scholarly journals Are Thyroid Hormone and Tumor Cell Proliferation in Human Breast Cancers Positive for HER2 Associated?

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Iordanis Mourouzis ◽  
Alexandros Tzovaras ◽  
Basil Armonis ◽  
Alexandros Ardavanis ◽  
Maria Skondra ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Thyroid Hormone ◽  
Cancer Patients ◽  
Breast Cancers ◽  
Newly Diagnosed ◽  
Breast Cancer Patients ◽  
Normal Range ◽  
Her2 Breast Cancer ◽  
Er Positive

Objective.This study investigated whether thyroid hormone (TH) levels are correlated to cell proliferation (Ki67), in euthyroid breast cancer patients.Design and Methods.86 newly diagnosed breast cancer patients with estrogen receptor (ER) positive tumors, who referred for surgery, were included in the study.Results.FT3, FT4, and TSH were within normal range. No correlation was seen between Ki67 and FT3 (r=-0.17,P=0.15), FT4 (r=-0.13,P=0.25), or TSH (r=-0.10,P=0.39) in all patients studied. However, subgroup analysis showed that, in HER2(+) patients, a negative correlation existed between FT3 levels and Ki67 (r=-0.60andP=0.004) but not between Ki67 and FT4 (r=0.04andP=0.85) or TSH (r=-0.23andP=0.30). In HER2(−) patients, there was no significant correlation between Ki67 and FT3 (r=-0.06,P=0.67), FT4 (r=-0.15,P=0.26), or TSH (r=-0.09,P=0.49). Phospho-p44/total p44 ERK levels were found to be increased by 2-fold in HER2(+) versus HER2(−) tumors. No difference was detected in phospho-p42/total p42 ERK levels.Conclusions.TH profile is not altered in patients with newly diagnosed breast cancer. However, FT3 levels, even within normal range, are negatively correlated with cell proliferation in HER2(+) breast cancer tumors. This response may be due to the interaction between ERK and TH signaling.

Correlation between triodothyronine levels and cancer cell proliferation in high Ki-67 estrogen receptor-positive breast cancer patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11073-e11073
Author(s):  
Alexandros Tzovaras ◽  
Iordanis Mourouzis ◽  
Nikos Tsapralis ◽  
Grecory Tsoukalas ◽  
Nikolaos Tsoukalas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Thyroid Hormone ◽  
Cancer Patients ◽  
Tumor Size ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Her2 Receptor ◽  
Estrogen Receptor Positive ◽  
Signaling Activation

e11073 Background: Although thyroid hormone is a critical regulator of cell growth, differentiation and survival during development, the relationship between thyroid hormone status and breast cancer has not been adequately explored. Recent findings suggest that T3 administration reduces cancer cell proliferation depending on the type of tumor cell line with aggressive tumors to be more sensitive to thyroid hormone treatment. Thus, the present study investigated the potential relationship between thyroid hormone levels and strong prognostic factors (such as tumor size, nodal status, and Ki67) in estrogen receptor positive (ER+) breast cancer patients. Methods: 86 ER(+) breast cancer patients were studied. Levels of TSH (μΙU/ml), FT3 (pg/ml) and FT4 (ng/ml) were measured in all patients before surgery. After surgical excision of the tumor, samples were taken for histopathological analysis to determine tumor size, an index of cell proliferation Ki67 and HER2 receptor expression. HER2 receptor when amplified, it results in an aggressive subtype of breast cancer. In addition, activation of Akt and ERK signaling was examined in tumor samples by western blotting analysis. Akt signaling activation is linked to cell differentiation, while ERK signaling activation induces cell proliferation and dedifferentiation. Results: See table. HER2(+) breast cancers were found to have 2.0 fold increase in levels of phospho-p44/total p44 ERK and 3.0 fold decrease in levels of phospho-Akt/total Akt as compared to HER2(-) breast cancers. In HER(-) breast cancers no correlation was found between TSH, FT3 or FT4 and tumor size, Ki67 and nodal status. However, in HER(+) breast cancers a strong negative correlation was found only between FT3 levels and Ki67, r = -0.60 and p = 0.004. Conclusions: Levels of FT3 show a negative strong correlation with cell proliferation of HER2(+) aggressive breast cancers. This finding may have important therapeutic implications. [Table: see text]

