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Early Triple Negative Breast Cancer: Conventional Treatment and Emerging Therapeutic Landscapes.

ABSTRACT: Triple negative breast cancers (TNBCs) are characterized by worse prognosis, higher propensity to earlier metastases, and shorter survival after recurrence compared with other breast cancer subtypes. Anthracycline- and taxane-based chemotherapy is still the mainstay of treatment in early stages, although several escalation approaches have been evaluated to improve survival outcomes. The addition of platinum salts to standard neoadjuvant chemotherapy (NACT) remains controversial due to the lack of clear survival advantage, and the use of adjuvant capecitabine represents a valid treatment option in TNBC patients with residual disease after NACT. Recently, several clinical trials showed promising results through the use of poly ADP-ribose polymerase (PARP) inhibitors and by incorporating immunotherapy with chemotherapy, enriching treatment options beyond conventional cytotoxic agents. In this review, we provided an overview on the current standard of care and a comprehensive update of the recent advances in the management of early stage TNBC and focused on the latest emerging biomarkers and their clinical application to select the best therapeutic strategy in this hard-to-treat population.

SUBMITTER: Diana A

PROVIDER: S-EPMC7225917 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Emerging Therapeutic Drugs in Metastatic Triple-Negative Breast Cancer.

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| S-EPMC7989121 | biostudies-literature

Emerging treatment strategies for metastatic triple-negative breast cancer.

Project description:Triple-negative breast cancer (TNBC) is a heterogeneous subtype of breast cancer that is often associated with an aggressive phenotype and a poor prognosis. Cytotoxic chemotherapy remains the mainstay of treatment for most patients with metastatic TNBC (mTNBC), but duration of response is often short and median overall survival is only 12-18 months. Therefore, it is critical to identify novel treatment strategies to improve outcomes for these patients. In this review article, we discuss recent advances in treatment strategies for patients with mTNBC including the use of immune checkpoint inhibitors, targeted therapies, and antibody-drug conjugates. For each topic, we summarize important preclinical and clinical data, discuss implications for clinical practice, and highlight future research directions.

| S-EPMC9003656 | biostudies-literature

Triple-Negative Breast Cancer: A Review of Conventional and Advanced Therapeutic Strategies.

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| S-EPMC7143295 | biostudies-literature

Molecular Mechanisms and Emerging Therapeutic Targets of Triple-Negative Breast Cancer Metastasis.

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| S-EPMC5827095 | biostudies-literature

Optimal Systemic Treatment for Early Triple-Negative Breast Cancer.

Project description:BackgroundApproximately 10-15% of all breast tumors are triple-negative breast cancer (TNBC). TNBC have a higher risk of relapse and distant metastases compared to other subtypes. The optimal systemic management of TNBC according to national and international guidelines is discussed herein.SummaryAnthracycline/taxane-based chemotherapy for patients with TNBC either in the neoadjuvant (NACT) or the adjuvant setting is considered standard of care. Exceptions are small tumors and a low-risk histology, in which chemotherapy can be spared. Dose-dense therapy is more effective in preventing recurrence and increasing survival. The use of nab-paclitaxel instead of a solvent-based taxane can lead to higher pathological complete response (pCR) rates and better outcomes. Platinum agents are effective in increasing pCR when added to anthracycline/taxane-based chemotherapy at the cost of increased toxicity. Long-term outcome data are lacking. In patients without a pCR, capecitabine leads to improved outcomes.Key messagesThe standard treatment approach of TNBC is anthracycline/taxane-based chemotherapy, preferably within the NACT setting. Dose-dense schedules as well as platinum should be considered in the NACT setting. For patients without a pCR, capecitabine is an option to improve the outcome. The role of nab-paclitaxel is under debate. In case of immunogenic tumors, checkpoint inhibitors are promising new agents that merit further investigation.

| S-EPMC7383279 | biostudies-literature

Update on systemic treatment in early triple negative breast cancer.

Project description:Triple negative breast cancer (TNBC) is a heterogeneous disease representing about 15% of all breast cancers. TNBC are usually high-grade histological tumors, and are generally more aggressive and difficult to treat due to the lack of targeted therapies available, and chemotherapy remains the standard treatment. There is a close relationship between pathological complete response after chemotherapy treatment and higher rates of disease-free survival and overall survival. In this review of systemic treatment in early triple negative breast cancer, our purpose is to analyze and compare different therapies, as well as to highlight the novelties of treatment in this breast cancer subtype.

| S-EPMC7871289 | biostudies-literature

Novel therapeutic strategies in the treatment of triple-negative breast cancer.

