The management of early-stage and metastatic triple-negative breast cancer: a review.
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ABSTRACT:
SUBMITTER: Anders CK
PROVIDER: S-EPMC3737488 | biostudies-literature | 2013 Aug
REPOSITORIES: biostudies-literature
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The management of early-stage and metastatic triple-negative breast cancer: a review.
Anders Carey K CK Zagar Timothy M TM Carey Lisa A LA
Hematology/oncology clinics of North America 20130618 4
Triple-negative breast cancer (TNBC), defined as lacking expression of the estrogen receptor, progesterone receptor, and HER2, comprises approximately 15% of incident breast cancers and is over-represented among those with metastatic disease. There are several biologically distinct subtypes within TNBC. Although the incidence of BRCA mutations across all subsets of breast cancer is low, BRCA mutations are more common among those with TNBC and may have therapeutic implications. The general princi ...[more]
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Project description:OBJECTIVES:To characterize the clinical pattern and evaluate real-life practices in the management of patients with triple-negative breast cancer (TNBC) in Thailand. METHODS:In this multicenter, prospective, observational cohort, females (aged ?18 years) with histologically and immunohistochemically confirmed TNBC were enrolled. Patient data was collected at four study visits-an inclusion visit (for enrollment), and three subsequent follow-up visits at 12±1, 24±1, and 36±1 months after completion of first day of any planned chemotherapy. RESULTS:Of the 293 enrolled patients, 262 (89.4%) had early-stage TNBC (Stage I: 46 patients, Stage II: 151 patients, and Stage III: 65 patients) and 31 (10.6%) had metastatic TNBC (mTNBC). Chemotherapy was prescribed to 95.4% of the early-stage patients and to 100.0% of the mTNBC patients; most commonly as anthracycline-based in combination with cyclophosphamide and other agents. Patients' performance status and consensus guidelines were the major factors affecting choice of treatment. In early-stage patients, median disease-free survival (DFS) and overall survival (OS) had not been reached for Stage I and II patients, and were calculated to be 37.0 months and 40.0 months, respectively, in Stage III patients. In mTNBC patients, progression-free survival (PFS) and OS were found to be 10.0 months and 14.0 months, respectively. In Stage III patients, anthracycline-based regimens were found to be associated with increase in DFS (p = 0.0181) and OS (p = 0.0027) compared to non-anthracycline-based regimens. In mTNBC patients, non-taxane-based regimens were associated with an increase in PFS (p = 0.0025). The 3-year survival rates in early-stage and mTNBC patients were 85.0% and 21.0%, respectively. CONCLUSION:Clinical management of TNBC in Thailand follows the general guidelines for treatment of TNBC. However, prognosis and survival outcomes are suboptimal, especially in progressive disease. This study is the first assessment in the existing practices in which the results could pave to way to improve the treatment outcome of TNBC in Thailand.
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Project description:Patients with breast cancer along with metastatic estrogen and progesterone receptor (ER/PR)- and human epidermal growth factor receptor 2 (HER2)-negative tumors are referred to as having metastatic triple-negative breast cancer (mTNBC) disease. Although there have been many new treatment options approved by the Food and Drug Administration for ER/PR-positive and Her2/neu-amplified metastatic breast cancer, relatively few new agents have been approved for patients with mTNBC. There have been several head-to-head chemotherapy trials performed within the metastatic setting, and much of what is applied in clinical practice is extrapolated from chemotherapy trials in the adjuvant setting, with taxanes and anthracyclines incorporated early on in the patient's treatment course. Select synergistic combinations can produce faster and more significant response rates compared with monotherapy and are typically used in the setting of visceral threat or symptomatic disease. Preclinical studies have implicated other possible targets and mechanisms in mTNBC. Ongoing clinical trials are underway assessing new chemotherapeutic strategies and agents, including targeted therapy and immunotherapy. In this review, we evaluate the standard systemic and future treatment options in mTNBC.
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Project description:Personalised approaches to the management of all solid tumours are increasing rapidly, along with wider accessibility for clinicians. Advances in tumour characterisation and targeted therapies have placed triple-negative breast cancers (TNBC) at the forefront of this approach. TNBC is a highly heterogeneous disease with various histopathological features and is driven by distinct molecular alterations. The ability to tailor individualised and effective treatments for each patient is of particular importance in this group due to the high risk of distant recurrence and death. The mainstay of treatment across all subtypes of TNBC has historically been cytotoxic chemotherapy, which is often associated with off-target tissue toxicity and drug resistance. Neoadjuvant chemotherapy is commonly used as it allows close monitoring of early treatment response and provides valuable prognostic information. Patients who achieve a complete pathological response after neoadjuvant chemotherapy are known to have significantly improved long-term outcomes. Conversely, poor responders face a higher risk of relapse and death. The identification of those subgroups that are more likely to benefit from breakthroughs in the personalised approach is a challenge of the current era where several targeted therapies are available. This review presents an overview of contemporary practice, and promising future trends in the management of early TNBC. Platinum chemotherapy, DNA damage response (DDR) inhibitors, immune checkpoint inhibitors, inhibitors of the PI3K-AKT-mTOR, and androgen receptor (AR) pathways are some of the increasingly studied therapies which will be reviewed. We will also discuss the growing evidence for less-developed agents and predictive biomarkers that are likely to contribute to the forthcoming advances in this field. Finally, we will propose a framework for the personalised management of TNBC based upon the integration of clinico-pathological and molecular features to ensure that long-term outcomes are optimised.
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Project description:The advent of immunotherapy, especially immune checkpoint inhibitors (ICIs), has revolutionized antitumor therapy. Programmed cell death receptor 1 (PD-1) and programmed cell death ligand 1 (PD-L1) are among the most promising targets for encouraging the immune system to eliminate cancer cells. PD-1/PD-L1 have made clinical remission for numerous solid tumors, including metastatic triple-negative breast cancer (TNBC). In recent years, integrating PD-1/PD-L1 inhibitors into existing treatments in early-stage TNBC has attracted wide attention. Herein, we summarize the clinical benefit of PD-1/PD-L1 inhibitors plus neoadjuvant chemotherapy, adjuvant chemotherapy, and targeted therapy in early-stage TNBC. Possible immunotherapy biomarkers, immune-related adverse events (irAEs), and the key challenges faced in TNBC anti-PD-1/PD-L1 therapy are also concluded. Numerous studies on immunotherapy are ongoing, and PD-1/PD-L1 inhibitors have demonstrated great clinical prospects in early-stage TNBC. To maximize the efficacy of anti-PD-1/PD-L1 therapy, further research into the challenges which still exist is necessary.
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