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1.
Cancer Genet ; 240: 23-32, 2020 01.
Article in English | MEDLINE | ID: mdl-31706072

ABSTRACT

The aim of this study was to identify the frequency and spectrum of germline BRCA1/2 pathogenic alterations in a cohort of patients with breast carcinoma. In this study, a total of 603 breast cancer subjects from Turkey were screened for BRCA1/BRCA2 mutations using HDA and Sanger sequencing. In the present study, 21 BRCA1 and BRCA2 pathogenic variants were detected in 30 patients and BRCA1/2 mutations were significantly associated with a family history of breast/ovarian cancer. Analysis of overall survival for BRCA1/BRCA2 mutation carriers showed a trend for poor overall survival only in BRCA1 carriers, although this was not statistically significant in BRCA1 and BRCA2 mutation carriers. The c.5266dupC mutation is one of the most frequently reported mutations in BRCA1 and was identified in five breast cancer patients in our study. The most common BRCA2 gene mutations in the present study were c.8940delA and c.9097dupA, which were found in seven patients. We found mostly BRCA1 and BRCA2 mutation carriers in those patients who showed hormone-positive features. In conclusion, our data showed differences in the distribution of the mutation spectrum of BRCA1 and BRCA2 in Turkey.


Subject(s)
BRCA1 Protein/genetics , BRCA2 Protein/genetics , Breast Neoplasms, Male/genetics , Breast Neoplasms/genetics , Adult , Breast/pathology , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Breast Neoplasms, Male/mortality , Breast Neoplasms, Male/pathology , DNA Mutational Analysis , Disease-Free Survival , Female , Follow-Up Studies , Genetic Predisposition to Disease , Germ-Line Mutation , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Mutation , Turkey/epidemiology
2.
Cancer Discov ; 8(3): 336-353, 2018 03.
Article in English | MEDLINE | ID: mdl-29242214

ABSTRACT

We sought to uncover genetic drivers of hormone receptor-positive (HR+) breast cancer, using a targeted next-generation sequencing approach for detecting expressed gene rearrangements without prior knowledge of the fusion partners. We identified intergenic fusions involving driver genes, including PIK3CA, AKT3, RAF1, and ESR1, in 14% (24/173) of unselected patients with advanced HR+ breast cancer. FISH confirmed the corresponding chromosomal rearrangements in both primary and metastatic tumors. Expression of novel kinase fusions in nontransformed cells deregulates phosphoprotein signaling, cell proliferation, and survival in three-dimensional culture, whereas expression in HR+ breast cancer models modulates estrogen-dependent growth and confers hormonal therapy resistance in vitro and in vivo Strikingly, shorter overall survival was observed in patients with rearrangement-positive versus rearrangement-negative tumors. Correspondingly, fusions were uncommon (<5%) among 300 patients presenting with primary HR+ breast cancer. Collectively, our findings identify expressed gene fusions as frequent and potentially actionable drivers in HR+ breast cancer.Significance: By using a powerful clinical molecular diagnostic assay, we identified expressed intergenic fusions as frequent contributors to treatment resistance and poor survival in advanced HR+ breast cancer. The prevalence and biological and prognostic significance of these alterations suggests that their detection may alter clinical management and bring to light new therapeutic opportunities. Cancer Discov; 8(3); 336-53. ©2017 AACR.See related commentary by Natrajan et al., p. 272See related article by Liu et al., p. 354This article is highlighted in the In This Issue feature, p. 253.


Subject(s)
Breast Neoplasms/genetics , Breast Neoplasms/mortality , Gene Fusion , Adult , Aged , Aged, 80 and over , Animals , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Cell Line, Tumor , Class I Phosphatidylinositol 3-Kinases/genetics , Estrogen Receptor alpha/genetics , Female , Gene Expression Regulation, Neoplastic , Heterocyclic Compounds, 3-Ring/pharmacology , Humans , Mice, Nude , Middle Aged , Protein Kinase Inhibitors/pharmacology , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-raf/genetics , Pyridones/pharmacology , Pyrimidinones/pharmacology , Receptors, Steroid/metabolism , Ribosomal Protein S6 Kinases/genetics , Ribosomal Protein S6 Kinases/metabolism , Xenograft Model Antitumor Assays
3.
Asian Pac J Cancer Prev ; 17(9): 4241-4246, 2016.
Article in English | MEDLINE | ID: mdl-27797225

