bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of androgen receptors expression in triple negative breast cancer patients and its correlation with clinicopathological criteria: Our institutes experience.
Authors: Farag Kamel , Elfarargy Ola , El Shorbagy Shereen , Ahmed Safa , Harb Ola , Amin Reham , Gertallah Loay , Megahed Ola , Abdel-latif Rasha 
Published: September 2018

e12584 Background: Triple negative breast cancer (TNBC) is a term that has been applied to breast cancers which lack expression of three receptors: estrogen receptor (ER), progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER2). It represents about 20% of breast cancers diagnosed worldwide. TNBC is a challenging type by its presentation criteria and limited options of treatment. Continuous research for finding specific target is the aim of scientists. Androgen receptors (AR) expression take special attention in this type of breast cancer as its expression can help for finding special targeted treatment as antiandrogen therapy.Purpose:is to assess the AR expression in TNBC patients and to correlate its expression with clinicopathological parameters and disease outcome of patients in study populations. Methods: This prospective study included 90 female patients confirmed as TNBC patients in medical oncology and clinical oncology departments, in Mansoura University and Zagazig University, Egypt, between December, 2013 to May, 2016. AR positive expression was defined as ≥10% nuclear immunostaining. Results: AR expression was positive in twenty seven (27/90) patients (30% ), and lack of its expression was significantly associated with younger age group(p < 0.001), higher grade(p = 0.017)& higher tumor stage(p < 0.001), presence of lymph node metastasis(p < 0.001) & distant metastases(p = 0.032), vascular(p = 0.044)& perineural invasion and high baseline CA 15-3 level (p < 0.001).Median follow up duration was 17.5months (range 6-40), 32/90 died (35.6%).Mean OS was 28months for AR negative TNBC patients versus 32months for AR positive patients. Twenty four of died patients (24/32) were AR negative. Three years OS was 50.8% and 44.1% for AR positive and AR negative respectively, but with nonsignificant P-value. Conclusions: Our study confirmed that AR positive expression in TNBC is a good prognostic feature and it can be sued as target for antiandrogen therapy in this group who is lacking any targettreatment.
Expression of androgen receptor and epidermal growth factor receptor in invasive breast cancer: A retrospective study of 1,438 patients from China.
Authors: Chen Junqing , Chen Zhanhong , Wang Xiaojia 
Published: September 2018

e12587 Background: Triple-negative breast cancer (TNBC) is lack of clinically efficient targeted therapies and usually more aggressive with higher rate of distant metastasis and poor overall survival as compared with other breast cancer subtypes. Recent evidence demonstrates that androgen receptor (AR) and epidermal growth factor receptor (EGFR) are involved in the pathogenesis of TNBC. The aim of this study was to explore the expression of AR and EGFR in invasive breast cancer and evaluate the potential of AR and EGFR as biomarkers in TNBC. Methods: In this retrospective study, we analyzed 1438 patients with invasive breast cancer in our hospital from 2015 to 2016. Estrogen receptor (ER) expression, progesterone receptor (PR) expression, Ki-67 index, AR and EGFR expression were detected by immunohistochemical assay. HER2 state was determined by immunohistochemical and FISH assay. χ2 test was used for the analysis. Results: Among 1438 breast cancer patients, 272 (18.9%) cases were TNBC and 1165 (81.0%) cases were non-TNBC. TNBC patients had a low AR expression as compared with non-TNBC patients (29.8% vs 90.2%). There was a significant difference in AR expression in TNBC compared in non-TNBC ( P= 0.000). In contrast, TNBC patients had a high EGFR expression as compared with non-TNBC patients (90.9% vs 21.1%) ( P= 0.000). There was also a significant difference in Ki-67 index in TNBC compared in non-TNBC (89.9% vs 70.1%) ( P= 0.000). AR-positive TNBC patients had a low Ki-67 index expression as compared to AR-negative TNBC (82.7% vs 93.6%). No significant difference of EGFR expression was found between AR-positive TNBC and AR-negative TNBC. Conclusions: AR expression is associated with Ki-67 index and may be as a potential biomarker for targeted therapy in AR-positive TNBC patients.
The association between neutrophil to lymphocyte ratio and overall survival in patients with triple-negative breast cancer.
Authors: Patel Dilan Anil , Hassan Bilal , Luo Jingqin , Ma Cynthia X. , Campian Jian Li 
Published: September 2018

