scholarly journals Correlation of DCE-MRI Perfusion Parameters and Molecular Biology of Breast Infiltrating Ductal Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Li Liu ◽  
Nan Mei ◽  
Bo Yin ◽  
Weijun Peng
Keyword(s):  
Triple Negative ◽  
Ductal Carcinoma ◽  
Growth Factor Receptor ◽  
Luminal A ◽  
Ki 67 ◽  
Dce Mri ◽  
Infiltrating Ductal Carcinoma ◽  
Breast Infiltrating Ductal Carcinoma ◽  
Her 2 ◽  
Epidermal Growth

ObjectiveWe aimed to investigate the correlation of the perfusion parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with the molecular biological expression of breast infiltrating ductal carcinoma (IDC) in order to guide appropriate therapeutic advice and clinical outcome prediction.Materials and MethodsIn a prospective analysis of 67 patients with breast IDC, preoperative DCE-MRI and routine MRI images were obtained. The double-chamber model (extended Tofts model) was employed to calculate the perfusion parameters. Postoperative pathological immunohistochemistry was examined, including human epidermal growth factor receptor 2 (HER-2), estrogen receptor (ER), progesterone receptor (PR), cell nuclear-associated antigen (Ki-67), cytokeratin 5/6 (CK5/6), and epidermal growth factor receptor (EGFR). Statistical analysis was applied to explore the relationship between the perfusion parameters and the molecular biomarkers of breast cancer.ResultsA total of 67 lesions were included in our study. The mean maximum diameter of lesions was 4.48 ± 1.73 cm. Perfusion parameters had no correlation with tumor diameters (p > 0.05). The volume transfer constant (Ktrans) and the rate constant (kep) had positive correlations with Ki-67 (p < 0.05). The plasma volume ratio (vp) had a statistical difference between CK5/6 positivity and CK5/6 negativity. The maximum rising slope (MAX Slope) was higher in HER-2-enriched tumors than that in luminal A or B tumors (p < 0.05). kep was higher in HER-2-enriched tumors than that in luminal A tumors (p < 0.05). The extravascular extracellular space volume fraction (ve) was higher in triple-negative tumors than that in HER-2-enriched and in luminal A and B tumors (p < 0.05). The time to peak enhancement (TTP) was lower in HER-2-enriched tumors than that in luminal A and B tumors (p < 0.05). Maximum concentration (MAX Conc) was higher in triple-negative tumors than that in luminal B tumors (p < 0.05).ConclusionDCE-MRI perfusion parameters can behave as a noninvasive tool to assess the molecular biological expression and the molecular subtypes of breast IDC. They may aid in predicting breast IDC invasiveness, metastasis, and prognosis.

scholarly journals Immunohistoochemical evaluation of GATA-3, pAKT and Ki-67 in triple negative breast carcinoma

2017 ◽  
Vol 7 (2) ◽  
pp. 1196-1201
Author(s):  
Gopi Aryal ◽  
Sameer Chhetri Aryal ◽  
Yurie Soejima ◽  
Victoria Sheckler ◽  
Yoshinobu Eishi ◽  
...  
Keyword(s):  
Triple Negative ◽  
Ductal Carcinoma ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Breast Carcinomas ◽  
Ki 67 ◽  
Triple Negative Breast Carcinoma ◽  
Epidermal Growth ◽  
Japanese Guidelines

Background: Triple-negative breast cancers lack expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor -2. These tumors have been known to be clinically aggressive. We evaluate GATA-3, pAKT and Ki-67 expression in 35 triple negative breast carcinomas.Materials and Methods: A total of 35 triple negative breast carcinomas were included in this study. The histological subtyping was done according to Japanese guidelines for breast cancer.Results: GATA-3 was positive in 60% (21/35) of tumors. High GATA-3 expression was observed in ductal carcinoma in situ.  pAKT expression was demonstrated in 85.7 % (30/35) of TNBCs. The levels of expression of GATA-3 and pAKT showed no significant association with nuclear grading. (P=0.761 and P=0.487, respectively). Ki-67 labeling index was positively correlated with nuclear grading (p<0.001).Conclusion: GATA-3 expression has no relation with ER and PR expression and pAKT and GATA-3 are strongly expressed in TNBCs. 

