lapatinib as a preventive? (seems to work vs her2+er- breast cancer in mice)!!

[Lani]

Hopefully this will speed up the day when lapatinib starts being used before Stage IV, and even better, if we could determine who was at risk for each subtype of breast cancer and put them on the specific preventative for that subtype--dream on!:


Lapatinib Reduces Mammary Tumor Development in Mouse Model of Breast Cancer
[Eureka News Service]
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."
ABSTRACT: Effect of Lapatinib on the Development of Estrogen Receptor-Negative Mammary Tumors in Mice
[Journal of the National Cancer Institute; Subscribe; Sample]
Lapatinib, a selective orally available inhibitor of epidermal growth factor receptor (EGFR) and ErbB2 receptor tyrosine kinases, is a promising agent for the treatment of breast cancer. We examined the effect of lapatinib on the development of mammary tumors in MMTV-erbB2 transgenic mice, which express wild-type ErbB2 under the control of the mouse mammary tumor virus promoter and spontaneously develop estrogen receptor (ER)-negative and ErbB2-positive mammary tumors by 14 months of age. Mice were treated from age 3 months to age 15 months with vehicle (n = 17) or lapatinib (30 or 75 mg/kg body weight; n = 16 mice per group) by oral gavage twice daily (6 d/wk). All statistical tests were two-sided. By 328 days after the start of treatment, all 17 (100%) of the vehicle-treated mice vs five (31%) of the 16 mice treated with high-dose lapatinib developed mammary tumors (P < .001). Among MMTV-erbB2 mice treated for 5 months (n = 20 mice per group), those treated with lapatinib had fewer premalignant lesions and noninvasive cancers in their mammary glands than those treated with vehicle (P = .02). Lapatinib also effectively blocked epidermal growth factor-induced signaling through the EGFR and ErbB2 receptors, suppressed cyclin D1 and epiregulin mRNA expression, and stimulated p27 mRNA expression in human mammary epithelial cells and in mammary epithelial cells from mice treated for 5 months with high-dose lapatinib. Thus, cyclin D1, epiregulin, and p27 may represent useful biomarkers of lapatinib response in patients. These data suggest that lapatinib is a promising agent for the prevention of ER-negative breast cancer