Triple-Negative Breast Cancers: An Updated Review on Treatment Options

Abstract

grade (severity). Identification of molecular markers such as expression of the estrogen (er) and progesterone receptors (pgr) and the human epidermal growth factor receptor 2 (her2) has offered additional predictive value for the therapeutic assessment of women diagnosed with breast cancer [1][2][3][4] . More recently, gene expression analysis using dna microarray technology has identified additional breast tumour subtypes that were not apparent using traditional histopathologic methods. Based on gene expression profiles, breast cancer can be classified into 5 main groups 5-8 :• Normal breast-like [6][7][8][9] Most breast cancers originate from the inner ("luminal") cells that line the mammary ducts. Luminal A and luminal B tumours are similar in that both are typically er+ or pgr+, or both. However, they are dissimilar in that the A type is usually her2-and the B type is more likely to be her2+ and lymph node-positive.Women with luminal A tumours are often diagnosed at a younger age. They tend to have the best prognosis, with relatively high rates of overall survival and relatively low rates of recurrence. Those with luminal B tumours tend to have a higher tumour grade and a poorer prognosis 10,11 (Table i).Basal-like tumours originate in the outer ("basal") cells that line the mammary ducts. Their incidence has been estimated to be between 13% and 25% 12-14 . These tumours are diagnosed more frequently among younger women and are associated with hereditary BRCA1-related breast cancers. They are often aggressive [15][16][17] and are associated with a prognosis poorer than those for the luminal A, luminal B, and normal breast-like types 11,16 . Metastatically, they seems to disseminate to the axillary nodes and, less frequently, to bone 18 . In a population-based study, basal-like breast cancer was suggested to be more prevalent ABSTRACTMorphologic features of tumour cells have long been validated for the clinical classification of breast cancers and are regularly used as a "gold standard" to ascertain prognostic outcome in patients. Identification of molecular markers such as expression of the receptors for estrogen (er) and progesterone (pgr) and the human epidermal growth factor receptor 2 (her2) has played an important role in determining targets for the development of efficacious drugs for treatment and has also offered additional predictive value for the therapeutic assessment of patients with breast cancer. More recent technical advancements in identifying several cancer-related genes have provided further opportunities to identify specific subtypes of breast cancer. Among the subtypes, tumours with triplenegative cells are identified using specific staining procedures for basal markers such as cytokeratin 5 and 6 and the absence of er, pgr, and her2 expression. Patients with triple-negative breast cancers therefore have the disadvantage of not benefiting from currently available receptor-targeted systemic therapy. Optimal conditions for the therapeutic assessment of women with triple-negative breast tum...

TCPTP Regulates SFK and STAT3 Signaling and Is Lost in Triple-Negative Breast Cancers

“…Breast cancers can be subclassified according to the expression of ER, progesterone receptor (PR), and ErbB2, tumor grade, and transcript profiles (1). Subtypes include (i) luminal A tumors that account for up to 60% of breast cancers and express ER and/or PR but not ErbB2, (ii) luminal B tumors that account for 4% to 19% of breast tumors, express ER or PR, and are highly proliferative and/or express ErbB2, (iii) highly aggressive ErbB2-positive (ErbB2 ϩ ) tumors that are negative for ER and PR (7% to 12% of breast cancers), and (iv) basal-like tumors that account for 14% to 20% of breast cancers and include the so-called "triple-negative" tumors that do not express ErbB2, ER, or PR and are resistant to endocrine-and trastuzumab-based therapies (1).…”

Genome and Transcriptome Sequencing in Prospective Metastatic Triple-Negative Breast Cancer Uncovers Therapeutic Vulnerabilities

“…Although significant progress has been made toward treatment of Luminal A&B (hormone receptor-positive), and HER2-neu-enriched su btypes of breast tumors due to receptor target expression, women diagnosed with TNBC have cancers that lack receptor targets, and therefore therapeutic options are limited (13). Median survival in the approximate 30% of patients with TNBC who develop metastatic disease is 1 year.…”

Role of Nek2 on centrosome duplication and aneuploidy in breast cancer cells

“…Such therapies, which include taxanes, aromatase inhibitors, and trastuzumab (2,3), have significantly improved outcomes for patients with breast cancers of the luminal or HER2 subtypes. Sadly, an effective targeted treatment is still lacking for patients whose tumors are of the highly aggressive triple negative breast cancer (TNBC) subtype (4,5).…”