via ER. This suggests that parabens might be active at lower exposure levels than those found to be toxicologically relevant in previous studies that examined their effects in isolation.