bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics of medullary breast carcinoma compared with invasive ductal carcinoma.
Authors: Park Inhye , Kim Jiyoung , Lee Se-Kyung , Choi Min-Young , Bae Su Yeon , Jung Seung Pil , Kil Won Ho , Lee Jeong Eon , Nam Seok Jin 
Published: February 2017

20 Background: Medullary carcinoma (MC) represents a rare breast cancer subtype associated with a rather favorable prognosis compared with invasive ductal carcinoma (IDC). It is characterized by the high-grade structure and lymphocytic infiltration, hemorrhagic necrosis. The purpose of this study is to compare the clinicopathologic characteristics and outcome of MC to IDC. Methods: We retrospectively reviewed the medical records of patients with invasive breast cancer managed with operation at Samsung Medical Center in Korea from January 1995 to June 2010 except patients diagnosed with ductal carcinoma in situ, patients with distant metastasis at diagnosis or neoadjuvant chemotherapy. 52 cases were identified with MC; 5,716 patients with IDC. The clinicopathologic features, disease-free survival (DFS) and overall survival (OS) for patients with MC were compared with those of the IDC patients. Results: The medullary group presented at younger age (43.9 ± 8.8 vs 47.7 ± 9.9, p=0.006). Also the medullary group was significantly associated with higher histological grade (poor; 80.0 vs 38.3%, p=0.003) and nuclear grade (grade3; 82.8 vs 41.7%, p<0.001) as well as negative ER (84.8 vs 31.0%, p<0.001) and PR status (91.3 vs 38.8%, p<0.001) regarded as poor prognostic factors. But lymphatic invasion was rare (0.0 vs 29.8%, p<0.001) and N stage was low (N0; 86.5 vs 58.4%, p<0.001). The DFS and OS were not significantly different between the medullary and IDC groups. (5-yr DFS : 88.0 vs 89.2 %, p=0.917, 5-yr OS : 94.4 vs 93.4%, p=0.502) In multivariable analysis, factors associated with DFS and OS included nuclear grade, histological grade, tumor size, lymph node metastasis, ER/PR/C-erbB2 status, chemotherapy and hormone therapy. When adjusting for other factors, histological type itself did not show significant difference from IDC in DFS and OS. Conclusions: Despite MC present specific clinicopathologic features, prognosis is not different from IDC and determined by already known prognostic factors such as tumor size, lymph node metastasis. Therefore, the patients with MC also need aggressive treatment like IDC.
The usefulness of ultrasonography in a ductal carcinoma in situ screening program for Japanese woman.
Authors: Kosaka Taijiro 
Published: February 2017

24 Background: Although varying among areas, the mammogram (MMG) screening rate is very low in Japan as compared to the U.S. at approximately 20% versus nearly 80% in the U.S. On the other hand, rates of ductal carcinoma in situ (DCIS) detection among diagnosed breast cancers differ minimally: 20% in the U.S., and 15% in Japan. This is a small difference considering the difference MMG screening rates. Racial differences have been suggested to be attributable to the organization of screening programs in Japan, which also use ultrasonography (US) breast cancer screening, as well as breast size in Japanese women. Methods: We retrospectively evaluated MMG and US images of 91 DCIS cases, all 91 Japanese women who under underwent surgery between May 2010 and February 2012. US (TOSHIBA Aplio, probe 9MHz) was performed with knowledge of MMG findings. The 91 cases were divided into group with tumor detected by MMG and US (M&U), MMG detection only (M), and US detection only (U). The following parameters were analyzed: US shape (Tumor-forming lesion: TFL, Non-tumor-forming lesion: NTFL, Cystic-forming lesion: CFL), Skin-Muscle distance: SMD. We excluded asynchronous bilateral breast cancers and micro-invasive DCIS. Results: Sixty-eight lesions (73.0%) were identified by US, which revealed a NTLF in 52 cases, TLF in 9 cases and CFL in 7 cases. All cases with false-negative findings on US (Group M, n = 23) showed micro-calcifications on MMG (n=22) and with the tumor (n=1). In the U group, SMD was only 23 mm versus 43.4mm in the M group. No difference was observed in body mass index or pathological tumor diameter between the U and M. Conclusions: We found US to reveal DCIS in 73% of our cases upon reevaluation. Although US examination would not likely increase the screening detection rate for DCIS in Japanese women, US may reveal more DCIS in Japanese women, in which the breasts are comparatively small, than in western women. Further comparison of possible racial difference is warranted.
Kinase activity signature of breast cancer using peptide phosphosensors.
Authors: Mori Miki , Coppe Jean-Philippe , Chen Zhongzhong , van't Veer Laura 
Published: February 2017

