About one in ten American women will develop breast cancer in her lifetime. Most breast cancers rely on estrogen for growth. Estrogen-receptor-positive breast cancer is often treated with the drug tamoxifen, which blocks the hormone's effect on the tumor. However, many tumors eventually become resistant to tamoxifen, leading to cancer recurrence or metastasis.
Now, a team of researchers at duke university’s cancer institute has found a possible link between leucine levels and tamoxifen resistance in ER+ breast cancer. At the same time, the researchers further identified a key protein that can introduce leucine into cells and modulate the sensitivity of ER+ breast cancer cells to tamoxifen, revealing a mechanism for overcoming endocrine drug resistance in ER+ breast cancer patients.
"The survival of ER+ breast cancer patients with drug-resistant and metastatic tumors is very short, usually less than three years, because their treatment options are very limited," says Helen piwnica-worms, Ph.D., director of the cell biology program at the BIDMC cancer institute." Our findings in the laboratory suggest that lowering leucine levels inhibits tumor cell proliferation, while increasing leucine levels enhances cancer cell proliferation." These findings also provide evidence for the possible benefits of a low-leucine diet.
Leucine is one of the 20 amino acids that make up all proteins in the body. It is also one of the nine essential amino acids that must be obtained through food. Beef, chicken, pork and fish are rich in leucine. Because cells by themselves don't produce leucine, Helen piwnica-worms and his colleagues were able to test how controlling leucine levels can affect the growth of human-derived ER+ breast cancer cells. Lowering leucine levels inhibited division in ER+ breast cancer cells, while increasing the number of amino acids by a factor of 10 increased the division, the researchers said.

"Because animal proteins have more leucine than plant proteins, this study is useful for developing a diet intervention strategy for ER+ breast cancer patients," Helen piwnica-worms said. "Our study does not mean that animal proteins promote the growth of breast cancer cells - just that lowering leucine levels is beneficial for patients diagnosed with ER+ breast cancer." The scientists also found that cells resistant to tamoxifen still grew at low leucine levels.

Further research showed that a protein on the cell surface called SKr, which is needed to transport leucine into cells, was present in higher levels in cells resistant to tamoxifen. Increasing Skr levels caused cells to absorb more leucine, enough to make breast cancer cells resistant to tamoxifen, while inhibiting Skr with chemical inhibitors reduced ER+ tumor size in mice.

In a follow-up study, Helen piwnica-worms' team is studying whether restricting leucine in the diet prevents the growth of ER+ breast cancer cells in mice or enhances the response to treatment.