scholarly journals A search for modifying genetic factors in CHEK2:c.1100delC breast cancer patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Camilla Wendt ◽  
Taru A. Muranen ◽  
Lotta Mielikäinen ◽  
Jessada Thutkawkorapin ◽  
Carl Blomqvist ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Familial Breast Cancer ◽  
Genetic Modifier ◽  
Familial Risk ◽  
Genetic Modifiers ◽  
Breast Cancer Patients ◽  
Genetic Loci ◽  
Risk Alleles ◽  
Increased Risk ◽  
Significant Difference

AbstractThe risk of breast cancer associated with CHEK2:c.1100delC is 2–threefold but higher in carriers with a family history of breast cancer than without, suggesting that other genetic loci in combination with CHEK2:c.1100delC confer an increased risk in a polygenic model. Part of the excess familial risk has been associated with common low-penetrance variants. This study aimed to identify genetic loci that modify CHEK2:c.1100delC-associated breast cancer risk by searching for candidate risk alleles that are overrepresented in CHEK2:c.1100delC carriers with breast cancer compared with controls. We performed whole-exome sequencing in 28 breast cancer cases with germline CHEK2:c.1100delC, 28 familial breast cancer cases and 70 controls. Candidate alleles were selected for validation in larger cohorts. One recessive synonymous variant, rs16897117, was suggested, but no overrepresentation of homozygous CHEK2:c.1100delC carriers was found in the following validation. Furthermore, 11 non-synonymous candidate alleles were suggested for further testing, but no significant difference in allele frequency could be detected in the validation in CHEK2:c.1100delC cases compared with familial breast cancer, sporadic breast cancer and controls. With this method, we found no support for a CHEK2:c.1100delC-specific genetic modifier. Further studies of CHEK2:c.1100delC genetic modifiers are warranted to improve risk assessment in clinical practice.

Molecular evaluation of HIF-1α gene variation and determination of its frequency, and association with Breast Cancer susceptibility in Saudi Arabia

2020 ◽  
Vol 20 ◽  
Author(s):  
Rashid Mir ◽  
Faisel M. Abu-Duhier ◽  
Ibrahim Altedlawi Albalawi
Keyword(s):  
Breast Cancer ◽  
Saudi Arabia ◽  
Cancer Patients ◽  
Genotype Distribution ◽  
Breast Cancer Patients ◽  
Data Set ◽  
Gene Variation ◽  
Increased Risk ◽  
Significant Difference ◽  
Inheritance Model

Aim: Hypoxia-inducible factor 1 (HIF-1) is responsible in regulating oxygen homeostasis in tissues. HypoxiaInducible Factor α (HIF1-α) is a central effector of the hypoxic response. HIF-1α protein overexpression has been shown to have prognostic relevance in breast cancer. HIF-1α polymorphism is associated with increased breast susceptibility reported by several case controls studies but results remained controversial. Therefore, we studied the relationship between the HIF1α gene polymorphism with the breast cancer risk in Saudi Arabia. Methods: This study was consisted of 114 histologically confirmed Breast cancer patients and 117 sex -matched healthy women. HIF-1α genotyping was done by Amplification refractory mutation system PCR method. The HIF-1α gene genotypes were correlated with different clinicopathological characteristics of breast cancer patients. Results: A significant difference was observed in genotype distribution of HIF-1α gene variation C1772T between breast cancer cases and sex matched healthy controls (p=0.001). Our findings showed that the HIF- 1α variant was associated with an increased risk of Breast cancer for HIF-1α CC vs CT genotype OR = 0. 38, 95% CI = (0. 22 -0. 65), P = 0.005) in codominant inheritance model. The significant association was reported for HIF1A for genotypes CC vs (CT+ TT) OR = 0. 39, 95% CI = (0. 231 -0. 67), P = 0.007) in dominant inheritance model tested. In case of recessive inheritance model, a significant association of HIF-1 alpha gene variants was reported for CC VS -(CC+ CT) vs TT) OR = 3.10, 95% CI = (0. 12- 77.03), P = 0.56). During the allelic comparison, A allele significantly increased the risk of Breast cancer with odd ratio (OR = 0. 66, 95% CI = 0. 53 -1. 21, P = 0.04) and risk ratio RR= 0. 51 (0. 32 -0. 80) P= 0.004). A significant association of HIF1α polymorphism was reported with stage as well as distant metastasis of the disease. Conclusion: A significant association of HIF- 1α-CT heterozygosity and T allele significantly increased the susceptibility and is associated with the metastasis of Breast cancer. Further studies with larger data set and well-designed models are required to validate our findings.

