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New Leukemia Compound Shows Promise for Breast Cancer

Combination of BH3-mimetic and tamoxifen affects tumor cell growth in early study (July 7)

Scientists at the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia, have discovered that anticancer compounds currently in clinical trials for some types of leukemia could offer hope for treating the most common type of breast cancer.

The researchers found that the compounds, called BH3-mimetics, were effective in treating aggressive estrogen receptor-positive (ER-positive) breast cancers when combined with the breast cancer drug tamoxifen in preclinical models. Approximately 70% of breast cancers are ER-positive.

Lead researcher Professor Geoff Lindeman said that BH3-mimetics work by neutralizing BCL-2 proteins in cancer cells, making them more susceptible to dying. Up to 85% of ER-positive breast cancers have high levels of BCL-2, which is a so-called “pro-survival” protein that helps cancer cells to become immortal, and can help them to survive chemotherapy and other treatments.

In the new study, the researchers used preclinical models of breast tumor samples donated by Melbourne women undergoing cancer surgery to understand how real human cancers would respond to treatment with BH3-mimetics.

The researchers looked at the effect of adding BH3-mimetics to tamoxifen in luminal B cancers, a subtype of ER-positive cancers that have high levels of BCL-2. They found that a BH3-mimetic called ABT-199/GDC-0199 improved the effectiveness of hormone therapy by stopping or delaying the growth of these aggressive tumors. In one of the tumor models, the combination treatment resulted in complete disappearance of the malignancy, whereas standard treatment with tamoxifen showed only a partial and unsustained benefit.

“We are excited by these results and what they could mean for women with breast cancer,” said researcher Professor Jane Visvader. “ER-positive breast cancers are the most common type of breast cancer, so even a small improvement could have a substantial impact if more effective upfront treatment could prevent relapse.”

Source: Walter and Eliza Hall Institute; July 7, 2013.

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