bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P6-08-06: Association of body mass index (BMI) with chemotherapy administration and emergency room (ER) visits among breast cancer patients
Authors: Giordano SH , Niu J , Zhao H , Zorzi D , Chavez-Mac Gregor M
Published: February 2018

Background: Obese patients may be more likely to have treatment-related complications. Little is known about the association between BMI and chemotherapy-related ER visits and hospitalizations among breast cancer patients. In this study we evaluated the association between BMI and ER visits/hospitalizations in a large sample of breast cancer patients.Methods: We identified beneficiaries from the commercial MarketScan Health Risk Assessment database with breast cancer-specific claims between 2009-2014. All patients underwent mastectomy or lumpectomy and had BMI data available. BMI was categorized as normal (<25), overweight (≥25 and <30) and obese (≥30). Descriptive statistics were used to compare patient and treatment variables by BMI. Chemotherapy-related ER visits/hospitalizations in the 6 months after diagnosis were identified. Cox regression models were used to identify factors associated with ER visits and hospitalizations. Results: Among 7,830 patients included, 33.2% were classified as normal/underweight, 29.5% as overweight and 37.2% as obese. 2,928 (37%) patients were treated with chemotherapy. BMI differed significantly according to age, geographic region, comorbidity score, and treatment received. Among patients not treated with chemotherapy, the rates of ER visits/hospitalizations were: 11.4% for normal patients, 13.7% for overweight and 15.2% for obese patients (p=0.004). For chemotherapy-treated patients, the rates of ER visit/hospitalization were: 22.6% for normal patients, 24.3% for overweight and 30.2% for obese patients (p<0.001). In the multivariable model, chemotherapy-treated patients with obesity had higher risk to have ER visits/hospitalizations (HR=1.37, 95%CI 1.14–1.64) than patients with normal BMI. No significant increase was seen among overweight patients (OR=1.09; 95%CI 0.90-1.33). Conclusions: In this cohort of patients, obesity was associated with increased risk of ER visits/hospitalizations, suggesting that careful follow–up is warranted in these patients, particularly among those receiving chemotherapy.

Citation Format: Giordano SH, Niu J, Zhao H, Zorzi D, Chavez-Mac Gregor M. Association of body mass index (BMI) with chemotherapy administration and emergency room (ER) visits among breast cancer patients [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 P6-08-06.
Abstract P6-11-10: Impact of disease progression on health-related quality of life in patients with metastatic breast cancer in the PRAEGNANT breast cancer registry
Authors: Wallwiener M , Nabieva N , Haeberle L , Taran FA , Hartkopf AD , Volz B , Overkamp F , Brandl AL , Kolberg H-C , Hadji P , Tesch H , Ettl J , Lux MP , Lueftner D , Belleville E , Fasching PA , Janni W , Beckmann MW , Wimberger P , Hielscher C , Fehm T , Brucker SY , Wallwiener D , Schneeweiss A , Mueller V
Published: February 2018

Background: Improved progression-free survival is considered as treatment goal for patients with metastatic breast cancer (MBC) since it is assumed to delay or prevent deterioration of quality of life.Aim of our analysis was to examine the influence of disease progression on health-related quality of life (HRQoL).

Methods: The PRAEGNANT study comprises a real-life registry for patients with MBC. HRQoL was assessed with the EORTC-QLQ-C30 Version 3.0 questionnaire at study entry and every 3 months thereafter. The primary endpoint was minimally important deterioration (MID) in global HRQoL score by ≥ five points between baseline and any follow-up assessment. A logistic regression model was built with MID (yes/no) at a follow-up timepoint as outcome variable and several covariates as predictors.

Results: In total, 329 patients were included in this analysis, with disease progression in 63 patients. Concerning the primary study aim, progression status predicted MID of global HRQoL status in addition to the other covariates. The adjusted odds ratio for the effect of progression status on MID was 2.22 (95% CI: 1.04 – 4.73). Comparisons of mean differences of QoL domains/scales yielded no differences.

Conclusions: We provide evidence that disease progression in patients with metastatic breast cancer in a real-world registry has a significant negative impact on HRQoL as measured by MID of HRQoL. This study emphasizes the relevance of avoiding progression and prolonging PFS to maintain QoL.