scholarly journals The concentration of matrix metalloproteinase 9 in the tumor and peritumoral tissue as prognostic marker in breast cancer patients

2019 ◽  
Vol 76 (5) ◽  
pp. 476-484 ◽  
Author(s):  
Danijela Cvetkovic ◽  
Bojan Milosevic ◽  
Aleksandar Cvetkovic ◽  
Srdjan Ninkovic ◽  
Jovana Jovankic ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Prognostic Marker ◽  
Clinicopathological Parameters ◽  
Cancer Tissue ◽  
Axillary Lymph ◽  
Breast Cancer Patients ◽  
Increased Risk ◽  
Significant Difference ◽  
Peritumoral Tissue

Background/Aim. Breast cancer is one of the most common malignancies among women all over the world. Tumor microenvironment represents one of the main regulators of tumorigenesis. We investigated the role of matrix metalloproteinases 9 (MMP-9) concentration in peritumoral tissue as a prognostic marker in the breast cancer patients. Methods. The ELISA test was used to determine a total MMP-9 concentration in carcinoma and peritumoral tissue sample in the patients with breast cancer. Comparison of MMP-9 protein expression with the clinicopathological parameters was evaluated. Results. Peritumoral tissue at 3 cm distance from the tumor produces more MMP-9 than the tumor itself. The ratio of concentrations of MMP-9 in the tumor and peritumoral tissue considerably changes in favor of peritumoral tissue with the increase of tumor size and the involvement of axillary lymph nodes. In N0 stage, the concentration ratio of MMP-9 in the tumor and peritumoral tissues was 1 : 1.44, but in the N2 stage, the ratio was 1 : 26.5. Conclusion. In patients with breast cancer even in an early stadium there is a change in MMP-9 concentration in peritumoral tissue. We can extract the group of patients at increased risk for the development of lymph node metastasis. A statistically significant difference between the concentrations of MMP-9 in the peritumoral tissue and cancer tissue exists only in case of metastatic disease not in MO stadium implying need for early detection of still unknown metastases in such patients.

scholarly journals Soluble IL-2R as a predictor of familial breast cancer

2020 ◽  
Author(s):  
Kenji Gonda ◽  
Shoichiro Horita ◽  
Yuko Maejima ◽  
Seiichi Takenoshita ◽  
Kenju Shimomura
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Familial Breast Cancer ◽  
Mononuclear Cells ◽  
Disease Free Survival ◽  
Suppressor Cells ◽  
Breast Cancer Patients ◽  
Peripheral Blood Mononuclear ◽  
Tissue Samples ◽  
Increased Risk

Abstract Background: The incidence of breast cancer has been increasing annually, and breast cancer-related diseases, such as breast cancer in the young, ovarian cancer, prostate cancer, and pancreatic cancer, have clearly and steadily increased in number and have become common among the family members of patients with breast cancer. Accordingly, an increase in the incidence of familial breast cancer (FBC) is anticipated in the future. Interleukin (IL)-2 is one of the cytokines that activate cytotoxic T lymphocytes (CTLs), which are important for cancer immunity. To identify the markers of increased risk for FBC, soluble IL-2 receptor (sIL-2R) levels and immunologic factors were investigated in patients with FBC and non-familial breast cancer (NFBC).Methods: Of the 106 untreated breast cancer patients who gave consent to participate in this study, 24 had FBC and 82 had NFBC. There were 11 healthy individuals included in this study. Serum and peripheral blood mononuclear cells were collected from all patients for measurement of sIL-2R, IL-10, Vascular endothelial growth factor (VEGF), IL-17, regulatory T cells (Tregs), Myeloid derived suppressor cells (MDSCs), neutrophil to lymphocyte ratio (NLR), white blood cell (WBC) and C-reactive protein (CRP) levels. Prognosis was assessed and compared according to sIL-2R levels (low vs. high). Tissue samples from postoperative patients with high sIL-2R levels were stained with programmed cell death ligand 1 (PD-L1) and Cluster of Differentiation (CD) 8.Results: sIL-2R level was significantly higher and had significantly stronger correlation with IL-10, VEGF, IL-17, Tregs, MDSCs levels, NLR, WBC count and CRP in FBC, than in NFBC. In cases with high sIL-2R levels, Tregs and MDSCs levels were significantly higher and the overall survival (OS) and disease free survival (DFS) rates were significantly worse in FBC than in NFBC. Among the FBC cases with high sIL-2R levels, triple negative breast cancer tissues stained well for PD-L1and CD8.Conclusions: Compared with NFBC, FBC was associated with higher sIL-2R level, Th2 predominance, and less aggressive cancer immunosuppressive cells. In the present study, sIL-2R was identified as a biomarker that can predict the prognosis of FBC. The ability to prospectively identify patients who are less likely to have NFBC is a vital step in improving the overall survival of this population.

