Although survival rates for early-stage breast cancer patients have improved over the last five years, many women still die from the disease. In this new study, the Georgetown team found that women whose tumors retain Stat5, a protein biomarker, have a highly favorable prognosis and may be cured by surgery and local therapy alone instead of additional regiments of chemotherapy or anti-estrogen therapy. Conversely, women whose tumors lost the Stat5 marker had a 7.6-fold increased risk of dying from recurrent breast cancer.
"Detection of the Stat5 marker in early stage breast cancer may lead to improved individualized therapy," said Hallgeir Rui, M.D., Ph.D., associate professor of oncology, Lombardi Comprehensive Cancer Center at Georgetown and principal investigator of the study. "This may include more careful follow-up and more aggressive treatment of patients at higher risk of breast cancer recurrence, and reduced treatment in patients with excellent prognosis."
Rui notes that the majority of promising breast cancer markers that have been identified over the last decade have failed to become useful in the clinical setting after follow-up studies. However, the design and results of this study give Rui and his colleagues room for optimism.
The study involved a retrospective analysis of two large, independent breast cancer patient materials that included over 1,100 patients, giving the study a solid statistical basis. Also, unlike some marker assays or tests, the assay for Stat5 is simple, inexpensive, and can be rapidly adapted to routine analysis in pathology laboratories using standard procedures.
"Although hurdles remain, we feel there are several reasons to be optimistic about the Stat5 marker," said Rui. "We are completing an even larger retrospective study now, and then look forward to launching an important prospective study this fall to determine the full extent of Stat5's importance in diagnosing and treating breast cancer."
Stat5 protein is a DNA-binding factor that regulates expression of certain genes, many of which remain unknown. During pregnancy, Stat5 is activated by the hormone prolactin, and stimulates milk production in the breast. Rui and colleagues have recently shown that Stat5 is also active at a lower level in healthy breast cells in non-pregnant women. In the new study they discovered that active Stat5 was lost in many breast cancers, especially as the tumors became more aggressive and metastatic.
The team investigated whether the tumor levels of active Stat5 were related to how well the patients did over the next 5-10 years after initial treatment. After analysis of over 1,000 patients' tumor samples, the team found that loss of Stat5 activity correlated with higher risk of death. This increased risk was especially pronounced in patients with early stage breast cancer, whose tumors did not show detectable evidence of spread to the nearby lymph nodes.
Previous studies in mice have indicated that Stat5 promotes breast tumor development; surprisingly in this study presence of Stat5 in human tumors were linked with more positive outcomes.
The work was done in international collaboration with Dr. Guido Sauter and Dr. Lukas Bubendorf and their research groups at the Institute of Pathology, University of Basel, Switzerland, and with Dr. Juha Kononen at the DioMeda Life Sciences (Diomeda.com). The collaborators have pioneered the tissue microarray technology, which was critical for rapid analysis of the large number of samples.
The Lombardi Comprehensive Cancer Center, part of Georgetown University Medical Center and Georgetown University Hospital, seeks to improve the diagnosis, treatment, and prevention of cancer through innovative basic and clinical research, patient care, community education and outreach, and the training of cancer specialists of the future. Lombardi is one of only 38 comprehensive cancer centers in the nation, as designated by the National Cancer Institute, and the only one in the Washington DC area. For more information, go to http://lombardi.georgetown.edu/
Journal
Journal of Clinical Oncology