bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P5-22-22: Breast tumor location in BRCA mutation carriers and implications for prevention
Authors: Hosseini A , Esserman LJ , Wallace AM , Au A , Mukhtar RA 
Published: February 2018

Abstract
Introduction:
Close to 65% of BRCA mutation carriers do not choose prophylactic mastectomy, despite their high breast cancer risk. Breast reduction mammoplasty is a surgical technique shown to reduce breast cancer risk and can be modified to target specific areas of the breast. We wondered if a majority of tumors in BRCA mutation carriers would be confined to one quadrant, allowing for the use of targeted cosmetic mammoplasty as a novel method of risk reduction.
Methods:
We reviewed imaging reports on 103 consecutive patients with BRCA mutations and invasive breast cancer, and categorized tumor location by quadrant. Tumors spanning &gt;1 quadrant were classified as being in both. Bilateral cancers were counted separately. Categorical variables were compared with the chi-squaredtest.
Results:
Mean age at breast cancer diagnosis was 44 years with mean tumor size of 2.2 cm (0.1-7cm). 92% of tumors were invasive ductal carcinoma, 46% were hormone receptor positive, 10% Her2 positive, and 44% triple negative. 70% of the tumors were unicentric. Tumors were significantly more likely to be in the upper outer quadrant whether or not multicentric tumors were included in the analysis (p&lt;0.00001). Her2 positive tumors were more likely to be multicentric than other subtypes (p=0.021).
Conclusions:
More than half of breast cancers in BRCA mutation carriers form in the upper outer quadrant, suggesting that removing this quadrant through breast reduction mammoplasty could significantly reduce breast cancer risk. For women who are not ready for prophylactic mastectomy, this data supports an intermediate risk reduction step instead of only offering surveillance.
Citation Format: Hosseini A, Esserman LJ, Wallace AM, Au A, Mukhtar RA. Breast tumor location in BRCA mutation carriers and implications for prevention [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-22-22.
Abstract P6-04-01: Rapalog everolimus induces G1 cell cycle arrest through autophagy-mediated protein degradation of cyclin D1 in breast cancer cells
Authors: Chen G , Ding X-F , Bouamar H , Pressley K , Yang J , Sun L-Z 
Published: February 2018

Abstract
Rapamycin analogs (rapalogs) inhibit mammalian target of rapamycin (mTOR) and are known to cause induction of autophagy and G1 cell cycle arrest. However, it remains unknown whether rapalog-induced autophagy plays a critical role in its regulation of cell cycle. We, for the first time, found that rapalog everolimus could stimulate autophagy-mediated Cyclin D1 degradation in breast cancer cells. Inhibiting mTOR with everolimus rapidly increased the degradation of Cyclin D1 in MCF-10DCIS.COM and MCF-7 cells. 3-Methyladenine (3-MA), a classic autophagy inhibitor, could attenuate everolimus-induced Cyclin D1 degradation. Furthermore, knockdown of autophagy related gene 7 (Atg-7) could also repress everolimus-triggered degradation of Cyclin D1 in MCF-10DCIS.COM. Moreover, everolimus-induced autophagy occurred earlier than its induction of G1 arrest and cell death. Blockade of autophagy attenuated everolimus-induced G1 cell cycle arrest. These preliminary data support the conclusion that the autophagy induced by rapalogs in breast cancer cells appears to cause Cyclin D1 protein degradation resulting in G1 cell cycle arrest. Our findings contribute to our knowledge of the interplay between autophagy and cell cycle regulation mediated by mTOR signaling and Cyclin D1 regulation.
Citation Format: Chen G, Ding X-F, Bouamar H, Pressley K, Yang J, Sun L-Z. Rapalog everolimus induces G1 cell cycle arrest through autophagy-mediated protein degradation of cyclin D1 in breast cancer cells [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-04-01.
Abstract P6-05-03: Attenuation of RNA polymerase II pausing mitigates BRCA1-associated R-loop accumulation and tumorigenesis
Authors: Zhang X , Chiang H-C , Wang Y , Jin VX , Hu Y , Li R 
Published: February 2018

