NEW YORK (Reuters Health) May 22 - Researchers report in the June issue of The American Journal of Pathology that a loss of stromal caveolin-1 expression is "the single strongest predictor of breast cancer patient outcome."
"Among patients with estrogen receptor-positive breast cancer taking tamoxifen, a loss of stromal caveolin-1 predicted recurrence and poor clinical outcome," Dr. Michael Lisanti and colleagues at Thomas Jefferson University in Philadelphia, Pennsylvania, say.
"We show that caveolin-1 is a single independent predictor that is stronger than the existing breast cancer classification system that is the standard for diagnosis and treatment. This includes estrogen receptor, progesterone receptor and HER-2 status, and the nodal and tumor staging system," Dr. Lisanti, who is also editor-in-chief of The American Journal of Pathology, told Reuters Health.
"We think this could be used as a new classification system or in conjunction with the existing classification system. Given the right validation, it could even replace the existing classification system."
Dr. Lisanti and colleagues analyzed breast tissue samples from 154 women with breast cancer, using three tissue cores from each tumor sample, and analyzing each core for stromal caveolin-1.
"The absence of stromal caveolin-1 was strongly associated with other predictors of more aggressive disease, such as higher tumor stage and lymph node metastasis," the researchers report.
When grouped by prognostic factors such as hormone status, disease stage or lymph node status, a loss of stromal caveolin-1 remained the single strongest predictor of breast cancer patient outcome.
Among patients with estrogen receptor-positive breast cancer taking tamoxifen, a loss of stromal caveolin-1 still predicted recurrence and poor clinical outcome.
"Resistance to tamoxifen is thought to be an epithelial 'cancer cell' phenomenon, but we show here that it is clearly a 'stromal' phenomenon," Dr. Lisanti said.
Progression-free survival was affected by the loss of stromal caveolin-1. An absence of stromal caveolin-1 was associated with a progression-free survival rate that was 3.6-fold lower than observed in patients with breast tissue that expressed caveolin-1.
Patients with lymph node involvement had even lower survival rates. The approximate 5-year survival rate for patients positive for stromal caveolin-1 was 80% compared with only 7% for patients negative for stromal caveolin-1.
"That is an approximate 11.5-fold reduction in 5-year progression-free survival," the researchers report.
"We believe that patients who lack caveolin-1 would benefit from angiogenesis inhibitors," Dr. Lisanti told Reuters Health. "The cancer fibroblasts, which lack caveolin-1, tend to become endothelial cells, therefore driving angiogenesis."
"Essentially, (caveolin-1) is a marker of angiogenic potential. It is sort of a 'crystal ball' that predicts angiogenesis, which leads to early tumor recurrence, metastasis and poor clinical outcome," Dr. Lisanti said.
Testing for stromal caveolin-1 expression "would be no more expensive than testing for current markers and doesn't require any fancy DNA tests," Dr. Lisanti said. "Currently, antibody staining is routine for these patients, so they would only have to add this antibody staining to their existing list of markers. But this marker, so far, outperforms other existing markers."
Before this can be used in clinical practice, "there need to be prospective clinical trials," Dr. Lisanti added. So far, caveolin-1 has been "validated in three independent cohorts, in two different countries." One of these studies is published in this same issue of The American Journal of Pathology.
Am J Pathol 2009;174.
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου