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Membranous Nectin-4 expression is a risk factor for distant relapse of T1-T2, N0 luminal-A early breast cancer.

ABSTRACT: Nectins are Ca(2+)-independent immunoglobulin-like cell adhesion molecules that compose a family of four members that regulate several cellular activities such as movement, proliferation, survival, differentiation, polarization, and the entry of viruses. Nectin-4 has recently emerged as a metastatis-associated protein in several cancers. Here, we have evaluated the association between the expression of Nectin-4 and the clinical outcome of patients with node-negative, T1/T2 breast cancers.The study group consisted of 197 patients presenting with primary unilateral breast carcinoma (T1/T2), with no evidence of nodal involvement and distant metastases. Nectin-4 protein expression was assessed by immunohistochemistry on tissue microarrays, and the results correlated with the clinical data using Kaplan-Meier curves and multivariate Cox regression analysis. Thirty-four out of 197 tumors (17.3%) exhibited Nectin-4 expression on cell membrane (m-Nectin-4) and 122 out of the 163m-Nectin-4 negative tumors (74.8%) showed high cytoplasmic expression of Nectin-4 (c-Nectin-4(High)). At Kaplan-Meier analysis, m-Nectin-4 positivity was significantly associated with a lower disease-free survival (DFS) and distant relapse-free survival (DRFS) rate in patients with a luminal-A phenotype (P=0.030 and P=0.002, respectively). Multivariate analysis showed that in luminal-A tumors m-Nectin-4 positivity is an independent prognostic factor for DFS (P=0.018) and DRFS (P=0.004), but not for local relapse-free survival (LRFS). On the other hand, c-Nectin-4(High) was significantly associated with higher rates of DFS and LRFS, but not DRFS, in the whole population (P=0.008 and P=0.004, respectively) and in patients with luminal-A tumors (P=0.022 and P=0.018, respectively). In patients with luminal-A tumors, multivariate analysis showed that the prognostic value of c-Nectin-4(Low/Negative) is limited to DFS (P=0.012) and LRFS (P=0.022). We suggest that Nectin-4 represents a prognostic factor and a therapeutic target in luminal-A early stage breast cancer.

SUBMITTER: Lattanzio R

PROVIDER: S-EPMC4183981 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Membranous Nectin-4 expression is a risk factor for distant relapse of T1-T2, N0 luminal-A early breast cancer.

Lattanzio R R Ghasemi R R Brancati F F Sorda R L RL Tinari N N Perracchio L L Iacobelli S S Mottolese M M Natali P G PG Piantelli M M

Oncogenesis 20140901

Nectins are Ca(2+)-independent immunoglobulin-like cell adhesion molecules that compose a family of four members that regulate several cellular activities such as movement, proliferation, survival, differentiation, polarization, and the entry of viruses. Nectin-4 has recently emerged as a metastatis-associated protein in several cancers. Here, we have evaluated the association between the expression of Nectin-4 and the clinical outcome of patients with node-negative, T1/T2 breast cancers.The stu ...[more]

PMID: 25178039

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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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Membranous Nectin-4 expression is a risk factor for distant relapse of T1-T2, N0 luminal-A early breast cancer.

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Membranous Nectin-4 expression is a risk factor for distant relapse of T1-T2, N0 luminal-A early breast cancer.

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