ANTIESTROGENS AND E-CADHERIN

Antiestrogens Can Enhance Cellular Invasion by Certain Breast Cancer Cells

NEW YORK (Reuters Health) Jan 02 - Antiestrogens like tamoxifen can promote an invasive phenotype in estrogen receptor (ER)-positive breast cancer cells with deficient intercellular adhesion, according to a report in the December 4th issue of Breast Cancer Research.

"This is a preclinical study, and its clinical relevance has yet to be proven," Dr. Stephen Hiscox from Cardiff University, Cardiff, UK, told Reuters Health. "Our data, if validated clinically, would add more weight to the use of aromatase inhibitors in breast cancer versus tamoxifen."

Dr. Hiscox and colleagues used Matrigel invasion assays to measure the effect of estrogen, 4-hydroxy-tamoxifen, and estrogen deprivation on the invasive capacity of endocrine-sensitive breast cancer cells in the presence or absence of functional E-cadherin.

In the absence of good intercellular contacts, tamoxifen promoted invasion of breast cancer cells in culture, the authors report, whereas estrogen deprivation had no effect on invasiveness.

Fulvestrant, a steroidal antiestrogen, also enhanced breast cancer cell invasion in the absence of E-cadherin expression, the investigators found.

"Taken together, our preclinical data generate the hypothesis that in patients whose primary breast cancers show reduced or aberrant E-cadherin expression, tamoxifen therapy may promote the development of an adverse cell phenotype that may have an impact on disease relapse, its invasive behavior, and, hence, patient survival," the authors conclude.

"Although our observations may only apply to a relatively small subset of patients, they may account for some of the superiority seen with aromatase inhibitors in the large adjuvant studies," they add.

If these findings are confirmed, the researchers say, endocrine therapy might be guided by E-cadherin expression.

"We are currently addressing levels of E-cadherin in breast tissues from patients who have received tamoxifen," Dr. Hiscox said. "We hope to determine whether low/absent levels of E-cadherin correlate with poor endocrine response."