bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigations of breast cancer screening using a novel in vitro diagnostics technology.
Authors: Tao Hongmei , Du Xuedong , Tang Xing , Lin Yue , Lou Da , Yu Chris Chang 
Published: February 2017

13 Background: A newly developed in-vitro diagnostic technology named Cancer Differentiation Analysis Technology (CDA) was investigated for breast cancer screening. The CDA technology is a blood-sample based, multi-level, multi-parameter diagnostic method which detects signals from both proteins and cells, in which multiple aspects and parameters of information were collected to improve diagnostic accuracy. Methods: Blood samples from breast cancer group (n = 222), and control subjects (n = 204) were collected in EDTA tubes. CDA values were measured using a CDA medical device. The results were shown in Table 1 and Figure 1 below. Results: The average CDA values of breast cancer and control groups were 50.43 and 34.03 (rel. units) respectively. The results indicated that breast cancer could be significantly distinguished from the control (p < 0.001). Area under ROC curve was 0.914. When Youden Index reached the maximum, sensitivity and specificity was 82.0% and 89.2% respectively. Conclusions: Initial results showed that CDA technology could be a potential candidate for breast cancer screening. [Table: see text]
The synergistic effect between celecoxib and luteolin and dependence on estrogen receptor in human breast cancer cells.
Authors: Jeon Ye-Won , Suh Youngjin 
Published: February 2017

135 Background: The anti-cancer effects of celecoxib and luteolin are well known. Although our previous study demonstrated that the combination of celecoxib and luteolin synergistically inhibits breast tumor growth compared with each of the treatments alone, we did not uncover the molecular mechanisms of these effects. The aims of our present study were to compare the effects of a celecoxib and luteolin combination treatment in four different human breast cell lines and to determine the mechanisms of action in vitro and in vivo. Methods: Using MCF-7, MCF7/HER18, MDA-MB-231 and SkBr3 human breast cancer cells, proliferation assay, apoptosis assay, inhibition assay with MEK and PI3K inhibitor in addition to western blotting and xenograft study after treatment with celecoxib and luteolin. Results: The synergistic effects of a celecoxib and luteolin combination treatment yielded significantly greater cell growth inhibition in all four breast cancer cell lines compared with the single agents alone. In particular, combined celecoxib and luteolin treatment significantly decreased the growth of MDA-MB-231 cancer cells in vivo compared with either agent alone. The celecoxib and luteolin combination treatment induced synergistic effects via Akt inactivation and extracellular signal-regulated kinase (ERK) signaling inhibition in MCF-7 and MCF7/HER18 cells and via Akt inactivation and ERK signaling activation in MDA-MB-231 and SkBr3 cells. Conclusions: These results demonstrate the synergistic anti-tumor effect of the celecoxib and luteolin combination treatment in different four breast cancer cell lines, thus introducing the possibility of this combination as a new treatment modality.
Neoadjuvant chemotherapy with docetaxel, carboplatin, and weekly trastuzumab (TCH) activity in HER2-positive early breast cancer: Results after a median follow-up of 4.5 years.
Authors: Kolberg Hans-Christian , Akpolat-Basci Leyla , Stephanou Miltiades , Hannig Carla , Liedtke Cornelia 
Published: February 2017

