scholarly journals Clinical Implications of Androgen-Positive Triple-Negative Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1642
Author(s):  
Maša Brumec ◽  
Monika Sobočan ◽  
Iztok Takač ◽  
Darja Arko
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Histological Grade ◽  
Proliferation Index ◽  
Clinical Implications ◽  
Ki 67 ◽  
Vast Array ◽  
Node Metastasis ◽  
Breast Cancer Subgroup

This review summarizes the recent findings of a vast array of studies conducted on androgen receptor-positive triple-negative breast cancer (AR-positive TNBC) to provide a better understanding of this specific breast cancer subgroup. AR expression is correlated with higher age, lower histological grade, lower proliferation index Ki-67, spiculated masses, and calcifications on mammography. Studies investigating the correlation between AR expression and lymph node metastasis are highly discordant. In addition, results regarding prognosis are highly contradictory. AR antagonists are a promising novel therapeutic approach in AR-positive TNBC. However, AR signaling pathways should be more investigated in order to understand the influence of AR expression on TNBC more thoroughly.

Predictors of Response and Survival Outcomes of Triple Negative Breast Cancer Receiving Neoadjuvant Chemotherapy

Chemotherapy ◽  
2020 ◽  
Vol 65 (3-4) ◽  
pp. 101-109
Author(s):  
Meizhen Zhu ◽  
Yang Yu ◽  
Xiying Shao ◽  
Liang Zhu ◽  
Linbo Wang
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Histological Grade ◽  
Disease Free Survival ◽  
Complete Response ◽  
Survival Outcomes ◽  
Ki 67 ◽  
Pre Treatment

<b><i>Background:</i></b> In triple negative breast cancer (TNBC) patients receiving neoadjuvant chemotherapy (NACT), pre-treatment predictors for pathological complete response (pCR) have been reported; however, those for progressive disease (PD) remain unidentified. <b><i>Methods:</i></b> We investigated pre-treatment clinicopathological predictors associated with pCR and PD by retrospectively reviewing data for 165 patients treated between 2015 and 2018. Patients with pCR and PD were compared to those without pCR and PD, respectively, using logistic regression and Kaplan-Meier methods. <b><i>Results:</i></b> Lack of androgen receptor (AR) was an independent predictor of pCR, while high histological grade, low Ki-67 index, and incomplete NACT courses were independent predictors of PD. Mean disease-free survival and overall survival were significantly poorer in PD patients than in pCR patients (15.7, 21.3 vs. 52.4, 56.3 months). <b><i>Conclusions:</i></b> Insights into the chemo-resistance mechanisms and exploration of novel targeted agents in subgroups as per AR and Ki-67 status are needed to improve survival outcomes in TNBC patients.

Expression and prognostic significance of ECT2 in invasive breast cancer

2017 ◽  
Vol 71 (5) ◽  
pp. 442-445 ◽  
Author(s):  
Hong-kun Wang ◽  
Jian-fang Liang ◽  
Hui-xia Zheng ◽  
Hong Xiao
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Triple Negative ◽  
Prognostic Significance ◽  
High Expression ◽  
Proliferation Index ◽  
Ki 67 ◽  
Node Metastasis

AimsTo investigate the expression of epithelial cell transforming sequence 2 (ECT2) in invasive breast cancer and its prognostic significance.MethodsECT2 immunohistochemical detection was performed in 165 breast cancer specimens and 100 normal control tissues. Univariable and multivariable Cox proportional hazards regression model analysis was used to confirm independent prognostic factors. The PHREG procedure linear hypotheses testing method was used to analyse survival data.ResultsExpression of ECT2 in breast cancer was significantly higher than that of the normal control group (p<0.001), and it was related to tumour grade, the status of lymph node metastasis, TNM staging, recurrence status, menopausal status, and the Ki-67 proliferation index (p<0.05), and not related to age, tumour size, tumour type, expression of estrogen receptor, progesterone receptor and human epidermal growth factor 2, and triple-negative disease (p>0.05). Univariable analysis showed that expression of ECT2, the status of lymph node metastasis, triple-negative disease and Ki-67 proliferation index were related to the overall survival of patients with breast cancer (p<0.001, p=0.006, p=0.001, p=0.041, respectively). PHREG procedure linear hypotheses testing results for overall survival revealed that high expression of ECT2, lymph node metastasis, triple-negative disease and high Ki-67 proliferation index predicted lower overall survival rates. Multivariable Cox regression indicated that high expression of ECT2 and triple-negative disease were independent prognostic factors for patients with breast cancer (p<0.001, p=0.004, respectively).ConclusionsExpression of ECT2 may be one of the main causes of the occurrence and development of breast cancer, and high expression of ECT2 as an independent prognostic factor predicts a poor prognosis. ECT2 could also be a potential molecular target for designing therapeutic strategies for breast cancer.

