scholarly journals Germline Mutation Analysis in Sporadic Breast Cancer Cases with Clinical Correlations

2021 ◽  
Author(s):  
Sadia Ajaz ◽  
Sani-e-Zehra Zaidi ◽  
Saleema Mehboob Ali ◽  
Aisha Siddiqa ◽  
Mohammad Ali Memon
Keyword(s):  
Breast Cancer ◽  
Sporadic Breast Cancer ◽  
Ductal Carcinoma ◽  
Germ Line ◽  
Copy Number Variations ◽  
P Value ◽  
Breast Cancers ◽  
Pakistani Population ◽  
Germ Line Mutations ◽  
Clinical Correlations

Demographics for breast cancers vary widely among nations. The frequency of germline mutations in breast cancers, which reflects the hereditary cases, has not been investigated adequately in Pakistani population. In the present study, germ-line mutations in twenty-seven breast cancer candidate genes were investigated in eighty-four sporadic breast cancer patients along with the clinical correlations. The germ-line variants were also assessed in two healthy controls. The most frequent parameters associated with hereditary cancer cases are age and ethnicity. Therefore, the clinico-pathological features were evaluated by descriptive analysis and Pearson χ2 test (with significant p-value <0.05). The analyses were stratified on the basis of age (<40 years vs >40 years) and ethnicity. The breast cancer gene panel assay was carried out by a genomic capture, massively parallel next generation sequencing assay on Illumina Hiseq2000 assay with 100bp read lengths. Copy number variations were determined by partially-mapped read algorithm. Once the mutation was identified, it was validated by Sanger sequencing. The ethnic analysis stratified on the basis of age showed that the frequency of breast cancer at young age (<40 years) was higher in Sindhis (n=12/19; 64%) in contrast to patients in other ethnic groups. Majority of the patients had stage III (38.1%), grades II and III (46.4%), tumor size 2-5cm (54.8%), and invasive ductal carcinoma (81%). Overall, the analysis revealed germ-line mutations in 11.9% of the patients. The mutational spectrum was restricted to three genes: BRCA1, BRCA2, and TP53. The identified mutations consist of seven novel germ-line mutations, while three mutations have been reported previously. All the mutations are predicted to result in protein truncation. No mutations were identified in the remaining twenty-four candidate breast cancer genes. The present study provides the framework for the development of preventive and treatment strategies against breast cancers in Pakistani population.

Germ-line BRCA1 mutations in women with sporadic breast cancer: clinical correlations.

1998 ◽  
Vol 16 (1) ◽  
pp. 115-120 ◽  
Author(s):  
E Garcia-Patiño ◽  
B Gomendio ◽  
M Provencio ◽  
J M Silva ◽  
J M Garcia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Sporadic Breast Cancer ◽  
Germ Line ◽  
Late Onset ◽  
Brca1 Gene ◽  
Peripheral Blood Lymphocytes ◽  
Missense Mutations ◽  
Direct Dna Sequencing ◽  
Brca1 Mutations ◽  
Germ Line Mutations

PURPOSE Sporadic nonhereditary breast cancer is recognized as the most common form of this malignancy. Presence of germ-line mutations in the BRCA1 gene of these tumors is an infrequent event. We undertook the present study to evaluate the prevalence of germ-line mutations in patients diagnosed with sporadic breast cancer, and to delimit the clinical spectrum of this subgroup of patients with germ-line mutations and their differences with respect to patients with no evidence of BRCA1 gene mutations. METHODS We studied 105 patients diagnosed with breast cancer, selected from among our living patients; those with carcinoma-in-situ and those with a definite family history of breast or ovarian cancer were excluded. Genomic DNA, obtained from peripheral-blood lymphocytes, was studied for BRCA1 mutations by polymerase chain reaction/single-strand conformation polymorphism (PCR-SSCP) and direct DNA sequencing. Fourteen clinicopathologic parameters were analyzed in each patient. RESULTS Six (5.7%) frameshift mutations that corresponded to truncating proteins and three missense mutations, the functional meaning of which remains speculative, were identified. The patients with germ-line mutations were found to have a more advanced age at diagnosis, as well as a longer median survival (51 months). CONCLUSION Women with sporadic breast cancer of late onset may display a significant incidence of germline BRCA1 mutations, which occur at a rate not previously determined in this group of patients. The presence of variations in the sequence of the BRCA1 gene could influence the longer survival observed in these patients.