ABSTRACT

BACKGROUND: Dysregulation of miRNA expression may be used as a biomarker for specific tumours because it may contribute to development of cancer. Circulating miRNA profiles have been highlighted for their potential as predictive markers in heterogeneous diseases such as breast cancer. In the literature, there is evidence that miR-195 levels are differentially expressed pre- and post-operative periods in breast cancer patients. At the same time, miRNA expression levels may vary because of ethnic origins. This study aimed to determine expression levels and potential roles of miR-195 in Turkish breast cancer patients. MATERIALS AND METHODS: The expression patterns of miR-195 were initially examined in breast cancer tissues (luminal A and B type) (n=96). Subsequently, blood samples were prospectively collected from preoperative and postoperative Turkish breast cancer patients and disease free controls. Total RNA was isolated, and the expression level of miR-195 was quantified by real-time PCR. RESULTS: We found that miR-195 level was altered in Turkish breast cancer patients, with down-regulation evident in breast cancer tissues compared to normal adjacent specimens. Furthermore, circulating levels of miR- 195 was significantly decreased in post-operative blood samples compared with pre-operative levels (p=0.01 and <0.05). However, miR-195 was significantly increased in pre-operative blood samples of the luminal B type (p= 0.04 and <0.05). CONCLUSIONS: This study represents the first report of a miR-195 expression profile in Turkish breast cancer patients. Our data suggests that miR-195 levels might be a clinically useful biomarker in the earliest stage of Turkish breast cancer patients.


Subject(s)
Biomarkers, Tumor/blood , Breast Neoplasms/blood , Carcinoma, Ductal, Breast/blood , Carcinoma, Lobular/blood , MicroRNAs/blood , Adult , Aged , Biomarkers, Tumor/genetics , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/secondary , Carcinoma, Ductal, Breast/surgery , Carcinoma, Lobular/secondary , Carcinoma, Lobular/surgery , Case-Control Studies , Female , Follow-Up Studies , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Lymphatic Metastasis , MicroRNAs/genetics , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Oligonucleotide Array Sequence Analysis , Prognosis , Real-Time Polymerase Chain Reaction , Turkey , Young Adult
4.
Gene ; 590(2): 278-84, 2016 Sep 30.
Article in English | MEDLINE | ID: mdl-27236032

ABSTRACT

The dysregulation of miRNA expression has frequently been observed in breast cancer. Therefore, we investigated the expression profile of miRNAs that may be associated with expression of the FHIT gene in breast cancer and assessed their clinicopathological significance. The expression levels of miR-143, miR-663a, miR-668, miR-922 and FHIT were analyzed in normal and malignant breast tissues from 65 patients with breast cancer. We studied the correlation between the expression of miR-143, miR-663a, miR-668, miR-922 and FHIT and the clinicopathological features presented by the patients. The expression levels of the miRNAs and FHIT were downregulated in breast cancer tissue. The expression levels of miR-143, miR-663a and miR-668 were significantly reduced in FHIT downregulated tumors. miR-668 expression was also significantly altered relative to FHIT down- and up- regulated tumor tissues. Reduced miR-663a expression was statistically associated with high-grade ER/PR (+) status, benign reactive hyperplasia, lymph-node metastasis, in-situ component >25% and Ki 67>15% compared with non-tumor tissues. Additionally, reduced miR-668 expression was significantly different between tumors with and without lymph-node metastasis. miR-668 may play an important role in breast cancer development and progression by regulating the expression of FHIT. Furthermore, miR-668 and miR-663a may be potential prognostic biomarkers for breast cancer.


Subject(s)
Acid Anhydride Hydrolases/genetics , Breast Neoplasms/genetics , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Neoplasm Proteins/genetics , Acid Anhydride Hydrolases/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Breast Neoplasms/pathology , Computational Biology , Female , Gene Expression Profiling , Humans , MicroRNAs/metabolism , Middle Aged , Neoplasm Proteins/metabolism , Young Adult
5.
J Breast Health ; 12(2): 86-87, 2016 Apr.
Article in English | MEDLINE | ID: mdl-28331740

ABSTRACT

Gestational gigantomastia is a rare condition characterized by fast, disproportionate and excessive breast growth, decreased quality of life in pregnancy, and presence of psychologic as well as physical complications. The etiology is not fully understood, although hormonal changes in pregnancy are considered responsible. Prolactin is the most important hormone. To date, 125 cases of gigantomastia have been reported in the literature. In this case presentation, we report a pregnant woman aged 26 years with a 22-week gestational age with gestational gigantomastia and review the diagnosis and treatment of this rare disease in relation with the literature.

