Abstract
Breast cancer is the most commonly occurring cancer in women. There were over two-million new cases in world in 2018. It is the second leading cause of death from cancer in western countries. At the molecular level, breast cancer is a heterogeneous disease, which is characterized by high genomic instability evidenced by somatic gene mutations, copy number alterations, and chromosome structural rearrangements. The genomic instability is caused by defects in DNA damage repair, transcription, DNA replication, telomere maintenance and mitotic chromosome segregation. According to molecular features, breast cancers are subdivided in subtypes, according to activation of hormone receptors (estrogen receptor and progesterone receptor), of human epidermal growth factors receptor 2 (HER2), and or BRCA mutations. In-depth analyses of the molecular features of primary and metastatic breast cancer have shown the great heterogeneity of genetic alterations and their clonal evolution during disease development. These studies have contributed to identify a repertoire of numerous disease-causing genes that are altered through different mutational processes. While early-stage breast cancer is a curable disease in about 70% of patients, advanced breast cancer is largely incurable. However, molecular studies have contributed to develop new therapeutic approaches targeting HER2, CDK4/6, PI3K, or involving poly(ADP-ribose) polymerase inhibitors for BRCA mutation carriers and immunotherapy.
Highlights
Breast cancer is a dramatically important health problem and it is one of the main causes of women death
The loss of ErbB2 in mammary epithelium delays ductal elongation and disorganizes terminal end buds of the mammary gland; in contrast, loss of ErbB3, whose expression is highest in luminal mammary cells and lowest in basal stem cells, impaired AKT and mitogen-activated protein kinase (MAPK) kinase signaling in luminal cells, with the consequent loss of luminal cell proliferation and survival: interestingly, the loss of ErbB3 concomitantly induced an expansion of basal cells, suggesting that the normal function of this receptor tyrosine kinase is required for maintaining the balance between luminal and basal breast epithelium [21]
Micropapillary carcinomas (MPCs) are a group of breast carcinomas, which are characterized by a unique histological pattern that consists of clusters of tumor cells with an inverted polarity, immersed in a spongy stroma; these tumors represent about 5–7% of all invasive breast cancers
Summary
Breast cancer is a dramatically important health problem and it is one of the main causes of women death. In these countries, more than 400,000 women in 2010 [1]. These numbers indicate that there is an absolute need to improve our understanding of the cellular and molecular basis of this tumor, to improve its prevention and therapy. Breast cancer rates in USA began to decrease in the year 2000, probably in relation with the reduced use of hormone replacement therapy by women [2]. It was estimated that one in eight USA women will display invasive breast cancer over the course of their lifetime [2,3]. Considerable progresses have been made over the past 50 years in the evaluation and treatment of patients with breast cancer, leading to a nearly 40% decrease in mortality of this disease (due to prevention strategies and the improvement of medical treatment) [2]
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