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 Apparent diffusion coefficient cannot predict molecular subtype and lymph node metastases in invasive breast cancer: a multicenter analysis

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Alexey Surov ◽  
Yun-Woo Chang ◽  
Lihua Li ◽  
Laura Martincich ◽  
Savannah C. Partridge ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Diffusion Coefficient ◽  
Triple Negative ◽  
Molecular Subtype ◽  
Luminal A ◽  
Ki 67 ◽  
Luminal B ◽  
Apparent Diffusion ◽  
Adc Values ◽  
Her 2

Abstract Background Radiological imaging plays a central role in the diagnosis of breast cancer (BC). Some studies suggest MRI techniques like diffusion weighted imaging (DWI) may provide further prognostic value by discriminating between tumors with different biologic characteristics including receptor status and molecular subtype. However, there is much contradictory reported data regarding such associations in the literature. The purpose of the present study was to provide evident data regarding relationships between quantitative apparent diffusion coefficient (ADC) values on DWI and pathologic prognostic factors in BC. Methods Data from 5 centers (661 female patients, mean age, 51.4 ± 10.5 years) were acquired. Invasive ductal carcinoma (IDC) was diagnosed in 625 patients (94.6%) and invasive lobular carcinoma in 36 cases (5.4%). Luminal A carcinomas were diagnosed in 177 patients (28.0%), luminal B carcinomas in 279 patients (44.1%), HER 2+ carcinomas in 66 cases (10.4%), and triple negative carcinomas in 111 patients (17.5%). The identified lesions were staged as T1 in 51.3%, T2 in 43.0%, T3 in 4.2%, and as T4 in 1.5% of the cases. N0 was found in 61.3%, N1 in 33.1%, N2 in 2.9%, and N3 in 2.7%. ADC values between different groups were compared using the Mann–Whitney U test and by the Kruskal-Wallis H test. The association between ADC and Ki 67 values was calculated by Spearman’s rank correlation coefficient. Results ADC values of different tumor subtypes overlapped significantly. Luminal B carcinomas had statistically significant lower ADC values compared with luminal A (p = 0.003) and HER 2+ (p = 0.007) lesions. No significant differences of ADC values were observed between luminal A, HER 2+ and triple negative tumors. There were no statistically significant differences of ADC values between different T or N stages of the tumors. Weak statistically significant correlation between ADC and Ki 67 was observed in luminal B carcinoma (r = − 0.130, p = 0.03). In luminal A, HER 2+ and triple negative tumors there were no significant correlations between ADC and Ki 67. Conclusion ADC was not able to discriminate molecular subtypes of BC, and cannot be used as a surrogate marker for disease stage or proliferation activity.

scholarly journals ER, PR, HER2, Ki-67 and CK5 in Early and Late Relapsing Breast Cancer—Reduced CK5 Expression in Metastases

2013 ◽  
Vol 7 ◽  
pp. BCBCR.S10701 ◽  
Author(s):  
Kristiina Joensuu ◽  
Marjut Leidenius ◽  
Mia Kero ◽  
Leif C. Andersson ◽  
Kathryn B. Horwitz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Triple Negative ◽  
Significant Risk ◽  
Growth Factor Receptor ◽  
Primary Therapy ◽  
Breast Cancers ◽  
Luminal A ◽  
Ki 67 ◽  
Luminal B

Breast cancer can recur even decades after the primary therapy. Markers are needed to predict cancer progression and the risk of late recurrence. The estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), proliferation marker Ki-67, and cytokeratin CK5 were studied to find out whether their expression or occurrence in subgroups of breast cancers correlated with the time of recurrence. The expression of HER2, ER, PR, Ki-67, and CK5 was studied by IHC in 72 primary breast cancers and their corresponding recurrent/metastatic lesions. The patients were divided into three groups according to the time of the recurrence/metastasis: before two years, after 5 years, and after 10 years. Based on their IHC profiles, the tumors were divided into surrogates of the genetically defined subgroups of breast cancers and the subtype definitions were as follows: luminal A (ER or PR+HER2–), luminal B (ER or PR+HER2+), HER2 overexpressing (ER–PR–HER2+), triple-negative (ER–PR–HER2–), basal-like (ER–PR–HER2–CK5+), non-classified (ER–PR–HER2–CK5–) and luminobasal (ER or PR+CK5+). In multivariate analysis, tumor size and HER2 positivity were a significant risk of early cancer relapse. The metastases showed a significantly lower CK5 expression. CK5 positivity distinguished triple negative tumors into rapidly and slowly recurring cancers. The IHC subtype ER or PR+HER2– luminal A presented a significantly lower risk of early tumor recurrence. Ki-67 expression denoted early-relapsing tumors and correlated linearly with tumor progression, since Ki-67 positivity declined gradually from early-relapsing toward late-recurring cancers.