6.
Asian Pac J Cancer Prev ; 16(1): 291-7, 2015.
Article in English | MEDLINE | ID: mdl-25640367

ABSTRACT

The Homeobox B13 (HOXB13):Interleukin 17 Receptor B (IL17BR) index of estrogen receptor (ER)-positive breast cancer (ER (+) BC) patients may be a potential biomarker of recurrence/ metastasis. However, effects of microRNA (miRNA) binding to the 3' untranslated region (3 ?UTR) of HOXB13 and IL17BR and its function on recurrence/metastasis in ER (+) BC remains elusive. The aims of this study were to determine the expression of miRNAs that bind to 3 ?UTR of HOXB13 and IL17BR in ER (+) BC patients and asess the effects of these miRNAs on recurrence/metastasis. The expression profiles of HOXB13 and IL17BR were evaluated using RT- PCR in tumors and normal tissue samples from 40 ER (+) BC patients. The expression level of 4 miRNAs, which were predicted to bind the 3 ?UTR of HOXB13 and IL17BR using TargetScan, microRNA.org and miRDB online databases, were further evaluated with RT-PCR. Our findings demonstrated that high miR-1266 levels might be significant prognostic factor for recurrence/metastasis occurrence (3.05 fold p=0.004) and tamoxifen response (3.90 fold; p=0.2514) in ER (+) BC cases. Although we suggest that modulation of miR-1266 expression may be an important mechanism underlying the chemoresistance of ER (+) BC, advanced studies and validation are required.


Subject(s)
Breast Neoplasms, Male/genetics , MicroRNAs/genetics , Neoplasm Metastasis/genetics , Neoplasm Recurrence, Local/genetics , Receptors, Estrogen/metabolism , 3' Untranslated Regions/genetics , Adult , Aged , Aged, 80 and over , Antineoplastic Agents, Hormonal/therapeutic use , Biomarkers, Tumor/genetics , Breast Neoplasms, Male/drug therapy , Drug Resistance, Neoplasm , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Homeodomain Proteins/genetics , Humans , Male , MicroRNAs/biosynthesis , Middle Aged , RNA, Messenger/biosynthesis , Receptors, Interleukin/genetics , Receptors, Interleukin-17 , Tamoxifen/therapeutic use
7.
Eur J Public Health ; 25(1): 9-14, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25096257

ABSTRACT

BACKGROUND: One of the most important factors in breast cancer (BC) mortality is treatment delay. The primary goal of this survey was to identify factors affecting the total delay time (TDT) in Turkish BC patients. METHODS: A total of 1031 patients with BC were surveyed using a uniform questionnaire. The time between discovering the first symptom and signing up for the first medical visit (patient delay time; PDT) and the time between the first medical visit and the start of therapy (system delay time; SDT) were modelled separately with multilevel regression. RESULTS: The mean PDT, SDT and TDT were 4.8, 10.5 and 13.8 weeks, respectively. In all, 42% of the patients had a TDT >12 weeks. Longer PDT was significantly correlated with disregarding symptoms and having age of between 30 and 39 years. Shorter PDT was characteristic of patients who: had stronger self-examination habits, received more support from family and friends and had at least secondary education. Predictors of longer SDT included disregard of symptoms, distrust in success of therapy and medical system and having PDT in excess of 4 weeks. Shorter SDT was linked to the age of >60 years. Patients who were diagnosed during a periodic check-up or opportunistic mammography displayed shorter SDT compared with those who had symptomatic BC and their first medical examination was by a surgeon. CONCLUSION: TDT in Turkey is long and remains a major problem. Delays can be reduced by increasing BC awareness, implementing organized population-based screening programmes and founding cancer centres.


Subject(s)
Breast Neoplasms/diagnosis , Breast Neoplasms/psychology , Early Detection of Cancer/statistics & numerical data , Health Knowledge, Attitudes, Practice , Patient Acceptance of Health Care/statistics & numerical data , Adult , Age Distribution , Aged , Analysis of Variance , Breast Neoplasms/therapy , Early Detection of Cancer/psychology , Female , Humans , Middle Aged , Patient Acceptance of Health Care/psychology , Societies, Medical , Surveys and Questionnaires , Time Factors , Turkey , Waiting Lists
8.
Gene ; 556(2): 163-9, 2015 Feb 10.
Article in English | MEDLINE | ID: mdl-25445393

