• Title, Summary, Keyword: Triple-negative breast neoplasms

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The Epigenetics of Triple-Negative and Basal-Like Breast Cancer: Current Knowledge

  • Temian, Daiana Cosmina;Pop, Laura Ancuta;Irimie, Alexandra Iulia;Berindan-Neagoe, Ioana
    • Journal of Breast Cancer
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    • v.21 no.3
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    • pp.233-243
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    • 2018
  • Breast cancer has the highest incidence among all malignancies diagnosed in women. Therapies have significantly improved over the years due to extensive molecular and clinical research; in a large number of cases, targeted therapies have provided better prognosis. However, one specific subtype remains elusive to targeted therapies - the triple-negative breast cancer. This immunohistochemically defined subtype is resistant to both endocrine and targeted therapies, leading to its poor prognosis. A field that is of great promise in current cancer research is epigenetics. By studying the epigenetic mechanisms underlying tumorigenesis - DNA methylation, histone modifications, and noncoding RNAs - advances in cancer treatment, diagnosis, and prevention are possible. This review aims to synthesize the epigenetic discoveries that have been made related to the triple-negative breast cancer.

Breast Cancer Recurrence According to Molecular Subtype

  • Shim, Hee Jin;Kim, Sung Hun;Kang, Bong Joo;Choi, Byung Gil;Kim, Hyeon Sook;Cha, Eun Suk;Song, Byung Joo
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.14
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    • pp.5539-5544
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    • 2014
  • Background: To evaluate the location of tumor relapse and imaging modality for detection according to the breast cancer subtype: luminal A, luminal B, HER2 positive luminal B, nonluminal HER2 positive, and triple negative. Materials and Methods: A total of 1244 patients with breast cancer with known estrogen receptor (ER), progesterone receptor (PR), Ki-67 and human epidermal growth factor receptor 2 (HER2), who underwent breast surgery from 2009 to 2012 were analyzed. Patients were classified into the following categories: luminal A (n=458), luminal B (n=241), HER2 positive luminal B (n=227), nonluminal HER2 positive (n=145) and triple negative (n=173). A total of 105 cases of relapse were detected in 102 patients: locoregional recurrence (n=46), recurrence in the contralateral breast (n=28) and distant metastasis (n=31). Comparison of proportions was used to determine the difference between subtypes. Results: Relapse rates by subtypes are as follows: luminal A 23 of 458 (5.02%), luminal B 19 of 241(7.88%), HER2 positive luminal B 15 of 227 (6.61%), nonluminal HER2 postive 19 of 145 (13.10%) and triple negative 29 of 173(16.76%). Luminal A tumors had the lowest rate of recurrence and had significantly lower recurrence rate in comparison with nonluminal HER2 postive (p=0.0017) and triple negative subtypes (p<0.0001). Compared with all other subtypes except nonluminal HER2 positive, triple negative tumors had the highest rate of tumor recurrence (p<0.01). Triple negatives were most likely to develop contralateral recurrence against all subtypes (p<0.05). Detection rate of locoregional and contralateral tumor recurrence were 28.3% on mammography (n=17/60). Conclusions: Luminal A tumors are associated with a low risk of recurrence while triple negative lesions have a high risk. In case of triple negative tumors, the contralateral breast has much more recurrence as compared with all other subtype. In terms of detection rates, breast USG was the best modality for detecting tumor recurrence, compared with other modalities (p<0.05). Subtyping of breast tumors using a molecular gene expression panel can identify patients who have increased risk of recurrence and allow prediction of locations of tumor recurrence for each subtype.

