Dietary xenoestrogens drastically reduce the effectiveness of palbociclib plus letrozole in the treatment of patients with breast cancer, according to a study published in Cell Chemical Biology.

The precise metabolic effects of letrozole plus palbociclib — a recently US Food and Drug Administration-approved combination therapy for estrogen receptor (ER)-positive breast cancer — is relatively unknown.

Researchers conducted a metabolomics study to investigate the effect of this combination therapy in cancer cells, which revealed that individually, palbociclib and letrozole only minimally modified cellular metabolism and had no major effect on cancer cell proliferation. In combination, however, investigators observed a highly pronounced impact on cancer cells.

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In addition to analyzing the effect of the combination, researchers additionally tested the effect of the phytoestrogen genistein and estrogenic mycotoxin zearalenone on cells exposed to therapy. Genistein is commonly found in plant-based foods such as soybeans, and zearalenone is produced by fungi and have estrogenic activity; with the incidence of breast cancer increasing, dietary estrogen has been thought to not only be potentially responsible but also possibly lower treatment efficacy.

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Results showed that genistein and zearalenone antagonized the metabolic effect of palbociclib plus letrozole in breast cancer cells. Upon exposure to either xenoestrogen, cancer cells returned to a level of activity similar to that of before treatment.

The authors concluded that “Our results shed light on the vast impact bioactive food-related molecules may pose on cancer metabolism and treatment. It will be important to translate the results obtained in these experiments to animal models and ultimately to patients to enable targeted nutritional recommendations for breast cancer patients while undergoing treatment”


Warth B, Raffeiner P, Granados A, et al. Metabolomics reveals that dietary xenoestrogens alter cellular metabolism induced by palbociclib/letrozole combination cancer therapy [published online January 11, 2018]. Cell Chem Biol. doi: 10.1016/j/chembiol.2017.12.010