scholarly journals Profiling of the germline mutation BRCA1: p.Ile1845fs in a large cohort of Han Chinese breast cancer

Hereditas ◽  
2019 ◽  
Vol 157 (1) ◽  
Author(s):  
Yu Wu ◽  
Huanhuan Zhang ◽  
Xiaoling Weng ◽  
Honglian Wang ◽  
Qinghua Zhou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Chinese Women ◽  
Gene Mutations ◽  
Pathogenic Mutation ◽  
Han Chinese ◽  
Clinicopathological Parameters ◽  
Healthy Controls ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Increased Risk

Abstract Background Breast cancer is a one of the malignant carcinomas partially caused by genetic risk factors. Germline BRCA1 gene mutations are reportedly associated with breast cancers. Identification of BRCA1 mutations greatly improves the preventive strategies and management of breast cancer. The aim of our study was to investigate the frequency of the deleterious BRCA1: p.Ile1845fs variant in breast carcinomas, as well as the correlation between p.Ile1845fs variant with clinicopathological parameters and clinical outcomes. Results A total of 23,481 clinically high-risk patients with breast cancer and 6489 healthy controls were recruited for p.Ile1845fs variant sequencing (either sanger or next generation sequencing). We identified 94 breast cancer patients (0.40%, 94/23481) as well as 11 healthy controls (0.17%, 11/6489) carried p.Ile1845fs variant. BRCA1: p.Ile1845fs variant showed a higher frequency in patients with TNBC molecular typing (20.21%, 19/94) and family history (37.23%, 35/94) compared with non-carriers (P = 3.62E-6 and 0.034, respectively). According to our data, we advanced the frequency of p.Ile1845fs variant and we confirmed that BRCA1: p.Ile1845fs variant was associated with increased risk of breast cancer (OR = 2.36, 95%CI = 1.26–4.89, P = 0.004). Conclusions BRCA1: p.Ile1845fs variant was a frequently pathogenic mutation in breast cancer in Han Chinese women and our data may be helpful for diagnosis and therapy of breast cancer.

The Pattern of Proline, Glutamic Acid, and Leucine-Rich Protein 1 Expression in Chinese Women with Primary Breast Cancer

2014 ◽  
Vol 29 (1) ◽  
pp. e1-e7 ◽  
Author(s):  
Yanzhi Zhang ◽  
Peng Wang ◽  
Mumu Shi ◽  
Hironobu Sasano ◽  
Monica S.M. Chan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Glutamic Acid ◽  
Primary Breast Cancer ◽  
Chinese Women ◽  
Cancer Prognosis ◽  
Clinicopathological Parameters ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Ki 67 ◽  
Her 2

Background Disparities of biomarkers’ expression in breast cancer across different races and ethnicities have been well documented. Proline, glutamic acid, and leucine-rich protein 1 (PELP1), a novel ER coregulator, has been considered as a promising biomarker of breast cancer prognosis; however, the pattern of PELP1 expression in Chinese women with breast cancer has never been investigated. This study aims to provide useful reference on possible racial or ethnic differences of PELP1 expression in breast cancer by exploring the pattern of PELP1 expression in Chinese women with primary breast cancer. Methods The expression of PELP1 in primary breast cancer samples from 130 Chinese female patients was detected by immunohistochemistry and correlated to other clinicopathological parameters; for comparison, the expression of PELP1 in 26 benign breast fibroadenomas was also examined. Results The overall value of the PELP1 H-score in breast cancer was significantly higher than that in breast fibroadenoma (p<0.001). In our breast cancer patients, the ER/HER-2-positive group had significantly higher PELP1 H-scores than their negative counterparts (p=0.003 for ER and p=0.022 for HER-2); the Ki-67-high group also showed significantly higher PELP1 H-scores than the Ki-67-low group (p=0.008). No significant association between PELP1 H-scores and other clinicopathological parameters was found. Finally, the PELP1 H-score in breast cancers of the luminal B subtype was significantly higher than that in the triple negative subtype (p=0.002). Conclusion Overexpression of PELP1 in Chinese women with primary breast cancer appears to be associated with biomarkers of poor outcome; these results are similar to other reports based on Western populations.