Phenotypic characteristics of triple negative breast cancer in a rural population

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 17060-17060
Author(s):  
M. Howard-McNatt ◽  
H. Hazard ◽  
A. Jaime ◽  
L. Vona-Davis
Keyword(s):  
Breast Cancer ◽  
African American ◽  
Triple Negative ◽  
Ductal Carcinoma ◽  
Stage Ii ◽  
P Value ◽  
African American Patient ◽  
Breast Cancers ◽  
Phenotypic Characteristics ◽  
Infiltrating Ductal Carcinoma

17060 Background: Triple negative breast tumors are a basal-like subtype of breast cancer associated with the poorest clinical outcomes. Typically they are found in younger patients, African-American women, and patients with the BRCA mutation. To date, however, the epidemiology of triple negative breast cancers in a rural, Caucasian population has not been described. Methods: 96 breast cancer patients presenting with a basal-like subtype of breast cancer had tumor biopsies and demographic and epidemiologic information were collected. Standard histologic and immunohistochemical analysis was done for ER, PR, HER-2/neu status for all high nuclear grade tumors from January 2000 to December 2005 at West Virginia University Hospital. The tumor registry was reviewed to determine tumor size, stage at diagnosis, age at diagnosis, race, menopausal status, body mass index (BMI) and BRCA1/BRCA2 status. Variables in the triple negative group were then compared to all patients who were diagnosed with infiltrating ductal carcinoma between 1999–2004. Results: The basal-like breast cancer subtype was more prevalent among the 40–59 year old group (52%, 50/96) versus women <40 years (12.5%, 12/96) (p= 0.01). Most patients presented with T2 tumors (57%) and the majority had stage II disease (61%, p-value = 0.01). 67% of the population was postmenopausal and were more likely to be overweight or obese (73%, p-value = 0.03). Only one African-American patient met all criteria (2.8%). Of the 7 patients with triple negative tumors who received BRCA testing, four were BRCA1 positive. Age, tumor stage and BMI were similar between the populations of triple negative tumors and infiltrating ductal carcinoma. Conclusions: The demographic and phenotypic characteristics of basal-like breast cancers are still being defined. In contrast to previous findings, triple negative tumors in a rural area were found in middle aged, postmenopausal Caucasian women with Stage II disease and a higher BMI. This analysis will help to identify possible risk factors such as obesity in triple negative cancer subtypes and may prompt further research into differences in breast cancer survival in obese populations from rural areas. No significant financial relationships to disclose.

scholarly journals Comparison of free radicals in blood in pre-operative and post-operative phases of breast malignancies: a clinicopathological study

2019 ◽  
Vol 7 (1) ◽  
pp. 210
Author(s):  
Abhishek Jina ◽  
U. C. Singh
Keyword(s):  
Breast Cancer ◽  
Free Radicals ◽  
Breast Carcinoma ◽  
Ductal Carcinoma ◽  
Lipid Peroxide ◽  
P Value ◽  
Breast Cancer Patients ◽  
Medical College ◽  
Surgery Department