scholarly journals Correlation of CK5 and EGFR with Clinicopathological Profile of Triple-Negative Breast Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Neelam Sood ◽  
Jitendra Singh Nigam
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Ductal Carcinoma ◽  
Histological Grade ◽  
Positive Association ◽  
Ki 67 ◽  
Significant Positive Association ◽  
Egfr Expression ◽  
Clinicopathological Profile

Purpose. Triple-negative breast cancer (TNBC) is defined by the loss of expression of ER, PR, and Her2neu expressions. The aim of this study was to examine the expression of the EGFR, CK5, and Ki-67 among triple-negative breast cancer cases and to correlate the expression of the basal markers with the clinicopathological prognostic parameters. Materials and Methods. Thirty-six female patients with TNBC based on ER, PR, and the HER2neu negativities were studied by immunohistochemistry for EGFR, CK5, and Ki-67 expression. Statistical analysis was done using the SPSS software version 20. Results. The mean and median ages were 45.18 years and 46.70 years, respectively. Infiltrating ductal carcinoma NOS was the predominant histopathological type (29/36 [80.6%]). The commonest histological grade was grade 2 (17/36 [47.2%]). Tumour necrosis was seen in 16/36 (44.4%) patients. Infiltrative margins were shown in 69.44% (25/36) cases. Ki-67 was positive in 80.56% (29/36) cases, 61.11% (22/36) were CK5-positive, and 86.11% (31/36) were EGFR-positive. The only significant positive association observed was between the CK5 and histological grade (P<0.05). Conclusion. CK5 shows a statistically significantly correlation with TNBC histological grade. The majority of the specimens show EGFR expression. Therefore TNBCs could potentially benefit from EGFR-targeted therapeutic strategies.

Androgen Receptor and Enzymes in Lymph Node Metastasis and Cancer Reoccurrence in Triple-Negative Breast Cancer

2015 ◽  
Vol 30 (2) ◽  
pp. 184-189 ◽  
Author(s):  
Keely May McNamara ◽  
Tomomi Yoda ◽  
Yasuhiro Miki ◽  
Yasuhiro Nakamura ◽  
Takashi Suzuki ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Androgen Receptor ◽  
Lymph Node Metastasis ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Ductal Carcinoma ◽  
University Hospital ◽  
Ki 67 ◽  
Node Metastasis

Background Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen receptor, progesterone receptor and HER2. TNBCs are a diverse subgroup, but one promising marker and therapeutic target of this breast cancer is the androgen receptor (AR). Previously we demonstrated that AR and cognate intracrine pathways are associated with decreased proliferation in invasive ductal carcinoma with their decrease also detected between organ-confined and invasive diseases. Therefore, in this study, we examined the status of AR and androgen-producing enzymes during the process of metastasis to lymph nodes and cancer recurrence. Materials and Methods We studied 2 series of patients with TNBC, one from Kumamoto University Hospital composed of 16 matched cases of primary and locally or distal recurrences and the other from Tohoku University Hospital examining 46 lymph node metastasis from 23 patients. In addition to studying concordance in AR expression, we also examined the interactions between AR and Ki-67 labeling index and AR and site of distal metastasis. Results In both series, AR status was concordant between primary and recurrent/metastatic disease, but coordinated expression of AR and androgenic enzymes was lost during the process. The inverse association between AR and Ki-67, previously reported in invasive ductal carcinoma (IDC), was markedly potentiated in both lymph node and recurrent cancers. In addition, AR expression appeared to have little effect on visceral metastasis but was associated directly with bone metastasis and inversely with brain metastasis. Conclusions The results of our present study demonstrated that AR remained in the majority of metastatic samples from AR-positive primary TNBCs and that AR manipulation could be exploited in the metastatic settings of TNBC.

scholarly journals FOXP3Allelic Variants and Haplotype Structures Are Associated with Aggressive Breast Cancer Subtypes