Citation Format: Wallwiener M, Nabieva N, Haeberle L, Taran FA, Hartkopf AD, Volz B, Overkamp F, Brandl AL, Kolberg H-C, Hadji P, Tesch H, Ettl J, Lux MP, Lueftner D, Belleville E, Fasching PA, Janni W, Beckmann MW, Wimberger P, Hielscher C, Fehm T, Brucker SY, Wallwiener D, Schneeweiss A, Mueller V. Impact of disease progression on health-related quality of life in patients with metastatic breast cancer in the PRAEGNANT breast cancer registry [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 P6-11-10.
Abstract P6-11-18: Ten year trends in antiemetic prescribing in cancer patients receiving highly emetogenic chemotherapy (HEC)
Authors: O'Sullivan CC , Van Houten HK , Sangaralingham L , Leal AD , Shinde S , Liu H , Ettinger D , Loprinzi CL , Ruddy KJ
Published: February 2018

Purpose: Prevention of chemotherapy-induced nausea and vomiting (CINV) is essential to preserve quality of life in cancer patients receiving highly emetogenic chemotherapy (HEC) such as doxorubicin-cyclophosphamide (AC) or cisplatin. Recently, new drugs (e.g. fosaprepitant and newer neurokinin 1 receptor antagonists [NK1RAs], rolapitant and netupitant) and updated guidelines for antiemetic use (e.g. adding olanzapine) have emerged. However, trends in real world antiemetic use are understudied.

Methods: We performed a retrospective study using the OptumLabs Data Warehouse (OLDW), which includes administrative claims for privately insured and Medicare Advantage enrollees in the U.S. We identified 34,236 patients age 18 years or older treated with either AC or cisplatin between January 2006 and June 2016. Data collected included baseline demographics (age, gender, census region and race), chemotherapy administered, and presence/absence of a central intravenous access device. Trends of anti-emetic use were presented overall and separately for 5-HT receptor antagonists (5HT3RAs) and NK1RAs.

Results: 23,030 patients (67.3%) received an anthracycline-based regimen (AC with or without docetaxel or paclitaxel), and 11,206 (32.7%) patients received cisplatin. Approximately two thirds of patients were female (n= 23,392). Dexamethasone use was stable over the decade (used by 85-90% in all years). Use of 5HT3RAs, primarily palonosetron and ondansetron, occurred in at least 95% of patients in all study years, consistent with guideline recommendations. NK1RAs were underutilized early on compared with guideline recommendations, but use increased to approximately 80% in the most recently evaluated year. Fosaprepitant use rose precipitously starting in 2009, preceding a sharp fall in aprepitant use beginning in 2011. The use of olanzapine, rolapitant and netupitant was minimal throughout the study period.

Conclusions: Dexamethasone and 5-HT3RAs were used in the vast majority of patients receiving HEC, in accordance with guideline recommendations. Less compliance with guidelines was seen with NK1RA use.

Citation Format: O'Sullivan CC, Van Houten HK, Sangaralingham L, Leal AD, Shinde S, Liu H, Ettinger D, Loprinzi CL, Ruddy KJ. Ten year trends in antiemetic prescribing in cancer patients receiving highly emetogenic chemotherapy (HEC) [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 P6-11-18.
Abstract P6-15-05: Randomized controlled trial of neoadjuvant eribulin mesylate versus paclitaxel in women with operable breast cancer (JONIE-3 study)
Authors: Miura D , Hasegawa Y , Ishikawa T , Tachibana A , Horiguchi J , Hayashi M , Miyashita M , Kubota T , Narui K , Suzuki M , Akazawa K , Kohno N
Published: February 2018

Background:

Although treatment of eribulin mesylate (E) improved overall survival in metastatic breast cancer (BC) patients, little is known about the efficacy in early BC. The hypothesis of this study is that sequential administration of E followed by FEC would have less toxic, particularly peripheral neuropathy, and also have similar effect compared to paclitaxel (P) followed by FEC as primary systemic therapy (PST) for woman with operable BC.

Methods:

This is a phase II multicenter open label study (UMIN000012817). Patients (pts) were randomly assigned to either E (1.4mg/m2, d1 and d8, q21 days, 4 cycles) + FEC (fluorouracil 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 500 mg/m2) or P (80mg/m2, weekly, 12 cycles) + FEC as PST. HER2+ patients were allowed to receive trastuzumab. Stratification factors were ER, HER2, and menopausal status. Primary endpoint was the incidence of peripheral sensory and motor neuropathy (PSN and PMN) with Grade 1 or higher according to CTCAE ver.4.0. Secondary endpoints were pathological complete response (pCR) rates (ypT0/is/ypN0), clinical response rates (CR+PR), and adverse events. Safety was assessed in all pts who received at least one dose of the study drug.

