Breast cancer remains one of the most prolific and life-threatening diseases among women worldwide. According to the American Cancer Society, among US women in 2017, there were approximately 253,000 new cases of invasive breast cancer resulting in 41,000 deaths. Approximately 6-10% of new breast cancer cases (15,000-25,000) are diagnosed as metastatic (Stage IV). However, it is thought that 20-30% of all breast cancers will become metastatic over time.
Animal models can be very powerful tools for analyzing the development and progression of cancer. One example of this is the transgenic polyoma middle T oncoprotein (PyMT) model. Expression of PyMT is restricted to the mammary glands by the MMTV promoter/enhancer and results in mice that experience four distinct stages of tumor progression from premalignant to malignant. These stages are comparable to human breast cancer. In addition to the morphological similarities with human breast cancer, the expression of biomarkers in MMTV-PyMT-induced tumors is also consistent with those associated with poor outcome in humans. These include a loss of estrogen and progesterone receptors and the persistent expression of ErbB2/Neu (Her2) and cyclinD1 in MMTV-PyMT tumors as they progress to the malignant stage.
Given the desperate need, and the uniqueness of the MMTV-PyMT model, Labcorp has developed and optimized a transplantable version of this model that’s derived from transgenic host mice (FVB/N-Tg(MMTV-PyVT)634Mul/J).
Primary Mammary Fat Pad Tumor Growth
Orthotopic primary tumor growth kinetics for the transplantable MMTV-PyMT (PyMT) model are shown in Figure 1. The median doubling time is ~8 days with a steady increase in tumor volume and no apparent tumor related body weight loss. As animals were euthanized due to primary tumor growth, lung nodules were noted. The growth rate allows for a four-week therapeutic window to evaluate anti-tumor responses.