A Review on Mammary Tumors in Rabbits: Translation of Pathology into Medical Care

Abstract

Simple SummaryIn recent years mammary cancer has been increasingly recognized in pet rabbits. In addition to uterine carcinomas—the most common tumor of female rabbits—mammary cancer can also markedly reduce the life expectancy of pet rabbits. The aim of this review is to raise awareness for these tumors and to report recent progress in related research. Their detailed characterization will likely improve medical care for affected rabbits. Moreover, study results will contribute to comparative pathology and may reveal if the rabbit is a suitable model for certain types of breast cancer in humans. Available information suggests that most invasive cancer cases develop through stepwise progression from non-invasive forms. Thus, early recognition will likely improve a complete cancer cure. So far, the only treatment option is surgical excision and prognostic factors are unknown. Recent investigations have identified tumor features with likely prognostic value. They have also revealed differences and similarities to mammary tumors in other species and breast cancer in women. Despite these initial data, continued research is necessary to gain more insights into the development of these tumors and their molecular features.AbstractThe aim of this review is to raise awareness for mammary tumors in rabbits and to report progress in related research. Currently, a standardized tumor classification for rabbits is not available, prognostic factors are unknown and the only treatment option is surgical excision. Studies showed that affected rabbits have a wide age range and are nearly exclusively female or female spayed. Most mammary tumors are carcinomas. These may occur together with non-neoplastic or benign mammary lesions. Frequent microscopic findings are lipid droplets in tumor cells, secretory activity and microscopic heterogeneity. Since carcinomas are often negative for estrogen and progesterone receptors (ER-α/PR), modulation of receptor function will unlikely be beneficial for most rabbits. ER-α and PR status may have prognostic significance, since ER-α- or PR-negative tumors have significantly higher mitotic rates than ER-α- or PR-positive tumors. The frequent secretory activity of rabbit mammary tumors may suggest an influence of prolactin on tumorigenesis. Available data contribute to comparative pathology and are the basis for future molecular studies into the identification of additional prognostic factors and novel therapeutic options. They will also reveal the suitability of the rabbit as a model for certain types of breast cancer in women.

Tumor Infiltrating Lymphocytes in Pet Rabbit Mammary Carcinomas: A Study with Relevance to Comparative Pathology

“…Since majority of rabbit mammary carcinomas are ERα and PR negative, the rabbit has been proposed as a potential animal model for ERα/PR negative breast cancer in humans [10] as well as potentially also for triple negative human breast carcinomas [12]. In addition, rabbits may be a suitable model for breast cancer types with a myoepithelial differentiation of tumor cells and a prolactin-associated tumorigenesis as well [10][11][12]15].…”

“…The suitability of rabbits as animal models for human diseases is facilitated by the availability of comprehensive data on their innate and adaptive immune mechanisms [1,8,9], close similarities between the rabbit and human immune systems [1,4], and very similar expression and functions of key genes between humans and rabbits [2]. Recent investigations on spontaneous mammary carcinomas of pet rabbits, identified the pet rabbit as potential animal model for certain types of spontaneous human mammary tumors [10][11][12]. This eligibility is further supported by the following aspects: In contrast to rodents, mammary glands of does and women contain independent ductal systems with separate teat orifices [13].…”

“…It has been shown that most rabbit mammary tumors are carcinomas, i.e., 50-98% depending on the respective study, the majority of these being adenocarcinomas [10][11][12]15,16]. Recent investigations on rabbit mammary carcinomas analyzed in detail the histological features [10,15,16], estrogen and progesterone receptor status [10], as well as the intra-tumoral presence of retained non-neoplastic myoepithelial cells and tumor cells with a myoepithelial differentiation [11,15].…”

“…Recent investigations on rabbit mammary carcinomas analyzed in detail the histological features [10,15,16], estrogen and progesterone receptor status [10], as well as the intra-tumoral presence of retained non-neoplastic myoepithelial cells and tumor cells with a myoepithelial differentiation [11,15]. Definitive prognostic factors are not available yet, and currently the only therapeutic option is surgical excision [12].…”

Avascular fat grafts show lower volume retention but higher hypoxia, angiogenesis, adipocyte proliferation, and macrophage infiltration than vascularized adipocutaneous flaps in an in vivo pilot mouse study Fat grafting vs. flap transfer in mice

“…Early successful attempts at in vivo modeling of fat grafting were realized in rabbits and have recently been upscaled into pigs, [27][28][29][30][31][32][33][34] but these large animals cannot be used in the context of oncologic questions, as no leporine or porcine breast cancer models exist. [35][36][37][38] In fact, immunocompetent and orthotopically implanted breast cancer dormancy models have only been described in mice. [39][40][41] However, lipofilling models in mice are scarce, and breast cancer models still suffer from several limitations.…”