Results:

Between 12/2013 to 3/2016, 121 pts were randomly assigned equally to E + FEC and P + FEC. Excluding 5 pts from the primary assessment, 116 pts (58 in each group) were included in the full analysis set. The characteristics of the pts were similar in the two arms. At the end of E or P administration, the incidences of PSN were 55.4% and 92.9% in E and P arm, respectively (p<0.001). The incidences of PMN were 25.9% and 44.9% in E and P arm, respectively (p=0.049). At the end of E or P + FEC, PSN accounts for 38.9% in E arm and 85.2% in P arm (p<0.001), and PMN accounts for 20.7% in E arm and 32.8% in P arm (p=0.201). The pCR rates in E and P arm were 20.7% and 29.8% (p=0.092). The clinical response rates in E and P arm were 82.2% and 91.0% (p=0.108). No statistical significant difference was found in efficacy of PST between E and P.

Conclusion:

This randomized phase II study revealed that eribulin had favorable peripheral neuropathy profile with modest efficacy in the neoadjuvant setting, compared with paclitaxel.

Citation Format: Miura D, Hasegawa Y, Ishikawa T, Tachibana A, Horiguchi J, Hayashi M, Miyashita M, Kubota T, Narui K, Suzuki M, Akazawa K, Kohno N. Randomized controlled trial of neoadjuvant eribulin mesylate versus paclitaxel in women with operable breast cancer (JONIE-3 study) [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 P6-15-05.
Abstract PD1-01: Triple negative breast cancer predisposition genes
Authors: Couch FJ , Shimelis H , LaDuca H , Hu C , Hart SN , Polley EC , Pesaran T , Tippin-Davis B , Goldgar DE , Dolinsky JS
Published: February 2018

Background: Germline cancer testing panels provide an effective method for identifying individuals at increased risk for breast cancer. However, estimates of risk for triple negative breast cancer (TNBC) (estrogen receptor-negative, progesterone receptor-negative, HER2-negative) associated with pathogenic mutations in panel genes have not been established. We sought to define the genes that contribute to TNBC.

Methods:Germline hereditary cancer multigene panel testing results were obtained for 8,753 TNBCs evaluated by a clinical testing laboratory. Associations between pathogenic mutations in individual genes and TNBC were assessed by comparing mutation frequencies in TNBCs and in the Exome Aggregation Consortium, non-Finn European, non-Cancer Genome Atlas reference controls.

Results: Inactivating mutations in 21 known cancer predisposition genes were identified in 14.6% of TNBCs. BRCA1, BRCA2, PALB2, BARD1, and RAD51D alterations were associated with high risks (odds ratio(OR)>5.0) of TNBC and variants in BRIP1, RAD51C, MSH6, and TP53 were associated with moderate risks (OR>2). In contrast, ATM, CHEK2, NBN, and RAD50 yielded no clinically relevant risks of TNBC. Pathogenic mutations in these established non-BRCA1/2 TNBC susceptibility genes were detected in 6.3% of TNBCs. Similar trends were observed among African American TNBCs. Overall, 5.5% of TNBCs with pathogenic mutations did not meet NCCN clinical testing criteria for BRCA1/2 due to a lack of significant family history and diagnosis over the age of 60.

Conclusions: The identification of genes associated with elevated risk of TNBC will improve understanding of the etiology of this aggressive form of breast cancer and inform risk management of individuals receiving panel testing. The high frequency of pathogenic variants suggests that all patients with TNBC, regardless of age of diagnosis or family history of cancer, should be considered for multigene panel testing.

