Hormonal Homologies between Canine Mammary Cancer and Human Breast Cancer in a Series of Cases

Simple Summary There is worldwide interest in understanding the cancerous diseases that are causing increasing deaths in humans. In recent years, interest has grown in finding suitable models of different types of cancer in animals to lead the scientific community to a better understanding of the disease, in order to win the battle against cancer. The aim of this investigation was to compare breast cancer samples and canine mammary tumors from a hormonal point of view to validate the canine species as a model to study human breast cancer. There was a close similarity between premenopausal human breast cancer and canine mammary cancer in terms of hormonal receptors. In both species, all hormones assayed were increased in tumors compared to normal mammary gland samples. This research not only further supports canine mammary cancer as a spontaneous model for the study of human breast cancer but is also important in providing a deeper understanding of the hormonal pathogenesis of breast/mammary cancer in each independent species. The validity of spontaneous canine mammary cancer (CMC) as a natural model for the study of human breast cancer (HBC) from a hormonal point of view has never been thoroughly investigated. In this study, we analyzed the immunohistochemical expression of aromatase (Arom) and steroid receptors [estrogen receptor alpha (ER alpha), estrogen receptor beta (ER beta), progesterone receptor (PR) and androgen receptor (AR)] and intratumor steroid hormone levels of 17 beta-estradiol (E2), estrone sulfate (SO4E1), progesterone (P4), androstenedione (A4), dehydroepiandrosterone (DHEA), and testosterone (T) in 78 samples of mammary cancer-51 human breast cancer (HBC) and 27 canine mammary cancer (CMC)-and corresponding controls. Frequency of tumors expressing Arom, ER beta, PR, and AR was similar in both species, whereas ER alpha+ tumors were less frequent in the canine species. There was a closer similarity between premenopausal HBC and CMC. In HBC and CMC, all hormones assayed were increased in tumors compared to control samples. Intratumor androgen levels were similar in the two species, although levels of progesterone and estrogens were higher in the HBC samples than the CMC samples. Statistical associations among Arom, receptors, and hormones analyzed suggest that the major hormonal influence in both species is estrogenic through the ER, being the alpha isoform predominant in the human samples. Our findings further support CMC as a spontaneous model for the study of HBC, especially premenopausal HBC, although several differences, such as the more prevalent ER alpha immunoexpression and higher intratumor levels of estrogens and P4 in HBC, should be taken into account in comparative hormonal studies.