scholarly journals A Cocktail of Specific Inhibitors of HER-2, PI3K, and mTOR Radiosensitises Human Breast Cancer Cells

2015 ◽  
Vol 1 (1) ◽  
Author(s):  
Roswita Hamunyela ◽  
Antonio Serafin ◽  
Mogammad Hamid ◽  
Sechaba Maleka ◽  
Daniel Achel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Growth Factor Receptor ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Her 2 ◽  
Epidermal Growth ◽  
Specific Inhibitors

Intrinsic tumour radioresistance limits the benefit of radiotherapy. Targeted treatment modalities that are singly effective for triple-negative breast cancer are lacking, partly due to paucity of relevant targets as they are devoidof the human epidermal growth factor receptor 2 (HER-2), progesterone receptor (PR), and oestrogen receptor (ER); or to resistance to single-target therapies as a consequence of cellular heterogeneity. Concomitant targeting of cell signaling entities other than HER-2, PR and ER may sensitise triple-negative tumours to radiotherapy. In this study, we investigated the effect of an HER-2 inhibitor (TAK-165) and a dual inhibitor of phosphoinositide 3-kinase (PI3K) and mammalian target for rapamycin (mTOR) (NVP-BEZ235) in three human breast cancer cell lines. The potential of simultaneous inhibition of HER-2, PI3K and mTOR with a cocktail of the specific inhibitors TAK-165 and NVP-BEZ235, to radiosensitise human breast cancer cells in vitro was examined using the colony forming assay. Combined inhibition of HER-2, PI3K, and mTOR resulted in significant radiosensitisation in all cell lines, independent of HER-2, ER, or PR status. Radiosensitisation was more prominent in ER- and PR-negative cells expressing higher levels of epidermal growth factor receptor (EGFR). These data suggest that a cocktail of TAK-165 and NVP-BEZ235 could potentially be effective in the treatment of triple-negative breast cancer. 

Phase II study of  a novel neoadjuvant chemotherapy (NAC) for breast cancer (BC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1060-1060
Author(s):  
Miguel E. Albino ◽  
Fernando Cabanillas ◽  
Orestes Antonio Pavia ◽  
Margarita Bruno ◽  
Miguel M. Echenique ◽  
...  
Keyword(s):  
Triple Negative ◽  
Ductal Carcinoma ◽  
Pathologic Response ◽  
Pet Scan ◽  
Ki 67 ◽  
Receptor Status ◽  
Residual Cancer Burden ◽  
Response To Chemotherapy ◽  
Her 2 ◽  
Md Anderson

1060 Background: The goal of this NAC study was to improve the pathologic response of pts with localized BC. Methods: 51 pts with localized BC >1 cm were treated with this novel regimen consisting first of docetaxel 75 mg/m2, epirubicin 80 mg/m2, and cyclophosphamide 500 mg/m2 (TEC) and PEG Filgrastim for 4 cycles. Pretreament PET scan was done and repeated after course 1. Following the 4th course, ER+/HER2- patients received 4 additional TEC cycles if they achieved CR by MRI, or were switched to a non cross-resistant regimen (vinorelbine, bevacizumab, capecitabine) if they had < CR. HER2+ pts were given docetaxel + trastuzumab for 4 additional cycles, or were switched to a different regimen if < PR. MD Anderson residual cancer burden (MDARCB) score was used to measure pathologic response and correlation with several prognostic factors was studied. Results: Median age = 53; 27 were postmenopausal; 42 had invasive ductal carcinoma, 5 invasive lobular; 12 triple negative, 11 HER2+, and 28 ER+ or PR+/HER2-. MDARCB was significantly better in HER-2+ and triple negative tumors (table). ER+ or PR+/Her2- pts had the least favorable MDARCB with none achieving 0 and only 21% attaining MDARCB=1. 59% of pts with > 5% SUV drop attained MDARCB score 0-1 vs 13% with ≤ 5% drop. %Ki-67 correlated well with MDARCB (table). Ki-67 correlated well with receptor status: 85% of Triple Neg or Her2+ pts had Ki-67 >17 vs only 29% of ER+ or PR+/Her2-. Conclusions: a) This novel NAC regimen leads to markedly favorable MDARCB scores in triple negative and Her-2+ cases. b) Several factors may be useful in predicting response to chemotherapy, including receptor status, Ki-67, and PET scan response after 1st chemotherapy course. c) Ki-67 proliferative rate is closely correlated with receptor status. d) Early PET could be used to predict MDARCB. The challenge now is to improve response in ER+ or PR+/Her2- pts. [Table: see text]

