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Protein Marker Identifies Breast Cancer Patients Who Won’t Respond to Tamoxifen

Differences in fibroblast cells give clues to potential treatment response (Nov. 1)

Scientists in the U.K. have identified a molecular “flag” in women with breast cancer who do not respond to or have become resistant to the hormone drug tamoxifen.

Tamoxifen — used along with traditional chemotherapy and radiotherapy — blocks the female hormone estrogen, which, in certain breast cancers, is required for tumors to grow. However, about one third of patients with estrogen receptor-positive (ERP) breast cancer do not respond to tamoxifen or develop resistance to the drug. ERP breast cancer is the most common form of the disease, accounting for 70% of cases.

Investigators at the University of Manchester’s Paterson Institute for Cancer Research have identified a molecular marker that will help physicians predict which patients will respond best to adjuvant hormone therapy with tamoxifen.

“Tamoxifen has been shown to be highly effective in some breast cancer patients when used alongside traditional cancer therapies but, in a third of cases, the result has not been what we would hope,” said study leader Professor Göran Landberg. “If we can predict which patients will respond to tamoxifen, and those who won’t, then this is clearly advantageous, as it means the correct treatment is provided instantly, which will improve disease outcomes.”

The research, published in the journal PLoS One, looked at the connective tissue surrounding breast tumors, which is known to send signals that help the cancer grow. The team found that fibroblast cells — the cells that make up the body’s connective tissues — differ in their characteristics from patient to patient and can give clues about the potential response to tamoxifen treatment.

The researchers analyzed tissue samples from 564 women with invasive breast cancer — some treated with tamoxifen, and some not.

“We discovered that women who had low levels of a protein known as pERK in their cancer-associated fibroblasts did not respond to tamoxifen,” co-author Dr. Susann Busch said. “Testing patients for the pERK flag could help doctors determine whether tamoxifen is an appropriate treatment for their patients or whether alternative therapies should be explored, so saving time and money.”

The researchers plan to further study molecular flags that are characteristic for cancer-associated fibroblasts. Understanding how fibroblasts help tumors grow may allow the development of new strategies to block their harmful signals and overcome drug resistance.

Source: University of Manchester, November 1, 2012.

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