The effects of tamoxifen on homocysteine levels in breast cancer patients

Open Medicine ◽  
2009 ◽  
Vol 4 (4) ◽  
pp. 450-453
Author(s):  
Aydan Eroğlu ◽  
Yonca Eğin ◽  
Nejat Akar
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Mthfr C677t ◽  
Breast Cancer Patients ◽  
Serum Homocysteine ◽  
Intron 1 ◽  
Increased Risk ◽  
Significant Difference ◽  
The Relationship ◽  
Control Study

AbstractTamoxifen is widely used in the treatment of breast cancer and associated with an increased risk of thromboembolism (TE). An elevated homocysteine is one of the risk factors for TE. The aim of the study was to assess the effect of tamoxifen on serum homocysteine levels in breast cancer patients. We performed a case-control study in 20 female subjects to evaluate the relationship between homocysteine levels, and 5,10-methylenetetrahyrofolate reductase (MTHFR) C677T and dihydrofolate reductase (DHFR) 19-bp intron-1 deletion polymorphisms in breast cancer patients and in control subjects. It was observed that homocysteine levels were decreased during tamoxifen therapy, but this finding was not statistically significant. There was also no statistically significant difference in homocysteine levels between the two groups (p> 0.05). MTHFR C677T and DHFR 19-bp deletion polymorphisms were not associated with serum homocysteine value in either group.

The number of metastatic lymph node in N3M0 breast cancer and influence on survival.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e12563-e12563
Author(s):  
Mustafa Solak ◽  
Fatma P. Turkoz ◽  
Özge Keskin ◽  
Hilbrahim Petekkaya ◽  
Saim Furkan Sarici ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Metastatic Lymph Node ◽  
Menopausal Status ◽  
Breast Cancer Patients ◽  
Metastatic Lymph ◽  
Group I ◽  
Increased Risk ◽  
Significant Difference ◽  
The Impact

e12563 Background: To evaluate the impact of the number of metastatic lymph node (MLN) in N3M0 breast cancer patients with a sufficient lymph node sampling. Methods: 200 patients with histopathologically confirmed N3M0 breast cancer were analyzed. Patients were divided into three groups according to the MLN; i) MLN:10-15, ii) MLN:16-20, iii) MLN:>20. Pearson Chi-square test and Kaplan-Meier test were used. Results: 25 patients had T1, 91 had T2, 69 had T3 and 15 had T4 tumor. The number of median MLN was 15 (10-48). HER-2, ER and PR status were similar. There were no significant differences in age at diagnosis, menopausal status, stage, grade and treatment among groups (p>0,05). The median follow-up period was 41.5 months. The median OS was 100, 98 and 58 months in group I, II and III, respectively (p=0.06). When we analyzed for two groups; the median OS was significantly shorter in patients with >20 MLN than patients with 10-15 MLN (98 vs. 58 months; p=0.04). We found no significant difference in DFS (p=0.52). The patients with >20 MLN had increased risk of mortality compared to patients with 10-15 MLN (adjusted-HR 1.96 (95%CI 1.1-3.5); p=0.025). Conclusions: To define the subgroups according to MLN in N3 disease may help determining the high-risk patients and making decision in clinical practice. However this finding should be supported by larger studies.