e12591 Background: Recent reports have suggested that an elevated neutrophil to lymphocyte ratio (NLR) is associated with poor outcomes in various malignancies. Furthermore, radiation therapy (RT) alone or in combination with chemotherapy often results in reduced absolute lymphocyte counts (ALC), which has been postulated to impair host immune surveillance and anti-tumor responses. We sought to better understand whether an elevated NLR results in impaired OS in patients with triple-negative breast cancer. Methods: Our retrospective analysis was performed on a database of patients with biopsy proven triple-negative breast cancer treated at Washington University in St. Louis between 2002 and 2010. Patients who received radiation therapy and had adequate follow up in terms of clinical documentations and laboratory data were included. NLR and ALC were collected at baseline, post-adjuvant chemotherapy, prior to RT, end of RT, 2 months post RT, 1 year post RT, and completion of all planned treatments. Results: Total of 155 patients were included. We used a cutoff value of 3.0 to classify high NLR. Wilcoxon rank-sum test was used to compare NLR at each time point between deceased and alive patients. High NLR post chemotherapy is associated with worse OS (HR 1.127, 95% CI = 1.016-1.249; p<0.05). In addition, NLRs from end of RT, 2 months post and 1 year post RT are associated with worse OS: (HR 1.109, 95% CI = 1.059–1.161; p < 0.001); (HR 1.074, 95% CI = 1.041–1.109; p < 0.001); (HR 1.069, 95% CI = 1.048–1.091; p < 0.001) respectively. Conclusions: High NLR post-chemotherapy and RT are associated with worse OS in patients with triple-negative breast cancer.Further studies are warranted to establish NLR as a prognostic marker and an addition to risk prediction models. [Table: see text]
BRCA mutation carriers undergoing combined mastectomy with immediate reconstruction and gynecologic risk-reducing surgery: An analysis of outcomes.
Authors: Ivanov Olga , Centers Nicole , Wiercinski Karen , Reina Eva , Buffington Cynthia , Caceres Aileen 
Published: September 2018

e13004 Background: The aim of this study was to assess outcomes of a multidisciplinary model for combined prophylactic and/or therapeutic mastectomy with immediate reconstruction and gynecologic risk-reducing surgery in patients with hereditary breast cancer syndromes. Methods: Between 2012 and 2016, 12 patients with documented BRCA1 and BRCA2 mutations underwent combined surgery at our facility. Procedures included bilateral mastectomy, axillary lymph node staging, immediate expander based reconstruction and minimally invasive salpingo-oophorectomy with added hysterectomy when indicated. All procedures were performed in a single operating room setting by rotating subspecialty teams. Results: Patient characteristics included a mean (+SD) BMI of 32.1±6.7 (23-44) kg/m2 and ASA of 2.2±0.4 (2-3). Fifty-eight percent (7/12) were premenopausal. Patient’s average age was 45.8+10.8 (30-73). Therapeutic mastectomy for breast cancer was performed in 4/12 patients. Of the 4 affected patients 2 had neo-adjuvant chemotherapy for locally advanced cancer. The remaining 8/12 had prophylactic mastectomies. Risk-reducing salpingo-oophorectomy was performed in 12/12 patients. Seventy-five percent (9/12) underwent concurrent minimally invasive hysterectomy for suspected gynecologic malignancy, leiomyoma, complex endometrial hyperplasia, dysmenorrhea and menorrhagia. Two gynecologic specimens required mini-laparotomy for removal. Mean total operative time was 283.3±66.5 (206-447) minutes and estimated blood loss (EBL) was 209.2±139.2 (50-500) ml. Hospital length of stay (LOS) was 1.4±0.7 (1-3) days. There were no significant differences (p > 0.05) in operative time, EBL, or LOS in comparing therapeutic to prophylactic mastectomies. Follow-up revealed no postoperative wound infections. Conclusions: Combined mastectomy with immediate reconstruction and gynecologic risk reducing surgery had no untoward surgical complications with a zero postoperative wound infection rate. Although a small study population, results indicate this approach is a prudent and feasible multidisciplinary model that can be offered to BRCA mutation carriers.
Germline and somatic SNVS calling in NGS panel tumor samples: Approaches to optimize tumor only genomic analysis for cancer precision medicine.
Authors: Sun Ruobai , Cingolani Pablo , Pantazi Angeliki , Eifert Cheryl , Huang Xiu , Bjonnes Andrew , Lyle Stephen , Protopopov Alexei , Vuzman Dana 
Published: September 2018