ABSTRACT

Triple negative breast cancer (TNBC) is the most aggressive and poorly understood subclass of breast cancer (BC). Over the recent years, miRNA expression studies have been providing certain detailed overview that aberrant expression of miRNAs is associated with TNBC. Although TNBC tumors are strongly connected with loss of function of BRCA genes, there is no knowledge about the effect of BRCA mutation status on miRNA expressions in TNBC cases. The aims of this study were to evaluate the expression profile of miRNAs that plays role in TNBC progression and the role of BRCA mutations in their regulation. The expression level of BC associated 13 miRNAs was analyzed in 7 BRCA mutations positive, 6 BRCA mutations negative TNBC cases and 20 non-tumoral tissues using RT-PCR. According to RT2 Profiler PCR Array Data Analysis, let-7a expression was 4.67 fold reduced in TNBCs as compared to normal tissues (P=0.031). In addition, miR-200c expression was 5.75 fold reduced in BRCA mutation positive TNBC tumors (P=0.005). Analysis revealed a negative correlation between miR-200c and VEGFA expressions (r=-468). Thus, miR-200c may be involved in invasion and metastasis in TNBC cases with BRCA mutation. In this study we provide the knowledge on the first report of association between microRNA-200c and BRCA mutations in TNBC. Further studies and evaluations are required, but this miRNA may provide novel therapeutic molecular targets for TNBC treatment and new directions for the development of anticancer drugs.


Subject(s)
BRCA1 Protein/genetics , BRCA2 Protein/genetics , MicroRNAs/genetics , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/pathology , Adult , Disease Progression , Female , Gene Expression Regulation, Neoplastic , Humans , Middle Aged , Mutation , Vascular Endothelial Growth Factor A/genetics
9.
Asian Pac J Cancer Prev ; 15(19): 8319-24, 2014.
Article in English | MEDLINE | ID: mdl-25339023

ABSTRACT

Although genetic markers identifying women at an increased risk of developing breast cancer exist, the majority of inherited risk factors remain elusive. Mutations in the BRCA1/BRCA2 gene confer a substantial increase in breast cancer risk, yet routine clinical genetic screening is limited to the coding regions and intron- exon boundaries, precluding the identification of mutations in noncoding and untranslated regions. Because 3' untranslated region (3'UTR) polymorphisms disrupting microRNA (miRNA) binding can be functional and can act as genetic markers of cancer risk, we aimed to determine genetic variation in the 3'UTR of BRCA1/BRCA2 in familial and early-onset breast cancer patients with and without mutations in the coding regions of BRCA1/ BRCA2 and to identify specific 3'UTR variants that may be risk factors for cancer development. The 3'UTRs of the BRCA1 and BRCA2 genes were screened by heteroduplex analysis and DNA sequencing in 100 patients from 46 BRCA1/2 families, 54 non-BRCA1/2 families, and 47 geographically matched controls. Two polymorphisms were identified. SNPs c.*1287C>T (rs12516) (BRCA1) and c.*105A>C (rs15869) (BRCA2) were identified in 27% and 24% of patients, respectively. These 2 variants were also identified in controls with no family history of cancer (23.4% and 23.4%, respectively). In comparison to variations in the 3'UTR region of the BRCA1/2 genes and the BRCA1/2 mutational status in patients, there was a statistically significant relationship between the BRCA1 gene polymorphism c.*1287C>T (rs12516) and BRCA1 mutations (p=0.035) by Fisher's Exact Test. SNP c.*1287C>T (rs12516) of the BRCA1 gene may have potential use as a genetic marker of an increased risk of developing breast cancer and likely represents a non-coding sequence variation in BRCA1 that impacts BRCA1 function and leads to increased early-onset and/or familial breast cancer risk in the Turkish population.


Subject(s)
3' Untranslated Regions/genetics , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Genetic Predisposition to Disease , Genetic Variation/genetics , MicroRNAs/genetics , Adult , Aged , Binding Sites , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Case-Control Studies , Female , Follow-Up Studies , Gene Expression Regulation, Neoplastic , Humans , Middle Aged , Neoplasm Staging , Prognosis , Risk Factors , Young Adult
10.
Cancer Invest ; 32(8): 375-87, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24884828

ABSTRACT

BRCA1/BRCA2 genes were screened in 117 patients with breast cancer by sequencing. Fourteen percent of patients tested positive for BRCA1/BRCA2 mutations. Four frame shift mutations, four pathogenic missense mutations, and 25 different sequence variations were detected. BRCA mutation positivity was significantly associated with Ki67 (p = .001). BRCA protein expressions were decreased in the patients harboring important mutations and polymorphisms (BRCA1;P508 stop, V1740G, Q1182R, Q1756P and BRCA2;V2466A) related with disease. Our findings contribute significantly to the types of germline BRCA1/BRCA2 mutations and their biological effects in Turkish women. These data could help guide the management of BRCA1/BRCA2 mutation-carrying patients when considering breast-conserving therapy.