scholarly journals Regression of Triple-Negative Breast Cancer in a Patient-Derived Xenograft Mouse Model by Monoclonal Antibodies against IL-12 p40 Monomer

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 259
Author(s):  
Madhuchhanda Kundu ◽  
Sumita Raha ◽  
Avik Roy ◽  
Kalipada Pahan
Keyword(s):  
Breast Cancer ◽  
Mouse Model ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Transforming Growth Factor ◽  
Healthy Controls ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Patient Derived Xenograft

Although some therapies are available for regular breast cancers, there are very few options for triple-negative breast cancer (TNBC). Here, we demonstrated that serum level of IL-12p40 monomer (p40) was much higher in breast cancer patients than healthy controls. On the other hand, levels of IL-12, IL-23 and p40 homodimer (p402) were lower in serum of breast cancer patients as compared to healthy controls. Similarly, human TNBC cells produced greater level of p40 than p402. The level of p40 was also larger than p402 in serum of a patient-derived xenograft (PDX) mouse model. Accordingly, neutralization of p40 by p40 mAb induced death of human TNBC cells and tumor shrinkage in PDX mice. While investigating the mechanism, we found that neutralization of p40 led to upregulation of human CD4+IFNγ+ and CD8+IFNγ+ T cell populations, thereby increasing the level of human IFNγ and decreasing the level of human IL-10 in PDX mice. Finally, we demonstrated the infiltration of human cytotoxic T cells, switching of tumor-associated macrophage M2 (TAM2) to TAM1 and suppression of transforming growth factor β (TGFβ) in tumor tissues of p40 mAb-treated PDX mice. Our studies identify a possible new immunotherapy for TNBC in which p40 mAb inhibits tumor growth in PDX mice.

scholarly journals Association of the CACNA2D2 gene with schizophrenia in Chinese Han population

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8521
Author(s):  
Yingli Fu ◽  
Na Zhou ◽  
Wei Bai ◽  
Yaoyao Sun ◽  
Xin Chen ◽  
...  
Keyword(s):  
Calcium Channel ◽  
Chinese Women ◽  
Han Chinese ◽  
Type I ◽  
Genotype Distribution ◽  
Healthy Controls ◽  
Nucleotide Polymorphisms ◽  
Chinese Han ◽  
Increased Risk ◽  
Significant Difference

Background Schizophrenia (SCZ) is a severely complex psychiatric disorder in which ~80% can be explained by genetic factors. Single nucleotide polymorphisms (SNPs) in calcium channel genes are potential genetic risk factors for a spectrum of psychiatric disorders including SCZ. This study evaluated the association between SNPs in the voltage-gated calcium channel auxiliary subunit alpha2delta 2 gene (CACNA2D2) and SCZ in the Han Chinese population of Northeast China. Methods A total of 761 SCZ patients and 775 healthy controls were involved in this case-control study. Three SNPs (rs3806706, rs45536634 and rs12496815) of CACNA2D2 were genotyped by the MALDI-TOF-MS technology. Genotype distribution and allele frequency differences between cases and controls were tested by Chi-square (χ2) in males and females respectively using SPSS 24.0 software. Linkage disequilibrium and haplotype analyses were conducted using Haploview4.2. The false discovery rate correction was utilized to control for Type I error by R3.2.3. Results There was a significant difference in allele frequencies (χ2 = 9.545, Padj = 0.006) and genotype distributions (χ2 = 9.275, Padj = 0.006) of rs45536634 between female SCZ patients and female healthy controls after adjusting for multiple comparisons. Minor allele A (OR = 1.871, 95% CI [1.251–2.798]) and genotype GA + AA (OR = 1.931, 95% CI [1.259–2.963]) were associated with an increased risk of SCZ. Subjects with haplotype AG consisting of rs45536634 and rs12496815 alleles had a higher risk of SCZ (OR = 1.91, 95% CI [1.26–2.90]) compared those with other haplotypes. Conclusions This study provides evidence that CACNA2D2 polymorphisms may influence the susceptibility to SCZ in Han Chinese women.