e13011 Background: Clinical NGS is often limited by tumor only profiling. Discrimination between somatic and likely germline mutations when calling from tumor patient samples is a critical step for clinical genotyping. Many algorithms have been developed for somatic single nucleotide variant (SNV) detection in matched tumor-normal whole genome and whole exome sequencing. Here, we demonstrate approaches of how a cost-effective large gene panel sequencing can be used to call somatic and germline SNVs for tumor only samples. Methods: Tumor, adjacent normal, and matched normal samples are collected from five patients. The somatic mutations were called with GATK Mutect2 in tumor only and adjacent normal. The germline mutations were called individually for all 15 samples with GATK Haplotype caller. To remove germline mutations from tumor only somatic calls, the filters ExAc pop freq, 1000G pop freq, COSMIC were applied on the tumor only somatic calls. PPV (Positive predictive value) for each filter was calculated by dividing the number of somatic mutations in the post-filtering mutation data by the total number of unfiltered mutations. TPR (True Positive Rate, representing sensitivity) was calculated by dividing the number of true somatic mutations in the tumor-only post-filter. Results: Compared with germline mutations called from matched normal, 70% germline mutations were called in RAWE somatic calls. A PPV of 0.71 and a TPR of 0.95 were optimally provided when the filter ExAc pop freq > 0.01 and COSMIC ( > 5 occurrence) applied. For germline mutations called in tumor samples, when compared with those in blood samples and in adjacent normal samples, PPV is 0.99 and TPR is 0.97. For somatic mutations called with tumor-adjacent normal pair mode in Mutect2, PPV is 0.5 and TPR is 0.99. Conclusions: Optimization of tools and parameters in NGS large panels could detect somatic and germline variants with high specificity, sensitivity and accuracy, without matched or adjacent normal. For the germline variants, when adjacent normal is available, it could replace matched normal with high accuracy.
Pan-cancer panel testing in individuals with abnormal immunohistochemistry (IHC) staining of the mismatch-repair (MMR) genes.
Authors: Pan Shujuan , Cox Hannah C , Brown Krystal , Willmott Jamie , Gorringe Heidi , Mundt Erin , Rosenthal Eric Thomas , Bowles Karla , Coffee Bradford , Mancini-Dinardo Debora 
Published: September 2018

e13014 Background: IHC staining of the MMR genes is often used to screen for Lynch syndrome (LS) in patients with newly diagnosed colorectal cancer (CRC) and endometrial cancer (EC). Genetic testing of MMR genes guided by IHC has historically been used to confirm a diagnosis of LS. Given the known genetic heterogeneity of LS-related cancers, we assessed the extent to which IHC results reliably predicted findings with pan-cancer panel testing. Methods: We analyzed results from pan-cancer panel testing of 750 individuals with abnormal IHC results from 2013-2016. The panel included the MMR genes and other genes associated with CRC and/or other cancers. All clinical data, including IHC results, were obtained from provider-completed test request forms. Results: CRC (66.0%) was the most common cancer among tested individuals with abnormal IHC results, followed by EC (35.1%). 236 pathogenic variants (PVs) were identified in 228 (30.4%) individuals, 8 of whom carried two distinct mutations. Overall, 191 (80.9%) PVs occurred in MMR genes that were concordant with IHC results. The remaining 45 (19.1%) PVs were not predicted by IHC results, and included two PVs in MMR genes ( MSH6 PV with MLH1/PMS1 absent in IHC, MSH2 PV with PMS2 absent in IHC). The majority of PVs that were not predicted by IHC results occurred in non-MMR genes associated with CRC and EC (n=27, 60.0%; see Table). Conclusions: In this cohort, PVs were identified in 30% of individuals with abnormal IHC who were tested with a pan-cancer panel. Nearly 20% of PVs occurred in non-MMR genes that would be missed by MMR gene-specific testing based on IHC results. Collectively, this suggests pan-cancer panel testing may increase diagnostic yield among individuals with abnormal IHC. [Table: see text]
Association of breast cancer risk in women of African ancestry with genetic variants in the TET-related DNA demethylation pathway.
Authors: Lee Kris M. , Wang Shengfeng , Huo Dezheng , Ogundiran Temidayo O. , Ojengbede Oladosu , Zheng Wei , Nathanson Katherine L. , Nemesure Barbara , Ambs Stefan , Zheng Yonglan , Olopade Olufunmilayo I. 
Published: September 2018