Gene Regulatory Network Analysis for Triple-Negative Breast Neoplasms by Using Gene Expression Data

  • Jung, Hee Chan;Kim, Sung Hwan;Lee, Jeong Hoon;Kim, Ju Han;Han, Sung Won
    • Journal of Breast Cancer
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    • v.20 no.3
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    • pp.240-245
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    • 2017
  • Purpose: To better identify the physiology of triple-negative breast neoplasm (TNBN), we analyzed the TNBN gene regulatory network using gene expression data. Methods: We collected TNBN gene expression data from The Cancer Genome Atlas to construct a TNBN gene regulatory network using least absolute shrinkage and selection operator regression. In addition, we constructed a triple-positive breast neoplasm (TPBN) network for comparison. Furthermore, survival analysis based on gene expression levels and differentially expressed gene (DEG) analysis were carried out to support and compare the network analysis results, respectively. Results: The TNBN gene regulatory network, which followed a power-law distribution, had 10,237 vertices and 17,773 edges, with an average vertex-to-vertex distance of 8.6. The genes ZDHHC20 and RAPGEF6 were identified by centrality analysis to be important vertices. However, in the DEG analysis, we could not find meaningful fold changes in ZDHHC20 and RAPGEF6 between the TPBN and TNBN gene expression data. In the multivariate survival analysis, the hazard ratio for ZDHHC20 and RAPGEF6 was 1.677 (1.192-2.357) and 1.676 (1.222-2.299), respectively. Conclusion: Our TNBN gene regulatory network was a scale-free one, which means that the network would be easily destroyed if the hub vertices were attacked. Thus, it is important to identify the hub vertices in the network analysis. In the TNBN gene regulatory network, ZDHHC20 and RAPGEF6 were found to be oncogenes. Further study of these genes could help to reveal a novel method for treating TNBN in the future.

Use of positron emission tomography-computed tomography to predict axillary metastasis in patients with triple-negative breast cancer

  • Youm, Jung Hyun;Chung, Yoona;Yang, You Jung;Han, Sang Ah;Song, Jeong Yoon
    • Korean Journal of Clinical Oncology
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    • v.14 no.2
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    • pp.135-141
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    • 2018
  • Purpose: Axillary lymph node dissection (ALND) and sentinel lymph node biopsy (SLNB) are important for staging of patients with node-positive breast cancer. However, these can be avoided in select micrometastatic diseases, preventing postoperative complications. The present study evaluated the ability of axillary lymph node maximum standardized uptake value (SUVmax) on positron emission tomography-computed tomography (PET-CT) to predict axillary metastasis of breast cancer. Methods: The records of invasive breast cancer patients who underwent pretreatment (surgery and/or chemotherapy) PET-CT between January 2006 and December 2014 were reviewed. ALNs were preoperatively evaluated by PET-CT. Lymph nodes were dissected by SLNB or ALND. SUVmax was measured in both the axillary lymph node and primary tumor. Student t-test and chi-square test were used to analyze sensitivity and specificity. Receiver operating characteristic (ROC) and area under the ROC curve (AUC) analyses were performed. Results: SUV-tumor (SUV-T) and SUV-lymph node (SUV-LN) were significantly higher in the triple-negative breast cancer (TNBC) group than in other groups (SUV-T: 5.99, P<0.01; SUV-LN: 1.29, P=0.014). The sensitivity (0.881) and accuracy (0.804) for initial ALN staging were higher in fine needle aspiration+PET-CT than in other methods. For PET-CT alone, the subtype with the highest sensitivity (0.870) and negative predictive value (0.917) was TNBC. The AUC for SUV-LN was greatest in TNBC (0.797). Conclusion: The characteristics of SUV-T and SUV-LN differed according to immunohistochemistry subtype. Compared to other subtypes, the true positivity of axillary metastasis on PET-CT was highest in TNBC. These findings could help tailor management for therapeutic and diagnostic purposes.

Bilateral Triple-Negative Invasive Breast Cancer with a BRCA2 Mutation, and Glioblastoma: A Case Report and Literature Review

  • Raufi, Ali;Alsharedi, Mohamed;Khelfa, Yousef;Tirona, Maria
    • Journal of Breast Cancer
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    • v.20 no.1
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    • pp.108-111
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    • 2017
  • Breast cancer is the second leading cause of death among women in North America. Glioblastoma is the most common primary malignant central nervous system tumor in adults. The majority of hereditary breast cancers are associated with deleterious mutations in the BRCA1 and BRCA2 genes. Although few case reports have described the incidence of glioblastoma in patients previously diagnosed with breast cancer, any association between BRCA2 mutations and glioblastoma has not been demonstrated to date. Herein, we report a woman who is a carrier of a familial BRCA2 mutation, and was previously diagnosed with triple-negative breast cancer (TNBC) and subsequently with a second primary TNBC and glioblastoma. Further investigation is required to define the possible relationship between these two aggressive malignances and the BRCA2 mutation, which might be critical for the proper management and treatment of this disease.