140 Background: Most patients with HER2-positive receive chemotherapy and trastuzumab. Data from adjuvant trials have shown that the combination of docetaxel, carboplatin and weekly trastuzumab (TCH) is well tolerated and as effective as anthracycline containing regimes. Previous investigations on neoadjuvant treatment with TCH showed pCR-rates in the range of 40%, however, survival data have not yet been presented. Here we present 4.5-year follow-up data for a cohort of 51 patients treated with neoadjuvant TCH. Methods: We treated 51 patients with operable HER2-positive breast cancer with a neoadjuvant schedule of docetaxel (75 mg/m2) and carboplatin (AUC 6) q3w and trastuzumab (2(4)mg/kg) q1w. Lymph node involvement was verified by SLNB or core-cut-biopsy. Mean age at diagnosis was 55 years, 68.6% had ER positive tumors, 39.2% presented with grade 3 disease and 49% of patients were node-positive. Patients were monitored by ultrasound. After 6 cycles of chemotherapy all patients had surgery. Axillary dissection was performed in case of positive lymph node status prior to TCH. After surgery trastuzumab was continued q3w up to one year. Results: Side effects were mild, no grade III/IV toxicities occurred and no case of cardiomyopathia was observed. 21 (41.18%) patients achieved a pCR, 18 (72.0%) patients converted from cN+ to ypN0. Outcome data at a median follow-up of 53.6 months are as follows (see table). Conclusions: Outcome following neoadjuvant TCH as observed in our analysis compares well to outcome data observed in adjuvant trastuzumab trials such as HERA or BCIRG006. Particularly among patients with ER positive disease and those experiencing axillary conversion we observed an excellent outcome. Importantly, TCH was well tolerated in our cohort. Therefore our data support the use of TCH as neoadjuvant therapy regimen for patients with HER-positive breast cancer. [Table: see text]
Correlation between Oncotype Dx score with histologic grade, tumor size and Ki67 in patients with early stage breast cancer: A single academic institution experience.
Authors: Lathrop Kate Ida , Mazo- Canola Marcela , Gelfond Jonathan , Hinojosa Barbara , Shiao Jay C , Terracina Katherine A 
Published: February 2017

146 Background: Oncotype DX is an RT-PCR based assay that calculates a recurrence score (RS) to predict chemotherapy benefit in patients with breast cancer. Some authors have proposed using Ki-67, receptor status, Nottingham grade, and tumor size as histo-pathologic variables that could potentially substitute for the RS. Comprehensive and larger reviews are still lacking in this filed. To our knowledge this is the largest retrospective review of cases in a single academic institution. Methods: We retrospectively reviewed and reported baseline patient demographic characteristics (including age, race and gender) and routine pathological features such as histologic grade, Ki-67, tumor size, and histologic type. All patients included in this study had an Oncotype Dx ordered between 2007 and 2014. Results: Our analysis included 252 patients of which 248 were females and 4 were males, median age was 56, median tumor size of 2.1 cm. The majority of cases were grade 2 with 49.4%, followed by grade 3 with 28.1% and grade one represented 22.5% of the sample. Ki-67 ranged from 2-98 %. Three variables correlated significantly with Oncotype Dx: tumor size (p = 0.0115), Ki-67 (p = 1.509e-09) and grade (p = 0.0307). Using these three variables together, the percentage of variance on the Oncotype Dx score was 0.35 (R2- coefficient of determination). Conclusions: While tumor size, grade and Ki-67 individually correlate significantly with Oncotype Dx score, taken together, they cannot reliably predict the RS. Also, the capability of these three factors to predict the RS decreases for tumors with high RS. Therefore, we conclude the RS can provide additional valuable information and should not be replaced by analysis of routine histologic variables alone.
Towards intraoperative microCT imaging of breast cancer resections.
Authors: Salmon Phil , Sasov Alexander 
Published: February 2017