Background: Various factors have been identified as influencing factors of breast cancer. The free radicals can cause increased oxidative stress by negatively affecting the body’s nucleic acids, lipids and proteins leading to various illnesses including cancer. Therefore, this study was aimed at discovering the progress of treatment of breast carcinoma by exploring the connections of the disease with free radical injury.Methods: The present study was conducted among 30 breast carcinoma patients received in the surgery department of BRD Medical College Gorakhpur. Determination of the levels superoxide dismutase (SOD) (the procedure of photoluminescence), catalase (method of Cavarochi) and the lipid peroxidise was done. The results were presented as mean and standard error (SE). P value of <0.05 was considered as statistically significant.Results: Among the total participants, 73% patients had infiltrating ductal carcinoma and 27% patients had intraductal carcinoma. The dismutase levels showed an increase in the post-operative patients for both the groups. The catalase levels and the lipid peroxide levels showed a reduction in the postoperative patients (p<0.05).Conclusions: The present study result showed that the low amounts of SOD and catalase may not be sufficient to detoxify high amounts of free radicals. The administration of catalase could help in reducing the symptoms. Though, low amounts of SOD and catalase may not be sufficient to detoxify high amounts of free radicals. The administration of enzymes could help in the treatment of breast cancer patients.

scholarly journals Microvessel Density and Mammaglobin A Expression as Prognostic Markers in Molecular Types of Breast Cancer

2019 ◽  
Vol 70 (7) ◽  
pp. 2671-2676
Author(s):  
Adriana Andreea Jitariu ◽  
Amalia Raluca Ceausu ◽  
Adriana Meche ◽  
Cristian Nica ◽  
Amelia Burlea ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Microvessel Density ◽  
Ductal Carcinoma ◽  
Hot Spot ◽  
Histopathological Diagnosis ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Mean Values

Increased microvessel density (MVD) values in breast cancer correlate with tumor growth and progression while mammaglobin (MGB) expression in tumor cells is associated with a favorable prognosis. We aim to evaluate and correlate MVD values with MGB expression in molecular types of breast cancer specimens and to determine their utility as prognostic biological markers. A number of 52 breast cancer specimens were included in the study. Specimens were processed for routine histopathological diagnosis followed by the molecular classification by means of estrogen (ER), progesterone (PR) and HER2 immunohistochemical reactions. After performing immunohistochemistry for CD34 and MGB, MVD evaluation was made using the �hot spot� method for each case and MGB was scored between 0 (negative) and +3 (strong positive) depending on the intensity and distribution of the staining. MGB expression in tumor cells and MVD mean values were extremely variable. The greatest MVD mean values were obtained in luminal B followed by HER2, luminal A and triple negative breast cancer (TNBC) (95.33, 69, 62, and 40, respectively). MGB expression in the tumor cells generally ranged from mild to weak and was strong only in a few invasive ductal carcinoma cases. In cases with TNBCs the expression of MGB in tumor cells was weak and focal or negative. This variability was noticed between the molecular types of breast cancers and even within the same molecular type. In a restricted number of cases, MGB positive tumors were associated with low MVD values while the negative cases were characterized by increased MVD mean values. The variable results we obtained regarding the correlation between MVD and MGB in breast cancer specimens may indicate a rather restricted use of MVD/MGB in estimating breast cancer patients� prognosis.

Epigenetic Reprogramming and Landscape of Transcriptomic Interactions: Impending Therapeutic Interference of Triple-Negative Breast Cancer in Molecular Medicine

2021 ◽  
Vol 21 ◽  
Author(s):  
Suman Kumar Ray ◽  
Sukhes Mukherjee
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Treatment Decision ◽  
Copy Number Variations ◽  
Molecular Medicine ◽  
Breast Cancers ◽  
Breast Carcinogenesis