Citation Format: Couch FJ, Shimelis H, LaDuca H, Hu C, Hart SN, Polley EC, Pesaran T, Tippin-Davis B, Goldgar DE, Dolinsky JS. Triple negative breast cancer predisposition genes [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 PD1-01.
Abstract PD1-05: Transgenerational epigenetic silencing of BRCA1 due to a germline variant unmasks a new mechanism for familial breast and ovarian cancer
Authors: van Veen EM , Smith MJ , Byers HJ , Wallace AJ , Lalloo FI , Newman WG , Evans DGR
Published: February 2018

In families with multiple affected individuals with early-onset breast/ovarian cancer pathogenic variants in BRCA1 or BRCA2 are identified in approximately 20% of the cases. Extensive efforts have been made to identify additional highly penetrant breast cancer genes or alternative mutational mechanisms affecting BRCA1 and BRCA2 to explain the missing heritability. It has been proposed that part of the missing heritability may be explained by gene silencing due to promoter methylation of cancer associated genes, as described in colorectal cancer (MLH1 and MSH2). Here, for the first time, we report two independent families with multiple individuals affected by breast and ovarian cancer with transgenerational promoter methylation of BRCA1.

RNA analysis of BRCA1 in the germline of breast/ovarian families, previously found to be BRCA1/2 mutation negative by Sanger sequencing and copy number analysis, identified two families with allelic loss of expression. To investigate the mechanism of transcriptional silencing, a total of 14 affected and unaffected family members from these two families were tested for BRCA1 promoter methylation by pyrosequencing in blood, buccal, and hair follicle cells. Allele specific methylation was determined by clonal bisulphite sequencing.

BRCA1 promoter methylation in all three germ layers was present in 11 of 14 family members. Of the 7 women with promoter methylation five were affected with grade 3 breast/high grade serous ovarian cancer. The four males with BRCA1 promoter methylation had no history of cancer. Methylation levels were ˜50%, consistent with the silencing of one allele detected in RNA in these family members. Clonal bisulphite sequencing of an affected family member of each family confirmed that the alternative allele was specifically methylated. Interestingly, in both families the methylation pattern of the BRCA1 promoter segregated with the same novel heterozygous variant in the 5'UTR of BRCA1.

These results indicate a novel mechanism for familial breast/ovarian cancer, caused by epigenetic silencing of one allele by transgenerational hypermethylation of the BRCA1 promoter, secondary to a variant in cis of BRCA1. We propose that methylation analyses are indicated in all families affected by early onset breast/ovarian cancer where standard mutation screening of BRCA1/2 has not identified a causative variant.

Citation Format: van Veen EM, Smith MJ, Byers HJ, Wallace AJ, Lalloo FI, Newman WG, Evans DGR. Transgenerational epigenetic silencing of BRCA1 due to a germline variant unmasks a new mechanism for familial breast and ovarian 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 PD1-05.
Abstract PD4-01: The role of FGF/FGFR axis in resistance to SERDs and CDK4/6 inhibitors in ER+ breast cancer
Authors: Mao P , Kusiel J , Cohen O , Wagle N
Published: February 2018

Approximately 70% of breast cancers express the estrogen receptor (ER), and estrogen signaling drives breast cancer cell growth and progression. ER-directed therapies are commonly used to treat ER+ breast cancer and have improved survival for patients, yet resistance to those therapies inevitably occurs. Mutations in the estrogen receptor itself occur in ∼25-30% of patients with ER+ metastatic breast cancer that has developed resistance to aromatase inhibitors. Beyond these ER mutations, other resistance mechanisms are not well described. Moreover, clinical mechanisms of resistance to another class of ER-targeted agents, selective estrogen receptor degraders (SERDs), such as fulvestrant have not been clearly identified.

Here we report two FGFR2 mutations identified in patients with resistant ER+ metastatic breast cancer, N550K and M538I. N550K is a well-known activating FGFR2 mutation; M538I stabilizes the active kinase conformation and it has not previously been described in breast cancer. When expressed in ER+ T47D cells, FGFR2 M538I and N550K led to resistance to fulvestrant, and the CDK4/6 inhibitor palbociclib and the combination of the two agents. FGFR2 M538I induced hyperactivity of p-FRS2, p-ERK and p-AKT, which is higher than wildtype FGFR2 and comparable to other known activating mutations N550K and K660N.

In addition, overexpression of M538I mutant reduced sensitivity to FGFR inhibitors PD173074 and dovitinib in T47D cells, suggesting M538I is also functionally activating. Due to the hyperactive downstream signaling elicited by the mutation, cells overexpressing FGFR2 M538I achieved optimal growth in the presence of low dose of FGFR inhibitor. Under such conditions, FGFR2 M538I conferred more potent resistance to fulvestrant as compared to wildtype FGFR2. However, drug resistance resulting from M538I mutant can be fully resensitized to fulvestrant and/or palbociclib with high dose of FGFR inhibitors.