147 Background: MicroCT analysis of breast cancer resections was shown by Rong et al. [Tang R et al. (2013) The Breast Journal 19(5), 485-489; Tang R et al. (2013) Breast Cancer Research and Treatment 139(2), 311-316] to attain equivalence with pathology-histology in the assessment of positive margin. However, Rong et al. noted that the 14 minute scan cycle time–7 minutes scan, 7 minutes reconstruction–was a potential limitation. Methods: This paper reports the development of microCT instrumentation and software to address this and other technical challenges. These include (a) reducing the scan-reconstruction time, (b) a small desktop footprint, (c) reconciling optimal soft tissue contrast with minimizing artefacts from inserted metal wires and large calcifications, and (d) features to aid hospital workflow such as a barcode reader, an optical camera to photograph the specimen, and process automation. Scans were done with the purpose-built SkyScan1275 table-top microCT scanner, on frozen anonymous archived breast cancer resection samples. Results: Minimum scan time retaining acceptable image quality was 3 minutes. Reconstruction time was reduced to less than a minute by PC graphics accelerators. Scan-reconstruction cycle time can thus be < 4 minutes. A small (105 x 64 cm) desktop footprint with a weight of 160 kg, requiring only a sturdy laboratory desk, has also been attained in this scanner. Artefacts from large calcifications and metal wires were reduced to non-obtrusive levels by scanning with 1mm aluminum filter and software techniques. An automated scan sequence was developed with sample holders recognized electronically in the scanner. On pressing a single button, the scanner automatically goes to the appropriate magnification and sample height, scans the sample, then reconstructs the scan with preset parameters, and finally opens the reconstructed dataset in software for interactive volume-rendered viewing. Sample barcode reading and optical photo taking can be included in this auto-scan sequence. Conclusions: These developments bring microCT nearer to realizing its potential as an intraoperative “back-table” technique in breast cancer surgery to obviate revisions and improve the surgery process and outcome.
The SSO/ASTRO Consensus on Breast Margins: Has it affected clinical practice?
Authors: Cate Sarah P. , Greenberg Arielle Brooke , Bassin Leah , Gillego Alyssa , Chadha Manjeet , Aharonoff Gina , Boolbol Susan K. 
Published: February 2017

148 Background: Adequate margin width remains a subject of much controversy in breast conserving surgery. The Society of Surgical Oncology (SSO) and the American Society for Radiation Oncology (ASTRO) presented a consensus statement on margins in December 2014. This guideline stated that re-excision is recommended only in cases where tumor is present on inked margin. In this study, we sought to determine the consensus statement’s impact on re-excision practices at our institution. We examined re-excision rates eleven months before the release and 17 months after the release of the statement. Methods: Patients included in this IRB approved study had a diagnosis of invasive breast carcinoma, underwent breast conserving surgery, and were treated with adjuvant radiotherapy. Patients with pure DCIS were excluded. Results: One hundred and two women treated from January to November 2013 were included in the pre-consensus group. One hundred and three women were treated from December 2013 to May 2015 in the post-consensus group. The women treated prior to the consensus statement (n = 102) and those women treated after the statement (n = 103) were equally matched in terms of patient age, hormone positivity, and tumor size. A close margin at our institution is defined as < 2mm from the tumor edge. There were 16/102 women prior to the consensus who had close margins and 32/103 women in the post-consensus group. Of these, 68.8% (11/16) underwent re-excision for close margins in the pre-consensus group compared to 3.1% (1/32) after the consensus statement was released (p value < 0.01). Conclusions: The rapid adoption of the SSO/ASTRO margin consensus statement at our institution, although not statistically significant, led to a decrease in the number of patients who underwent a re-excision for close margins. Women with a close surgical margin were less likely to undergo additional surgery for re-excision after the guidelines were released. In our institution, using a standard criterion for re-excision, the re-excision rate for close margins decreased from 68.8% to 3.1%. Further studies are needed to examine the impact of the consensus statement on re-excision practices in a larger group of patients.
Phase III randomized, placebo-controlled trial of carboplatin (C) and paclitaxel (P) with/without veliparib (ABT-888) in HER2- BRCA-associated locally advanced or metastatic breast cancer (BC).
Authors: Huggins-Puhalla Shannon Leigh , Han Hyo S. , Diéras Véronique , Friedlander Michael , Somlo George , Arun Banu , Wildiers Hans , Kaufman Bella , Ayoub Jean-Pierre M. , Shah Melissa , Burmedi David , Qin Qin , Qian Jane , Giranda Vincent L. , Shepherd Stacie Peacock 
Published: February 2017

