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Update on triple-negative breast cancer: prognosis and management strategies.

ABSTRACT: Triple negative breast cancer (TNBC) is a heterogeneous disease comprehending different orphan breast cancers simply defined by the absence of ER/PR/HER-2. Approximately 15%-20% of all breast cancers belong to this phenotype that has distinct risk factors, distinct molecular features, and a particular clinical presentation and outcome. All these features will be discussed in this review. The risk of developing TNBC varies with age, race, genetics, breastfeeding patterns, and parity. Some TNBC are very chemo-sensitive and the majority of patients confronted with and treated for TNBC will never relapse. Some (histological) subgroups of TNBC may have good prognosis even in the absence of chemotherapy. Distinct molecular subgroups within TNBC have been defined now as well. In case metastatic relapse occurs, this is usually within 5 years following surgery, and survival following metastatic relapse is shorter compared to other breast cancer subtypes; treatment options are few and responses lack durability. Novel drug targets and new biomarkers are needed to improve breast cancer care for patients presenting with TNBC. Further molecular/biological unraveling of TNBC is needed.

SUBMITTER: Brouckaert O

PROVIDER: S-EPMC3469230 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Update on triple-negative breast cancer: prognosis and management strategies.

Brouckaert Olivier O Wildiers Hans H Floris Giuseppe G Neven Patrick P

International journal of women's health 20120924

Triple negative breast cancer (TNBC) is a heterogeneous disease comprehending different orphan breast cancers simply defined by the absence of ER/PR/HER-2. Approximately 15%-20% of all breast cancers belong to this phenotype that has distinct risk factors, distinct molecular features, and a particular clinical presentation and outcome. All these features will be discussed in this review. The risk of developing TNBC varies with age, race, genetics, breastfeeding patterns, and parity. Some TNBC ar ...[more]

PMID: 23071421

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Project description:IntroductionTriple-negative breast cancer (TNBC) is a heterogeneous disease with no definitive prognostic markers. As a major component of tight junctions, claudins (CLDNs) presumably play an important role in carcinogenesis and progression of breast cancer. This study was aimed at determining the relationship between the expression of CLDNs and the clinical outcomes of TNBCs.Materials and methodsThe surgical specimens of primary breast tumors from a consecutive cohort of 173 TNBC patients were retrospectively collected. The membranous expression of CLDN1, CLDN2, CLDN4, and CLDN7 was measured by immunohistochemistry. Then, the associations between CLDN expression, clinicopathological features, and clinical outcomes were assessed.ResultsPositive CLDN1, CLDN2, CLDN4, and CLDN7 membrane expression was detected in 44.5%, 54.9%, 76.9%, and 73.4% of the cohort specimens, respectively. A lack of CLDN1 expression was related to only lymph node metastasis (P?=?0.014). The rate of CLDN4-positive tumors was significantly increased in tumors of a higher grade (P?=?0.003). Importantly, negative CLDN1 expression was associated with worse relapse-free survival (RFS) in both lymph node positive (LN+) and negative (LN-) cases (both P<0.001). Similarly it was also associated with shorter overall survival (OS)(P?=?0.003 in LN+ cases; P?=?0.018 in LN- cases). In the LN+ subgroup, CLDN2-negative cases had a significantly higher risk of recurrence (P?=?0.008). Multivariate analysis revealed that negative CLDN1 expression was an independent prognostic factor for high risk of both recurrence and death (HR 5.529, 95% CI 2.664-11.475, P<0.001; HR 3.459, 95% CI 1.555-7.696, P?=?0.002). However, neither CLDN4 nor CLDN7 expression was associated with survival.ConclusionIn TNBC, the CLDN1-negative phenotype predicts a high risk of recurrence and death. The absence of CLDN1 expression is strongly suggested to be an independent adverse prognostic factor in this heterogeneous subtype of breast cancer.