scholarly journals Estrone and Estradiol Levels in Breast Cancer Patients Using Anastrozole Are Not Related to Body Mass Index

2017 ◽  
Vol 39 (01) ◽  
pp. 14-20 ◽  
Author(s):  
Eduardo Coscia ◽  
Maricene Sabha ◽  
Marli Gerenutti ◽  
Francisco Groppo ◽  
Cristiane Bergamaschi
Keyword(s):  
Breast Cancer ◽  
Body Mass Index ◽  
Body Mass ◽  
High Body Mass Index ◽  
Breast Cancer Patients ◽  
Hormone Levels ◽  
Increased Risk ◽  
Significant Difference ◽  
Plasma Hormone ◽  
Estradiol Levels

Objective Obesity is associated with an increased risk for breast cancer. Recent studies have shown that aromatase inhibitors may be less effective in women with a high body mass index (BMI). The aim of this study was to establish the relationship between the BMI and plasma estrone and estradiol levels in postmenopausal women with hormone receptor-positive breast cancer using anastrozole. Methods In this cohort study, the patients were divided into three groups according to BMI (normal weight, overweight and obese) to compare and correlate plasma hormone levels before starting anastrozole hormone therapy and three months after treatment. Plasma hormone levels were compared for age and use of chemotherapy. Results A statistically significant reduction in estrone and estradiol levels was observed between baseline and three months after starting the anastrozole treatment (p < 0.05). There was no statistically significant difference in plasma estrone and estradiol levels among the BMI groups (p > 0.05), but a significant reduction in plasma estrone levels was observed after three-months' treatment relative to baseline in all groups, as well as a reduction in estradiol in the obese group (p < 0.05). The use of chemotherapy and age > 65 years had no influence on plasma steroid levels. Conclusion Changes in estrone and estradiol levels in the studied groups were not associated with BMI, chemotherapy or age.

scholarly journals Soluble IL-2R as a predictor of familial breast cancer

2019 ◽  
Author(s):  
Kenji Gonda ◽  
Shoichiro Horita ◽  
Yuko Maejima ◽  
Seiichi Takenoshita ◽  
Kenju Shimomura
Keyword(s):  
Breast Cancer ◽  
Familial Breast Cancer ◽  
Mononuclear Cells ◽  
Breast Cancer Patients ◽  
Peripheral Blood Mononuclear ◽  
Tissue Samples ◽  
Aggressive Cancer ◽  
Increased Risk ◽  
Immunosuppressive Cells ◽  
Cancer Tissues

Abstract Background: The incidence of breast cancer has been increasing annually, and breast cancer-related diseases, such as breast cancer in the young, ovarian cancer, prostate cancer, and pancreatic cancer, have clearly and steadily increased in number and have become common among the family members of patients with breast cancer. Accordingly, an increase in the incidence of familial breast cancer (FBC) is anticipated in the future. Interleukin (IL)-2 is one of the cytokines that activate CTLs, which are important for cancer immunity. To search for the markers of increased risk for FBC, we examined the sIL-2R levels and immunologic factors in patients with breast cancer and nonfamilial breast cancer (NFBC). Methods: Of the 106 untreated breast cancer patients who gave consent to participate in this study, 24 had FBC and 82 had NFBC. There were 11 healthy individuals included in this study. Serum and peripheral blood mononuclear cells were collected from all patients for the measurement of the levels of sIL-2R, IL-10, VEGF, IL-17, Tregs, and MDSC. Prognosis was assessed and compared, according to the sIL-2R levels (low vs. high). Tissue samples from postoperative patients with high sIL2 were stained with PD-LI and CD8. Results: The sIL-2R level was significantly higher and had significantly better correlations with IL-10, VEGF, IL-17, Tregs, and MDSC levels in FBC than in NFBC. In cases with high sIL-2R level, the Tregs and MDSC levels were significantly higher and the OS and DFS rates were significantly worse in FBC than in NFBC. Among the FBC cases with high sIL-2R level, triple-negative breast cancer tissues stained well for PD-LI and CD8. Conclusions: Compared with NFBC, FBC was associated with higher sIL-2R levels, Th2 significance, and less aggressive cancer immunosuppressive cells. We have identified sIL-2R as a biomarker that can predict the prognosis of FBC. The ability to prospectively identify patients who are less likely to have NFBC is a vital step in improving the overall survival of this population.