In summary, we have identified activating FGFR2 mutations (M538I and N550K) in ER+ breast cancer patients, which may contribute to the development of resistance to SERDs and CDK4/6 inhibitors. Additional FGFR2 mutations have been recently identified in other cohorts of patients with resistant ER+ metastatic breast cancer, suggesting that this may be a clinical mechanism of resistance in some patients. Patients with activating FGFR2 mutations may benefit from the treatment with an FGFR inhibitor in combination with SERDs and CDK4/6 inhibitors.

Citation Format: Mao P, Kusiel J, Cohen O, Wagle N. The role of FGF/FGFR axis in resistance to SERDs and CDK4/6 inhibitors in ER+ 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 PD4-01.
Abstract PD5-02: Not presented
Authors: Guerrero-Zotano AL , Stricker TP , Hutchinson KE , Stover DG , Formisano L , Lee K-M , Schwarz LJ , Giltnane JM , Jansen VM , Gavila J , Perez-Fidalgo A , Lluch A , Llombart A , Bayar MA , Michiels S , André F , Arnedos M , Ruiz A , Arteaga CL
Published: February 2018

This abstract was not presented at the symposium.
Abstract PD5-11: Not presented
Authors: Bardia A , Yardley DA , Hurvitz S , Wright G , Moroose R , Ma C , Hart L , Tan-Chiu E , Blau S , Sanft T , Dichmann R , Zelnak A , DeMichele A , Clark A , Small T , Tucci C , Samant TS , Purkayastha D , Karuturi M , Moulder S
Published: February 2018

This abstract was not presented at the symposium.
Abstract PD6-12: Withdrawn
Authors: Schmid P , Dent R , Sohn J , Park YH , Muñoz-Couselo E , Kim S-B , Im S-A , Holgado E , Chen E , Dang T , Aktan G , Cortés J
Published: February 2018

This abstract was withdrawn by the authors.
Abstract PD7-04: Contribution of radiation therapy to the overall cost of cancer care for clinical stage IA breast cancer patients
Authors: Dvorak T , Coltey D , Waters J , Kelly P , Buchholz D
Published: February 2018

Background: Cost of cancer care continues to rise and there is an increasing interest in episode-of-care and bundled payments. Radiation therapy is a well-established component of clinical Stage IA breast cancer care. However, the contribution of radiation to the cost of breast cancer care is not well understood. We were interested in evaluating the contribution of radiation cost to our overall Cancer Center breast cancer care cost, by using revenue received as a proxy.

Methods: Patients with clinical Stage IA breast cancer managed completely at our Cancer Center between 1/1/2014 and 12/31/2014 were identified from cancer registry. An IRB-approved retrospective review of clinical charts and financial data of patients was performed. Individual chart review identified whether and which kind of surgery, chemotherapy, and radiation therapy was delivered. Financial review identified actual technical revenue received for 365 days after the date of first contact, and apportioned it accordingly to the various cost centers, including radiation oncology. All patients were included regardless whether they were Commercial, Medicare, Medicaid, self-pay, or free-care.

Results: There were 110 patients treated with clinical Stage IA breast cancer. All patients (100%) underwent surgery (lumpectomy 69%; mastectomy 5%, mastectomy with reconstruction 26%). Chemotherapy was delivered in 20% of patients (neoadjuvant 13%; adjuvant 7%). Seventy seven percent saw a radiation oncologist, and 57% received radiation therapy. Radiation technique was 3D in 92% and IMRT in 8%. Fractionation was conventional in 55%, accelerated in 43%, and APBI in 2%. Most common treatment pathways were lumpectomy with radiation (46%), mastectomy with reconstruction alone (18%), and lumpectomy alone (14%). Concordance with national guidelines was ≥90%. Overall cost of care for these patients was $6.3 million. Medicare accounted for 35% of patients. Radiation cost was $1.1 million (17%), compared with $2.1 million (33%) for surgery, $2.4 million (38%) for chemotherapy, and $0.7 million for other costs (imaging, lab, ED visits, etc).