Subject(s)
Breast Neoplasms/genetics , Genes, BRCA1 , Genes, BRCA2 , Germ-Line Mutation , Adult , Aged , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Female , Genetic Variation , Humans , Middle Aged , Polymorphism, Genetic , Turkey , Young Adult
11.
Mol Cell Biochem ; 395(1-2): 77-88, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24942235

ABSTRACT

The genetic factors of cancer predisposition remain elusive in the majority of familial and/or early-onset cases of breast cancer (BC). This type of BC is promoted by germ-line mutations that inactivate BRCA1 or BRCA2. On the other hand, recent studies have indicated that alterations in the levels of miRNA expression are linked to this disease. Although BRCA1 and BRCA2 gene mutations have been reported to commonly lead to alterations in genes that encode cancer-related proteins, little is known regarding the putative impact of these mutations on noncoding miRNAs. In the present study, we aimed to determine whether miRNA dysregulation is involved in the pathogenesis of BRCA-mutated BC. An expression analysis of 14 human miRNAs previously shown to be related to BC diagnosis, prognosis, and drug resistance was conducted using tissues from 60 familial and/or early-onset patients whose peripheral blood samples had been screened for BRCA1 and BRCA2 mutations through sequence analysis. Let-7a and miR-335 expression levels were significantly downregulated in the tumors of patients with a BRCA mutation compared with those of patients without a BRCA mutation (P = 0.04 and P = 0.02, respectively). Our results defined the associations between the expression status of let-7a and miR-335 and BRCA mutations. The expression analysis of these miRNAs might be used as biomarkers of the BRCA mutation status of early-onset and/or familial BC.


Subject(s)
BRCA1 Protein/genetics , BRCA2 Protein/genetics , Breast Neoplasms/genetics , Breast Neoplasms/pathology , MicroRNAs/genetics , Adult , Aged , Down-Regulation , Female , Gene Expression Regulation, Neoplastic , Germ-Line Mutation , Humans , Middle Aged , Prognosis , Young Adult
12.
Tumori ; 98(2): 243-51, 2012.
Article in English | MEDLINE | ID: mdl-22677992

ABSTRACT

AIMS AND BACKGROUND: The major cause of death in breast cancer patients is metastasis. Various biomarkers have been used for the early detection of circulating tumor cells in the peripheral blood of breast cancer patients. The aims of the current study were to analyze circulating tumor cells in the blood of breast cancer patients by investigating EGFR, CK19, CK20 and HER2 expression profiles and to evaluate their prognostic importance. METHODS: CK19, CK20 and EGFR gene expression profiles were evaluated in the blood samples of 84 female patients with primary invasive ductal breast cancer and 20 healthy female volunteers using SYBR green-based real-time qPCR assays. HER2 expression analyses were conducted in 46 patients who had an HER2-positive primary tumor and in 30 healthy women to determine the cutoff level of positivity. RESULTS: The positive rates of CK20, EGFR, CK19 and HER2 mRNA expression in the peripheral blood were 28.57% (24/84), 20.23% (17/84), 5.95% (5/84) and 2.17% (1/46), respectively. The high positive ratio of CK20 mRNA expression in the peripheral blood of breast cancer was identified for the first time in the current study. Significant differences were identified in CK20 expression status and several clinical parameters related with aggressiveness of tumors using a binary logistic regression analysis. Higher CK20-positive levels were observed in patients who had lymph node metastasis and advanced-grade primary tumors, which were estrogen receptor-negative. We have demonstrated that CK20 may be a novel biomarker that is useful to identify circulating tumor cells and predict breast cancer progression. CONCLUSIONS: The results suggest that the investigation of CK20 mRNA with other biomarkers in the peripheral blood of breast cancer patients may be useful to monitor the presence of disseminated tumor cells in the blood circulation and to predict the prognosis of breast cancer.


Subject(s)
Biomarkers, Tumor/analysis , Breast Neoplasms/chemistry , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/chemistry , Carcinoma, Ductal, Breast/pathology , ErbB Receptors/analysis , Keratin-19/analysis , Keratin-20/analysis , Neoplastic Cells, Circulating/chemistry , Receptor, ErbB-2/analysis , Adult , Aged , Breast Neoplasms/blood , Carcinoma, Ductal, Breast/blood , Disease-Free Survival , Early Detection of Cancer , ErbB Receptors/genetics , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Keratin-19/genetics , Keratin-20/genetics , Logistic Models , Lymphatic Metastasis , Middle Aged , Neoplasm Grading , Neoplasm Staging , Odds Ratio , Predictive Value of Tests , Prognosis , RNA, Messenger/analysis , ROC Curve , Real-Time Polymerase Chain Reaction , Receptor, ErbB-2/genetics , Sensitivity and Specificity
13.
Diagn Microbiol Infect Dis ; 58(4): 477-9, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17509793

ABSTRACT

Breast tuberculosis is an uncommon illness. It is predominant in young women. To our knowledge, only 7 cases of tuberculous mastitis in men have been reported in the English literature since 1945. Furthermore, there are no male patients who have breast and osteoarticular tuberculosis in the literature. We presented a 41-year-old man who was admitted with a fixed tender mass in the right retromammary region and pain in the right hip. Mycobacterium tuberculosis colonies were isolated from the semisolid mass of breast. Histopathologic examination revealed caseous granulomatous infection in the right hip synovial tissue. He was treated successfully with only antituberculous drugs.


