The feasibility and added value of indocyanine green tracing in guiding sentinel lymph node biopsy for breast cancer.

OBJECTIVE: To compare the effectiveness of combined (indocyanine green [ICG]+ blue dye) tracing versus blue dye alone in guiding sentinel lymph node biopsy (SLNB) in breast cancer. METHODS: A total of 112 female patients (mean ± SD age: 51.9 ± 11.9 years) with clinically node-negative (cN0) early-stage breast cancer were evaluated based on SLN tracing technique including methylene blue + ICG (n = 17), isosulfan blue + ICG (n = 19) and methylene blue alone (n = 76). Mapping patterns of each SLN, the number of total lymph nodes (TLNs) removed, including metastatic and hyperplastic lymph nodes, and the metastatic lymph node detection rate were analyzed for each tracing technique. RESULTS: SLN detection rate was 100 % with complementary use of ICG. No significant difference was noted between methylene blue + ICG, isosulfan + ICG and methylene blue alone groups in terms of the mean ± SD number of TLNs removed (3.9 ± 2.5, 4.7 ± 3 and 3.7 ± 2.3, respectively) and metastatic lymph node detection rates (16.0 %, 16.25 % and 13.98 %, respectively). Complementary use of ICG revealed the N0 stage for 66.6 % of cases considered as Nx (cannot be detected) on blue dye alone. Also, 20.0 % of N0 and 11.1 % of N1 cases on blue dye were diagnosed with more advance nodal status (N1 and N2 respectively) after complementary use of ICG. CONCLUSIONS: The combined tracing (ICG + blue dye) seems valuable not only in terms of the SLN detection rates and lymph node yield but also has an added value in providing more accurate nodal stating and thus a proper final tumor staging with considerable therapeutic implications.

Circulating miR-195 as a Therapeutic Biomarker in Turkish Breast Cancer Patients.

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.

Evaluation of genetic variations in miRNA-binding sites of BRCA1 and BRCA2 genes as risk factors for the development of early-onset and/or familial breast cancer.

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.