: The mechanisms governing the development and progression of cancers are believed to be the consequence of hereditary deformities and epigenetic modifications. Accordingly, epigenetics has become an incredible and progressively explored field of research to discover better prevention and therapy for neoplasia, especially triple-negative breast cancer (TNBC). It represents 15–20% of all invasive breast cancers and will, in general, have bellicose histological highlights and poor clinical outcomes. In the early phases of triple-negative breast carcinogenesis, epigenetic deregulation modifies chromatin structure and influences the plasticity of cells. It up-keeps the oncogenic reprogramming of malignant progenitor cells with the acquisition of unrestrained selfrenewal capacities. Genomic impulsiveness in TNBC prompts mutations, copy number variations, as well as genetic rearrangements, while epigenetic remodeling includes an amendment by DNA methylation, histone modification, and noncoding RNAs of gene expression profiles. It is currently evident that epigenetic mechanisms assume a significant part in the pathogenesis, maintenance, and therapeutic resistance of TNBC. Although TNBC is a heterogeneous malaise that is perplexing to describe and treat, the ongoing explosion of genetic and epigenetic research will help to expand these endeavors. Latest developments in transcriptome analysis have reformed our understanding of human diseases, including TNBC at the molecular medicine level. It is appealing to envision transcriptomic biomarkers to comprehend tumor behavior more readily regarding its cellular microenvironment. Understanding these essential biomarkers and molecular changes will propel our capability to treat TNBC adequately. This review will depict the different aspects of epigenetics and the landscape of transcriptomics in triple-negative breast carcinogenesis and their impending application for diagnosis, prognosis, and treatment decision with the view of molecular medicine.

Results of a population-based screening for hereditary breast cancer in a region of North-Central Italy: contribution of BRCA1/2 germ-line mutations

2007 ◽  
Vol 112 (2) ◽  
pp. 343-349 ◽  
Author(s):  
Ian J. Seymour ◽  
Silvia Casadei ◽  
Valentina Zampiga ◽  
Simonetta Rosato ◽  
Rita Danesi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hereditary Breast Cancer ◽  
Germ Line ◽  
Central Italy ◽  
Population Based ◽  
North Central ◽  
Germ Line Mutations

scholarly journals Ki67 index in intrinsic breast cancer subtypes and its association with prognostic parameters

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Atif Ali Hashmi ◽  
Kashif Ali Hashmi ◽  
Muhammad Irfan ◽  
Saadia Mehmood Khan ◽  
Muhammad Muzzammil Edhi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ductal Carcinoma ◽  
Prognostic Significance ◽  
Breast Cancer Subtypes ◽  
Prognostic Parameters ◽  
Ki67 Index ◽  
Breast Cancers ◽  
Cancer Subtypes ◽  
Luminal B ◽  
Cancer Management

Abstract Objectives Ki67 is the most commonly used marker to evaluate proliferative index in breast cancer, however no cutoff values have been clearly defined for high ki67 index. Cancer management should be according to loco-regional profile; therefore, we aimed to determine ki67 index in 1951 cases of intrinsic breast cancer subtypes and its association with other prognostic parameters in our set up. Results Triple negative breast cancers showed highest ki67 index (mean 50.9 ± 23.7%) followed by Her2neu (mean 42.6 ± 21.6%) and luminal B cancers (mean 34.9 ± 20.05%). Metaplastic and medullary breast cancers significantly showed higher ki67 index as compared to ductal carcinoma, NOS. No significant association of ki67 index was noted with any of the histologic parameters in different subtypes of breast cancer expect for tumor grade. Although, ki67 index is a valuable biomarker in breast cancer, however no independent prognostic significance of ki67 could be established in our study.

scholarly journals Transcriptome and genome evolution during HER2-amplified breast neoplasia

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Peipei Lu ◽  
Joseph Foley ◽  
Chunfang Zhu ◽  
Katherine McNamara ◽  
Korsuk Sirinukunwattana ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Ductal Carcinoma ◽  
Copy Number Variations ◽  
Neoplastic Progression ◽  
Interferon Signaling ◽  
Her2 Amplification ◽  
Cancer Multiple ◽  
Spatially Oriented