Hereditary Breast Cancer: A Systematic Review

2019 ◽  
Vol 2 (1) ◽  
pp. 48-52
Author(s):  
Preeti Chauhan ◽  
Arockia M Babu ◽  
Palki sahib kaur ◽  
vikas Menon
Keyword(s):  
Breast Cancer ◽  
Germ Line ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Reproductive Risk ◽  
Increased Risk ◽  
Risk Of Disease ◽  
Germ Line Mutation ◽  
Total Burden ◽  
Common Association

Breast cancer is a heterogeneous group of tumours with variable prognosis. It is the second leading cause of cancer related death among women.Hereditary breast cancers (HBC) showed around ten percent of the total burden of breast cancer. Most of the breast cancer cases found due to a BRCA germ line mutation. According to estimation, 15–20% breast cancer patients to have one or more 1st or 2nd degree relatives affected with breast cancer. The factors included the genotypic and phenotypic heterogeneity. Many studies found association of HBC with different carcinoma syndromes. The most common association is with ovarian carcinoma so known as hereditary breast ovarian (BO) carcinoma syndrome involving BRCA1 and 2 mutations. Some other factors like reproductive risk factors including age at diagnosis of breast cancer, pregnancy history, and twin history were also studied and were found associated with breast cancer risk. In this review it is reported that knowledge of genetics of hereditary breast cancers may contribute to identification of patient’s increased risk of disease. These patients could be subjected to genetic counseling that can be definitely benefited from early diagnosis.

The potential benefit of trastuzumab-based therapy upon lapatinib progression in heavily preatreated patients with advanced HER2 positive breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11576-e11576
Author(s):  
Anastasios L. Boutis ◽  
Sofia Chatzileontiadou ◽  
Nikolaos Diamantopoulos ◽  
Athanasios Pouptsis ◽  
Chariklia Fotiou
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Ductal Carcinoma ◽  
Advanced Breast ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Metastatic Setting ◽  
Increased Risk

e11576 Background: Overexpression of human epidermal growth factor receptor 2 (HER2) occurring in about 20% of breast cancers is associated with increased risk of disease recurrence and worse prognosis. Despite the advent of therapies that target HER2, particularly, trastuzumab and lapatinib, that have altered the natural course of HER2-positive advanced breast cancer, tumor progression remains inevitable. New agents are in clinical development, but up to date there are limited data to direct the treatment of patients after lapatinib progression. Methods: We retrospectively searched for HER2-positive advanced breast cancer patients treated at our clinic, who received both trastuzumab-based therapy and lapatinib upon trastuzumab-progression in the metastatic setting. Thirty patients, all female, suffering from HER2-positive advanced breast cancer were identified. HER-2 positivity was assessed by immunohistochemistry (IHC 3+) or chromogenic in situ hybridization (CISH+). Results: Of the 30 patients, 83.3% had invasive ductal carcinoma; 60% had positive hormone receptor status, and 80% grade 3 tumours. Half of the patients received adjuvant trastuzumab. Median age was 57 years, range 37-79 years. 36.6% were switched to lapatinib after a median of three (range 2-6 lines) trastuzumab-based treatment lines. In 8 pts (37.5%) trastuzumab was re-started after lapatinib progression. In 7 of these patients, trastuzumab was combined with chemotherapy. Median progression free survival and overall survival in these patients was 4.75 and 8.87 months respectively. 3 patients received bevacizumab-based therapy upon lapatinib failure. Conclusions: Trastuzumab rechallenge after lapatinib progression may be active in a subgroup of heavily pre-treated patients. Clinical benefit of this strategy has to be balanced especially in limited resource settings with unavailability of novel agents or early phase clinical trials. As of now, there is no uniform accepted standard to define the optimal treatment approach of patients upon lapatinib progression showing the real need for new therapies in this population.

