Paclitaxel’s Mechanistic and Clinical Effects on Breast Cancer

Taxol breast cancer

2. Breast Cancer from the View of Prevalence and Intrinsic Subtypes

BC is the most frequent type of cancer among females, as it constitutes 24% of all female malignancies. BC affects nearly two million females worldwide and is responsible for more than 620,000 deaths annually [2]. Factors such as age, frequency of pregnancies, genetic predisposition, ethnic background, and intake of oral contraceptives all contribute to the increased risk of BC in women [17]. Despite the massive progress in the field of screening tools and programs, the incidence and mortality rates are still rising [18].

Importantly, breast malignancy is a heterogeneous disease characterized by enormous variability in phenotypes and genotypes, meaning that no two patients experience the same clinical features [19]. These differences make the process of targeting BC more complicated. BC can be categorized into 3 main types and 5 subtypes characterized by alterations in the expression of specific genes and the presence or absence of surface receptors resulting in the difference in prognosis and therapy approaches for patients [20]. According to signatures, including the immunohistochemical analysis of receptors, the expression profile of human epidermal growth factor receptor 2 (HER2), and the KI67 proliferative index, these subtypes are classified into HER2 positive (HER2+), luminal types, and triple-negative BC (TNBC) [21].

HER2+ BC is the result of the over-expression of the HER2 (ERBB2) gene that encodes a transmembrane glycoprotein receptor p185HER2 [22]. Amplification of HER2 was detected in approximately 15–0% of invasive BC cases. Moreover, a higher frequency of the mutation in HER2 leading to increased expression of the protein was also identified in gastric, esophageal, and other types of cancer [23].

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The prevalence of TNBC as the most aggressive form is 10–20%, with higher abundance in the cohort of young women. This molecular subtype is associated with an advanced stage, higher grade of the tumor, overall worse survival rates of patients associated with cancer recurrence, and development of metastasis [24]. Immunohistochemically, TNBC is characterized by the lack of three receptors: estrogen receptor (ER), progesterone receptor (PR), and HER2. Due to the lack of receptors to target, this type of BC is resistant to available treatments [25,26]. Furthermore, TNBC can be classified into claudin-low, basal-like, and molecular apocrine types as a consequence of alterations in gene signatures and histological features (as referred to in Table 1) [27]. Furthermore, hereditary mutations in tumor suppressor genes BRCA1/2 were detected in 15% of patients with diagnosed TNBC [28]. Additionally, recent evidence suggested an association between genes including BARD1, PALB2, and RAD51D and high risk for TNBC [29].

Luminal BC is characterized by the definite presence of ER and the possibility of the presence of PR. Luminal BC can be classified into luminal A and B according to the HER2 profile and the presence of proliferation genes such as CCNB1, MKI67, and MYBL2, which are generally expressed in luminal B subtype. Moreover, luminal B is characterized by a higher expression of genes connected with growth receptor signaling [30,31,32]. Based on a clinical prediction and patients’ prognosis, luminal A represents molecular subtypes with a better prognosis, low relapse, and higher overall survival rate when compared to luminal B [33].

Importantly, human cancer-derived cell lines, which are specific for each molecular subtype, represent powerful tools to study biological processes in cancer research because they carry specific genetic alterations of tumors they were derived from [34]. Table 1 summarizes BC subtypes associated with specific immunohistochemical signatures and the corresponding cell line used in in vitro experiments.

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