Clinical relevance of miR-143 expression in ER-positive breast cancer patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12574-e12574
Author(s):  
Yoshihisa Tokumaru ◽  
Masanori Oshi ◽  
Eriko Katsuta ◽  
Nobuhisa Matsuhashi ◽  
Manabu Futamura ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Immune Cells ◽  
High Expression ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Immune Microenvironment ◽  
Anti Cancer ◽  
Tumor Immune Microenvironment ◽  
Er Positive

e12574 Background: MicroRNA-143(miR-143) is a well-known tumor suppressive microRNA in various malignancies, including breast cancer. Recently, the tumor immune microenvironment has been reported to associate with progression of breast cancers. However, the association with the tumor immune microenvironment and miR-143 in breast cancers remains ambiguous. Given these backgrounds, we hypothesized that high expression of miR-143 is associated with favorable effect to the tumor immune microenvironment which leads to better survival of ER positive breast cancer patients. Methods: Two major publicly available breast cancer cohorts were used for this study. A total of 753 patients from The Cancer Genome Atlas (TCGA) and total of 1283 patients from Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) were used. Results: We defined the higher quartile of miR-143 expression levels as high and the remainder as low expression groups. There was no significant difference in patient clinicopathlogical features between two groups. Gene set enrichment analysis (GSEA) revealed that miR-143 high expression tumors enriched Helper T cell type 1 (Th1) related gene sets indicating the upregulation of anti-cancer immune cells. Also, the cell composition of anti-cancer immune cells, such as Th1 and Macrophage M1 were higher with miR-143 high tumors (p < 0.001 and p < 0.01 respectively) in whole group. On the contrary, pro-cancer immune cells such as Th2 and M1 were lower with miR-143 high tumors (p < 0.01 and p < 0.001 respectively) in whole group. Interestingly, among the subtypes, we found that ER positive subgroup followed this trend of high infiltration rate of anti-cancer immune cells and low infiltration rate of pro-cancer immune cells. Furthermore, only ER positive subgroup demonstrated the survival benefit with miR-143 high expression tumors. Conclusions: We demonstrated that high expression of miR-143 in ER breast cancer associate with favorable tumor immune microenvironment, upregulation of the anti-cancer immune cells and suppression of the pro-cancer immune cells, and associate with better survival of the breast cancer patients.

scholarly journals Performing Data Mining to Explain the Correlation between the BIRC5 Gene and Prognosis in Breast Cancer Patients

2020 ◽  
Author(s):  
Hong Dongsheng ◽  
Zhang YanFang ◽  
Ye Ziqi ◽  
Chen Jing ◽  
Lu Xiaoyang
Keyword(s):  
Breast Cancer ◽  
Mrna Expression ◽  
Cancer Patients ◽  
Cancer Cell Line ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Luminal B ◽  
Kaplan Meier ◽  
Er Positive

Abstract Background: Breast cancer is the most commonly malignant cancers in women, and BIRC5 has been found to be overexpressed in a variety of human tumors. Its expression is associated with the prognosis of many cancers. However, whether BIRC5 mRNA could be used as an independent prognostic factor for breast cancer remains inconsistent in previous studies.Methods: Altered BIRC5 expression in normal tissue relative to various tumor tissue and in breast cancer patients with different molecular subtypes, clinical outcomes and chemotherapy responses were examined using the Oncomine, GOBO and Kaplan-Meier plotter datasets.Results: We found that many breast cancers had increased BIRC5 mRNA expression, and GOBO analysis showed that triple-negative cell lines displayed highest BIRC5 mRNA expression levels in the breast cancer cell line panel. Moreover, BIRC5 high mRNA expression was significantly associated with longer relapse-free survival (RFS) in all breast cancer patients. In particular, sub analysis revealed that high mRNA expression of BIRC5 was significantly associated with better survival in ER positive (HR = 2.05, p = 1e-16), but not in ER negative breast cancer (HR = 1.24, p = 0.1), furthermore, the results also demonstrated that BIRC5 high expression was significantly associated with longer RFS in luminal A (HR = 1.51, p = 3.1e-06) and luminal B (HR = 1.28, p = 0.026).Conclusions: In conclusion, BIRC5 is involved in the development and progression of breast cancer and may be a suitable prognostic marker for human breast cancer.