Mutations of the Epidermal Growth Factor Receptor Gene in Triple-Negative Breast Cancer

  • Kim, Aeri;Jang, Min Hye;Lee, Soo Jung;Bae, Young Kyung
    • Journal of Breast Cancer
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    • v.20 no.2
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    • pp.150-159
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    • 2017
  • Purpose: Epidermal growth factor receptor (EGFR) is considered a potential therapeutic target for anti-EGFR therapy in triple-negative breast cancer (TNBC). However, the frequency of EGFR gene mutation in TNBC is low and varies with ethnicity. This study aimed to investigate the incidence of EGFR gene mutation in TNBC. Methods: EGFR protein expression was evaluated by immunohistochemistry in tissue microarrays of 493 TNBC cases using four different primary antibodies, which included mutation-specific antibodies. For cases with an immunoreactivity level ${\geq}1+$, we performed pyrosequencing analysis for EGFR gene mutation. A case was considered mutation-positive when its mutation frequency minus its limit of detection (LOD) was >10%. Cases with mutation frequency higher than LOD were assessed for EGFR gene mutation status using the Cobas assay and by peptide nucleic acid-mediated polymerase chain reaction (PNA-clamping). Results: Among 493 TNBCs, 148 (30.0%) exhibited staining ${\geq}1$+ for EGFR, including 78 with 1+, 49 with 2+, and 21 with 3+. Positive EGFR expression (${\geq}2+$) was significantly associated with lymphovascular invasion (p=0.010), but not with overall survival (p=0.444) or disease-free survival (p=0.388). None of the 493 TNBCs harbored an EGFR gene mutation. Among 148 cases with an EGFR staining result ${\geq}1+$, five (3.4%) showed mutation frequencies (4.4%-10.9%) higher than LOD (2.6%-4.3%) in exons 19 (L747_P753>Q) or 21 (L858R and L861Q) as determined by pyrosequencing. However, Cobas and PNA-clamping failed to detect the presence of EGFR gene mutation in these five cases. Conclusion: No activating mutation of EGFR gene of clinical significance was observed in 148 TNBC cases using three commercially available methods. Thus, EGFR gene mutation appears to be an extremely rare event in patients with TNBC.

Imaging Surveillance for Survivors of Breast Cancer: Correlation between Cancer Characteristics and Method of Detection

  • Chu, A Jung;Chang, Jung Min;Cho, Nariya;Moon, Woo Kyung
    • Journal of Breast Cancer
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    • v.20 no.2
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    • pp.192-197
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    • 2017
  • Purpose: The aim of our study was to investigate the characteristics of primary and recurrent breast cancers and the correlation between cancer subtypes and detection modes. Methods: Between 2003 and 2013, 147 cases of recurrent breast cancer in 137 women (mean age, $45.30{\pm}10.78years$) were identified via an annual clinical examination using radiological studies among 6,169 patients with a breast cancer history (mean followup period, $13.26{\pm}1.78years$). Clinical, radiological, and pathological findings including immunohistochemistry findings of primary and recurrent cancers were reviewed. The size of the tumor in primary and recurrent cancers, disease-free survival, methods of surgery, and the recurrence detection modalities were analyzed with respect to the breast cancer subtype. Results: Ipsilateral and contralateral in-breast recurrence occurred in 105, 21 had axillary lymph node recurrence, and 21 had chest wall recurrences. The subtypes of the primary cancers were hormone receptor (HR) positive and human epidermal growth factor receptor 2 (HER2) negative (HR+HER2-) in 57, HER2 positive (HER2+) in 39, and triple-negative type in 51, and the recurrent cancers in each subtype showed the same type as the primary cancer in 84.3% of cases. In the in-breast recurrent cancers, the HR+HER2- cancers were most frequently detected using ultra-sonography (15/43) followed by mammography (MG) (11/43). The HER2+ recurrent cancers were most commonly detected using MG (14/31, 45.2%), whereas triple-negative type recurrent cancers most commonly presented as symptomatic masses (15/31) (p=0.028). Conclusion: Most recurrent breast cancers showed the same cancer subtype as the primary tumor, and recurrent breast cancer subtypes correlated with the detection modality. Imaging surveillance of survivors of breast cancer might be more beneficial in cases of HR+HER2- type breast cancer or HER2+ type breast cancer than in cases of triple-negative type breast cancer.

