Lapatinib Reduces Mammary Tumor Development in Mouse Model of Breast Cancer
Lapatinib delayed tumor development in a mouse model of hormone receptor-negative breast cancer and reduced the number of tumors per animal compared with mice treated only with vehicle (an inert solution lacking lapatinib).
Lapatinib is a small-molecule inhibitor that blocks the tyrosine kinase activities of epidermal growth factor receptor and ErbB2, both of which promote cell proliferation and are associated with tumor formation. MMTV-erbB2 transgenic mice, which express wild-type ErbB2 in mammary tissue, develop mammary tumors that are estrogen receptor (ER)–negative and ErbB2-positive by 14 months of age.
To examine whether lapatinib may prevent development of breast tumors that are driven by ErbB2, Powel H. Brown, M.D., Ph.D., of Baylor College of Medicine in Houston, and colleagues treated MMTV-erbB2 transgenic mice with either high- or low-dose lapatinib or vehicle alone.
By 328 days after the start of treatment (age of 418 days), five of 16 mice, or 31 percent, treated with high-dose lapatinib had developed mammary tumors compared with 100% of the 17 mice treated with vehicle alone. The lapatinib-treated mice developed statistically significantly fewer tumors per animal than the vehicle-treated animals.
"Our results show that lapatinib suppresses the development of ER-negative ErbB2-positive invasive mammary tumors in MMTV-erbB2 mice," the authors conclude. "Thus, lapatinib may be useful for the prevention of ER-negative, ErbB2-positive mammary tumors in humans."
Contact: Kimberlee Norton, email@example.com; 713.798.7971
Multi-Institutional Study Validates Predictive Biomarker in Bladder Cancer
A high expression level of the protein Ki-67 in a tumor is an independent predictor of disease recurrence and disease-specific mortality in patients with advanced urothelial bladder cancer.
Several small studies have suggested that elevated Ki-67 expression correlated with poorer patient outcomes. Before the biomarker can be used to help guide patient care, however, it needed to be validated in a larger multi-institutional trial.
In the current study, Shahrokh Shariat, M.D., Ph.D., of the University of Texas Southwestern in Dallas, and colleagues tested the biomarker in a larger trial that included 713 patients from six institutions from the United States, Canada, and Europe. All of the patients had undergone radical cystectomy and bilateral pelvic lymph node removal between 1983 and 2005. Tumor samples were scored for Ki-67 staining using an automated system for staining and microscopy coupled with advanced color detection software.
KI-67 was a strong predictor of outcomes for individual patients, even after adjusting for the effects of known risk factors such as age, gender, tumor stage, grade, number of positive lymph nodes, and surgical margins status. Patients whose tumors expressed a high level of Ki-67 were 2.4 times more likely to have disease recurrence than those whose tumors had a low level of Ki-67, and disease-specific mortality was 1.8-fold higher. To prove the clinical importance of KI-67 in the clinical setting, the authors developed a model that included the biomarker. The addition of Ki-67 increased the accuracy of a model that includes all known risk factors for predicting which individual patient will experience disease recurrence; accuracy improved by 2.9 percent for all patients and by 4.1 percent in a subgroup of patients with lymph node-negative disease. For disease-specific mortality, predictive accuracy improved by 2.4 percent for all patients and 4.6 percent for patients with lymph node-negative disease.
"In conclusion, routine assessment of Ki-67 expression status along with assessment of other established predictors of urothelial carcinoma outcome has the potential to improve identification of patients who are at increased risk for disease progression after radical cystectomy and thus may benefit from perioperative systemic chemotherapy," the authors write.
Contact: Shahrokh Shariat, firstname.lastname@example.org; (469) 363 8500
Tandem Autologous Hematopoietic Cell Transplants Not Justified in Multiple Myeloma
A systematic review and meta-analysis of prospective randomized trials indicates that tandem autologous hematopoietic cell transplantation (AHCT) does not improve overall survival or event-free survival in patients with multiple myeloma compared to single AHCT.
It has been suggested that myeloma patients who undergo tandem AHCT have better clinical outcomes than those who undergo only a single transplant. To get a more comprehensive view of the effect of tandem AHCT on event-free and overall survival, Ambuj Kumar, M.D.,M.P.H, of the Moffitt Cancer Center in Tampa, Fla., and colleagues performed a systematic review and meta-analysis of six prospective randomized controlled trials that compared single versus tandem AHCT and included a total of 1,803 patients.
Neither overall survival nor event-free survival was statistically significantly improved by tandem AHCT relative to single AHCT. Although the response rate was statistically significantly higher following tandem AHCT compared with single AHCT, treatment-related mortality was also statistically significantly higher with tandem transplants.
"In conclusion, based on the synthesis of all currently available data, the routine use of tandem transplant in its current form is not justified," the authors write.
Contact: Patricia Kim, Patty.Kim@moffitt.org; 813-745-7322
Also in the Jan. 13 JNCI: