**1. Introduction**

Mammary cancer is one of the most common malignancies neoplasms and the leading cause of mortality that affects female dogs and cats worldwide. It is similar to human breast cancer as cancer initially arises from the mammary gland. In humans, it is commonly known as breast cancer since the anatomical location which is at the breast [1]. There are approximately 54,000 and 207,000 new cases of *in situ* and invasive breast carcinoma in humans [2]. Breast cancer

also represents the highest cancer mortality rates in women across the globe [3]. Mammary cancer can also occur in animals, including companion animals such as female dogs over six years of age. The incidence of mammary tumors in dogs is around 46.79%, while other tumors are about 53.21% [4]. In animals, female dogs and cats have a high prevalence of mammary cancer, which account for 52% and 17%, respectively [1].

Many factors like molecular and cellular pathways are believed to be involved in mammary gland development and carcinogenesis [5, 6]. Factors that can cause breast/mammary cancer include the loss of tumor suppressors, the presence of abnormal estrogenic activity, and the presence of carcinogens or cancer-causing agents that can cause genetic mutations [7]. Mammary cancers that arise in animals are similar to human breast cancers in clinical, histopathological, and molecular features. For this reason, studies on animal models of mammary cancer are highly relevant to correlate prognosis and therapeutic value prior to inclusion in clinical trials [1]. Genetic mutagens from cancer-causing carcinogens or exposure to radiation have led researchers to develop breast cancer in animal models containing carcinogens. Recently, the prevention of breast cancer has received much attention. Several of the established experimental animal models of mammary cancer offer a wide range of options for studying environmental and genetic factors and therapeutics associated with breast cancer. Using a chemical-induced rat mammary cancer model, it can be concluded that the histopathological changes in rat mammary cancer are similar to those in humans [8].

One substance that is known to be carcinogenic is 7,12-dimethylbenz(α) anthracene (DMBA), which is mutagenic, teratogenic, carcinogenic, cytotoxic, and immunosuppressive. DMBA is a synthetic polycyclic aromatic hydrocarbon. Researchers have concluded that DMBA is a potential carcinogen and may act on multiple sites, including the skin [9], mammary glands [10], oral cavity [11], and pancreas [12]. The risk of developing mammary cancer may also be influenced by the role of estrogen. Estrogen is a potent stimulator of mammary epithelial cell proliferation. The most potent and abundant estrogen in the body is 17β-estradiol (E2) [13]. Cancer cells can transform, proliferate, and metastasize, thus altering the histopathological appearance of the cells. Studies have shown that breast/mammary cancer development is a multi-step process that progresses from normal to generalized hyperplasia, atypical hyperplasia, carcinoma *in situ*, and finally the invasive stage of cancer. Continuing advances in understanding the molecular pathology of breast cancer progression have contributed to the discovery of new pathwayspecific targeted therapies, and with the advent of such potent therapeutics, now molecular-based "patient-specific" is an increasing need for treatment plans. Insights gained from studying the molecular pathology of mammary cancer progression in animal models, and the integration and translation of these insights into the clinical setting, have the potential to further reduce breast/mammary cancer morbidity and mortality.

In this chapter, we describe the histopathological alterations in a Sprague–Dawley (SD) rats mammary cancer model induced by the combination of 7,12-dimethylbenz (a) anthracene (DMBA) and estrogen and molecular histopathology pattern of some protein markers of mammary carcinogenesis. This chapter also describes the theoretical classification of breast cancer based on histopathology and molecular histopathology. Understanding correlations between animal mammary cancer and human breast cancer can contribute to further investigation for treatment and prevention. Similar

#### *Molecular Histopathology of Mammary Carcinogenesis as Approach to Cancer Prediction… DOI: http://dx.doi.org/10.5772/intechopen.110840*

to the structure of human breast cancer, the rat mammary gland is also known to have a terminal duct-lobular unit (TDLU). The animal model mammary cancer induced by DMBA closely resembles human breast cancer originating from TDLU, and the histopathological changes and premalignant to malignant progression are similar to those of human breast cancer [8]. Therefore, DMBA-induced mammary cancer in rats is a valuable tool for investigating the mechanisms of pathogenesis and development of human breast cancer and its prevention.