scholarly journals Other Primary Malignancies Among Women With Adult-Type Ovarian Granulosa Cell Tumors

2018 ◽  
Vol 28 (8) ◽  
pp. 1529-1534 ◽  
Author(s):  
Saara Bryk ◽  
Eero Pukkala ◽  
Anniina Färkkilä ◽  
Markku Heikinheimo ◽  
Leila Unkila-Kallio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Soft Tissue ◽  
Granulosa Cell ◽  
Uterine Cancer ◽  
Primary Diagnosis ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Adult Type ◽  
Increased Risk ◽  
Shared Risk

ObjectiveThe aim of this study was to determine the incidence of new primary malignancies after adult-type granulosa cell tumor (AGCT) and the incidence of AGCT after breast and uterine cancer using nationwide population-based registry data.MethodsWe used the Finnish Cancer Registry to identify all patients diagnosed with AGCT in 1968 to 2013 (n = 986). The number of subsequent primary malignancies among women with AGCT and the number of AGCTs in women with previous breast or uterine cancer were compared with the expected number of cases and expressed as standardized incidence ratios (SIRs).ResultsThere were 122 cases of subsequent cancers diagnosed at least 6 months after the primary diagnosis of AGCT (SIR, 1.09; 95% confidence interval [CI], 0.91–1.3). In particular, the observed number of cancers of the soft tissue (SIR, 4.13; 95% CI, 1.33–12.8), thyroid (SIR, 3.42; 95% CI, 1.54–7.62), and leukemia (SIR, 2.67; 95% CI, 0.98–5.82) exceeded the number of expected cases. The SIR for breast cancers after AGCT was 1.26 (95% CI, 0.92–1.73), and the SIR for AGCT after breast cancer was 1.59 (95% CI, 1.04–2.29). The risk for subsequent AGCT was more than 2-fold in breast cancer patients younger than 50 years, and over 15 years after primary diagnosis.ConclusionsThere is an increased risk for thyroid and soft tissue cancer as well as leukemia after AGCT, which may be associated with late effects of carcinogenic treatments and possibly shared risk factors. After breast cancer, the risk for AGCT was higher, which may indicate a shared hormonal etiology.

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 Quantitative Mammographic Density Measurements and Molecular Subtypes in Chinese Women with Breast Cancer

2020 ◽  
Author(s):  
Yuan Tian ◽  
Jennifer L Guida ◽  
Hela Koka ◽  
Er-Ni Li ◽  
Bin Zhu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Mammographic Density ◽  
Chinese Women ◽  
Statistical Tests ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Cancer Subtypes ◽  
Luminal B

Abstract Background Studies investigating associations between mammographic density (MD) and breast cancer subtypes have generated mixed results. We previously showed that having extremely dense breasts was associated with the HER2-enriched subtype in Chinese breast cancer patients. Methods In this study, we re-evaluated the MD-subtype association in 1,549 Chinese breast cancer patients, using VolparaDensity software to obtain quantitative MD measures. All statistical tests were two-sided. Results Compared to women with luminal A tumors, women with luminal B/HER2- (odds ratio [OR]=1.20, 95% confidence interval [CI]: 1.04-1.38, p = 0.01), luminal B/HER2 + (OR = 1.22, 95% CI: 1.03-1.46, p = 0.03), and HER2-enriched tumors (OR = 1.30, 95% CI: 1.06-1.59, p = 0.01) had higher fibroglandular dense volume. These associations were stronger in patients with smaller tumors (&lt;2cm). In contrast, the triple negative subtype was associated with lower non-dense volume (OR = 0.82, 95% CI: 0.68-0.99, p = 0.04), and the association was only seen among older women (&gt;50 years old). Conclusion Although biological mechanisms remain to be investigated, the associations for the HER2-enriched and luminal B subtypes with increasing MD may partially explain the higher prevalence of luminal B and HER2+ breast cancers previously reported in Asian women.

