# Pleomorphic Lobular Carcinoma of the Mammary Gland in Women and Female Dogs: A Comparative Clinical-Pathological and Immunophenotypic Analysis

## TL;DR

This study compares pleomorphic lobular breast cancer in women and dogs, finding similarities and differences in tumor features, supporting the use of dogs as a model for breast cancer research.

## Contribution

The study identifies shared and distinct immunophenotypic features of pleomorphic lobular carcinoma in humans and dogs, supporting the canine model for comparative oncology.

## Key findings

- Canine PLC tumors show higher cell proliferation and consistent PR positivity, differing from human tumors.
- Both species show E-cadherin loss, potentially linked to cancer spread.
- Dogs predominantly exhibit the Luminal B subtype, while humans show equal prevalence of Luminal A and B.

## Abstract

Pleomorphic lobular carcinoma is a rare and aggressive type of breast cancer in both women and female dogs. This study aimed to better understand this tumor by comparing cases from humans and dogs. Tissue samples were analyzed using traditional staining and immunohistochemical techniques to assess pathological and immunophenotypic features. The findings showed that, although the tumors in both species share many similarities in their appearance and behavior, there are important differences, particularly in how they express hormone receptors and proliferation rate. In dogs, these tumors showed a higher rate of cell growth and consistent positivity for the progesterone receptor, while in women, most tumors were positive for both estrogen and progesterone receptors. Both species showed a loss of a protein important for cell adhesion, which may relate to neoplastic cell dissemination. Recognizing these similarities and differences helps to better understand breast cancer and opens the door to using dogs as a model to study this disease. Despite the current limitations such as the lack of follow-up data and clinical staging, this study provides an important first step in recognizing pleomorphic lobular carcinoma as a comparable tumor in dogs. Future research should focus on clinical outcomes, distant metastasis, and tumor microenvironment to clarify prognostic factors and confirm the translational relevance of this spontaneous model in comparative oncology.

Pleomorphic invasive lobular carcinoma (PILC or PLC) is a malignant breast tumor considered a rare variant of invasive lobular carcinoma in women, characterized morphologically by marked nuclear pleomorphism, with cells resembling plasmacytoid, histiocytoid, or apocrine cells. One of its defining features is the loss of E-cadherin expression. Considering the biological similarities between species and the limited data available for female dogs, this study aimed to characterize PLC in canines, with an emphasis on its histopathological and immunophenotypic features and its potential applicability as a comparative model. Histopathological analysis of PLC was performed alongside immunohistochemical evaluation using HER2, estrogen receptors (ER), progesterone receptors (PR), E-cadherin, and Ki-67 (cell proliferation indexing) markers. All canine PLCs tested positive for PR, with the majority being negative for ER, and all were negative for HER2 and E-cadherin. In contrast, in women, all cases were positive for ER, most were positive for PR, and all were negative for HER2. The Luminal B molecular subtype was the most frequent in dogs, whereas Luminal A and Luminal B subtypes showed equal prevalence in women. These findings reveal shared and distinct immunophenotypic features between species. The similarities and differences observed emphasize the relevance of the canine model for comparative oncology. Furthermore, the use of spontaneous tumors in immunocompetent dogs in this study strengthens the translational potential of the findings, thereby reinforcing the use of the canine model in breast cancer research and supporting its role within the One Medicine concept.