155 Background: BRCA-mutated tumors are more susceptible to platinum therapy and PARP inhibitors due to underlying defects in homologous recombination repair of DNA damage. In preclinical models the potent oral PARP1/2 inhibitor veliparib was shown to enhance sensitivity to C and to have single-agent activity in BRCA+ cell lines. Phase 1 trials suggest promising antitumor activity and acceptable toxicity of veliparib plus C/P in triple-negative BC (Puhalla et al. Cancer Res 2012;72:PD09-06) and single-agent activity of veliparib in BRCA+ BC (Somlo et al. J Clin Oncol 2014;32:abstr. 1021). This phase III trial assesses efficacy and toxicity of veliparib plus C/P vs C/P alone in patients with HER2− BRCA-associated locally advanced or metastatic BC (NCT02163694). Methods: Phase III randomized, double-blind, placebo-controlled, multicenter trial. Eligible patients (female or male; ≥ 18 years) have HER2−metastatic/locally advanced unresectable BC with (suspected) deleterious BRCA1/2 germline mutations and received 2 or fewer prior lines of DNA-damaging chemotherapy for metastatic BC. In addition, patients must have received ≤ 1 prior line of platinum therapy (any setting) without progression within 12 months of completing treatment. Patients are randomized 2:1 to C/P with veliparib or C/P with placebo, stratified by estrogen and/or progesterone receptor expression, prior platinum therapy, and central nervous system metastases. Veliparib (120 mg p.o. BID) or placebo will be given on Days −2 to 5, C (AUC 6 mg/mL/min i.v.) on Day 1, and P (80 mg/m2i.v.) on Days 1, 8, and 15 (21-day cycles). Treatment continues until unacceptable toxicity or progressive disease (PD). Patients in the placebo arm who discontinue due to PD are eligible for crossover to veliparib monotherapy. The primary objective is to assess if the addition of veliparib to C/P increases progression-free survival; additional objectives include evaluation of overall survival, clinical benefit rate, objective response rate, quality of life, and safety. Enrollment began in July 2014 with a planned sample size of 270 patients. Clinical trial information: NCT02163694.
Benefits and safety of multigene panel testing in patients at risk for hereditary breast cancer.
Authors: Kapoor Nimmi S. , Curcio Lisa D. , Blakemore Carlee A. , Bremner Amy K. , McFarland Rachel E. , West John G. , Banks Kimberly C. 
Published: February 2017

16 Background: Recently introduced multi-gene panel testing including BRCA1 and BRCA2 genes (BRCA1/2) for hereditary cancer risk has raised concerns with the ability to detect all deleterious BRCA1/2 mutations compared to older methods of sequentially testing BRCA1/2 separately. The purpose of this study is to evaluate rates of pathogenic BRCA1/2mutations and variants of uncertain significance (VUS) between previous restricted algorithms of genetic testing and newer approaches of multi-gene testing. Methods: Data was collected retrospectively from 966 patients who underwent genetic testing at one of three sites from a single institution. Test results were compared between patients who underwent BRCA1/2testing only (limited group, n = 629) to those who underwent multi-gene testing with 5-43 cancer-related genes (panel group, n = 337). Results: Deleterious BRCA1/2 mutations were identified in 37 patients, with equivalent rates between limited and panel groups (4.0% vs 3.6%, respectively, p = 0.86). Thirty-nine patients had a BRCA1/2 VUS, with similar rates between limited and panel groups (4.5% vs 3.3%, respectively, p = 0.49). On multivariate analysis, there was no difference in detection of either BRCA1/2 mutations or VUS between both groups. Of patients undergoing panel testing, an additional 3.9% (n = 13) had non-BRCA pathogenic mutations and 13.4% (n = 45) had non-BRCA VUSs. Mutations in PALB2, CHEK2, and ATM were the most common non-BRCA mutations identified. Conclusions: Multi-gene panel testing detects pathogenic BRCA1/2 mutations at equivalent rates as limited testing and increases the diagnostic yield. Panel testing increases the VUS rate, mainly due to non-BRCA genes. Patients at risk for hereditary breast cancer can safely benefit from upfront, more efficient, multi-gene panel testing.
Outcomes of retesting BRCA-negative patients using multigene panels.
Authors: Yadav Siddhartha , Fulbright Jennifer , Dreyfuss Heidi , Reeves Ashley , Campian Sarah , Thomas Vicky , Zakalik Dana 
Published: February 2017