MRI versus breast-specific gamma imaging (BSGI) in the detection of synchronous breast cancer: A prospective head-to-head trial.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 72-72
Author(s):  
L. J. Kirstein ◽  
J. L. Keto ◽  
D. P. Sanchez ◽  
T. Fulop ◽  
I. Cohen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Imaging Study ◽  
Axillary Lymph Nodes ◽  
Axillary Lymph ◽  
Breast Cancers ◽  
Imaging Findings ◽  
Newly Diagnosed ◽  
Breast Cancer Patients ◽  
Significant Difference

72 Background: Literature suggests that MRI identifies additional mammographically and sonographically occult cancers in 8-10% of newly diagnosed breast cancer patients. We have reported comparable sensitivity of BSGI to MRI in the detection of the known index cancer. We sought to prospectively compare BSGI to MRI in the identification of additional occult malignancies in newly diagnosed breast cancer patients. Methods: Patients with newly diagnosed breast cancer from June 1, 2009 through February 4, 2011 were consented for an IRB approved protocol in which they underwent both breast MRI and BSGI. Each imaging study was read by a dedicated breast radiologist, with one reading all MRI, and another reading all BSGI studies. All subsequent biopsies were performed percutaneously under image guidance and reviewed by dedicated pathologists. The identification of additional occult breast cancers by MRI and BSGI was compared. Results: Eighty-five patients underwent both MRI and BSGI. Twenty-one patients elected to undergo mastectomy without further management of imaging findings and were excluded, leaving 64 eligible patients. No additional lesions were found in 22 patients. Twenty-one patients had benign pathology on biopsied imaging findings. Metastatic axillary lymph nodes, satellite lesions or larger extent of disease was identified in 11 patients. Eleven occult breast cancers were identified in 10 patients (15.6%), 6 on MRI alone (9.4%), 3 on BSGI alone (4.7%), and 2 by both modalities (3.1%). There was no significant difference in the identification of occult cancer between MRI and BSGI (chi-square 0.77, p>0.1; Table). Conclusions: BSGI has previously been shown to be as sensitive as MRI for detecting known invasive and in situ breast carcinoma. This study shows that BSGI is equally sensitive to MRI in the detection of synchronous mammographically and sonographically occult cancers in newly diagnosed breast cancer patients. Further research is needed to identify the false positive rates of BSGI and the effect on surgical management in comparison to MRI. [Table: see text]

Our act on fertility preservation for young breast cancer patients in our single institute.

2016 ◽  
Vol 34 (3_suppl) ◽  
pp. 109-109 ◽  
Author(s):  
Yasuyuki Kojima ◽  
Kyoko Tsuchiya ◽  
Chie Nishijima ◽  
Nao Suzuki ◽  
Koichiro Tsugawa
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Fertility Preservation ◽  
Reproductive Age ◽  
Ovarian Tissue Cryopreservation ◽  
Embryo Cryopreservation ◽  
Newly Diagnosed ◽  
Breast Cancer Patients ◽  
Er Positive ◽  
Young Breast Cancer

109 Background: Along with increasing number of newly diagnosed Japanese breast cancer patients, the number of breast cancer survivors in reproductive age is also increasing. Among newly diagnosed Japanese breast cancer patients, 3182(6.6%) are under age 40 in 2011, which was 1610 in 2006. In our institute, we have been cooperating with gynecologists and providing fertility preservation program since 2010. Our aim is to access our team management, clinical impact and outcome of fertility preservation among young breast cancer patients in our institute. Methods: A patient, 1)without distant metastasis, 2)systemic chemotherapy and/or hormonal therapy planned, 3)within reproductive age and 4)willing to preserve fertility, will be referred to oncofertility clinic. Chart review was done retrospectively. Results: Ninety-five patients had consultation to the oncofertility clinic between April 2010 and April 2015. The average age at consultation was 34.1(range 22-44). Almost all patient had invasive cancer; cStage0:4%, cStageI:31%, cStageII:53%, cStageIII:11%. Fifty-five percent had estrogen receptor (ER) positive/HER2 negative, 31% had ER positive/HER2positive, 2% had ER negative/HER2 positive and 12% had ER negative/HER2 negative breast cancer. Forty-five had counseling without any procedure, 22 underwent ovarian tissue cryopreservation, 17 underwent embryo cryopreservation and 8 underwent oocyte cryopreservation. Because observation period is still short, we haven’t had any case that got pregnant or delivered, yet. Conclusions: The number of patient who choose to underwent fertility preservation is increasing. We have actually started facing proposition, when we shall lay aside adjuvant therapy and let them plan to be conceived. Taking risk into account, we are now evaluating the safety of cancer treatment and outcome of each procedure which undergone multidisciplinary deliberate decision-making process.

