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. Huang C-N, Huang S-P, Pao J-B, Hour T-C, Chang T-Y, Lan Y-H, Lu T-L, Lee H-Z, Juang S-H, Wu P-P, Huang C-Y, Hsieh C-J, Bao B-Y (Kaohsiung Medical University Hospital, Kaohsiung; Kaohsiung Medical University, Kaohsiung; Taipei City Hospital, Taipei; Kaohsiung Medical University, Kaohsiung; China Medical University, Taichung; National Taiwan University Hospital; Oriental Institute of Technology; National Taiwan University, Taipei; China Medical University Hospital, Taichung, Taiwan). Genetic polymorphisms in oestrogen receptor-binding sites affect clinical outcomes in patients with prostate cancer receiving androgen-deprivation therapy. J Intern Med 2012; 271: 499-509. Background. Accumulating evidence indicates that oestrogens have significant direct effects on normal prostate development and carcinogenesis. The majority of the biological activities of oestrogens are mediated through the oestrogen receptor (ER), which functions as a hormone-inducible transcription factor to regulate target gene expression by binding to oestrogen response elements (EREs) in the regulatory regions of target genes. Sequence variants in EREs might affect the ER-ERE interaction and subsequent physiological activities. Therefore, we tested whether common single-nucleotide polymorphisms (SNPs) inside EREs are related to the clinical outcomes of androgen-deprivation therapy (ADT) in men with prostate cancer. Methods. We systematically evaluated 49 ERE SNPs predicted using a genome-wide database in a cohort of 601 men with advanced prostate cancer treated with ADT. The prognostic significance of these SNPs on disease progression, prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) after ADT was assessed using Kaplan-Meier analysis and a Cox regression model. Results. Based on multiple hypothesis testing, BNC2 rs16934641 was found to be associated with disease progression; in addition, TACC2 rs3763763 was associated with PCSM, and ALPK1 rs2051778 and TACC2 rs3763763 were associated with ACM. These SNPs remained significant in multivariate analyses that included known clinicopathological predictors. Moreover, a combined genotype effect on ACM was observed when ALPK1 rs2051778 and TACC2 rs3763763 were analysed in combination. Patients with a greater number of unfavourable genotypes had a shorter time to ACM during ADT ( P for trend <0.001). Conclusion. The incorporation of ERE SNPs into models with known predictors might improve outcome prediction in patients with prostate cancer receiving ADT. [ABSTRACT FROM AUTHOR]

Background: Activated androgen receptor binds to androgen-responsive elements (AREs) in genome to regulate target gene transcription and, consequently, mediates physiological or tumorigenic processes of the prostate. Our aim was to determine whether genetic variants in AREs are associated with clinical outcomes after androgen-deprivation therapy (ADT) in prostate cancer patients. Patients and methods: We systematically investigated 55 common single-nucleotide polymorphisms (SNPs) in the genome-wide insilico-predicted AREs in a cohort of 601 men with advanced prostate cancer treated with ADT. The prognostic significance of these SNPs on disease progression, prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) after ADT was assessed by Kaplan–Meier analysis and Cox regression model. Results: In univariate analysis, two, five, and four SNPs were associated with disease progression, PCSM, and ACM, respectively. After adjusting for known prognostic factors, ARRDC3 rs2939244, FLT1 rs9508016, and SKAP1 rs6504145 remained as significant predictors for PCSM and FBXO32 rs7830622 and FLT1 rs9508016 remained as significant predictors for ACM in multivariate analysis. Moreover, strong combined genotype effects on PCSM and ACM were also observed (Ptrend < 0.001). Conclusion: Our results suggest that SNPs in AREs influence prostate cancer survival and may further advance our understanding of the disease progression. [ABSTRACT FROM PUBLISHER]

Background In response to Choosing Wisely recommendations that sentinel lymph node biopsy (slnb) should not be routinely performed in elderly patients with node-negative (cN0), estrogen receptor-positive (er+) breast cancer, we sought to evaluate how nodal staging affects adjuvant treatment in this population. Methods From a prospective database, we identified patients 70 or more years of age with cN0 breast cancer treated with surgery for er+ her2-negative invasive disease during 2012-2016. We determined rates of, and factors associated with, nodal positivity (pN+), and compared the use of adjuvant radiation (rt) and systemic therapy by nodal status. Results Of 364 patients who met the inclusion criteria, 331 (91%) underwent slnb, with 75 (23%) being pN+. Axillary node dissection was performed in 11 patients (3%). On multivariate analysis, tumour size was the only factor associated with pN+ (p = 0.007). Nodal positivity rates were 0%, 13%, 23%, 33%, and 27% for lesions preoperatively sized at 0-0.5 cm, 0.5-1 cm, 1.1-2.0 cm, 2.1-5.0 cm, and more than 5.0 cm. Compared with patients assessed as node-negative, those who were pN+ were more likely to receive axillary rt (lumpectomy: 53% vs. 1%, p < 0.001; mastectomy: 43% vs. 2%, p < 0.001), and adjuvant systemic therapy (endocrine: 82% vs. 69%; chemotherapy plus endocrine: 7% vs. 2%, p = 0.002). Conclusions Of elderly patients with cN0 er+ breast cancer, 23% were pN+ on slnb. Size was the primary predictor of nodal status, and yet significant rates of nodal positivity were observed even in tumours preoperatively sized at 1 cm or less. The use of rt and systemic adjuvant therapies differed by nodal status, although the long-term oncologic implications require further investigation. Multidisciplinary input on a case-by-case basis should be considered before omission of slnb. [ABSTRACT FROM AUTHOR]

Background In 2009, a Rapid Access Breast Clinic (RABC) was opened at our urban hospital. Compared with the traditional system (TS), the navigated care through the clinic was associated with a significantly shorter time to surgical consultation. Since 2009, many radiology facilities have introduced facilitated-care pathways for patients with breast pathology. Our objective was to determine if that change in diagnostic imaging pathways had eliminated the advantage in time to care previously shown for the RABC. Methods All patients seen in the RABC and the office-based TS in November-December 2012 were included in the analysis. A retrospective chart review tabulated demographic, surgeon, pathology, and radiologic data, including time intervals to care for all patients. The results were compared with data from 2009. Results In 2012, time from presentation to surgical consultation was less for the RABC group than for the TS group (36 days vs. 73 days, p < 0.001) for both malignant (31 days vs. 55 days, p = 0.008) and benign diagnoses (43 days vs. 79 days, p < 0.001). Comparing the 2012 results with results from 2009, a decline in mean wait time was observed for the TS group (86 days vs. 73 days, p = 0.02). Compared with patients having investigations in the TS, RABC patients with cancer were more likely to undergo surgery within 60 days of presentation (33% vs. 15%, p = 0.04). Conclusions The coordination of radiology and clinical care reduces wait times for diagnosis and surgery in breast cancer. To achieve recommended targets, we recommend implementation of more systematic coordination of care for a breast cancer diagnosis and of navigation to surgeons for patients needing surgical care. [ABSTRACT FROM AUTHOR]