Resveratrol and its derivative pterostilbene both have been reported to inhibit breast cancer development and metastasis. Now a new study has examined the effects of both in mouse models of hormone receptor negative breast cancer (ER-/PR-/HER2- and ER-/PR-/HER2+). The results suggest that the treatment favorably influenced epigenetic mechanisms associated with anticancer gene regulation.
Both polyphenols are relatively abundant in blueberries and red or black grapes. Resveratrol is also found in cranberries and currants (more so in black than red currants).

Pterostilbene and breast cancer

Pterostilbene is chemically similar to resveratrol but does not have identical properties. In fact, pterostilbene appears to have somewhat more diverse and powerful anti-cancer effects than resveratrol. For example, pterostilbene showed significantly more potent activity than resveratrol in suppressing brain metastasis in one study.
Pterostilbene has been shown to induce dose-dependent reductions in proliferation of hormone receptor positive, HER2 overexpressing and triple negative breast cancer cells without harming normal breast cells. Pterostilbene administered orally also has been shown to significantly suppress mammary tumor growth and metastasis in mouse models of triple negative breast cancer.
Pterostilbene also has been found to inhibit the formation of breast cancer stem cells and reduce their metastatic activities. The combination of resveratrol and pterostilbene was shown in one study to reactivate estrogen receptor expression in triple negative breast cancer cells, thereby reducing their aggressiveness. In addition, pterostilbene has been shown to have additive effects when combined with tamoxifen in estrogen receptor positive (ER+) breast cancer cells and to significantly increase the cytotoxic effects of Taxol (paclitaxel). Furthermore, pterostilbene has been shown to reduce obesity-related breast cancer cell growth and proliferation.
Pterostilbene has also been demonstrated to reduce expression of mutant p53 (a tumor suppressor gene that is often mutated in cancer) in both triple negative and hormone receptor positive (ER+/PR+) cells. Pterostilbene thereby has the potential to inhibit the development and progression of breast cancer caused by mutant p53.

Latest research reports epigenetic mechanisms for the combination

The study referenced above was designed to investigate the effects of the combination of pterostilbene plus resveratrol in mouse models of hormone receptor negative breast cancer (i.e., triple negative and ER-/PR-/HER2+). The goal was to evaluate the efficacy of the two stilbenes while examining their bioavailability, the tumor microenvironment, the immune system, alterations in metabolism, and changes in the gut microbiome.
To conduct the study, the authors administered dietary pterostilbene plus resveratrol 3:1 (w/w) for an extended period in transgenic mice. The intervention slowed occurrence of mammary tumors and produced a significant delay in tumor progression, as well as lower tumor volume and weight, in treated mice compared to untreated control mice.
The treated mice were found to experience significant changes serving to impede the mammary cancer phenotype. For example, there were meaningful differences in expression of tumor suppressor genes associated with HER2 (Erbb2) signaling pathways such as p53, PTEN, and p21, as well as oncogenes such as HER2/neu, Ras, Bcl2 and Myc. In addition, there were important changes in the expression of epigenetic modulators such as histone deacetylases (HDACs), histone demethylases (KDMs) and DNA methyltransferases (DNMTs). The treatments also increased the abundance of bacteria that are markers for recuperation from diseased condition.
The authors conclude that the combination of pterostilbene and resveratrol was effective in inhibiting breast cancer in mouse models of aggressive hormone receptor negative disease in their study. This outcome was the result of changes in the gut microbiome and metabolome, accompanied by the possible influence of epigenetic mechanisms related to anticancer gene regulation.
Please see our articles on HER2+ diet and triple negative diet, as well as the pterostilbene and resveratrol tags for more information.