New research led by the University of Manchester in the UK has found a biomarker or molecular “flag” in women with breast cancer who do not respond, or who have become resistant, to treatment with the hormone drug tamoxifen. The researchers say their discovery will help doctors predict which breast cancer patients are likely to respond best to complementary (adjuvant) hormone therapy with tamoxifen.
Senior author Göran Landberg, a professor at the University of Manchester who works at their Paterson Institute for Cancer Research and other research units in the area, and colleagues, write about their findings in a September 2012 issue of PLoS ONE.
In a statement released on Wednesday, Landberg says:
“The identification of molecular flags to classify subgroups of breast cancer and so determine the best treatment for each patient is of increasing importance in cancer therapy.”
Tamoxifen is a drug that blocks the female hormone estrogen, which fuels tumor growth in a common type of breast cancer known as estrogen receptor positive (ER+). About 70% of breast cancers are of this type.
In ER+ tumors, growth is spurred by estrogen binding to and activating the estrogen receptor in the breast cancer cells. Once in the body, tamoxifen breaks down into compounds that also bind to the estrogen receptor, but they do not activate it, they occupy it, thus denying the hormone the chance to promote cancer cell growth.
Tamoxifen is given as an “adjuvant” therapy, that is alongside other anti-cancer treatments like chemotherapy and radiotherapy. Studies show where it works, the drug is highly effective and can increase cancer survival by up to one third.
But one third of patients with ER+ breast cancer either do not respond to tamoxifen, or they develop resistance to it.
For their study, which was funded by the charity Breakthrough Breast Cancer, Landberg and colleagues examined the connective tissue that surrounds the breast cancer tumor. This is known to send signals that help the tumor to grow.
They discovered that the clue to tamoxifen response may lie in fibroblasts, the cells that make up the connective tissue. These cells differ in some characteristics from person to person.
The researchers analyzed tissue samples from 564 women with invasive breast cancer. Some of the women had been given tamoxifen, while the others had not. They found that women with low levels of a protein called pERK in the fibroblasts in the tissue surrounding their tumors did not respond to tamoxifen.
First author Susann Busch, also of Manchester, says:
“Testing patients for the pERK flag could help doctors determine whether tamoxifen is an appropriate treatment for their patient or whether alternative therapies should be explored, so saving time and money.”
The team now plans to look for other biomarker clues in the cancer-linked fibroblasts. Knowing more about how these connective tissue cells help tumor growth will help treatment developers find better ways to block their harmful signals and overcome resistance to cancer drugs.
Written by Catharine Paddock PhD