Triple Negative Breast Cancer: A Brief Review of its Characteristics and Treatment Options

2012 ◽  
Vol 25 (3) ◽  
pp. 319-323 ◽  
Author(s):  
Carrie L. Griffiths ◽  
Jacqueline L. Olin
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Her 2 ◽  
Epidermal Growth

Triple negative breast cancer (TNBC), an aggressive variant of breast cancer, is characterized by lack of expression of the estrogen (ER) and progesterone receptors (PRs) and the human epidermal growth factor receptor (HER-2) that are commonly observed in other breast cancer subtypes. The TNBC subtype primarily occurs in younger women of African American or Hispanic descent and tumors tend to be high grade and initially responsive to chemotherapy. However, TNBC is characteristically aggressive with high recurrence, metastatic, and mortality rates. Treatment options are limited since the hormonal receptor and HER-2 antagonists typically used for other breast cancers are ineffective. As such, the mainstay of treatment of TNBC is traditional systemic cytotoxic chemotherapy. Potential future therapies for TNBC include targeted molecular strategies including poly (adenosine diphosphate ribose) polymerase (PARP) and epidermal growth factor receptor (EGFR) inhibitors and antiangiogenic agents. Further research aimed at identifying unique genetic characteristics of TNBC may allow development of other targeted molecular chemotherapy treatment options.

scholarly journals Correlation of Ki67 Expression with Hormone Receptors, Human Epidermal Growth Factor Receptor-2 (HER-2) Status, P53 Mutation and Clinicopathological Characteristics in Pathologic Specimens of Breast Cancer Patients

2016 ◽  
Vol 5 (2) ◽  
pp. 90-97
Author(s):  
Seyed Abbas Mirmalek ◽  
Maedeh Ghorbani ◽  
Ala Gholamrezaei Boushehrinejad ◽  
Masoud Salehi ◽  
Seyed Alireza Salimi-Tabatabaee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Lymph Node ◽  
Growth Factor ◽  
Tumor Size ◽  
Growth Factor Receptor ◽  
Breast Cancer Patients ◽  
Ki 67 ◽  
Her 2 ◽  
Epidermal Growth

Background: Breast cancer is the main cause of cancer in women and the second cause of ma­lignancy deaths. Ki-67 is one of the molecular markers used to evaluate cancer prognosis along with other factors such as age, tumor size, lymph node involvement, estrogen receptor (ER), progesterone receptor (PR), P53, human epidermal growth factor receptor-2 (HER-2), histolog­ical and nuclear grades. This study was aimed to evaluate the correlation of KI-67 expression with some biomarkers and clinico-pathological characteristics in breast cancer patients. Mate­rials and Methods: A total of 513 cases (all female) aged 40- 80 years, were randomly selected from patients who were admitted in two centers affiliated with Tehran University of Medical Sciences (Buo-alli and Kasra hospitals) over a 7-year period (2010-2015). Assessment of tumors for HER-2, P53, ER PR, pathological type and histologic grade was performed. Ki-67 labelling index (Ki-67LI) was defined as the percentage of MIB1-positive cells among a total number of 1,000 malignant cells at high-power magnification (×400). Results: Our study showed that age, ER and PR status were negatively correlated with Ki-67LI (P<0.05). Moreover, number of lymph nodes involved, HER-2, P53 and nuclear grades had a positive correlation with Ki-67LI (P<0.05), whereas, tumor size and histological grade showed no significant correlation with Ki-67LI (P =0.195 and P=0.721, respectively). Conclusion: Results of our study and other studies confirm that the expression of Ki-67 is significantly associated with ER, PR, HER-2 and P53 status. On the other hand, Ki-67 relationship with clinical characteristics such as age, tumor size and lymph node metastasis is not completely established and needs further research.[GMJ.2016;5(2):90-97]

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