ER, PR & HER2 Receptor status in recurrent breast cancer: Its relation to age & time of recurrence

2020 ◽  
Vol 22 (1) ◽  
pp. 16-20
Author(s):  
Abu Khaled Muhammad Iqbal ◽  
Nasima Akhter ◽  
Hasan Shahrear Ahmed ◽  
Md Rassell ◽  
AMM Yahia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Approach ◽  
Recurrent Breast Cancer ◽  
Breast Cancer Patients ◽  
Her2 Receptor ◽  
Younger Patients ◽  
Receptor Status ◽  
Increased Risk ◽  
Neoplastic Lesions ◽  
Recurrent Breast

Background: Malignant neoplastic lesions of the breast are one of the main causes of cancer death among women. In tumor cells the expression status of Estrogen receptor (ER), progesterone receptor (PR), and c-ERBB2 (HER2/neu) are therapeutically and prognostically important markers affecting the treatment approach, management and prognosis of breast carcinoma. Objective: To explore the relation of receptor status in recurrent breast cancer to age and time of recurrence. Methods: This study was conducted in National Institute of Cancer Research and Hospital (NICRH) and included 81 female patients between 20 to 75 years with recurrent breast cancer. Detection of receptor status of ER +ve/-ve, PR +ve/-ve, Her-2+ve/-ve was based on the immunohistochemistry staining of tissue samples of malignant neoplastic lesions prepared from tissue biopsies of patients with recurrent breast cancer. All the information were recorded through the pre-structured data collection sheet and analyzed. Results: This study showed that most of the recurrent breast cancer patients were Triple negative breast cancer (TNBC) (39.5%) and among them most of them were younger patients. Younger patients with TNBC had increased risk of recurrence. Most of the recurrence occurred within 1-2 years. Conclusion: It can be concluded that the assessment of the expression of these biornarkers in recurrent tumors provides reliable information for the treatment approach of locoregional tumors. Journal of Surgical Sciences (2018) Vol. 22 (1): 16-20

Contribution of Magnetic Resonance Imaging in Determining Lumpectomy Cavity in Breast Radiotherapy

2020 ◽  
Vol 16 (8) ◽  
pp. 997-1003
Author(s):  
Ozlem Demircioglu ◽  
Huseyin Tepetam ◽  
Ayfer Ay Eren ◽  
Zerrin Ozgen ◽  
Fatih Demircioglu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Supine Position ◽  
Radiotherapy Planning ◽  
Breast Cancer Patients ◽  
Breast Radiotherapy ◽  
Lumpectomy Cavity ◽  
Breast Cancer Radiotherapy ◽  
Significant Difference ◽  
Mean Diameter ◽  
Ct And Mri

Background: Accurate localization of the lumpectomy cavity is important for breast cancer radiotherapy after breast-conserving surgery (BCS), but the LC localization based on CT is often difficult to delineate accurately. The study aimed to compare CT-defined LC planning to MRI-defined findings in the supine position for higher soft-tissue resolution of MRI. Methods: Fifty-nine breast cancer patients underwent radiotherapy CT planning in supine position followed by MR imaging on the same day. LC was contoured by the radiologist and radiation oncologist together by CT and MRI separately. T2 weighted MR images and tomography findings were combined and the LC volume, mean diameter and the longest axis length were measured after contouring. Subsequently, patients were divided into two groups according to seroma in LC and the above-mentioned parameters were compared. Results: We did not find any statistically significant difference in the LC volume, mean diameter and length at the longest axis between CT and MRI but based on the presence or absence of seroma, statistically significant differences were found in the LC volumes and the length at the longest axis of LC volumes. Conclusion: We believe that the supine MRI in the same position with CT will be more effective for radiotherapy planning, particularly in patients without a seroma in the surgical cavity.

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