e13015 Background: Imbalance in DNA methylation/demethylation cycles due to mutations in TET1, TET2, TET3, and TDG has been implicated in the onset and progression of breast cancer. However, few studies have assessed the relationship between genetic variants in the TET-related DNA demethylation pathway and breast cancer risk, particularly among women of African ancestry. Methods: We investigated 4095 single-nucleotide polymorphisms (SNPs) in four TET-related DNA demethylation pathway genes in the ROOT consortium, which includes women of African ancestry, in 1657 cases [403 estrogen receptor-positive (ER+) and 374 ER-negative (ER-)] and 2029 controls. Pathway and gene-level analyses were conducted using the adaptive rank truncated product (ARTP) test for 925 SNPs that were not highly correlated (r2 < 0.8), and SNP-level analyses were conducted with logistic regression, which was used to estimate the odds ratio (OR) and 95 % confidence intervals (CI). Results: The Tet-related DNA demethylation pathway was significantly associated with ER-negative breast cancer (pathway level P = 0.049). Gene-level analyses showed that TET1 was the candidate gene responsible for the association at the pathway level ( P = 0.008). SNP TET1 rs10998376 (OR = 1.21, 95% CI = 1.02-1.42, Padj = 0.0032) was statistically significant even after gene-level correction for multiple comparisons, and was associated with increased risk. There were no SNPs in genes with P > 0.05 in the ARTP tests that were significant after Boferroni correction. Conclusions: In conclusion, specific TET-related DNA demethylation pathway genes may contribute to breast cancer risk, in particular, to risk of ER-negative tumors in women of African ancestry.
Do BRCA 1 mutations affect selected molecular variables in women with breast and ovarian cancer carrying cerebral metastases?
Authors: Markowska Janina , Markowska Anna , Szarszewska Monika , Sajdak Stefan , Knapp Pawel , Grybos Anna , Olejek Anita , Bednarek Wiesława , Marszalek Andrzej , Markwitz Ewa , Jach Robert , Tomczak Piotr , Chudecka-Glaz Anita Monika , Ramlau Rodryg , Filas Violetta , Grybos Marian , Stanislawiak-Rudowicz Joanna , Jaszczyńska-Nowinka Karolina , Adamska Krystyna 
Published: September 2018

e13017 Background: Cerebral metastases develop in 10-30% of patients with breast cancer and in around 3.3 to 4% of patients with ovarian cancer. The present study evaluates the expression of ER alpha and beta receptors, PR, HER2 and markers associated with metastases: stromal cell-derived factor-1 (SDF1) and its receptor CXCR4, breast cancer metastasis suppressor (BRMS1), astrocyte elevated gene (AEG-1), depending on the status of BRCA1 protein in cancerous cells of the patients (somatic mutation). Methods: The material originated from 30 women with breast cancer and 22 patients with ovarian cancer in whom cerebral metastases were detected. The studies were conducted on paraffin block sections, the markers were detected using immunocytochemistry, employing specific antibodies. Results: In the breast cancer group, BRCA 1 protein expression was detected in 11 patients, absence of the protein in 19. No significant differences were disclosed in the grade of ER, PR, HER2, SDF1, CXCR4, BRMS1 or AG-1 expression which would be dependent on the status of BRCA1. Expression of the proteins failed to correlate with patients' age, clinical advancement at diagnosis, presence of metastases to lymph nodes. Patients with no PR expression significantly more frequently manifested high expression of CXCR4 (p = 0.0436). The ovarian cancer group included 7 patients with expression of BRCA1 protein, absence of such expression was recorded in 15 patients. No statistically significant differences were disclosed in the expression of the studied factors which would be related to the status of BRCA1 in cancer cells. Also, no differences were detected in the expression of the studied factors which would depend on the patient’s age, primary advancement of the disease or histological type of the cancer. Conclusions: Among numerous molecular factors examined in women with breast or ovarian cancer no statistically significant differences were detected which would depend on BRCA1 protein status in cancer cells. The absence of PR expression in women with breast cancer was associated with high expression of CXCR4, which might indicate that PR-negative women with breast cancer exhibit higher metastatic potential.
Minnesota healthcare providers’ breast cancer screening practices at the extremes of age.
Authors: Teoh Deanna Gek Koon , Vogel Rachel Isaksson , Allen Alicia , Blaes Anne Hudson , Mason Susan , Nagler Rebekah , Raymond Nancy , Talley Kristine , Wyman Jean 
Published: September 2018