27 Background: Improper control of phosphorylation networks represents one of the most relevant regulator and biomarkers of cell dysfunctions leading to cancer. Surprisingly however, measuring the phosphorylation activity of kinases, and potentially monitoring the functionality of the entire kinome at once, remains largely unexplored. Specifically, a highly convenient tool for clinical applications or research purposes would be the advent of a microarray-like chip to comprehensively map phosphorylation networks. While developing such a kinase-sensing platform, we had to establish a library of probes capable of reporting on the catalytic activity of kinases. We present here strategies and results supporting such methodology. Methods: The devised kinase activity-sensing system we are currently exploiting, relies on peptide probes that act as beacons to evaluate enzymes functionality, which emit distinctive signals before and after (de-)phosphorylation. As presented below, computational and molecular biology methods were used to create and test such (phospho-)peptide sensors. Results: First, in order to use baits relevant to human cancer etiology, we created a protein and peptide repertoire from thousands of publications and >30 public databases computationally curated, filtered and merged. Such library catalogues 6173 distinctive kinase-substrate active nodes and compiles 2702 unique biological kinase peptide targets that all represent latent nano-sensors usable to comprehensively track kinase signaling networks. Second, real-time kinetics, kinase inhibitor and dilution experiments using 5 recombinant enzymes and cell extracts in ATP consumption assays demonstrated peptide 50 probes can directly and specifically assess the functionality of kinases. A panel of 10 peptides shows that the increased presence of activated Src kinase protein in breast cancer cell extracts is related to a significantly elevated kinase activity signature. Conclusions: Biological peptides can serve as phospho-sensing probes to evaluate the activity of kinases. Our efforts will now focus on expending this approach into a functional kinomic-screening platform to map phosphorylation signatures relevant for breast cancer.
Mutation analysis of PALB2 in high-risk and lower-risk patients negative for BRCA1 and BRCA2 mutations.
Authors: Cummings Shelly , Peterson Jenny , Hughes Elisha , Kaldate Rajesh R. , Chen Sonia , Trost Jeffrey T. , Arnell Christopher , Saam Jennifer R. , Roa Benjamin , Fernandes Priscilla H. 
Published: February 2017

30 Background: PALB2 has been identified as a breast cancer susceptibility gene conferring ~ 2-4 fold increased risk of breast cancer. A number of studies have estimated the PALB2 mutation prevalence to range from 0.5% - 2.9% in populations of breast cancer patients. We performed an analysis to determine the PALB2 mutation prevalence in a large U.S. referral testing population. Methods: DNA samples were anonymized from two subsets of patients: 955 early onset breast cancer patients with severe family history, and 524 patients with later onset of breast cancer and/or less severe family history. All patients were negative for deleterious sequence mutations or large rearrangements in BRCA1 and BRCA2. Results: We identified 10 disease associated PALB2 mutations in the high risk group of 955 patients and 2 deleterious PALB2 mutations in the lower risk group of 524 patients. Identified PALB2 mutations included 8 nonsense, 3 frameshift mutations and a splice site mutation. The mutation prevalence for the high risk population was 1.05% (95% C.I., 0.5 -1.92) whereas that for the lower risk population was 0.38% (95% C.I., 0.05-1.37). The observed rate of PALB2 variants of unknown significance (VUS) identified in this study was ~5% (78 VUS were in 75 of the 1479 patients that were tested). Our variant classification program which successfully decreased the VUS rate in BRCA1 and BRCA2 is similarly expected to enhance mutation classification on an on-going basis for PALB2 genetic testing. Conclusions: Genetic testing for PALB2 may be indicated as a reflex test for breast cancer patients who test negative for BRCA1 and BRCA2.
Identification of AGR3 as a potential biomarker though public genomic data analysis of triple-negative (TN) versus triple-positive (TP) breast cancer (BC).
Authors: Umesh Anita , Park Jenny , Shima James , Delaney Joseph , Wisotzkey Robert , Kelly Erin , Chiu Elizabeth Beatrice , Madhusoodanan Jyoti , Shekar Mamatha , Kupershmidt Ilya 
Published: February 2017