Subject(s)
Mastitis/microbiology , Mycobacterium tuberculosis/isolation & purification , Tuberculosis, Osteoarticular/pathology , Tuberculosis/complications , Adult , Antitubercular Agents/therapeutic use , Humans , Male , Mastitis/drug therapy , Tuberculosis/drug therapy , Tuberculosis, Osteoarticular/drug therapy
14.
Tumori ; 93(6): 597-603, 2007.
Article in English | MEDLINE | ID: mdl-18338496

ABSTRACT

AIMS AND BACKGROUND: The character, role and impact of FHIT gene alterations, for which recent studies have shown that the gene has a role in the early stage of carcinogenesis in breast cancer, are still unclear. Thus, the current study evaluated FHIT gene mutations from breast tissue of women with malignant and benign breast disease and to elucidate the frequency and type of mutations in this gene. PATIENTS AND METHODS: Mutations in exons 5-9 of the FHIT gene were screened using the intronic primer pairs in 83 breast (67 malignant and 16 benign) tissue samples by single-strand conformational polymorphism and sequencing analysis. RESULTS: FHIT mutations were detected in 13 of the 67 malignant cases (19.4%) and 2 of the 16 benign cases (12.5%). Four different sequence variants were determined: two novel frame shift mutations (codon 90 insA, codon 146 delT), one intronic novel mutation (IVS8 -17 insA), and one previously identified silent transition type alteration (codon 88 C to T). In addition, determination of this silent alteration caused formation of new exonic splicing enhancer (ESE) motifs on mutated sequences by using the ESEfinder program. CONCLUSIONS: Our data contribute significantly to that currently known about the presence of FHIT gene mutations on the formation of breast cancer.


Subject(s)
Acid Anhydride Hydrolases/genetics , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Mutation , Neoplasm Proteins/genetics , Adult , Aged , Alanine , Carcinoma/genetics , Female , Fibroadenoma/genetics , Frameshift Mutation , Glutamine , Humans , Hyperplasia/genetics , Lymphatic Metastasis , Middle Aged , Phenylalanine , Polymerase Chain Reaction , Polymorphism, Single-Stranded Conformational , Sequence Analysis, DNA , Threonine
15.
Tumori ; 92(5): 416-22, 2006.
Article in English | MEDLINE | ID: mdl-17168435

ABSTRACT

AIMS AND BACKGROUND: The status of the axillary lymph nodes at the time of diagnosis has been accepted as one of the most important prognostic factors for the overall and disease-free survival of patients with breast cancer. The aim of our study was to determine which factors influence axillary node involvement in invasive breast cancer. METHODS: The data presented here were obtained from 344 patients who were treated for invasive breast cancer at the Department of Radiation Oncology, Uludag University Medical College, Bursa, Turkey. Possible prognostic factors were categorized as patient related and tumor related. The Mann-Whitney U test was used for univariate analysis and logistic regression was used for multivariate analysis. RESULTS: In univariate analysis, a familial cancer history (P = 0.0042), age < 40 years (P = 0.0276), higher T stage (P < 0.0000), nipple involvement (P = 0.0345), skin involvement (P = 0.0270), perineural invasion (P = 0.0231), and lymphatic vessel invasion (P < 0.0000) were correlated with increased axillary node involvement. A higher incidence of > or = 4 involved lymph nodes was associated with higher T stage (P = 0.0004), nipple involvement (P = 0.0292), presence of an extensive intraductal component (P = 0.0023), skin involvement (P = 0.0008), perineural invasion (P = 0.0523), and lymphatic vessel invasion (P < 0.0000) in univariate analysis. In multivariate analysis, age < 40 years (P = 0.0454), cancer history within the family (P = 0.0024), higher T stage (P = 0.0339), lymphatic vessel invasion (P = 0.0003), and perineural invasion (P = 0.0408) were found to be independent factors for axillary lymph node positivity. Age < 40 years (P = 0.0221), perineural invasion (P = 0.0408), and an extensive intraductal component (P = 0.0132) were associated with an increased incidence of > or = 4 involved nodes in the logistic regression analysis. In patients with breast cancer, the incidence of axillary lymph node involvement was independently influenced by age < 40 years, presence of cancer history within the family, higher T stage, lymphatic vessel invasion, and perineural invasion. CONCLUSIONS: In conclusion, absence of familial cancer history, presence of lymphatic vessel invasion, higher T stage, and age below 40 years independently increased the risk of axillary node involvement. Presence of perineural invasion and lymphatic vessel invasion, age below 40, and an extensive intraductal component of more than 25% independently affected the risk of having > or = 4 nodes involved. Patients characterized by these factors may be classified into a higher risk group for nodal involvement, but more data are needed to define factors that can help in the decision-making regarding the omission of axillary treatment.