Identification of ERBB pathway-activated cells in triple-negative breast cancer

  • Cho, Soo Young
    • Genomics & Informatics
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    • v.17 no.1
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    • pp.3.1-3.4
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    • 2019
  • Intratumor heterogeneity within a single tumor mass is one of the hallmarks of malignancy and has been reported in various tumor types. The molecular characterization of intratumor heterogeneity in breast cancer is a significant challenge for effective treatment. Using single-cell RNA sequencing (RNA-seq) data from a public resource, an ERBB pathway activated triple-negative cell population was identified. The differential expression of three subtyping marker genes (ERBB2, ESR1, and PGR) was not changed in the bulk RNA-seq data, but the single-cell transcriptomes showed intratumor heterogeneity. This result shows that ERBB signaling is activated using an indirect route and that the molecular subtype is changed on a single-cell level. Our data propose a different view on breast cancer subtypes, clarifying much confusion in this field and contributing to precision medicine.

Impressive effect of cisplatin monotherapy on a patient with heavily pretreated triple-negative breast cancer with poor performance

  • Baek, Dong Won;Park, Ji-Young;Lee, Soo Jung;Chae, Yee Soo
    • Yeungnam University Journal of Medicine
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    • v.37 no.3
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    • pp.230-235
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    • 2020
  • Systemic therapy for metastatic triple-negative breast cancer (TNBC) still remains challenging because there are no targeted agents or endocrine therapies currently available. The present case report documents the successful use of cisplatin monotherapy to manage a heavily pretreated TNBC patient showing poor response to therapy. The patient was a 51-year-old woman who had already undergone several lines of systemic chemotherapy for widespread TNBC. Although the mutation analysis performed on DNA isolated from blood cells and progressed lesion samples confirmed the tumor to be germline BRCA wild-type, cisplatin monotherapy was administered based on the increasing evidence of safety and efficacy of platinum for breast cancer. After three cycles of cisplatin treatment, the patient's metastatic lesions dramatically improved without any major toxicity, and she completed 17 cycles with good response. This case study indicates that patients with heavily pretreated TNBC can potentially achieve a good response to cisplatin monotherapy.

Clinical Features and Survival Analysis of Very Young (Age<35) Breast Cancer Patients

  • Wei, Xue-Qing;Li, Xing;Xin, Xiao-Jie;Tong, Zhong-Sheng;Zhang, Sheng
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.10
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    • pp.5949-5952
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    • 2013
  • Objectives: To compare the clinicalpathological features and prognosis between premenopausal breast cancer patients aged of <35 and ${\geq}35$ years old. Methods: The clinical data and survival status of 1498 cases premenopausal operable breast cancer treated in our hospital from 2002.1 to 2004. 12 were collected, 118 cases were aged <35. They were divided into 4 groups: Luminal A, Luminal B, HER2-positive, Triple-negative. The disease free survival (DFS) and overall survival (OS) were identified. Results: The 5-year DFS and OS rates were significantly lower in age<35 than in $age{\geq}35$ patients. In the Luminal B, HER2-positive, Triple-negative group, the 5-year recurrence risk was higher in age<35 than in $age{\geq}35$ patients, and age<35 patients' 5-year death risk was higher only in Luminal B, Triple-negative group. Regardless of whether lymph node involved, age<35 patients had a bad prognosis in both DFS and OS. Conclusions: Compared with premenopausal age ${\geq}35$ breast cancer, age<35 patients had a worse outcome.