31 Background: TNBCs have an aggressive clinical phenotype with worse prognosis than TPBC. Here we sought to identify other genomic changes in patients with TN vs. TPBC, by mining TCGA breast cancer genomic data using the NextBio Clinical platform. Methods: Breast cancer patients with decreased (n=51) and increased (n=46) ER/PR/HER2 mRNA levels were selected with the molecular filter in NB Clinical. Top-ranked differentially expressed genes were identified then analyzed via NB Research, which comprises a library of individually curated publically available research and clinical grade genomic data. Results: Whole transcriptome analysis of TNBC and TPBC patients identified anterior gradient-3 (AGR3), a protein disulfide isomerase, as most downregulated (TNBC vs. TPBC, fold change = -178.2, p=2.7E-32). AGR3 mRNA was reduced in 94% of TNBC and increased in 96% of TPBC patients. AGR3 was hypomethylated in 50% of TPBC vs. 4% of TNBC patients, suggesting regulation by methylation. When the entire breast cancer cohort was stratified by AGR3 expression, underexpression was prevalent in younger patients (<50 yr, 39%) compared to those with overexpression (<50 yr, 23%). Further, 63% of AGR3 underexpressing patients had severe TP53 mutations vs. 19% with AGR3 overexpression. Breast cancer was most correlated to AGR3 in the NextBio Disease Atlas, with supporting data from 110 studies. AGR3 expression was decreased in ER- vs. ER+, PR- vs. PR+, HER2- vs. HER2+, and G3 vs. G1 tumors, and AGR3 promoter was hypermethylated in ER- vs. ER+, consistent with the TCGA results. Body Atlas showed strongest AGR3 expression in mucosa, fallopian tube, breast, and epithelial cells, in line with its proposed role in epithelial barrier function. Knockdown Atlas results showed TP53 mutation associated with reduced AGR3 mRNA, and the PharmacoAtlas showed positive regulation of AGR3 by estrogen analogues. Conclusions: Using the NextBio Clinical and Research platforms, we identified AGR3 as a marker of TNBC vs. TPBC that correlates with TP53 mutation status. AGR3 may provide an alternate route of TNBC treatment. Its potential in regulating epithelial barrier function may provide insights into the mechanism of disease progression.
Implications prognostics of methylation 14-3-3 sigma promoter in peripheral blood cell DNA with nodal involvement status and tumor size for breast cancer patients.
Authors: Martínez-Galán Joaquina , González Rivas Cynthia S. , Ruiz Vozmediano Julia , Ballesteros Pedro , Delgado Juan Ramón , Ríos Sandra , Núñez M. Isabel , Lopez-Peñalver Jesus , Torres-Torres Blanca 
Published: February 2017

33 Background: Expression of 14-3-3 σ is a tumor suppressor gene induced in response to DNA damage, and has been implicated in G2/M cell cycle arrest by p53. Hypermethylation of CpG islands located in the promoter regions of tumor suppressor genes is now firmly established as an important mechanism for gene inactivation. To correlation methylation levels of promoter 14-3-3σ with association prognostic factors in breast cancer. Methods: This is a prospective study we quantified methylation levels of promoter 14-3-3σ gene in 107 women with breast cancer and 108 control subjects by Real Time QMS-PCR SYBR green and analyzed association with prognostics factor in breast cancer. Results: Median age was 58 years (32-88); 69% were postmenopausal women. Nodal involvement N0; 63%,N1;30%,N2;7%), tumor size (T1;58%,T2;35%,T3;4%,T4;4%) and grade G1; 20%,G2;37%,G3;30%). The methylation of 14-3-3σ were 60% of sporadic breast cancer patients and were 34% of normal breast (p=0.0047). The methylation of 14-3-3σ gene in serum was markedly related with T3-4 stage (p<0.05),nodal positive status (p<0.05) and poor outcome. With a median follow up 6 years we saw more probability of developing distance metastasis in patients with methylation 14-3-3σ (p>0.05). Conclusions: Hypermethylation of the 14-3-3σ a promoter is an early and frequent event in breast neoplastic transformation, leading to the suggestion that silencing of 14-3-3σ may be an important event in tumor progression and particularly in breast carcinogenesis.Therefore, it is possible that loss of σ expression contributes to malignant transformation by impairing the G2 cell cycle checkpoint function, thus allowing an accumulation of genetic defects. Perhaps in the detection of CpG methylation of 14-3-3σ may be used for diagnostic and prognostic purposes.
SIRT1 against breast cancer through downregulating Bcl-2 protein.
Authors: Chen Dar-Ren 
Published: February 2017

