Advantages of adjuvant chemotherapy for patients with triple-negative breast cancer at Stage II: usefulness of prognostic markers E-cadherin and Ki67

Kashiwagi, Shinichiro; Yashiro, Masakazu; Takashima, Tsutomu; Aomatsu, Naoki; Ikeda, Katsumi; Ogawa, Yoshinari; Ishikawa, Tetsuro; Hirakawa, Kosei

doi:10.1186/bcr3068

Cited by 64 publications

(58 citation statements)

References 47 publications

(48 reference statements)

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“…TNBC has proven to be remarkably heterogeneous with various prognoses stratified by clinical, pathological, genetic factors, and treatment modalities [1]–[5]. For example, stage II TNBC cases treated with adjuvant chemotherapy would have a better prognosis than those receiving no chemotherapy [5].…”

Section: Introductionmentioning

confidence: 99%

A CLDN1-Negative Phenotype Predicts Poor Prognosis in Triple-Negative Breast Cancer

Ding²,

Fan³

et al. 2014

PLoS ONE

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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.

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Section: Introductionmentioning

confidence: 99%

A CLDN1-Negative Phenotype Predicts Poor Prognosis in Triple-Negative Breast Cancer

Ding²,

Fan³

et al. 2014

PLoS ONE

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“…Some publications emphasize that adding chemotherapy to endocrine therapy is a recommended treatment in this population of patients [15]. Different cutoff values of Ki-67 LI have been proposed for the indication of chemotherapy for these patients [9,12,16,17,18]. Owing to the relevance of this factor in recommending the addition of chemotherapy, the reproducibility of Ki-67 LI evaluation is highly important.…”

Section: Introductionmentioning

confidence: 99%

“…The anti-Ki-67 antibody labeling index (LI, percentage of nuclear antigen-positive cells) has been proposed as a prognostic and predictive marker for breast cancer, especially for estrogen receptor (ER)-positive, HER2-negative early breast carcinoma [1,6,7,8]. Different studies have demonstrated that a high Ki-67 LI indicates an increased risk of recurrence [7,9,10], metastasis [7,8,9,11,12,13,14,15] and faster progression of the disease. Some publications emphasize that adding chemotherapy to endocrine therapy is a recommended treatment in this population of patients [15].…”

Section: Introductionmentioning

confidence: 99%

An Intra- and Interobserver Reproducibility Analysis of the Ki-67 Proliferation Marker Assessment on Core Biopsies of Breast Cancer Patients and Its Potential Clinical Implications

Vörös¹,

Csörgő²,

Nyári

2012

Pathobiology

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Objective: The Ki-67 proliferation index has received an important role in treatment tailoring and molecular classification of estrogen receptor-positive breast carcinomas. The aim was to analyze the reproducibility of assessing proliferation on the basis of Ki-67 immunohistochemistry. Methods: Thirty core biopsy samples of breast cancer patients were analyzed after immunostaining with B56, SP6 and MIB-1 monoclonal Ki-67 antibodies. All samples were evaluated twice and independently by 3 pathologists, with each observer performing his daily routine practice. The ratio of Ki-67-positive cells was estimated with 5% accuracy. Correlation was calculated for the results of each investigator for all pairs of antibodies and for the results of each antibody for all pairs of investigators. Ki-67 scores were divided into categories of either 4 quarters or into 3 groups reflecting the St. Gallen consensus recommendations with 15 and 30% as cutoff values. The reproducibility of classifying the tumors into these categories was assessed with ĸ statistics. Results: Altogether, 540 evaluations were made. Good to excellent correlation (Spearman’s and Pearson’s coefficient range 0.74–0.92 and 0.73–0.93, respectively) was noted for the pairwise comparison of antibodies by observer and of observers by antibody. The inter- and intraobserver reproducibility of the Ki-67 score classification into equal quarters (1–25, 26–50, 51–75 and 76–100%) or into 3 categories with cutoffs at 15 and 30% was fair to poor in the middle categories, but moderate to substantial in the low and high ranges. Interobserver differences in practice potentially impacted on less consistent classification. Conclusion: Our results indicate that the three different Ki-67 antibodies tested do not substantially influence the reproducibility of the estimated proliferation rates. Although reproducibility is better in the clinically more relevant distinction of high versus low proliferation, without standardization, the current practice of Ki-67 assessment in many laboratories does not allow proper and consistent therapeutic decision-making.

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“…Ki67 expressed significantly in a higher stage of TN tumors and high lymph node metastasis [36]. They also suggested that the patients having higher expression of ki67 showed a significantly worse overall survival (OS) time.…”

Section: Ki67mentioning

confidence: 97%

Prognostic Biomarkers in Triple Negative Breast Cancer as a Potential Target for Future Drug Discovery

Gupta

Singh

et al. 2017

Asian J Pharm Clin Res

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Breast cancer is the most common malignancy in women globally, in which triple-negative breast cancer (TNBC) is more aggressive with poor prognosis and very less response to targeted hormone based treatment. It is a major cause of deaths among the women with breast cancer because of very few treatment options. The biomarkers could be a product of cancerous cell or molecule generated in response to cancer. It is used to understand the mechanism, prognosis, diagnosis as well as target for design and discovery of new drugs. The purpose of the study is to give a brief review on markers of TNBC.

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Advantages of adjuvant chemotherapy for patients with triple-negative breast cancer at Stage II: usefulness of prognostic markers E-cadherin and Ki67

Cited by 64 publications

References 47 publications

A CLDN1-Negative Phenotype Predicts Poor Prognosis in Triple-Negative Breast Cancer

A CLDN1-Negative Phenotype Predicts Poor Prognosis in Triple-Negative Breast Cancer

An Intra- and Interobserver Reproducibility Analysis of the Ki-67 Proliferation Marker Assessment on Core Biopsies of Breast Cancer Patients and Its Potential Clinical Implications

Prognostic Biomarkers in Triple Negative Breast Cancer as a Potential Target for Future Drug Discovery

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