As therapies for breast cancer continue to emerge, the issues of how to best monitor success and gauge prognosis remain important questions.
At the CTRC-AACR Annual San Antonio Breast Cancer Symposium, researchers will present new data on Herceptin, circulating tumor cells, mucinous breast carcinoma and the role of the Ki67 antigen during a press conference on Saturday, Dec. 12, 2009, at 8:00 a.m. CT, in room 217C of the Henry B. Gonzales Convention Center.
Claudine Isaacs, M.D., will host this press conference. Isaacs is director of the Clinical Breast Cancer Program and medical director of the Cancer Assessment and Risk Evaluation Program at Georgetown's Lombardi Comprehensive Cancer Center.
Reporters who cannot attend in person may call in using the following information:
•U.S. & Canada: (888) 282-7404
•International: (706) 679-5207
•Access Code: 39119499
•Topic: AACR
The following abstracts will be presented at the press conference:
80. Results of chemotherapy alone, with sequential or concurrent addition of 52 weeks of trastuzumab in the NCCTG N9831 HER2-positive adjuvant breast cancer trial
Clinicians can now recommend that trastuzumab, currently sold as Herceptin by Genentech-Roche, be given concurrently with chemotherapy to achieve maximum benefit in terms of disease-free survival.
Researchers, led by Edith Perez, M.D., director of the breast cancer program at the Mayo Clinic in Jacksonville, Fla., found a 25 percent reduction in the risk of breast cancer recurrence when trastuzumab was administered concurrently, rather than following chemotherapy.
Perez said these findings are very important and estimated that they will inform treatment decisions for about 50,000 women in the United States and 200,000 women around the world every year.
"Often the research community conducts studies that conclude with 'that was interesting, but let's do more research.' This is an important finding on how we can help prevent breast cancer recurrence and improve survival," said Perez.
All patients enrolled in this phase III trial were receiving standard chemotherapy of doxorubicin and cyclophosphamide followed by paclitaxel.
The researchers conducted two separate comparisons.
The first included 2,448 patients randomly assigned to chemotherapy alone or chemotherapy followed by trastuzumab. After 5.5 years, the researchers observed 386 events. After adjustment for possible confounding variables, they found that event-free survival increased from 72 percent with chemotherapy alone to 80 percent with chemotherapy followed by trastuzumab.
The second comparison included 1,903 women. The researchers compared those who received trastuzumab after chemotherapy with those who received it concurrently with paclitaxel. At five years, disease-free survival increased from 80 percent to 84 percent.
"This study has global implications. In the United States, Herceptin is approved for use either following or concurrently with chemotherapy," said Perez. "However, currently in some countries trastuzumab is only approved for use following chemotherapy as adjuvant therapy for HER2-positive breast cancer. We hope our findings will change those policies. In the United States, this will clearly inform physician decision making."
3011. Circulating Tumor Cells (CTCs) and Epithelial Mesenchymal Transition (EMT) in Breast Cancer: Describing the Heterogeneity of Microscopic Disease
Embargoed until 5:30 p.m. CT, Dec. 11, 2009
Circulating tumor cells (CTCs) are an important predictor of survival in metastatic breast cancer patients. When CTCs undergo epithelial-mesenchymal transition (EMT), resulting in a loss of epithelial markers, they may escape conventional detection, according to data presented at the CTRC-AACR San Antonio Breast Cancer Symposium.
"Our data suggest that current CTC detection methods may underestimate the most important subpopulation of CTCs, which are involved in tumor dissemination," said Michal Mego, M.D., Ph.D., a scientist at the National Cancer Institute in the Slovak Republic. The research was conducted while Mego was an International Union Against Cancer Scholar in the Morgan Welch Inflammatory Breast Cancer Research Program and Clinic at The University of Texas M. D. Anderson Cancer Center.
The presence of an increased number of CTCs is associated with poor prognosis in breast cancer patients, Mego explained. Cells with this EMT phenotype are probably involved in tumor dissemination and represent tumor initiating cells. Identification of therapeutic targets on these cells could lead to eradication of micrometastatic disease in breast cancer, as well as in other epithelial tumors.
"When we retrospectively evaluated the outcome of breast cancer patients, we observed that there were subgroups of patients, such as those with brain metastasis, triple negative or inflammatory breast cancer, who had poor prognosis and low or undetectable CTCs by conventional methods," Mego said. "We found that the low or undetectable CTCs were due to the existence of a subpopulation of cancer cells that undergoes a process of EMT."
When epithelial cells undergo EMT, they lose their epithelial receptors. As a result, they are no longer detected by current detection assays.. In addition, these cancer cells become resistant to chemotherapy or radiation therapy, according to Mego.
"This observation led us to hypothesize that EMT CTCs are responsible for tumor dissemination," Mego said. "Hence, we developed a novel detection method that would be capable of identifying EMT CTCs in peripheral blood from breast cancer patients."
In this prospective study, Mego and colleagues used approximately 5 mL of peripheral blood from patients with varying stages of breast cancer and isolated the CTCs using magnetic beads coated with monoclonal antibodies. Using a polymerase chain reaction, they then isolated RNA to detect genes that are involved in EMT.
Patients who had triple-negative breast cancer more commonly overexpressed EMT genes compared to non-triple-negative patients.
"Our data indicate that a subpopulation of CTCs with EMT really exists, and that these cells are more commonly detected in patients with poor prognosis such as those with triple-negative breast cancer or in patients pretreated by neoadjuvant chemotherapy who have developed resistance to therapy," Mego said. "A novel detection method such as ours that is capable of detecting CTCs after EMT could add new important prognostic information, and could be useful for monitoring treatment efficacy."
Mego and colleagues also initiated a confirmatory study in metastatic breast cancer patients as well as in prostate and colorectal cancer patients to confirm their findings. These studies were aimed to identify therapeutic targets on these cells.
Ongoing research at The University of Texas M. D. Anderson Cancer Center and the National Cancer Institute in the Slovak Republic will continue to focus on the detection of CTCs with tumor-initiating properties, as well as the identification of potential therapeutic targets for CTCs. Trastuzumab treatment based on detection of HER-2/neu amplification on CTCs represents proof of this new concept of targeted therapy, according to Mego.
4117. Mucinous Breast Carcinoma: Occult Multifocality/Multicentricity in a Favorable Disease
Embargoed until 7:00 a.m. CT, Dec. 12, 2009
A large sample of patients with pure mucinous breast cancer demonstrated a favorable prognosis. However, researchers also found an association with significant occult multicentricity/multifocality.
"Our findings indicate another potentially unfavorable aspect associated with a widely accepted as favorable breast cancer subtype," said George H. Perkins, M.D., associate professor in the Division of Radiation Oncology at The University of Texas M. D. Anderson Cancer Center.
"In an era of concern regarding overtreatment, we caution in our findings that undertreatment could also become a significant hazard for patients and thus should be a significant area of concern," he said.
Perkins presented results of this study at the CTRC-AACR Annual San Antonio Breast Cancer Symposium, held Dec. 9-13, 2009.