Tackling the Biological Diversity in Early Triple-Negative Breast Cancer.
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ABSTRACT:
SUBMITTER: Oliveira M
PROVIDER: S-EPMC7383273 | biostudies-literature | 2020 Jun
REPOSITORIES: biostudies-literature
Publications
Tackling the Biological Diversity in Early Triple-Negative Breast Cancer.
Oliveira Mafalda M Saura Cristina C
Breast care (Basel, Switzerland) 20200609 3
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Project description: Not available
| S-EPMC10486188 | biostudies-literature
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
Project description: Not available
| S-EPMC10477652 | biostudies-literature
Project description:Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast cancers and is characterized by an aggressive nature and a high rate of recurrence despite neoadjuvant and adjuvant chemotherapy. Although novel agents are constantly being introduced for the treatment of breast cancer, conventional cytotoxic chemotherapy based on anthracyclines and taxanes is the mainstay treatment option for TNBC. Based on CTNeoBC pooled analysis data, the achievement of pathologic CR (pCR) in TNBC is directly linked to improved survival outcomes. Therefore, the treatment paradigm for early TNBC has shifted to neoadjuvant treatment, and the escalation of neoadjuvant chemotherapy to improve the pCR rate and the addition of post-neoadjuvant chemotherapy to control the residual disease have been investigated. In this article, we review the current treatment landscape for early TNBC, from standard cytotoxic chemotherapy to recent data on immune checkpoint inhibitors, capecitabine, and olaparib.
| S-EPMC9962369 | biostudies-literature
Project description:Triple negative breast cancer is the most aggressive kind of breast cancer with high risk of recurrences and poor outcomes. Systemic chemotherapy has significantly improved long term outcomes in early stage patients; however, metastatic recurrences still develop in a significant number of patients. Anthracycline and taxane based chemotherapy regimens are standard of care for early stage patients. Neoadjuvant treatment is preferred due to the ability to assess pathologic responses providing important prognostic information and guidance in adjuvant therapy decisions. Carboplatin addition to the anthracycline and taxane backbone is associated with a significant improvement in pathologic complete response but is associated with more toxicity. Understanding the immune microenvironment of triple negative disease is an exciting field and immune checkpoint inhibitors have shown great promise in further improving response rates in early stage patients. Patients with residual disease after neoadjuvant chemotherapy have a significantly higher risk of recurrence compared to those with complete responses. Adjuvant capecitabine for these high-risk patients have shown significant improvement in long term outcomes and is routinely used in this setting. Given the heterogeneity within triple negative tumors, molecular subtypes with variable genomic makeup and chemo sensitivities have been identified and will likely aid in further clinical developmental therapeutics.
| S-EPMC7446736 | biostudies-literature
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
Project description:Perou's molecular classification defines tumors that neither express hormone receptors nor overexpress HER2 as triple-negative (TN) tumors. These tumors account for approximately 15% of breast cancers. The so-called basaloid tumors are not always synonymous with TN tumors; they differ in the fact that they express different molecular markers, have a higher histologic grade, and have a worse prognosis. Clinically they occur in younger women as interval cancer, and the risk of recurrence is higher within the first 3 years. Distant recurrences in the brain and visceral metastases are more common than in hormone receptor-positive tumors. Therapeutically, despite being highly chemosensitive, their progression-free time is generally short. In terms of chemotherapeutic treatment, anthracyclines and taxanes are useful drugs, and high response rates have been described for the combination of ixabepilone-capecitabine and platinums. The combination with antiangiogenic drugs has also proven useful. A group of new drugs, poly-(ADP-ribose)-polymerase inhibitors, showed favorable results in TN tumors with BRCA mutation. There are currently several ongoing studies with new drugs including epidermal growth factor receptor inhibitors, c-kit inhibitors, Raf/Mek/Map kinase inhibitors and mTOR inhibitors.
| S-EPMC2972557 | biostudies-literature
Project description:The tumour stroma regulates nearly all stages of carcinogenesis. Stromal heterogeneity in human triple-negative breast cancers (TNBCs) remains poorly understood, limiting the development of stromal-targeted therapies. Single cell RNA-sequencing of five TNBCs revealed two cancer-associated fibroblast (CAF) and two perivascular-like (PVL) subpopulations. CAFs clustered into two states, the first with features of myofibroblasts and the second characterised by high expression of growth factors and immunomodulatory molecules. PVL cells clustered into two states consistent with a differentiated and immature phenotype. We showed that these stromal states have distinct morphologies, spatial relationships and functional properties in regulating the extracellular matrix. Using cell-signalling predictions, we provide evidence that stromal-immune crosstalk acts via a diverse array of immunoregulatory molecules. Importantly, the investigation of gene signatures from inflammatory-CAFs and differentiated-PVL cells in independent TNBC patient cohorts revealed strong associations with cytotoxic T-cell dysfunction and exclusion, respectively. Such insights present promising candidates to further investigate for new therapeutic strategies in the treatment of TNBCs.
| S-SCDT-EMBOJ-2019-104063 | biostudies-other
Project description:Triple negative breast cancer is treated primarily with chemotherapy, even before surgery (neoadjuvant chemotherapy or NAC). The prognosis and need for adjuvant therapy depends greatly on the tumor response assessed by pathology (pCR). Highly sensitive and specific ctDNA assays have been shown to be of prognostic value in the metastatic setting but not yet in earlier settings. To evaluate the value of ctDNA to predict response to NAC and prognosis we analyzed 149 plasma samples from 26 patients with TNBC. Our results show that ctDNA detection after NAC prior to surgery is strongly predictive of disease-free survival and overall survival and is comparable to RCB as a prognostic factor in our cohort.
| PRJEB32259 | ENA
Project description:PurposeCompare overall survival (OS) and breast cancer-specific survival (BCSS) outcomes of breast conservative therapy (BCT) and mastectomy in a large cohort of patients with early-stage triple negative breast cancer (TNBC), using a propensity score-based matching approach.MethodsSurveillance, Epidemiology, and End Results (SEER) database was used to study the role of RT in early stage TNBC. Primary end points were OS and BCSS. Cox proportional hazard regression models and Kaplan-Meier plots were used to generate the desired outcomes. Propensity score matching was done to minimize bias.Results12,761 patients with T1-2N0M0 TNBC as their first malignancy were retrieved. Of these 7237 had lumpectomy with RT, and 5524 had mastectomy only. Age, race, marital status, tumor laterality, grade and stage, and receipt of chemotherapy were prognostic variables for OS and BCSS. Among 4848 matched subjects, the 5-year OS was significantly higher in patients with lumpectomy and RT (89%) compared to mastectomy alone (84.5%) (p-value <0.001). Similarly, BCSS was significantly higher in patients with lumpectomy and RT (93%) compared to mastectomy alone (91%) (p-value <0.001). On subgroup analysis, patients who are younger than 40 had similar survival outcomes after either mastectomy alone or lumpectomy with RT. However, those who are older than 60, have any grade or T stage had better survival outcomes with lumpectomy and RT.ConclusionsOverall, lumpectomy followed by RT is associated with better OS and BCSS compared to mastectomy in T1-2N0M0 TNBC patients. Further research is needed to determine the optimal treatment strategy for specific patient subgroups.
| S-EPMC8859006 | biostudies-literature