Amino Acid Leucine Found In Meat May Fuel Resistance To Breast Cancer Treatment Tamoxifen

Breast cancer patients who are resistant to the drug tamoxifen have poor health outcomes, but reducing meat protein in the diet could offer better results.

Tamoxifen is the standard treatment for estrogen-receptor-positive breast cancer. Many tumors became resistant to this endocrine drug that treating breast cancer becomes more difficult due to limited treatment options.

A group of researchers from the Cancer Center Institute at Beth Israel Deaconess Medical Center, a Harvard Medical School Teaching Hospital, discovered the relationship between levels of amino acid leucine and tamoxifen resistance.

Details of the study were published in the journal Nature.

Role Of Amino Acid Leucine

Leucine is one of the 20 types of amino acid that is not naturally produced in the body. Its common sources are beef, chicken, pork, and fish.

Lead author Senthil Muthuswamy, director of the cell biology program and deputy director of translational research in the Cancer Center Institute at BIDMC, said reducing the levels of amino acid leucine could potentially suppress tamoxifen resistance in ER-positive breast cancer patients.

"Our findings in the lab demonstrate that decreasing leucine levels suppresses proliferation of tumor cells, whereas increasing leucine enhances it. Furthermore, the findings open up the possibility that a low-leucine diet could be beneficial for patients with ER+ breast cancer," Muthuswamy said.

Researchers manipulated the levels of leucine in cultured cells and found that a tenfold increase in the amino acid enhanced the ER-positive breast cancer cells' division.

Further investigation also showed that cancer cells that grew to become resistant to tamoxifen were able to grow even with decreased leucine levels.

Decreasing the amount of leucine in the diet can improve the patients' metabolic functions and overall health outcomes. Low-leucine, protein-rich plant-based diet will provide daily nutrients to ER-positive breast cancer patients.

Benefits Of Anti-Estrogen Drug

The addition of an anti-estrogen drug to the first-line treatment for ER-positive breast cancer is found beneficial to women who were initially exposed to endocrine therapy.

Dr. Rita Mehta, clinical professor at University of California Irvine, said fulvestrant can limit the supply of estrogen to the tumor. Low levels of estrogen reduces the growth of the cancer cells and delays the resistance to the drug anastrozole.

"The addition of fulvestrant to anastrozole was associated with increased long-term survival as compared with anastrozole alone, despite substantial crossover to fulvestrant after progression during therapy with anastrozole alone," reported Mehta's team in the study recently published in The New England Journal of Medicine.

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