**5. The molecular histopathology classification of breast cancer**

In the era of modern medicine, it is not enough to predict the actual behavior of breast tumor pathophysiology based on morphological classification and clinicopathological parameters alone [19]. Many studies have therefore focused on analyzing the molecular patterns of breast cancer to classify these tumors into classes or entities to aid clinical management. According to Perou et al. (2003), breast cancer is molecularly classified based on similarity of gene expression profiles. Based on extensive studies of gene expression profiles, four clinically relevant molecular subtypes have been identified, including Luminal A, Luminal B, enriched HER2 (HER2+), and Triple Negative (TN). The gene clusters primarily responsible for segregating the molecular subtypes of breast cancer are estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and cell growth regulator (Ki-67). An immunohistochemistry (IHC) panel using these four biomarkers (ER/PR/HER2/Ki-67) was considered efficient and important in stratifying these molecular entities (**Table 1**).

The use of molecular subtyping enables the possibility of stratifying the neoplasm in different entities that may require specific treatments and different monitoring strategies, in addition to a better understanding of the pathophysiological pattern and clinical prognosis.

#### **6. Conclusion**

A series of morphological changes have been observed in the mammary glands of DMBA-estrogen-treated rats. These changes are taken to be representative of the multi-step process that occurs on the development of mammary cancer. Our study also confirmed that many types of mammary gland lesions that occurred in rats

induced by DMBA and estrogen combination are similar to lesions in human breast cancer, and being adapted also for histopathological classification. Analysis of histopathology and molecular histopathology classification has a high potential implication for diagnosis, prognosis, and drug targets, and predict the therapeutic response.