Abstract
Most BRCA1-associated breast tumours are basal-like yet originate from luminal progenitors. BRCA1 is best known for its functions in double-strand break repair and resolution of DNA replication stress. However, it is unclear whether loss of these ubiquitously important functions fully explains the cell lineage-specific tumorigenesis. In vitro studies implicate BRCA1 in elimination of R-loops, DNA-RNA hybrid structures involved in transcription and genetic instability. Here we show that R-loops accumulate preferentially in breast luminal epithelial cells, not in basal epithelial or stromal cells, of BRCA1 mutation carriers. Furthermore, R-loops are enriched at the 5' end of those genes with promoter-proximal RNA polymerase II (Pol II) pausing. Genetic ablation of Cobra1, which encodes a Pol II-pausing and BRCA1-binding protein, ameliorates R-loop accumulation and reduces tumorigenesis in Brca1-knockout mouse mammary epithelium. Our studies show that Pol II pausing is an important contributor to BRCA1-associated R-loop accumulation and breast cancer development.
Citation Format: Zhang X, Chiang H-C, Wang Y, Jin VX, Hu Y, Li R. Attenuation of RNA polymerase II pausing mitigates BRCA1-associated R-loop accumulation and tumorigenesis [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-05-03.
Abstract P6-07-08: Dual TGFβ/BMP inhibition allows in vitro expansion of multiple cell types from normal and cancerous breast
Authors: Nakshatri H , Ananappa M , Prasad MS , Kumar B , Liu Y , Storniolo AM , Miller KD , Bhat-Nakshatri P 
Published: February 2018

Abstract
Functional modeling of breast epithelial hierarchy and stromal-epithelial cell interactions has been difficult due to inability to obtain sufficient stem-progenitor-mature epithelial cells and stromal cells. The recently developed epithelial reprogramming assay has partially overcome this limitation, allowing propagation of epithelial cells with stem, luminal progenitor and mature cell features. However, characterizing stromal cells using this assay is difficult because irradiated fibroblasts which can be difficult to distinguish from stromal cells are needed as feeder layer. A recent study demonstrated expansion of airway basal stem cells without a feeder layer through pharmacologic inhibition of TGFβ/BMP/SMAD signaling. We sought to develop this method for culture and expansion of cells from normal and cancerous breast samples. With appropriate modifications to growth media, we were able to obtain normal and stromal cells from breast biopsies of healthy women. The expanded cell population included CD10+/EpCAM- basal/myoepithelial cells, CD49f+/EpCAM+ luminal progenitor cells, CD49f-/EpCAM+ mature luminal cells, CD73+/EpCAM+/CD90- rare endogenous pluripotent somatic stem cells, CD73+/CD90+/EpCAM- mesenchymal stem cells, ALCAM (CD166)+/EpCAM+ cells, CD44+/CD24- cells, CD44+/CD24+ cells and ALDFLUOR+ stem/luminal progenitor cells. Epithelial cells were KRT14+, KRT19+ or both further documenting heterogeneity within epithelial cell population. We have extended this technique to grow breast epithelial cells from high-risk patients including BRCA1 mutant-carriers, tumor-adjacent normal and tumor cells from the same patient, pleural effusions and liver metastasis from breast cancer patients. Phenotypic characterization showed differences in the differentiation state of adjacent-normal and tumor cells. Tumor cells from pleural effusions showed remarkable phenotypic heterogeneity with a fraction of these cells expressing estrogen receptor. The assay described here, therefore, is versatile and provides resources to model epithelial-stromal interactions under normal and cancerous conditions as well as for genomics and screening of drugs to target metastasis on an individual level.
Susan G. Komen for the Cure and Department of Defense supported this work.
Citation Format: Nakshatri H, Ananappa M, Prasad MS, Kumar B, Liu Y, Storniolo AM, Miller KD, Bhat-Nakshatri P. Dual TGFβ/BMP inhibition allows in vitro expansion of multiple cell types from normal and cancerous breast [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-07-08.
Abstract P6-09-11: Ki67 cut offs and oncotype DX recurrence score in early breast cancer
Authors: Namuche F , Ruiz R , Flores C , Gomez HL , Aguilar A 
Published: February 2018