Subject(s)
Breast Neoplasms/pathology , Lymph Nodes/pathology , Adult , Analysis of Variance , Axilla , Breast Neoplasms/therapy , Female , Humans , Logistic Models , Lymphatic Metastasis , Predictive Value of Tests , Prognosis , Risk Factors
16.
Cancer Invest ; 24(5): 484-91, 2006.
Article in English | MEDLINE | ID: mdl-16939956

ABSTRACT

BRCA1 and BRCA2 gene mutations in patients with breast and/or ovarian cancer have been not characterized in the Turkish population until now. A total of 87 female subjects from two sets of families (38 families total) provided blood samples from which DNA was extracted. All coding exons of the BRCA1 and BRCA2 genes were screened for mutations with heteroduplex analysis and sequencing. Fourteen of the families (49 subjects comprising 17 patients and 32 unaffected relatives) had at least 2 women affected by breast and/or ovarian cancer. The other 24 families (38 subjects unaffected by breast and/or ovarian cancer) also had a history of these 2 forms of cancer. Six different sequence variants were detected: one previously described truncating mutation (5382insC) and one novel polymorphism (3663C-->A) in BRCA1, and 2 novel truncating mutations (9329insC and 9934insG), one novel intronic polymorphism 7069+41(TTTT-->AAAG), and one previously reported global polymorphism (1093A-->C) in BRCA2. BRCAPRO software was used for analysis, and the results showed that the level of risk for both breast and ovarian cancer increased with age in women who carried the mutation. In conclusion, these findings contribute significantly to what currently is known about the types and impact of germline BRCA1 and BRCA2 mutations in Turkish women.


Subject(s)
BRCA1 Protein/genetics , BRCA2 Protein/genetics , Breast Neoplasms/genetics , Ovarian Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Base Sequence , Family , Female , Gene Frequency , Genetic Predisposition to Disease , Germ-Line Mutation , Heterozygote , Humans , Middle Aged , Models, Genetic , Molecular Sequence Data , Polymorphism, Genetic , Risk Assessment , Software , Turkey
17.
Tumori ; 92(3): 244-5, 2006.
Article in English | MEDLINE | ID: mdl-16869244

ABSTRACT

Breast cancer in both spouses is extremely rare. There are 7 metachronous cases and 1 synchronous case in the English literature. No case has been reported in which 1 of the spouses had bilateral breast cancer. In this paper, we report a synchronous pair of cases where 1 of the spouses (wife) had bilateral breast cancer and the other (husband) had breast cancer.


Subject(s)
Breast Neoplasms, Male , Breast Neoplasms , Neoplasms, Multiple Primary , Spouses , Adenocarcinoma/diagnosis , Adenocarcinoma/therapy , Breast Neoplasms/diagnosis , Breast Neoplasms/therapy , Breast Neoplasms, Male/diagnosis , Breast Neoplasms, Male/genetics , Breast Neoplasms, Male/therapy , Carcinoma, Ductal, Breast/diagnosis , Carcinoma, Ductal, Breast/therapy , Female , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Neoplasms, Multiple Primary/diagnosis , Neoplasms, Multiple Primary/therapy
18.
Cancer Invest ; 23(5): 386-91, 2005.
Article in English | MEDLINE | ID: mdl-16193637