34 Background: SIRT1, a member of the class III histone deacetylase (HDAC) family, is the mammalian orthologue of yeast Sir2. It has been reported to play a key role in a variety of physiological processes such as genomic stability, metabolism, neurogenesis and cell survival due to its ability to deacetylate both histone and numerous non-histone substrates. The deacetylase function of SIRT1 has been suggested as playing a role in prolonging the life of mammals. However, the suggested functions of SIRT1 as a potential tumor promoter have been challenged by observations of their respective down- and up-regulation in various cancers. The aim of the present study was to simultaneously evaluate the expression levels of SIRT1 and Ki67, the index of cellular proliferation, in normal and tumor tissues of the breast from 27 breast cancer patients and to determine the role of SIRT1 in breast tumorigenesis. Methods: A total of 27 breast cancer patients were included. Tumor tissues and matched normal breast tissues were immediately frozen after collection between 2007 and 2008. Immunohistochemistry and reverse transcription-polymerase chain reaction were applied for analyses of patients’ specimens. Cell proliferation assay, cell cycle analysis and Western blotting were used to investigate the effects of sirtinol on the human breast cancer lines MCF-7 and MDA-MB-231 cells. Results: Immunohistochemistry showed that there is a high correlation between SIRT1 and Ki67 expression. In addition, our results showed that inhibition of SIRT1 induces anti-cell growth in both MCF-7 (ER-positive, non-invasive) and MDA-MB-231 (ER-negative, invasive) breast cancer cell lines, especially in MDA-MB-231 cells. The levels of pro-survival protein Bcl-2 were dramatically decreased in both breast cell lines following sirtinol treatment. Conclusions: Our present study revealed that inhibition of SIRT1 activity may be a promising chemotherapeutic strategy against breast cancer.
Staging evaluation with bone scan, liver ultrasound, and chest radiograph in patients with primary breast cancer: A systematic review.
Authors: Staley Stuart-Allison Moffat 
Published: February 2017

4 Background: Routinely, radiological investigation with bone scan, chest radiograph, and liver ultrasound are employed as baseline staging tests. The aim of this review was to examine indications for this costly routine screening, and, thus, we posed the following question: Among women with newly diagnosed breast cancer who are otherwise asymptomatic, does evaluation with bone scanning, liver ultrasound, and chest radiograph help to determine the extent of metastatic disease? Methods: We searched PubMed and EMBASE databases for relevant articles to find articles using detection rate, defined as the number of patients with an abnormal test result divided by the total number of patients tested, as the primary outcome of interest. In addition to detection rate, false-positive and false-negative rates are reported if provided in the study reports reviewed. In order to obtain overall estimates of detection rates in each test, the results from the studies were pooled and summed according to pathological stage. A 95% confidence interval was calculated for each of the pooled rates. Results: Eight articles out of 232 reviewed were included in the final analysis. The following pooled detection rates for bone scan were calculated according to stage: Stage I 7 of 544 (1.29%), Stage II 29 of 938 (3.09%), Stage I and II 36 of 1,482 (2.43%), and Stage III 39 of 312 (12.5%). For liver ultrasound: Stage I 1 of 213 (0.47%), Stage II 4 of 400 (1.00%), Stage I and II 5 of 613 (0.82%), and Stage III 6 of 143 (4.20%). And, for chest radiograph: Stage I 0 of 223, Stage II 2 of 473 (0.42%), Stage I and II 9 of 1,782 (0.51%), and Stage III 8 of 175 (4.57%). Conclusions: The routine use of bone scan, liver ultrasound, and chest radiograph in the staging evaluation of primary breast cancer patients is of little value in detecting metastatic disease in women with clinical stage I and stage II cancer, and therefore, should not be performed.
Statin use and the development of bone metastasis in breast cancer patients.
Authors: King Gentry Teng , Yun Jeong H. , Chae Young K. , Valsecchi Matias E. , Morginstin Mark S. 
Published: February 2017