Abstract
Background: The gene expression profiling assay OncotypeDx (ODX) predicts the likelihood of estrogen receptor (ER) positive breast cancer (BC) recurrence and assesses the likely benefit from both hormonal therapy and chemotherapy. Many clinical scores that estimate the risk category of ODX are being tested. Ki67 is frequently incorporated into these assessments, although there is no standard cut-off for its use.
Methods: We retrospectively reviewed the electronic medical records of 190 patients with early stage ER+ BC for whom ODX recurrence score (RS) was available. Patients were diagnosed and treated at a specialized cancer center between 2014 and 2016. Our objective was to find out the degree to which an optimal ki67 cut-off correlates with ODX risk category. We also aim to determine an association between classical clinicopathological variables (St. Gallen (SG) 2015) could predict ODX risk category. Chi square test was used.
Results: The characteristics of patients according to ODX risk category are shown in Table 2. Mean age at diagnosis was 59 years (range 28-89). Mean tumor diameter was 15mm, 84.2% were intermediate grade and 4.7% patients had lymph node involvement. Mean expression of ER, PR and Ki67 were 87%, 53% and 22%, respectively. According to ODX 62.1% patients were low risk, 30.5% were intermediate risk and 7.4% were high risk. An overall concordance of 46.8% (73/190) was found between SG 2015 and the risk category of ODX (75.7% for low, 33.3% for intermediate and 23.9% for high RS). When changing SG Ki67 cutoffs to ≤20% (for low Ki67) and ≥30% (for high Ki67), an overall concordance of 56.3% (107/190) was found (69.6% for low, 47.3% for intermediate and 23.9% for high RS) and this was statistically significant (p=0.00) (Table 3).
Conclusion: In our population there is no a direct correlation between classical clinicopathological variables and ODX score. Despite being a specialized center, the utility of classical clinicopathological variables for predicting ODX risk category is limited.
Citation Format: Namuche F, Ruiz R, Flores C, Gomez HL, Aguilar A. Ki67 cut offs and oncotype DX recurrence score in early breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-09-11.
Abstract P6-13-01: Withdrawn
Authors: Janni WJ , Harbeck N , Rack B , Gluz O , Schneeweiss A , Kates R , Fehm T , Kreipe H , Kümmel S , Würstlein R , Hartkopf A , Clemens M , Reimer T , Friedl T , Häberle L , Fasching P , Nitz U 
Published: February 2018

Abstract
This abstract was withdrawn by the authors.
Abstract P6-15-04: Characterization of tumor infiltrating lymphocytes and its association response in breast cancer
Authors: Galvez M , Castaneda C , Villegas V 
Published: February 2018

Abstract
Background: The magnitude of tumor infiltrating lymphocytes (TIL) is a predictor of good prognosis in the context of neoadyuvant chemotherapy (NAC) in breast cancer, and is expressed in the capacity to achieve a pathological complete response (pCR) and therefore to obtain a major survival. The characteristics of TIL are influenced of different clinical and pathological features as well as its predictive value. The goal of this study is to define the different associations between level of stromal (sTIL) and interstitial (iTIL) tumor infiltrating lymphocytes and pathological and clinical feature of breast cancer. Methods: The level of TIL was analyzed in 483 patients diagnosed with breast cancer of the Instituto Nacional de Enfermedades Neoplasicas from 2003 to 2014. We evaluate patient characteristics such as age, clinical stage, histological subtype and grade, clinical T, N and M, presence of estrogen (ER) and progesterone (PgR) receptors, HER-2 expression and molecular subtype as well as pathological response. Results: We found a positive association between sTIL and iTIL proportion and histological grade (G1-2 vs G3, p&lt;0.05 and p&lt;0.05 respectively), hormone receptor (ER- vs ER+PgR- vs ER+PgR+, p&lt;0.05 and p=0.001 respectively), molecular subtype (Luminal A vs Luminal B vs HER2 vs Triple Negative (TN), p&lt;0.05 and p=0.002 respectively), clinical N (positive vs negative, p=0.006 and p&lt;0.05 respectively). Also we found association between sTIL with lymph nodes after surgery (negative vs positive, p=0.028) and pathological response (pCR vs &lt;pCR, p=0.018), there was no association between sTIL and iTIL with age, histological subtype, clinical T and M. Conclusions: The level of tumor infiltrating lymphocytes are affected by different clinical and pathological features, they are present in both lobular and ductal breast cancer without significant difference; higher level of TIL are associated with high histological grade, ER-, TNBC and high clinical N to diagnosis; and specially sTIL are associated with to achieve a negative lymph node after NAC and obtain a pathological complete response.
Citation Format: Galvez M, Castaneda C, Villegas V. Characterization of tumor infiltrating lymphocytes and its association response in breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-15-04.
Abstract PD2-17: Dual energy: Potentialities of contrast enhanced mammography in breast desease diagnosis and follow-up
Authors: Cossu E , Costano E , Di Trapano R , Pensabene MC , Di Stefano C , Fosi S , Fiaschetti V , Portarena I , Buonomo O 
Published: February 2018