scholarly journals Differences in plasma microRNA content impair microRNA-based signature for breast cancer diagnosis in cohorts recruited from heterogeneous environmental sites

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jeanne P. Uyisenga ◽  
Ahmed Debit ◽  
Christophe Poulet ◽  
Pierre Frères ◽  
Aurélie Poncin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Diagnosis ◽  
Breast Cancer Diagnosis ◽  
Circulating Microrna ◽  
Cancer Tissue ◽  
Healthy Controls ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Cancer Subtypes ◽  
Plasma Microrna

AbstractCirculating microRNAs are non-invasive biomarkers that can be used for breast cancer diagnosis. However, differences in cancer tissue microRNA expression are observed in populations with different genetic/environmental backgrounds. This work aims at checking if a previously identified diagnostic circulating microRNA signature is efficient in other genetic and environmental contexts, and if a universal circulating signature might be possible. Two populations are used: women recruited in Belgium and Rwanda. Breast cancer patients and healthy controls were recruited in both populations (Belgium: 143 primary breast cancers and 136 healthy controls; Rwanda: 82 primary breast cancers and 73 healthy controls; Ntot = 434), and cohorts with matched age and cancer subtypes were compared. Plasmatic microRNA profiling was performed by RT-qPCR. Random Forest was used to (1) evaluate the performances of the previously described breast cancer diagnostic tool identified in Belgian-recruited cohorts on Rwandan-recruited cohorts and vice versa; (2) define new diagnostic signatures common to both recruitment sites; (3) define new diagnostic signatures efficient in the Rwandan population. None of the circulating microRNA signatures identified is accurate enough to be used as a diagnostic test in both populations. However, accurate circulating microRNA signatures can be found for each specific population, when taken separately.

scholarly journals Comparison of Incidental Thyroid Nodules Between Early Breast Cancer Patients and Healthy Controls: Higher Incidence and Thyroid Imaging Reporting and Data System (TI-RADS) Score of Patients with Cancer

2021 ◽  
Vol 14 (9) ◽  
Author(s):  
Masoomeh Raoufi ◽  
Robab Anbiaee ◽  
Zohre Soltani ◽  
Fatemeh Shojaeian ◽  
Seyed Amir Ahmad Safavi-Naini
Keyword(s):  
Breast Cancer ◽  
Thyroid Nodules ◽  
Ductal Carcinoma ◽  
Data System ◽  
Healthy Controls ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Thyroid Imaging ◽  
Risk Of Malignancy ◽  
Us Findings

Background: Breast and thyroid cancers remain among the most common malignancies in women. In previous studies, the co-occurrence of thyroid and breast cancers has been reported. Objectives: The aim of this study was to evaluate and compare the risk and incidence of incidental thyroid nodules (ITNs) between patients with breast cancer and healthy controls, based on the Thyroid Imaging Reporting and Data System (TI-RADS). Methods: This case-control study was conducted on 140 patients with breast cancer and 140 cancer-free women in a similar age range. Thyroid ultrasonography (US) was performed before the onset of treatment. The risk stratification of thyroid nodules was based on the TI-RADS. Results: The mean age of the participants was not significantly different between the case (43.35 ± 7.85 years) and control (42.11 ± 3.69 years) groups (P = 0.094). Invasive ductal carcinoma was the most frequent type of breast cancer in the patients. Normal thyroid US findings were significantly less frequent in patients with breast cancer (35.7%) compared to the healthy controls (76.4%) (P = 0.001). On the other hand, thyroid nodules were more frequent in the patients and associated with a higher risk of malignancy (i.e., high TI-RADS scores) compared to healthy women (P = 0.001 and P = 0.001, respectively). Besides, patients with breast cancer showed more thyroid abnormalities in the US examinations. Conclusions: A higher frequency of ITN, with an elevated TI-RADS score, which raised the suspicion of malignancy, was seen in patients with breast cancer. Overall, patients with breast cancer may benefit from a regular thyroid US examination.

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