Study Shows Estrogen Not the Only Hormone Feeding Tumors in Breast Cancer

Myles Brown, MD

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Although researchers know that estrogen plays a role in most cases of breast cancer, they don’t fully understand how, and study evidence published in the July 12, 2011 issue of Cancer Cell, demonstrates that the “male” hormone, androgen, also plays a key role in some types of breast cancer.

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Endocrine therapies used to treat breast cancer, such as selective estrogen receptor modulators and aromatase inhibitors, target the estrogen receptor (ER), but are ineffective in the 25% to 30% of cases that are ER negative (ER—).

The androgen receptor (AR) is expressed in 60% to 70% of breast tumors, independent of ER status, and the study found that AR is enriched in ER— breast tumors that overexpress human epidermal growth factor receptor 2 (HER2).²

"We identified a novel subtype of breast tumor, which grows in response to androgen but not estrogen, and have uncovered the signaling pathways involved in its growth," said senior author Myles Brown, MD, of the Dana-Farber Center for Functional Cancer Epigenetics in a press release.³

Through analysis of the AR cistrome and androgen-regulated gene expression in ER—/HER2+ breast cancers, researchers from the Center found that AR mediates ligand-dependent activation of Wnt and HER2 signaling pathways through direct transcriptional induction of Wnt7B and HER3.² Specific targeting of AR, Wnt, or HER2 signaling weakens androgen-stimulated tumor cell growth suggesting potential therapeutic approaches for ER—/HER2+ breast cancers.²

Study researchers used drugs to block the androgen receptor (or the Wnt or HER2) proteins in ER— breast cancer cells, and tumor growth slowed in laboratory cell cultures and in mice grafted with the cells.³

"We've demonstrated that drugs capable of blocking these pathways, including the receptor for androgen itself, can inhibit tumor growth,” Brown said. “This opens new avenues to the treatment of some women with breast cancer that doesn't respond to standard endocrine therapies."

References

1. The American Cancer Society. Learn About Cancer: Breast Cancer Overview. Available at: www.cancer.org. Accessed July 12, 2011.
2. Ni, M, Chen Y, Lim, E, et al. Targeting Androgen Receptor in Estrogen Receptor-Negative Breast Cancer. Cancer Cell. 2011;20:119-131.
3. Dana-Farber Cancer Institute. News Release: Study finds new points of attack on breast cancers not fueled by estrogen. Available at: www.dana-farber.org. Accessed July 12, 2011.