Abstract
Purpose: Contrast-enhanced Dual-Energy digital mammography (DE) is a recently
used investigation that consists in acquiring low and high energy images after
intravenous injection of iodinated contrast medium. The purpose of this study is to describe our experience about the role of DE in the diagnosis and follow-up of breast cancer.
Materials and Methods: 50 patients, with heterogeneous breast pattern, already studied
by mammography and ultrasound, were selected. They underwent DE mammography: 17
for mammographic or ultrasonographic suspicious findings (9/17 also examined with MRI), 21 for loco-regional staging (21/21 studied with MRI), 10 for oncologic follow-up (6/10 also underwent MRI). DE has been interrupted in two cases due to technical problems. Exclusion criteria of the study were: breast implants, pregnancy or lactation and contraindications to administration of contrast medium. DE results were compared with the post-operative or post-bioptical (Tru-cut or Vacuum Assisted Biopsy) histological findings.
Results: DE showed a sensitivity of 76% in evaluation of Patients with mammographic or ultrasonographic suspicious findings: in comparison with MRI (9 patients), DE had a 55 % specificity (vs 22% of MRI). In locoregional staging DE proved to be more accurate than MRI in dimensional evaluation of unifocal cancer: DE accuracy was 91% vs 62% of MRI, which overestimated the size of most of lesions. In the count of tumor foci number in case of multifocal/multicentric disease MRI corresponded in 9/11 cases with histology (vs 3/11 cases of DE). DE showed a sensitivity of 100% and a 85.7% specificity in assessing oncologic follow-up Patients: in the comparison between DE and MRI (6 patients), DE got 1 false positive result, while MRI 3.
Conclusion: DE can be a valuable diagnostic tool to help conventional techniques; it is also a possible alternative to MRI in some selected type of patients or where MRI is not available.
Citation Format: Cossu E, Costano E, Di Trapano R, Pensabene MC, Di Stefano C, Fosi S, Fiaschetti V, Portarena I, Buonomo O. Dual energy: Potentialities of contrast enhanced mammography in breast desease diagnosis and follow-up [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD2-17.
Increasing Incidence and Prevalence of World Health Organization Groups 1 to 4 Pulmonary Hypertension
Authors: Wijeratne D. Thiwanka , Lajkosz Katherine , Brogly Susan B. , Lougheed M. Diane , Jiang Li , Housin Ahmad , Barber David , Johnson Ana , Doliszny Katharine M. , Archer Stephen L. 
Published: February 2018

Background:
The World Health Organization recognizes 5 groups of pulmonary hypertension (PH), categorized by pathogenesis or comorbidity: 1-pulmonary arterial hypertension 2-left-heart disease, 3-lung disease and hypoxia 4-chronic thromboembolic disease, and 5-miscellaneous. The epidemiology of PH, apart from group 1, is largely unknown.

Methods and Results:
We describe incidence, prevalence, comorbidities, mortality and prescribing patterns for groups 1 to 4 PH from 1993 to 2012. Case definitions are based on hospitalizations and emergency department visits, using the Institute for Clinical Evaluative Sciences data, which comprises linked databases of universal coverage health service records for Ontario residents. This cohort included 50 529 patients with PH. The annual incidence of adult PH increased from 2003 to 2012 from 24.1 to 28.7 cases/100 000 population and the annual prevalence from 1993 to 2012 from 99.8 to 127.3 cases/100 000 population, respectively. The most common form of adult PH was group 2, alone (34.2%) or combined with group 3 PH (29.3%). A diagnosis of PH increased the 1-year standardized mortality ratio 7.2-fold. Mortality in adults with PH was 13.0%, 36.4%, and 62.4%, at 30 days, 1 year, and 5 years, respectively. Mortality was highest in groups 2 and 3 and lowest in group 1. PH was present in only 3.6% of people with left heart disease, 0.7% with lung disease, and 1.4% with thromboembolic disease, suggesting that PH is a relatively rare complication of these common diseases. Children (age<16 years) accounted for 3.6% of the cohort. In children group 1 PH was most common (65.2%), and 5-year mortality was lower (21.4%) than in adults. Group 1–specific PH therapies were increasingly prescribed over time and paradoxically were often used in patients who seemed to have group 2, PH based on diagnostic codes indicating left heart disease.