e13037 Background: Breast cancer screening guidelines disagree on the age to initiate and discontinue screening. We sought to determine the age at which Minnesota providers initiate and discontinue breast cancer screening. Methods: A cross-sectional online survey of Minnesota primary care providers was conducted in 2016. The survey queried providers’ breast screening practices for average-risk women. Data were summarized using descriptive statistics and comparisons by professional characteristics were conducted using Chi-squared tests. Results: There were 805 respondents (8% of 10,392 invitees), of which 456 (56.7%) provided primary care to women and were included in the analysis. 316 (72%) were women, 193 (44%) were physicians, 50 (11%) were physician assistants (PAs), and 197 (45%) were advanced practice nurses (APNs). 85% practiced in a community setting. 38% had practiced > 20 years, and 27% had practiced < 10 years. Among respondents, 67%, 77% and 72% recommended screening mammography for women age 40-44, 45-49 and 70+ years, respectively. Compared to male providers, female providers were more likely to screen women age 40-44 years (73% vs. 49%; p < 0.0001) and 45-49 years (81% vs. 66%; p = 0.002), but there was no difference by gender for patients age 70+ years (72% vs. 74%; p = 0.89). Respondents reporting specialized interest in women’s health were more likely to screen women age 40-44 years (73% vs. 61%; p = 0.006), 45-49 years (83% vs 72%; p = 0.007) and older than age 70 years (77% vs. 69%; p = 0.04). Physicians were less likely to screen women age 40-44 and 45-49 years (57% and 71%, respectively; p = 0.001) than PAs (72%, 78%) and APNs (74%, 83%), but APNs were less likely to screen women age 70+ years (65% vs. physicians 79% vs. PAs 76%; p = 0.006). Number of years in practice was not associated with a difference in age at initiation of screening, however, increasing number of years in practice was associated with screening women age 70+ years (p = 0.02). Conclusions: Although breast cancer screening practices for average risk women vary by healthcare provider characteristics, a majority of Minnesota primary care providers initiate breast cancer screening between ages 40-49 years, and continue screening women age 70 years and older.
Cost-effectiveness of surveillance and prevention strategies in BRCA 1/2 mutation carriers.
Authors: Yamauchi Hideko , Nakagawa Chizuko , Kobayashi Makoto , Kobayashi Yusuke , Mano Toshiki , Nakamura Seigo , Arai Masami 
Published: September 2018

e13051 Background: Cost-effectiveness analysis is important in healthcare, especially in Japan, where preventive measures for carriers of BRCA 1/2 mutations are not covered by health insurance. Methods: We developed Markov models in a simulated cohort of women aged 35–70, and compared outcomes of surveillance with risk-reducing mastectomy at age 35 (RRM), risk-reducing salpingo-oophorectomy at age 45 (RRSO), and both (RRM&RRSO), with quality adjustment. We used breast and ovarian cancer incidence, and adverse event rates from previous studies, adjuvant chemotherapy and hormonal therapy rates from Hereditary Breast and Ovarian Cancer Registration 2015, mortality rates from the National Cancer Center Hospital, Japan Society of Clinical Oncology and Ministry of Health, Labour and Welfare, and direct costs in 2016 Japanese yen from St. Luke’s International Hospital and Keio University Hospital. We used preference ratings for both of mutation carriers and controls (without known high risk) from a published study to adjust survival for quality of life (QALYs). Discount rate was 2%. Results: Compared with surveillance, RRSO and RRM & RRSO were dominant (cost-saving and more effective) and RRM was cost effective for BRCA 1 mutation carriers. RRM and RRM & RRSO were dominant, and RRSO was cost effective for BRCA 2 mutation carriers. Among four strategies including surveillance, RRM & RRSO was the most cost effective for BRCA 1 mutation carriers and RRM was the most cost effective for BRCA 2 mutation carriers based on preference ratings of controls. Conclusions: With quality adjustment, all the preventive strategies (RRM, RRSO and RRM&RRSO) were cost effective for BRCA 1 and 2. Using QALYs from the control group, RRM & RRSO for BRCA 1 and RRM for BRCA 2 were the most cost effective. We will use this result to promote insurance coverage for BRCA mutations carriers in Japan.