Project description:One year into the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic, the 2020 San Antonio Breast Cancer Symposium (SABCS) was another large congress held in a virtual format. Despite these circumstances, clinically relevant data were presented, and this short review focuses on developments in the fields of triple-negative breast cancer (TNBC) and metastatic HER2-positive breast cancer. A quality-of-life (QoL) analysis from IMPassion031 showed that adding atezolizumab to neoadjuvant chemotherapy was not associated with a detrimental effect on QoL, while the burden of treatment-induced side effects increased with each cycle of neoadjuvant therapy in both treatment arms. KEYNOTE-355 evaluated the addition of pembrolizumab to chemotherapy as first-line treatment in metastatic TNBC (mTNBC); a significant improvement of progression-free survival (PFS) was reported in the pembrolizumab arm. At the 2020 SABCS, results with respect to different chemotherapy backbones were reported and the benefit of pembrolizumab was maintained irrespective of the type of taxane. Disappointingly, the phase III IPATunity130 study could not confirm a PFS improvement with the AKT inhibitor ipatasertib when added to paclitaxel as first-line treatment in mTNBC. A biomarker analysis from the phase III ASCENT study showed that the antibody-drug conjugate sacituzumab govitecan was superior to chemotherapy by investigator's choice independent of Trop‑2 expression and BRCA mutation status. In HER2-positive breast cancer, the PRECIOUS trial suggested a small albeit significant benefit with reinduction of pertuzumab in later treatment lines in patients progressing on prior dual HER2-blockade in the first- or second-line setting. The HER2-specific tyrosine kinase inhibitor tucatinib when added to trastuzumab and capecitabine was shown to improve PFS and overall survival (OS) over trastuzumab and capecitabine alone in pretreated patients in the randomized HER2CLIMB trial; this benefit was apparently independent of hormone-receptor expression. An update from the DESTINY-Breast01 trial reported a median PFS of 19.4 months with trastuzumab deruxtecan in heavily pretreated patients. Finally, an analysis from the PERTAIN trial with > 6 years median follow-up showed excellent OS in patients with luminal B/HER2-positive receiving first-line trastuzumab/pertuzumab in combination with endocrine therapy suggesting that chemotherapy-free treatment is an option in highly selected patients.

Project description:: Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancers and is associated with poor long-term outcomes compared with other breast cancer subtypes. Because of the lack of approved targeted therapy, at present chemotherapy remains the mainstay of treatment for early and advanced disease. TNBC is enriched for germline BRCA mutation, providing a foundation for the use of this as a biomarker to identify patients suitable for treatment with DNA-damaging agents. Inherited and acquired defects in homologous recombination DNA repair, a phenotype termed "BRCAness," may be present in a large proportion of TNBC cases, making it an attractive selection and response biomarker for DNA-damaging therapy. Triple-negative breast cancer is a diverse entity for which additional subclassifications are needed. Increasing understanding of biologic heterogeneity of TNBC has provided insight into identifying potentially effective systemic therapies, including cytotoxic and targeted agents. Numerous experimental approaches are under way, and several encouraging drug classes, such as immune checkpoint inhibitors, poly(ADP-ribose) polymerase inhibitors, platinum agents, phosphatidylinositol-3-kinase pathway inhibitors, and androgen receptor inhibitors, are being investigated in TNBC. Molecular biomarker-based patient selection in early-phase trials has the potential to accelerate development of effective therapies for this aggressive breast cancer subtype. TNBC is a complex disease, and it is likely that several different targeted approaches will be needed to make meaningful strides in improving the outcomes.Triple-negative breast cancer (TNBC) is an aggressive subtype that is associated with poor outcomes. This article reviews clinical features and discusses the molecular diversity of this unique subtype. Current treatment paradigms, the role of germline testing, and platinum agents in TNBC are reviewed. Results and observations from pertinent clinical trials with potential implications for patient management are summarized. This article also discusses the clinical development and ongoing clinical trials of novel promising therapeutic agents in TNBC.

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Update on triple-negative breast cancer: prognosis and management strategies.

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Update on triple-negative breast cancer: prognosis and management strategies.

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