A research team from Georgetown University Medical Center presented a study on a new approach to breast cancer treatment during last week’s American Society of Clinical Oncology’s Breast Cancer Symposium 2008.

Early data from their research indicates that tumors that have become resistant to anti-hormonal drugs can be re-sensitized using the drug sorafenib.

The trial began enrolling postmenopausal women with metastatic breast cancer in 2005. After treatment of three subjects, the study advanced to a second phase, which included the treatment of 27 patients. Current results show a clinical benefit in 26 percent of the women in the study who received both the drugs sorafenib and anastrozole.

Sorafenib is the primary drug for treatment of kidney cancer and advanced liver cancer, while anastrozole is used to treat breast cancer in postmenopausal women.

The team hopes to complete the trial within the year, said Deepa Subramaniam, M.D., lead author of the study.

Women with either estrogen-receptor or progesterone-receptor (ER or PR) positive metastatic breast cancer commonly take anti-hormonal drugs to stymie the progression of the cancer, according to Medical News Today.

Hormone-receptor positive breast cancer cells have estrogen receptors on the cells surfaces. When an estrogen molecule binds to the receptor on the cancer cell, the binding causes a signal cascade that promotes growth of the tumor, Subramaniam said.

Previous treatments have targeted this estrogen binding, but anastrozole halts tumor development by shutting down the estrogen-growth pathway. However, after prolonged periods of this estrogen-free environment, the cancer adapts and the treatment is ineffective.

“There is pre-clinical data to support the hypothesis that resistance develops by the tumor learning to use alternative pathways of growth signaling other than the estrogen receptor pathway. Thus, the tumor becomes independent of the estrogen receptor for its growth stimulus,” Subramaniam said.

In the past, when anti-estrogen drugs failed, chemotherapy was the only treatment option. However, the approach proposed by the GUMC team combines the aromatase inhibitors with sorafenib. Sorafenib blocks tumor blood vessel growth as well as an alternative growth pathway.

“Simultaneously blocking the estrogen-receptor pathway with anastrozole and the alternative pathway with sorafenib, the hope is that we will be able to arrest the growth of the breast cancer tumor cells,” Subramaniam added.

By putting a halt to the alternative growth pathway, sorafenib, in essence, re-sensitizes the tumor aromatase inhibitors. Since the tumor is no longer resistant to the anti-hormonal drugs, the cancer is sensitive to the lack of estrogen and as a result, the growth of the tumor will slow.

The trial is sponsored by the Cancer Theory Evaluation Program, a division of the National Cancer Institute of the National Institutes of Health.

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