Robust Scoring System to Evaluate Animal Well-Being in Murine (Mus musculus) Orthotopic Breast Cancer and Ovarian...

Orthotopic tumor models are critical to the development of new cancer therapies, as they have the greatest potential to mimic human cancer progression. However, such models are often underutilized due to practical challenges. These challenges include the need for specialized surgeries and the presence of complicating symptoms, such as ascites fluid accumulation in ovarian cancer and liver disease models, as well as ulceration of breast tumors growing in the mammary fat pad. An adaptable, quantitative animal health assessment system that employs simple, noninvasive visual measurements can enable researchers to realize the full potential of these models while safeguarding humane endpoints. The goal of this work was to establish health-scoring systems for translationally relevant ovarian (ID8-Defb29/Vegf-A) and breast cancer (triple-negative 4T1) models. We developed a tractable health assessment system by monitoring a combination of activity and responsiveness, hair coat condition, respiratory function, changes in body weight, posture, gait, tumor size (where measurable), and extent of ulceration, and scoring each parameter on a simple numerical scale. The scores at which euthanasia or other interventions were required were estimated and then adjusted based on clinical assessment by a team of researchers and veterinarians. These semiquantitative health-scoring systems were applied to survival experiments, in which mice were euthanized at a predetermined score or upon meeting a superseding health criterion, to confirm their applicability and effectiveness in maintaining humane endpoints. The scoring systems presented are intended to build on previously established generic tumor model scoring systems that do not account for the particular phenotypes present in orthotopic breast and ovarian cancer models.