ABSTRACT

UNLABELLED: Chemotherapy provides palliation and modest prolongation of symptom-free survival in metastatic breast cancer. Taxane containing regimens are commonly considered to be among the initials in metastatic setting due to earlier use of anthracyclines in the course of breast cancer. Therefore, we conducted this Phase II study to assess efficacy and safety of gemcitabine plus paclitaxel (GT) combination therapy in anthracycline pretreated metastatic first-line setting. PATIENTS AND METHODS: The study enrolled 26 women with pathologically confirmed and measurable metastatic breast cancer who were previously treated with anthracycline but no prior chemotherapy for metastatic disease. Twenty six and twenty four patients were eligible for toxicity and efficacy evaluations respectively. Mean age was 47.3 years and median ECOG performance status was 0. Twenty patients (76.9 percent) had visceral metastases, most commonly located in liver and lung. Treatment schedule was as follows: paclitaxel 175 mg/m2 was administered intravenously in 3 hours on Day 1 and gemcitabine 1000 mg/m2 was administered intravenously in 30 minutes on Day 1 after paclitaxel application, and on Day 8 every 21 days. RESULTS: Objective response rate was 41.7 percent (95 percent CI: 21.9-61.4) with 16.7 percent (95 percent CI: 1.7-31.6 percent) CR, and 25.0 percent (95 percent CI: 7.6-42.3 percent) PR. Median time to progression and overall survival were 9.6 and 14.5 months, respectively. Grade 3-4 toxicity was observed in 34.6 percent (9) patients. Treatment of two patients was discontinued due to toxicity, consisting of Grade 3 hypersensitivity reactions and Grade 4 infections in one patient each. Dose reductions due to myelotoxicity were performed in 4 (15.3 percent) patients. Hematologic toxicities were generally manageable with appropriate dose modifications and supportive care. CONCLUSION: Gemcitabine and paclitaxel combination regimen is effective and has manageable toxicity profile as first line metastatic setting.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Deoxycytidine/analogs & derivatives , Paclitaxel/adverse effects , Paclitaxel/therapeutic use , Adult , Anthracyclines/administration & dosage , Anthracyclines/therapeutic use , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/therapeutic use , Female , Humans , Middle Aged , Neoplasm Metastasis , Paclitaxel/administration & dosage , Treatment Outcome , Gemcitabine
19.
Eur J Radiol ; 56(3): 382-5, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16024205

ABSTRACT

OBJECTIVE: To evaluate the role of US-guided core biopsy in detection of metastatic axillary lymph nodes in preoperative staging of breast cancer. MATERIALS AND METHODS: US-guided core biopsy of suspicious axillary lymph nodes was performed in 39 patients with breast cancer. Biopsy results were compared to the axillary dissection results. Sensitivity, specificity and accuracy of the core biopsy in the detection of malignancy were calculated. RESULTS: Thirty-nine patients were assessed with biopsy; 30 patients were found to have metastatic carcinoma and nine had benign reactive hyperplasia. In 26 of 30 cases with biopsy-proven metastatic disease, there were malignant lymph nodes detected at axillary dissection. Four cases that had positive biopsy results and negative axillary dissection were accepted as complete response to chemotherapy. In three of nine cases with benign reactive hyperplasia, axillary dissection revealed metastatic disease. No significant complications were observed other than pain responding to analgesics. The sensitivity, specificity and accuracy of core biopsy in detection of malignancy were 90%, 100% and 92%, respectively. The results were statistically significant (p<0.001). CONCLUSION: Ultrasonographically detected lymph nodes can be easily assessed by US-guided biopsy. Core biopsy is a reliable and easily performed method without significant complications.


Subject(s)
Biopsy, Needle/methods , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Lymph Nodes/diagnostic imaging , Lymph Nodes/pathology , Sentinel Lymph Node Biopsy/methods , Ultrasonography, Mammary/methods , Adult , Aged , Axilla/diagnostic imaging , Axilla/pathology , Female , Humans , Lymphatic Metastasis , Middle Aged , Radiography , Reproducibility of Results , Sensitivity and Specificity
20.
Dermatol Online J ; 10(1): 9, 2004 Jul 15.
Article in English | MEDLINE | ID: mdl-15347491

ABSTRACT

Acquired lymphangiectasis is a dilatation of lymphatic vessels that can result as a complication of surgical intervention and radiation therapy for malignancy. Acquired lymphangiectasis shares clinical and histological features with the congenital lesion, lymphangioma circumscriptum. Diagnosis and treatment of these vesiculobullous lesions is important because they may be associated with pain, chronic drainage, and cellulitis. We describe patient who had these lesions after treatment for cancer. Although a number of treatment options are available, we have found cryosurgery and electrocautery to be particularly effective.


Subject(s)
Breast Neoplasms/therapy , Carcinoma, Lobular/therapy , Lymphangiectasis/etiology , Postoperative Complications/etiology , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Carcinoma, Lobular/drug therapy , Carcinoma, Lobular/radiotherapy , Carcinoma, Lobular/surgery , Chemotherapy, Adjuvant , Combined Modality Therapy , Cryosurgery , Electrocoagulation , Female , Humans , Lymphangiectasis/surgery , Mastectomy, Segmental/adverse effects , Postoperative Complications/surgery , Radiotherapy, Adjuvant/adverse effects
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