Cancer Progression Is not Different in Mice of Different Gender Inoculated With Cells of the Triple-Negative 4T1 Breast Cancer Model

Exsal Manuel Albores-Mendez, Rocio Guadalupe Casanas-Pimentel, Indira Raquel Reyes-Chacon, Juan Maldonado Cubas, Jaime Lopez-Cruz, Jorge Alberto Rincon-Huerta, Alejandro Camacho-Ibarra, Eduardo San Martin-Martinez


Background: Breast cancer in men is a rare and poorly studied disease, and its treatment is based on women breast cancer studies. However, clinical outcome is not the same in men and women. Basic studies and clinical trials in animal models provide detailed information on cancer, origin, development, cell signaling pathways, sites of metastasis, and target molecules. It is necessary to explore the biology of breast cancer in male animal models that allow observing their similarity.

Methods: The triple-negative 4T1 breast cancer model was developed in both male and female mice and studied weekly during 4 weeks. For that, twenty 8-week-old female and male BALB/c mice were used. Sixteen mice (eight males and eight females) were inoculated into the second left thoracic mammary pad with 20,000 4T1 cells, resuspended in 20 µL phosphate-buffered saline (PBS). All samples were processed for immunodetection, characterized histopathologically and immunohistochemically.

Results: In this work, we describe the development of a triple-negative 4T1 breast cancer model in male BALB/c mice. Breast tumors were characterized histopathologically at different time points and corresponded to a moderately differentiated invasive ductal carcinoma, estrogen receptor ER-/progesterone receptor PR-/human epidermal growth factor receptor 2 HER2-/Ki67+, with histological grade II (moderately differentiated; a solid mass with occasional duct formation and moderate to severe nuclear pleomorphism), infiltrating the adipose and muscular tissue, and metastasis to lungs. From the results, we did not observe differences in the time of tumor development, necrosis, color change of tumor tissue, and lung metastasis between male and female mice. Even though we did not find histological differences, response to treatment and molecular signaling may be different.

Conclusions: The histogenesis of male breast tumors was similar to that of female BALB/c mice. The histological and immunohistochemical characteristics of male tumors also match the features reported for stage IV human breast cancer of men and women. The murine male breast cancer model described here can be a significant tool to explore the molecular mechanisms involved in male breast cancer tumorigenesis and metastasis and may bring new approaches for clinical treatment of triple-negative breast cancer in men.

World J Oncol. 2022;13(5):249-258


Breast cancer; Histopathological; Immunohistochemical; Animal model; TNBC; BALB/c mice; 4T1; Male

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