The Role of Estrogen in Breast Carcinogenesis in Dogs

A major factor in favor of sterilization and neutering animals, the role of estrogen in breast cancer in animals is detailed in a new study. Estrogen is a known and major driver of breast carcinogenesis in women and dogs. The risk of breast cancer is directly correlated with the duration of breast tissue exposure to this hormone. Thus, women and dogs with breast cancer have higher serum estrogen levels. Estrogen initiates and drives breast cancer, among other mechanisms, via the nuclear estrogen receptor in breast epithelial cells. By binding to this receptor and entering the cells, estrogen alters the transcription of estrogen-sensitive genes. This phenomenon increases the expression of cell proliferation regulators and decreases the activity of anti-proliferative and pro-apoptotic genes. Cell division increases. Continuous tissue growth is observed, which further promotes the occurrence of deleterious spontaneous mutations. While in women, due to their short menstrual cycle, fluctuations in serum estrogen levels are too variable to provide reliable information on carcinogenic potential, the study in dogs could be informative. Indeed, their estrous cycle is generally biennial, with relatively short proestrus and estrus phases (1 to 3 weeks). Fluctuations in serum estrogen levels are therefore less pronounced, more stable, and thus more informative regarding the animal’s condition. A new study shows that serum estrogen levels in dogs with mammary carcinomas can provide clarity and new insights into tumor biology . The researchers investigated the associations and relationships between hormonal factors (serum estrogen, estrogen receptors, and ovariohysterectomy) and other clinical and histological prognostic factors to identify their impact in dogs with mammary carcinomas. Thus, high serum estrogen levels and the presence of estrogen receptors on the tumor are associated with a longer time to metastasis only in dogs that have undergone sterilization. Elevated serum estrogen levels are also associated with improved survival in dogs subjected to sterilization and with estrogen receptors on their tumors. However, the effect of sterilization is reversed in dogs without estrogen receptors on their tumors. Furthermore, intact dogs with high serum estrogen levels but no estrogen receptors on their tumors have a significantly longer time to metastasis. The results highlight the dual effect of estrogen in cancer . Estrogen can act as a carcinogen in mammary tumors with estrogen receptors, but conversely can have a protective effect when the receptors are absent. The researchers also identified an important phenomenon. Low serum estrogen levels are associated with an increased risk of developing non-mammary tumors in the postoperative period. This would explain the increased incidence of certain non-mammary tumors in dogs subjected to sterilization at an early age. It is therefore important to better characterize tumors to ensure more effective treatment and a better prognosis for dogs with mammary carcinogenesis.