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Molecular marker predicts success of breast cancer treatment

June 03, 2004

A new study demonstrates that the ratio of the expression levels of two genes can be used to accurately predict the clinical outcome of tamoxifen treatment for early stage breast cancer. It is the first method to reliably differentiate between patients who experienced disease-free survival and those at risk for tumor recurrence. The findings also provide new insight into the molecular mechanisms that may contribute to tamoxifen resistance.

Tamoxifen is one of the most widely used therapies for breast cancer. It works by blocking the action of estrogen on breast cancer cells. Estrogen directs the growth of normal breast cells, but can also stimulate the abnormal and unregulated cell growth associated with breast cancer. Unfortunately, nearly 40% of breast cancer patients fail to respond to tamoxifen or eventually become resistant to treatment, and there is no reliable way to predict treatment outcome. Dr. Dennis C. Sgroi from the Pathology Department at Massachusetts General Hospital and Dr. Mark G. Erlander from Arcturus Bioscience, Inc. in Mountain View, California examined the gene expression levels in 60 breast cancers from patients who were treated with tamoxifen after their surgery. Measuring gene expression is a way to examine whether or not a gene is functioning. They discovered that the ratio of the expression levels of two genes, HOXB13 and IL17BR, accurately predicted whether tumors reoccurred after treatment with tamoxifen. The researchers also found that when HOXB13 levels were experimentally elevated in cells from normal breast tissue cultured in the laboratory, the cells showed obvious morphological changes and became more invasive in response to growth signals. "This suggests that HOXB13 may directly contribute to tumor invasion and metastasis," explains Dr. Sgroi.

The researchers conclude that the HOXB13:IL17BR expression ratio may provide an effective molecular marker for identifying breast cancer patients who will be less likely to successfully respond to tamoxifen and would therefore benefit from an alternative therapeutic strategy for treatment of early stage breast cancer. According to Dr. Erlander, "This collaboration has us looking at which patients may benefit from tamoxifen and, as a result, many doors of inquiry have been opened."

Xiao-Jun Ma, Zuncai Wang, Paula D. Ryan, Steven J. Isakoff, Anne Barmettler, Andrew Fuller, Beth Muir, Gayatry Mohapatra, Ranelle Salunga, J. Todd Tuggle, Yen Tran, Diem Tran, Ana Tassin, Paul Amon, Wilson Wang, Wei Wang, Edward Enright, Kimberly Stecker, Eden Estepa-Sabal, Barbara Smith, Jerry Younger, Ulysses Balis, James Michaelson, Atul Bhan, Karleen Habin, Thomas M. Baer, Joan Brugge, Daniel A. Haber, Mark G. Erlander, Dennis C. Sgroi: " A two-gene expression ratio predicts clinical outcome in breast cancer patients treated with tamoxifen"

Published in Cancer Cell Online on 3 June 2004, DOI: 10.1016/j.ccr.2004.05.015. The article will appear in Cancer Cell, Volume 5, Issue 6, June 2004.
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Cell Press

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