Conclusions:
The incidence and prevalence of adult PH are increasing. Groups 2 and 3 are the most common and lethal forms of PH. This study identifies an emerging epidemic of PH that likely has substantial adverse health and economic implications.
Traditional Thought and Utopian Egalitarianism in the Tianyi bao: The Rise of an Anarchist Ideal among Chinese Communities in Tokyo
Authors: Gaudino Emanuela 
Published: February 2018

This essay discusses the experience of anarchism among young Chinese intellectuals based in Japan between 1907-1908. The rise of an anarchist ideal among Chinese intellectuals was firstly related to their acquaintance with Japanese radicals. In 1907 division among the Tongmenghui leadership and the conversion of Japanese intellectuals to anarchism made Chinese students and intellectuals based in Tokyo more susceptible to radical political doctrines. Anarchism emerged as a new trend out of this political turmoil. Liu Shipei, He Zhen and Zhang Ji were the central figures of the Tokyo Group and the main supporters of the anarchist propaganda in Japan. Through the acquaintance with the Kinyōkai 金矅会 (Friday Group), the radical socialist faction led by Kōtoku Shūsui, they were able to bring together the Chinese overseas communities in Japan, who were dissatisfied with the principle of Tongmenghui and its leadership.
The close relations with Kōtoku and Japanese socialists, the affiliation with the Tongmenghui and the quarrels within the same Alliance concerning Sun’s leadership, the establishment of societies among Chinese students in Japan and the publication of a journal, all consent to define the contours of anarchist activities in Japan between the years 1907-1908.
My goal in the following pages is to highlight the Japanese route of Chinese anarchism outlining anarchist thinking and propaganda as delineated in the pages of their official organ, the Tianyi bao (Journal of Natural Justice). Overall, I will try to answer these three questions. First, how did Chinese traditional thought become a means to sustain utopian egalitarianism? Second, how did Kōtoku Shūsui and Japanese anarchists influence the rise of an anarchist ideal among Chinese intellectuals based in Japan? And third, how did the Tianyi bao promote a racial, social and political revolution in order to create an ideal society?
Observations of Seasonal Upwelling and Downwelling in the Beaufort Sea Mediated by Sea Ice
Authors: Meneghello Gianluca , Marshall John , Timmermans Mary-Louise , Scott Jeffery 
Published: February 2018

AbstractWe present observational estimates of Ekman pumping in the Beaufort Gyre region. Averaged over the Canada Basin, the results show a 2003–14 average of 2.3 m yr−1 downward with strong seasonal and interannual variability superimposed: monthly and yearly means range from 30 m yr−1 downward to 10 m yr−1 upward. A clear, seasonal cycle is evident with intense downwelling in autumn and upwelling during the winter months, despite the wind forcing being downwelling favorable year-round. Wintertime upwelling is associated with friction between the large-scale Beaufort Gyre ocean circulation and the surface ice pack and contrasts with previous estimates of yearlong downwelling; as a consequence, the yearly cumulative Ekman pumping over the gyre is significantly reduced. The spatial distribution of Ekman pumping is also modified, with the Beaufort Gyre region showing alternating, moderate upwelling and downwelling, while a more intense, yearlong downwelling averaging 18 m yr−1 is identified in the northern Chukchi Sea region. Implications of the results for understanding Arctic Ocean dynamics and change are discussed.
Dopo il Boom. Romanzi napoletani negli anni Settanta
Authors: Cannavacciuolo di Laura 
Published: February 2018

Il saggio propone una investigazione degli sviluppi del romanzo d’area napoletana tra la fine degli anni Sessanta e i primi anni Settanta del ’900. Si definiscono i temi dominanti dei principali romanzi pubblicati in questa stagione— Amore e Psiche, Tanto la rivoluzione non scoppierà, Dentro la Stella, Malacqua—, i modelli di riferimento, il contributo degli scrittori rispetto al dibattito teorico nazionale e internazionale. Infine, si analizza il rapporto degli scrittori in oggetto con le forme del Nuovo Romanzo e il filone del cosiddetto romanzo “apocalittico”.