40 Background: The Mevalonic Acid Pathway has been implicated in the promotion of a microenvironment suitable for establishment of bony metastasis from breast cancer. The statins, which act on this pathway, have been shown to have in vitro antineoplastic activity against breast cancer. This study was designed to evaluate the association of statin use and development of bony metastasis in breast cancer patients. Methods: Medical records of patients treated for stage II-III breast cancer from 1999 to 2010 were retrospectively reviewed. Statin use was defined as medication use for at least 3 months in patients with no evidence of disease after initial diagnosis and treatment. The primary outcome was development of metastasis to bone. Secondary outcomes were overall survival, disease free survival and other sites of distant metastasis. Results: A total of 841 patients were included in the study of which 223 used statins. Both unadjusted and multivariate analysis adjusted for age, race, grade, stage, BRCA status, showed that patients on statins had a significantly lower incidence of metastasis to bone (OR 0.49, 95% CI 0.25-0.96, p=0.04). Adjusted analysis for other sites showed a trend towards decreased incidence of metastasis for statin users, but was not statistically significant (95% CI 0.39-1.08, p=0.10). Overall survival was increased in statin users with mean survival of 66.45 +/- 2.48 months versus non-users 58.78 +/ - 1.41 months (p=0.05). Statin users had significantly longer disease free survival with a mean of 63.65 +/- 2.49 months versus 53.96 +/- 1.42 months in non statin users (p=0.00). Conclusions: The use of statin drugs in patients with breast cancer was significantly associated with decreased incidence of metastasis to bone, but not to other distant sites. The role of statins in chemoprevention of bone metastasis should be further explored.
Risk-reducing surgery by skin-sparing mastectomy (SSM) and immediate implant-based reconstruction with and without titanized meshes and quality of life.
Authors: Rezai Mahdi , Scherag Andre , Kessel Stefanie , Kimmig Rainer , Kern Peter 
Published: February 2017

48 Background: The impact of risk-reducing surgery with skin sparing mastectomy and immediate reconstruction on quality of life using new textured implants and titanized meshes (Tiloop bra) has not beed evaluated by standardized quality of life questionnaires (EORTC) with regards to surgery-related morbidity and patients' satisfaction. Methods: This large case cohort trial (n=197) evaluates safety, aesthetic outcome and patient's satisfaction with immediate reconstruction with and without the use of titanized a mesh versus a corial flap after SSM. Results: This large retrospective case cohort trial analysed 197 skin sparing mastectomies (SSM) in 161 patients (45 bilateral cases) and immediate breast reconstruction (IBR). We used a double-plane technique covering the implant by the submuscular pouch in its cranial half and a corial-fat-flap or titanized mesh (Tiloop bra) for covering its lower pole or a de-epithelized corial flap in breasts with macromastia following an inferior-pedicled reduction mammaplasty pattern according to Ribeiro in the modification of Rezai. Conclusions: 163 women, with a median age of 41 years, with a total of 197 SSMs were evaluated. The majority did not experience pain and expressed satisfaction with volume, symmetry, aesthesis and quality of life in general. Partner interaction after breast reconstruction was normal. The use of titanized meshes was perceived as favourable with regards to better fitting of the breast in the bra and clothing and yielded low complication rates. The rating of patients in terms of self-perception after the reconstruction was good. Immediate reconstruction has a significant positive impact and gives the patient a considerable physical and psychological support.The oncological safety of the method is high with 2 recurrences only in this cohort of 163 women (1.2% ) and a follow-up of up to 6 years.