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Bruna Karina Banin Hirata ◽  
Roberta Losi Guembarovski ◽  
Glauco Akelinghton Freire Vitiello ◽  
Alda Losi Guembarovski ◽  
Karen Brajão de Oliveira ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Histological Grade ◽  
Tnm Staging ◽  
Proliferation Index ◽  
Ki 67 ◽  
Cancer Subtypes ◽  
Luminal B ◽  
Polymerase Chain ◽  
Aggressive Breast Cancer

FOXP3genetic polymorphisms have been associated with cancer development and prognosis. In this context, the present study aimed to evaluate the g.10403A>G (rs2232365) polymorphisms and g.8048A>C (rs3761548), in aggressive breast cancer (BC) subtypes, including, Luminal B HER2+ (LB), HER2-enriched (HER2+), and triple-negative (TN). Polymerase chain reaction followed by enzymatic restriction was performed to genotyping 117 BC samples and 300 controls. A significant association of AA genotype (g.10403A>G) in relation to BC susceptibility (OR = 1.93; 95% CI = 1.01–3.66;p=0.046) was observed. The GG (g.10403A>G) genotype was correlated with higher proliferation index (Ki-67) in HER2+ subtype (τ = 0.47;p=0.019) and advanced TNM staging in TN (τ = 0.23;p=0.032). A correlation of AA genotype (g.8048A>C) with higher Ki-67 (τ = −0.47;p=0.018) and lower histological grade (τ = 0.39;p=0.026) in HER2+ was also found. GA haplotype was correlated with lower histological grade (τ = −0.15;p=0.009) and higher Ki-67 (τ = 0.43;p=0.036) in HER2+ and advanced staging in TN (τ = 0.29;p=0.044). On the other hand, AC haplotype was correlated with lower Ki-67 (τ = −0.54;p=0.005) and staging (τ = −0.29;p=0.027) in HER2+ and TN respectively. Results showed thatFOXP3influence regarding clinical outcome depends greatly on the BC subtype and indicated this transcription factor as a promising marker in aggressive BC subtypes.

scholarly journals Distinct Somatic Alteration Features Identified by Gene Panel Sequencing in Korean Triple-Negative Breast Cancer with High Ki67 Expression

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 416
Author(s):  
Woo Young Sun ◽  
Jina Lee ◽  
Bong Kyun Kim ◽  
Jong Ok Kim ◽  
Joonhong Park
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Hormone Receptor ◽  
Mutation Frequency ◽  
Triple Negative ◽  
Genetic Difference ◽  
Her2 Positive ◽  
Ki 67 ◽  
Hormone Receptor Positive ◽  
Somatic Alteration

This study aimed to clarify the genetic difference between Korean triple-negative breast cancer (TNBC) and other breast cancer (BC) subtypes. TNBC was defined as the absence of hormonal receptors and human epidermal growth factor receptor 2 (HER2) amplification. DNA panel of the Ion Torrent Oncomine Comprehensive Assay (OCA) v3 was performed to identify somatic alteration in 48 specimens. In a total of 102 alterations (37 nonsense, 35 missense, 8 frameshift and 22 amplifications), 30 nucleotide alterations (24 nonsense, 1 missense, and 5 frameshift) were newly identified. The eight most commonly altered genes were PIK3CA, TP53, ERBB2, BRCA2, FANCD2, AKT1, BRCA1, and FANCA. TNBC had significantly lower mutation frequency in PIK3CA (TNBC vs. hormone receptor-positive and HER2-negative BC [HRPBC], p = 0.009), but higher mutation frequency in TP53 (TNBC vs. HRPBC, p = 0.036; TNBC vs. hormone receptor-positive and HER2- positive BC [HHPBC], p = 0.004). TNBC showed frequently higher Ki-67 expression than any positive BC (p = 0.004) due to HRPBC (p < 0.001). TNBC with high Ki-67/unmutated PIK3CA/mutated TP53 appears at a younger age (52.2 ± 7.6 years), compared to other subtypes (63.7 ± 11.0 years). TNBC with high Ki-67/unmutated PIK3CA/mutated TP53 may be related to relatively early onset BCThese findings demonstrate the genomic heterogeneity between TNBC and other BC subtypes and could present a new approach for molecular targeted therapy in TNBC patients.