23 Background: New technologies for identifying hereditary predisposition to breast cancer have led to the discovery of novel genes associated with cancer risk. This has prompted re-evaluation of patients who previously tested negative for BRCA1/2 gene mutations, with a possibility of discovering new genes which may impact management. This study reports on the results of retesting patients who previously were negative for BRCA1/2. Methods: Patients who tested negative for BRCA1/2 mutations who had significant personal and family history were referred back to the Cancer Genetics Center between February 1, 2012 and May 30, 2105 for discussion of additional testing. A detailed personal and family history was reviewed, and patients were counseled about the genetics and clinical implications of panel testing for multiple breast cancer genes. Panel testing using next generation sequencing technologies was ordered. Patients were seen in follow up for discussion of results and management. Results: A total of 12 pathogenic mutations were identified during the study period. The genes and frequencies of these mutations were: CHEK2(3), PALB2(3), ATM(2), APC(1), BARD(1), CDH(1), MUTYH(1). There were 33 variants of undetermined significance(VUS) in 27 patients. 5 of these were seen in patients with a known pathogenic mutation; 3 others were later classified as benign. The frequencies of these VUSs were: ATM (9), PALB2(3), BARD1 (3), PTEN(3), PMS2(3), MSH6(2), CHEK2 (1), MYH(1), RAD51(1), BRIP1(2), NF1(1), BMPR1A(1). Of the 46 patients who had their initial BRCA testing and repeat panel testing between February 1, 2012 and May 30, 2015, 6 (13%) tested positive for a pathogenic mutation. Conclusions: This study demonstrates the feasibility and potential clinical benefit of retesting individuals who previously tested negative for BRCA1/2 mutation. This approach had a significant management impact on patients and their families, with a 13% detection rate of pathogenic mutations. The success of retesting is predicated upon an infrastructure of provider and patient education, pre and post genetic counseling and serves as a model for other centers.
Neutrophil lymphocyte ratio (NLR) change after systemic treatment as a predictive factor of cancer specific survival in stage IV breast cancer.
Authors: Shin Hae-na , Kim Jisun , Kim Hee Jeong 
Published: February 2017

29 Background: Inflammatory response exacerbates mechanisms linked to tumor growth and dissemination. As an index of systemic inflammatory status, neutrophil lymphocyte ratio (NLR) may be a predictive biomarker of both prognosis and response to therapy. We evaluated initial pre-treatment NLR and post-treatment NLR change to assess whether initial and change in NLR would be predictive of disease outcome in stage IV breast cancer patients. Methods: This study included 250 stage IV breast cancer patients diagnosed at Asan Medical Center between 1997 and 2012. The NLR was calculated from the differential count by dividing neutrophil percentage by lymphocyte percentage. All initial (pre-treatment) NLR was evaluated at the first visit day in Asan medical center. Post-treatment NLR was obtained at the first follow-up visit at the outpatient department after first treatment (chemotherapy first: about after 3weeks/endocrine therapy: after 3~6 months). The initial (pre-treatment) NLR was divided by quartile, and the NLR change was calculated by dividing post-treatment NLR by pre-treatment NLR. If the value was ≥ 1.2, NLR change was increased; if not, it was not changed or decreased. We evaluated prognostic value of NLR by comparison with Cancer Specific Survival (CSS). Results: When comparing pre-treatment NLR and post-treatment NLR, the NLR was increased in 85 patients (34%) and stationary or decreased in 165 patients (66%). There was no significant difference between two groups in baseline characteristics. On the other hand, in CSS, the difference between two groups are shown, but does not have statistical significance (log rank p = 0.052). The 1, 3, 5 year CSS rate was 78.8%, 35.7%, 20.5% in increased NLR group, and 87.1%, 49.3%, 26.9% in the other group. Multivariate analysis suggested that increased NLR change (Post/Pre NLR ≥ 1.2) had statistical significance as prognostic factor of stage IV breast cancer patients after treatment (HR = 1.750, 95% CI 1.130-2.709, p-value = 0.012). Conclusions: After start of treatment, increased NLR can be correlated with poor cancer specific survival in stage IV breast cancer. The NLR change might be an index of response of systemic treatment.