Project description:Triple-negative breast cancer (TNBC) is a heterogeneous subtype of breast cancer that is defined by negative estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status. Treating patients with TNBC remains clinically challenging, as patients are not candidates for endocrine or HER2-directed therapy. As a result, chemotherapy with traditional agents such as anthracyclines and taxanes remains the only available option with moderate success. Recent discoveries have revealed that TNBC is a heterogeneous disease at the clinical, histological and molecular levels. The use of biomarkers to identify distinct subsets of TNBC that derive the greatest benefit from presently approved as well as novel therapeutics has become the main focus of current research. The aim of this review is to explore the clinical and biological complexity of TNBC as well as identify novel therapeutic options that target the various molecular subsets of TNBC.

| S-EPMC5502951 | biostudies-literature

Triple-negative breast cancer: adjuvant therapeutic options.

Project description:Triple-negative breast cancer (TNBC), a subtype distinguished by negative immunohistochemical assays for expression of the estrogen and progesterone receptors (ER/PR) and human epidermal growth factor receptor-2(HER2) represents 15% of all breast cancers. Patients with TNBC generally experience a more aggressive clinical course with increased risk of disease progression and poorer overall survival. Furthermore, this subtype accounts for a disproportionate number of disease-related mortality in part due to its aggressive natural history and our lack of effective targeted agents beyond conventional cytotoxic chemotherapy. In this paper, we will review the epidemiology, risk factors, prognosis, and the molecular and clinicopathologic features that distinguish TNBC from other subtypes of breast cancer. In addition, we will examine the available data for the use of cytotoxic chemotherapy in the treatment of TNBC in both the neoadjuvant and adjuvant setting and explore the ongoing development of newer targeted agents.

| S-EPMC3265248 | biostudies-literature

Antisense Oligonucleotide-Based Therapeutic against Menin for Triple-Negative Breast Cancer Treatment.

Project description:The tumor suppressor menin has dual functions, acting either as a tumor suppressor or as an oncogene/oncoprotein, depending on the oncological context. Triple-negative breast cancer (TNBC) is characterized by the lack of expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (ERBB2/HER2) and is often a basal-like breast cancer. TNBC is associated with a dismal prognosis and an insufficient response to chemotherapies. Previously, menin was shown to play a proliferative role in ER-positive breast cancer; however, the functions of menin in TNBC remain unknown. Here, we have demonstrated that menin is expressed in various TNBC subtypes with the strongest expression in the TNBC Hs 578T cells. The depletion of menin by an antisense oligonucleotide (ASO) inhibits cell proliferation, enhances apoptosis in Hs 578T cells, highlighting the oncogenic functions of menin in this TNBC model. ASO-based menin silencing also delays the tumor progression of TNBC xenografts. Analysis of the menin interactome suggests that menin could drive TNBC tumorigenesis through the regulation of MLL/KMT2A-driven transcriptional activity, mRNA 3'-end processing and apoptosis. The study provides a rationale behind the use of ASO-based therapy, targeting menin in monotherapy or in combination with chemo or PARP inhibitors for menin-positive TNBC treatments.

| S-EPMC8301388 | biostudies-literature

Emerging trends in the treatment of triple-negative breast cancer in Canada: a survey.

Project description:Triple-negative breast cancer (TNBC) has a poor prognosis compared to other subtypes and lacks common therapeutic targets, including HER 2 and the estrogen and progesterone receptors. The clinicopathological heterogeneity of the disease and limited treatment options make clinical management particularly challenging. Here we present the results of a survey of Canadian clinical oncologists regarding treatment of TNBC, and review recent and ongoing clinical research in this area. Our survey results show that the majority of respondents use a combination of anthracyclines-taxanes as adjuvant therapy for early TNBC. For the first-line treatment of metastatic TNBC, most clinicians recommend taxanes, while single agent capecitabine and platinum-based therapies are more common for subsequent lines of therapy. Despite the ongoing development of novel targeted therapies, chemotherapy remains the mainstay of treatment for TNBC.

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