scholarly journals Low KIBRA Expression Is Associated with Poor Prognosis in Patients with Triple-Negative Breast Cancer

Medicina ◽  
2021 ◽  
Vol 57 (8) ◽  
pp. 837
Author(s):  
So-Woon Kim ◽  
Jinah Chu ◽  
Sung-Im Do ◽  
Kiyong Na
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Poor Prognosis ◽  
Triple Negative ◽  
Histological Grade ◽  
Growth Factor Receptor ◽  
Hippo Signaling ◽  
Luminal A ◽  
Luminal B ◽  
Epidermal Growth

Background and Objectives: Kidney and brain protein (KIBRA) is a protein encoded by the WW and C2 domain containing 1 (WWC1) gene and is involved in the Hippo signaling pathway. Recent studies have revealed the prognostic value of KIBRA expression; however, its role in breast cancer remains unclear. The aim of this study was to examine KIBRA expression in relation to the clinical and pathological characteristics of patients with breast cancer and to disease outcomes. Materials and Methods: We analyzed the expression of KIBRA and its correlation with event-free survival (EFS) outcomes in resected samples from 486 patients with breast cancer. Results: KIBRA expression was significantly different among the molecular subgroups (low KIBRA expression: luminal A, 46.7% versus 50.0%, p = 0.641; luminal B, 32.7% versus 71.7%, p < 0.001; human epidermal growth factor receptor 2 (HER2)-enriched, 64.9% versus 45.5%. p = 0.001; triple-negative, 73.6% versus 43.8%, p < 0.001). Low KIBRA expression was also associated with high nuclear grade (60.4% versus 37.8%, p < 0.001), high histologic grade (58.7% versus 37.0%, p < 0.001), and estrogen receptor (ER) negativity (54.2% versus 23.6%, p < 0.001). Low KIBRA expression was significantly associated with poor EFS (p = 0.041; hazard ratio (HR) 1.658; 95% confidence interval (CI), 1.015–2.709). Low KIBRA expression was an independent indicator of poor prognosis (p = 0.001; HR = 3.952; 95% CI = 1.542–10.133) in triple-negative breast cancer (TNBC). Conclusion: Low KIBRA expression was associated with higher histological grade, ER negativity and poor EFS of breast cancer. In particular, our data highlight KIBRA expression status as a potential prognostic marker for TNBC.

scholarly journals Immunohistochemical analysis of CD155 expression in triple-negative breast cancer patients

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253176
Author(s):  
Katsuhiro Yoshikawa ◽  
Mitsuaki Ishida ◽  
Hirotsugu Yanai ◽  
Koji Tsuta ◽  
Mitsugu Sekimoto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Tumor Cells ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Expression Profiles ◽  
Histological Grade ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Antitumor Immunotherapy

Introduction CD155 is an immune checkpoint protein. Its overexpression is an indicator of poor prognosis in some types of cancer. However, the significance of CD155 expression in patients with triple-negative breast cancer, and the relationship between CD155 and programmed death-ligand 1 (PD-L1) expression, have not yet been analyzed in detail. Methods Using immunohistochemical staining and tissue microarrays, we analyzed the expression profiles of CD155 and PD-L1 in 61 patients with triple-negative breast cancer. Relapse-free survival and overall survival rates were compared according to CD155 expression. The correlation between CD155 expression and clinicopathological factors, including PD-L1 expression (using SP142 and 73–10 assays), was also examined. Results CD155 expression was noted in 25 patients (41.0%) in this cohort. CD155 expression did not correlate with pathological stage, histological grade, Ki-67 labeling index, or stromal tumor-infiltrating lymphocytes. Only PD-L1 expression in tumor cells by SP142 assay significantly correlated with CD155 expression (p = 0.035); however, PD-L1 expression in tumor cells by 73–10 assay did not show a correlation (p = 0.115). Using the 73–10 assay, 59% of patients showed CD155 and/or PD-L1 expression in tumor cells. Moreover, using the SP142 assay, 63.3% of patients showed CD155 and/or PD-L1 expression in immune cells. CD155 expression did not correlate with either relapse-free survival or overall survival (p = 0.485 and 0.843, respectively). Conclusions CD155 may be a novel target for antitumor immunotherapy. The results of this study indicate that CD155 may expand the pool of candidates with triple-negative breast cancer who could benefit from antitumor immunotherapy.

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