Abstract Background The acquisition of oncogenic drivers is a critical feature of cancer progression. For some carcinomas, it is clear that certain genetic drivers occur early in neoplasia and others late. Why these drivers are selected and how these changes alter the neoplasia’s fitness is less understood. Methods Here we use spatially oriented genomic approaches to identify transcriptomic and genetic changes at the single-duct level within precursor neoplasia associated with invasive breast cancer. We study HER2 amplification in ductal carcinoma in situ (DCIS) as an event that can be both quantified and spatially located via fluorescence in situ hybridization (FISH) and immunohistochemistry on fixed paraffin-embedded tissue. Results By combining the HER2-FISH with the laser capture microdissection (LCM) Smart-3SEQ method, we found that HER2 amplification in DCIS alters the transcriptomic profiles and increases diversity of copy number variations (CNVs). Particularly, interferon signaling pathway is activated by HER2 amplification in DCIS, which may provide a prolonged interferon signaling activation in HER2-positive breast cancer. Multiple subclones of HER2-amplified DCIS with distinct CNV profiles are observed, suggesting that multiple events occurred for the acquisition of HER2 amplification. Notably, DCIS acquires key transcriptomic changes and CNV events prior to HER2 amplification, suggesting that pre-amplified DCIS may create a cellular state primed to gain HER2 amplification for growth advantage. Conclusion By using genomic methods that are spatially oriented, this study identifies several features that appear to generate insights into neoplastic progression in precancer lesions at a single-duct level.

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.

Early-stage male breast cancer: A 10-year experience

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11630-e11630
Author(s):  
N. Gercovich ◽  
E. Gil Deza ◽  
M. Russo ◽  
C. Garcia Gerardi ◽  
C. Diaz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Male Breast Cancer ◽  
Ductal Carcinoma ◽  
Early Stage ◽  
Male Breast ◽  
Stage I ◽  
Stage Ii ◽  
Breast Cancers ◽  
Breast Cancer Patients

e11630 Introduction: Male breast cancer is very rare, representing only between 0.7% and 1% of all breast cancers, and only half of them are early stage cases. Objective: The present study has been designed with the aim of studying retrospectively the clinical onset and evolution of male invasive breast cancer patients (stages I and II) treated at IOHM between 1997 and 2008. Methods: The records of 3,000 breast cancer cases followed between 1997 and 2008 were searched, looking for male stage I and II breast cancer patients. A database was designed following the recommendations of the Directors of Surgical Pathology of the USA. The information registered encompassed: adjuvant treatments, recurrence date and date of final consultation or death. Results: Twelve pts were identified. Mean age (range)= 66 yo (50–89 yo). Tumoral type= Invasive Ductal Carcinoma 12 pt. Tumoral subtype= NOS 9 pt (75%) Apocrine 2 pt (17%) Micropapillar 1 pt (8%). Nottingham´s grade= Grade 2: 8 pt, Grade 3: 3 pt, N/A=1 pt. Stage= I= 6 pt, II=6 pt. ER (Positve= 9 pt, Negative=1 pt, N/A= 2 pt). PR (Positve= 8 pt, Negative= 2 pt, N/A=2 pt). Her2neu (0+= 3 pt, 1+= 3 pt, 2+= 2 pt, N/A= 4 pt). Surgery= Mastectomy= 11 pt, Lumpectomy 1= pt. Radiotherapy=5 pt. Adjuvance= No=2 pt, Hormonotherapy (HT)= 3 pt, Chemotherapy (CHT) = 3 pt, CHT+HT= 4 pt. Recurrence= Yes= 2 pt, No= 10 pt. Survival: Dead= 1 pt, Alive =11 pt. Mean Time To Progression= Stage I =66 months, Stage II =42 months. Global survival: Stage I =66 months, Stage II =52 months. Conclusions: 1. Twelve stage I and II male breast cancer patients were identified out of 3000 (0.4%) breast cancer cases diagnosed and followed in the past 10 years at the IOHM. 2. Mastectomy was the surgical procedure in 11 of the 12 cases 3. Ten pt underwent adjuvant treatment. 4. With a mean follow up time of 60 months, all stage I patients are alive and there were no recurrences. Two of the 6 stage II pts progressed and one died. No significant financial relationships to disclose.

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