Researchers from the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia have implicated the loss of a stromal protein called caveolin-1 as a major new prognostic factor in patients with breast cancer, predicting early disease recurrence, metastasis and breast cancer patient survival, according to an article published online before print May 1 in the American Journal of Pathology.
The absence of caveolin-1 in the stroma also appeared to be a marker for drug resistance in patients receiving tamoxifen, according to Michael Lisanti, MD, PhD, professor in the departments of cancer biology, medical oncology and biochemistry and molecular biology at Jefferson Medical College of Thomas Jefferson University.
Previously, researchers showed that caveolin-1 (Cav-1) expression is down-regulated in human breast cancer-associated fibroblasts. However, it remains unknown whether loss of Cav-1 occurs in the breast tumor stroma in vivo, the authors noted.
Lisanti and colleagues analyzed breast tissue samples from 154 women diagnosed with breast cancer. All samples were obtained from the University of Michigan. They used three tissue cores from each patient tumor sample, and analyzed each core for stromal Cav-1 using immunohistochemistry staining.
An absence of stromal Cav-1 was associated with early disease recurrence, advanced tumor stage, and lymph node metastasis, resulting in an approximate 3.6-fold reduction in progression-free survival (PFS). In lymph-node positive patients, the difference in PFS was especially pronounced: The approximate five-year survival rate for patients positive for stromal caveolin-1 was 80 percent, versus 7 percent for patients negative for stromal caveolin-1-and approximate 11.5-fold reduction in five-year PFS.
Among patients with ER-positive breast cancer who were taking tamoxifen, a loss of stromal caveolin-1 still predicted recurrence and poor clinical outcome. As many as 40 percent of patients who take tamoxifen in this setting relapse despite its significant effect on survival when used in the early stages of the disease, the researchers noted.
""The idea that a prognostic biomarker is present in the stroma rather than the epithelial cancer cell is paradigm-shifting," Lisanti said. "Importantly, these findings could be developed into a diagnostic test that would not require DNA-based technologies. This inexpensive and cost-effective test would allow doctors to identify high-risk breast cancer patients at diagnosis and treat them more aggressively."
Based on related mechanistic studies, Lisanti and colleagues suggest that breast cancer patients lacking stromal Cav-1 might benefit from anti-angiogenic therapy in addition to standard regimens, concluding that Cav-1 functions as a tumor suppressor in the stromal microenvironment.