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Triple-negative breast cancer: adjuvant therapeutic options.

ABSTRACT: 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.

SUBMITTER: Gucalp A

PROVIDER: S-EPMC3265248 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Triple-negative breast cancer: adjuvant therapeutic options.

Gucalp Ayca A Traina Tiffany A TA

Chemotherapy research and practice 20110621

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 p ...[more]

PMID: 22312556

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Project description:PurposeTriple-negative breast cancer (TNBC) is an aggressive tumor with poor prognosis, it has higher recurrence and metastatic rates than other breast cancer subtypes. This study aims to investigate biomarkers and potential targets for TNBC related to ferroptosis through data mining and bioinformatics analysis. The findings may provide new insights for treating TNBC.MethodsThe TNBC patients' data from the Cancer Genome Atlas (TCGA) database were extracted for differential expression and prognosis analysis. Consensus genes obtained by intersecting differential expressed and ferroptosis-related genes was used to establish the prognostic model by the univariate and multivariate Cox analyses. Besides, TNBC data from the Gene Expression Omnibus (GEO) database was used to confirm the reliability of the prognosis model. Moreover, clinical information was analyzed by multifactorial independent analysis to identify independent prognostic factors. The expression of genes constituting the prognostic model was further validated using the Human Protein Atlas (HPA) database. Finally, the Comparative Toxicogenomic Data (CTD) database was used to explore possible treatment drugs for TNBC.ResultsWe obtained 13,245 differential expressed genes, and 177 consensus genes. 98 genes with prognostic implication were obtained by univariable Cox. Then, a prognostic model including 12 ferroptosis-related genes was constructed by multivariable Cox. The area under curve (AUC) value of the prognostic model for TNBC was 0.82. The GEO database validated that the model (AUC = 0.77) could predict the patient outcomes. The staining results of 10 out of 12 prognostic model genes in HPA database showed that their expression was consistent with our predictions. Clinical risk analysis indicated that risk score of patients could act as an independent prognostic factor. Finally, six drugs that may have interaction with 12 ferroptosis-related genes were obtained using the CTD database.ConclusionThe prognostic model composed of 12 ferroptosis-related genes could predict the prognosis of TNBC patients, and seven genes (ASNS, LAMP2, CAV1, DPP4, HELLS, TF, ZFP69B) could be potential new therapeutic targets for TNBC, and two drugs (1-methyl-3-isobutylxanthine, rosiglitazone) could act as potential therapeutic drugs for the treatment of TNBC.

Project description:ImportanceAdjuvant chemotherapy remains the only recommended treatment for patients with triple-negative breast cancer (TNBC). However, the existing evidence is not enough to recommend adjuvant therapies to patients with T1 N0 M0 TNBC.ObjectiveTo evaluate the association of different adjuvant therapies with survival outcome in patients with T1 N0 M0 TNBC stratified by cancer stage and age.Design, setting, and participantsPostoperative patients diagnosed as having T1 N0 M0 TNBC between 2010 and 2015 who were enrolled in the Surveillance, Epidemiology, and End Results cancer registry program were included in this population-based cohort study. Data analysis was performed from March 27, 2019, to August 10, 2020.ExposuresChemotherapy and radiotherapy.Main outcomes and measuresKaplan-Meier curve and univariate and multivariable Cox proportional hazards regression analyses were performed to compare overall survival (OS) and breast cancer-specific survival (BCSS) between the different treatments.ResultsA cohort of 7739 eligible patients (mean [SD] age, 59.5 [12.4] years; all female) were included in the present study. The 5-year OS of the total patients was 91.7% (95% CI, 90.9%-92.5%), and median follow-up was 45 months (95% CI, 44-46 months). Patients aged 70 years and older or with T1a TNBC were more likely to receive adjuvant radiotherapy than chemotherapy. Although any adjuvant therapy could improve OS in T1 N0 M0 TNBC, only chemotherapy was associated with significantly better breast cancer-specific survival (BCSS adjusted hazard ratio: 0.657; 95% CI, 0.460-0.939; P = .02). Adjuvant radiotherapy after breast-conserving surgery was associated with better OS and BCSS in patients aged 70 years and older but not in those younger than 70 years. For patients with T1c BC, chemotherapy after breast-conserving surgery or other surgery was associated with improved OS, whereas only chemotherapy after other surgery was associated with better BCSS.Conclusions and relevanceThe findings of this cohort study suggest that adjuvant therapies could improve OS in patients with T1 N0 M0 TNBC, whereas only chemotherapy was associated with better BCSS. Older patients with early-stage TNBC may benefit from adjuvant radiotherapy. Administration of adjuvant therapies to patients with different ages and cancer stages should be discussed carefully, which necessitates guidance from updated guidelines.

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Triple-negative breast cancer: adjuvant therapeutic options.

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Triple-negative breast cancer: adjuvant therapeutic options.

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