scholarly journals The impact of COVID-19 pandemic on the rate of newly diagnosed gynecological and breast cancers: a tertiary center perspective

2021 ◽  
Author(s):  
Katharina Knoll ◽  
Elisabeth Reiser ◽  
Katharina Leitner ◽  
Johanna Kögl ◽  
Christoph Ebner ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Gynecological Cancer ◽  
Performance Status ◽  
Tumor Stage ◽  
Breast Cancers ◽  
Newly Diagnosed ◽  
Breast Cancer Patients ◽  
Tertiary Center ◽  
The Impact

Abstract Purpose The aim of the present study was to assess the impact of postponed screening examinations and lockdown measures on gynecological and breast cancer diagnoses throughout the year 2020 in a gynecological oncological center in Austria. Methods Data of 889 patients with either newly diagnosed gynecological or breast cancer between January 2019 and December 2020 were collected. Clinical parameters including symptoms, performance status, comorbidities and referral status were compared in patients, who were newly diagnosed with cancer in the period of the first lockdown from March 2020 to April 2020 and the second lockdown from November 2020 to December 2020 and compared to the same period in 2019. Results Our results showed a strong decline in newly diagnosed cancers during the lockdown periods: −45% in gynecological cancer and -52% in breast cancer compared to the same period in 2019. Compared to the analogue period of 2019, breast cancer patients reported significantly more tumor-associated symptoms (55% vs. 31%, p = 0.013) during and in between (48% vs. 32%, p = 0.022) the lockdowns. During the lockdown, periods in the group of breast cancer patients’ tumor stage varied significantly compared to 2019 (T2–T4; p = 0.047). Conclusion Both lockdowns led to a strong decrease in newly diagnosed gynecological and breast cancers. Treatment delays in potentially curable disease could lead to inferior clinical outcomes, with the risk of missing the optimal treatment window. As the COVID-19 pandemic will be a challenge for some time to come, new strategies in patient care are needed to optimize cancer screening and management during the pandemic.

Cell Proliferation of the Primary Tumor Predicts Ipsilateral Axillary Node Disease in Elderly Breast Cancer Patients

2013 ◽  
Vol 28 (1) ◽  
pp. 24-31
Author(s):  
Rosella Silvestrini ◽  
Gabriele Martelli ◽  
Rosalba Miceli ◽  
Roberto Agresti ◽  
Silvia Veneroni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Tumor Cell ◽  
Cancer Patients ◽  
Cumulative Incidence ◽  
Elderly Women ◽  
Axillary Node ◽  
Tumor Cell Proliferation ◽  
Breast Cancer Patients ◽  
Er Positive

The present study investigated whether tumor markers such as cell proliferation and steroid receptor status, which have been shown to have relevance for important endpoints (relapse-free and overall survival), can also predict axillary disease in elderly patients with breast cancer. We evaluated 351 consecutive elderly women with breast cancer ≥70 years of age with estrogen receptor (ER)-positive tumors with no palpable axillary nodes, for whom information on cell proliferation determined by the 3H-thymidine labeling index (TLI) and progesterone receptor (PgR) was available. Patients underwent quadrantectomy (70.1%) or quadrantectomy plus radiotherapy (29.9%) without axillary node dissection, followed by adjuvant tamoxifen for at least 2 years. Univariable (cumulative incidence curves) and multivariable analyses (Fine and Gray models) were carried out. After a median follow-up of 16 years, ipsilateral axillary relapse was not related to PgR status but was strongly associated with tumor cell proliferation in both small (pT1) and large (pT2-4b) tumors. Axillary relapse cumulative incidence increased from 1% in patients with low-TLI (≤3%), PgR-positive and pT1 tumors to a maximum of 20% in patients with high-TLI, PgR-negative and pT2-4b tumors. Tumor cell proliferation, determined by TLI at primary surgery, is an important predictor of axillary relapse in elderly ER-positive breast cancer patients and could help to identify patients who should undergo axillary surgery.

scholarly journals Loss of progesterone receptor is associated with distinct tyrosine kinase profiles in breast cancer

2020 ◽  
Vol 183 (3) ◽  
pp. 585-598
Author(s):  
Andliena Tahiri ◽  
Xavier Tekpli ◽  
Somisetty V. Satheesh ◽  
Rik DeWijn ◽  
Torben Lüders ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tyrosine Kinase ◽  
Mrna Expression ◽  
Cancer Patients ◽  
Cell Lines ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Sequencing Data ◽  
Chip Sequencing ◽  
Her2 Breast Cancer

