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Old 09-07-2005, 02:30 PM   #1
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Growth factor receptor expression increased in ER+/PR- breast cancers

Posted: September 07, 2005

NEW YORK (Reuters Health) - Expression of the growth factor receptors HER-1 and HER-2 is increased in estrogen receptor-positive/progesterone receptor-negative (ER+/PR-) breast cancers compared with ER+/PR+ tumors, new research shows.

This finding may, in part, explain why ER+/PR- cancers are relatively resistant to tamoxifen therapy, senior author Dr. Richard M. Elledge, from the Breast Care Center in Houston, and colleagues note.

Previous reports have shown that tamoxifen is more effective against ER+/PR+ tumors than ER+/PR- tumors. Moreover, there is also evidence that the drug is less effective in tumors with high expression of HER-1/HER-2. Still, it was unclear if these two observations were somehow related.

As reported in the Journal of the National Cancer Institute for September 7th, the researchers compared the clinical and biologic features of 31,415 women with ER+/PR+ tumors to those of 13,404 women with ER+/PR- tumors. HER-1 and HER-2 expression was analyzed in a subgroup of 11,399 patients receiving adjuvant tamoxifen therapy.

Compared with ER+/PR+ tumors, ER+/PR- tumors were more common in older patients and had more aggressive features. In addition, ER+/PR- tumors were three times more likely to express HER-1 and 50% more likely to overexpress HER-2 (p < 0.001 for both).

In the overall analysis of tamoxifen-treated patients, HER-1 expression was associated with an increased risk of disease recurrence and HER-2 overexpression was tied to worse disease-free survival. Further analysis, however, revealed that this finding was confined to patients with ER+/PR- disease.

"This study is, to our knowledge, the largest comprehensive evaluation of the biologic and chemical characteristics of invasive breast cancers that are ER+/PR- compared with those that are ER+/PR+," the authors point out.

In a related editorial, Dr. Cindy A. Wilson and Dr. Dennis J. Slamon, from the University of California at Los Angeles, comment that the results indicate that "PR status has important clinical relevance not only for predicting response to antiendocrine therapy but also possibly for the presence of altered peptide growth factor signaling."
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