Abstract Purpose The aim of this study was to assess protein tyrosine kinase profiles in primary breast cancer samples in correlation with the distinct hormone and growth receptor profiles ER, PR, and HER2. Experimental design Pamchip® microarrays were used to measure the phosphorylation of 144 tyrosine kinase substrates in 29 ER+ breast cancer samples and cell lines MCF7, BT474 and ZR75-1. mRNA expression data from the METABRIC cohort and publicly available PR chip-sequencing data were used for validation purposes, together with RT-PCR. Results In ER+ breast tumors and cell lines, we observed that the loss of PR expression correlated to higher kinase activity in samples and cell lines that were HER2−. A number of kinases, representing mostly proteins within the PI3K/AKT pathway, were identified as responsible for the differential phosphorylation between PR− and PR+ in ER+/HER2− tumors. We used the METABRIC cohort to analyze mRNA expression from 977 ER+/HER2− breast cancers. Twenty four kinase-encoding genes were identified as differentially expressed between PR+ and PR−, dividing ER+/HER2− samples in two distinct clusters with significant differences in survival (p < 0.05). Four kinase genes, LCK, FRK, FGFR4, and MST1R, were identified as potential direct targets of PR. Conclusions Our results suggest that the PR status has a profound effect on tyrosine kinases, especially for FGFR4 and LCK genes, in ER+/HER2− breast cancer patients. The influence of these genes on the PI3K/AKT signaling pathway may potentially lead to novel drug targets for ER+/PR− breast cancer patients.

Low expression of microRNA-195 is a poor prognostic marker for ER-positive breast cancer patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12576-e12576
Author(s):  
Yoshihisa Tokumaru ◽  
Masanori Oshi ◽  
Eriko Katsuta ◽  
Vijayashree Murthy ◽  
Nobuhisa Matsuhashi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cancer Patients ◽  
Breast Cancer Patients ◽  
Poor Survival ◽  
Er Positive ◽  
Small Cohort ◽  
Low Expression ◽  
Positive Breast Cancer

e12576 Background: MicroRNA-195 (miR-195) is a tumor suppressive microRNA in breast cancer; however, its clinical relevance remains debatable because most data is either in vitro or from small cohort studies. In this study, we hypothesized that miR-195 low expressing tumors associate with high proliferative characteristics and poor survival. Methods: We obtained the clinical data and survival information of breast cancer patients from two large publicly available databases and one small cohort; The Cancer Genome Atlas (TCGA),The Molecular Taxonomy of Breast Cancer International Consortium (METARBRIC), and GSE45666. Total of 755, 1287, and 116 patients’ data were obtained from TCGA, METABRIC, and GSE45666 respectively. Survival analysis, Overall survival (OS) and Disease-free survival (DFS) was performed by comparing the high and low expression groups. CYT score, xCell, and other immunological factors were used to evaluate intratumoral immune cell composition. Also, gene set enrichment analysis (GSEA) was performed between miR-195 high and low expression groups. Results: The patients were divided into miR-195 high and low groups by utilizing median cutoff. At first, we confirmed that miR-195 expression was significantly lower in tumors compared to normal breast tissue in TCGA as well as GSE45666. Advanced grades were significantly associated with lower expression of miR-195 in ER positive/HER2 negative (ER+/HER2) subtype with both TCGA and METABRIC cohorts ( p< 0.001 and p< 0.001, respectively). On the contrary this was not consistent with other subtypes, HER2+ and triple negative (TN). Also, Low miR-195 expressing tumors demonstrated higher MKI67 expressions in ER+/HER2- subtype with TCGA ( p< 0.001). This was validated with METABRIC cohort ( p< 0.001). Furthermore, GSEA demonstrated that low miR-195 expressing tumors enriched the gene sets related with cell cycle or cell proliferation, such as MYC signaling, mTOR signaling, E2F signaling, G2M Checkpoint signaling and PI3K_Akt_mTOR signaling, compared with high miR-195 expressing tumors in ER+/HER2-. Conclusions: Low expression of miR-195 was associated with improved OS in ER positive breast cancer patients. Also, low miR-195 expressing tumors were found to associate with advanced grades as well as enriching the genes relating to cell proliferation and cell cycle, which may explain the poor survival of low miR-195 expressing patients in ER positive breast cancer.

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