Conclusions: Radiation therapy was used in ˜60% of clinical Stage IA patients, but accounted for only ˜20% of the overall cost to the health care system. Given the demonstrated survival benefit of radiation therapy in the care of breast cancer patients, and our high concordance with national guidelines, radiation therapy in our Cancer Center provides high value to our patients, as we move toward value-based episodes of care.

Citation Format: Dvorak T, Coltey D, Waters J, Kelly P, Buchholz D. Contribution of radiation therapy to the overall cost of cancer care for clinical stage IA breast cancer patients [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 PD7-04.
Abstract PD8-02: Mechanisms of recurrence: Paired analysis of primary and metastatic triple negative breast cancer
Authors: Zhao Z-M , Yost S , Yuan Y-C , Warden C , Chuang J , Yuan Y
Published: February 2018

Background: Triple negative breast cancer (TNBC) is the most aggressive subtype of invasive breast cancer that lacks ER, PR, and HER2 expression. It is a heterogeneous disease with several molecular subtypes: basal-like1 (BL-1), basal-like 2 (BL-2), mesenchymal (M), and luminal androgen receptor (LAR). Treatment for TNBC is normally limited to chemotherapy, and relapse is common. Here we report molecular alterations associated with TNBC metastasis by analyzing the genomic profiles of paired primary and metastatic TNBCs.

Methods:50 paired TNBCs were identified through an IRB-approved protocol via the City of Hope (COH) Biospecimen Repository. DNA mutation and mRNA expression profiles of 10 paired primary and metastatic TNBCs were analyzed. DNA mutations were identified using exome sequencing by FoundationOne®. Affymetrix Human Genechip 2.0 was used for mRNA expression profiling. Raw data were normalized and processed using Expression Console, and linear regression was performed using Limma to identify the differentially expressed genes between primary and metastatic TNBCs.

Results: DNA mutation profiling showed that multiple mutations occurred within genes covering pathways of PI3K/AKT/mTOR, DNA repair, RAS/MAPK, cell cycle, and growth factor receptor signaling, reconfirming genomic heterogeneity of TNBCs. Gene expression profiles were analyzed for Lehmann's TNBC molecular subtypes (BL-1, BL-2, M, and LAR). Six of ten TNBCs showed phenotype shift between the primary and metastatic TNBCs. Several unique gene expression patterns were identified by comparing the paired TNBCs. CCNE1 and TPX2 were co-overexpressed in metastatic TNBCs compared to paired primaries. This mirrored prior studies in ovarian cancer, where co-overexpression of CCNE1 and TPX2 were found related to clonal resistance against chemotherapy. Splicing factors TRA2B and SRSF7 were also over-expressed in metastatic TNBCs compared with primaries. The analysis studying the association of CCNE1 and TPX2 with overall survival is ongoing using TCGA.

Conclusion: Overall, these results show the comparative changes between primary and relapsed TNBCs and indicate the heterogeneity of molecular mechanisms of recurrence. CNNE1 and TPX2 may represent important genes involved in TNBC metastasis. Further analyses including a total of 50 paired TNBCs are currently underway.

Study Contact: Yuan Yuan MD PhD, City of Hope Comprehensive Cancer Center; Duarte, CA 91030; Email: yuyuan@coh.org

Citation Format: Zhao Z-M, Yost S, Yuan Y-C, Warden C, Chuang J, Yuan Y. Mechanisms of recurrence: Paired analysis of primary and metastatic triple negative 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 PD8-02.
The Placental Secretome: Identifying Potential Cross-Talk Between Placenta and Islet β-Cells
Authors: Drynda Robert , Persaud Shanta J. , Bowe James E. , Jones Peter M
Published: February 2018

Background/Aims: Insulin-secreting islet β-cells adapt to the insulin resistance associated with pregnancy by increasing functional β-cell mass, but the placental signals involved in this process are not well defined. In the current study, we analysed expression of G-protein coupled receptor (GPCR) mRNAs in mouse islets and islet GPCR ligand mRNAs in placenta during pregnancy to generate an atlas of potential interactions between the placenta and β-cells to inform future functional studies of islet adaptive responses to pregnancy. Methods: Quantative RT-PCR arrays were used to measure mRNA expression levels of: (i) 342 GPCRs in islets from non-pregnant mice, and in islets isolated from mice on gestational days 12 and 18; (ii) 126 islet GPCR ligands in mouse placenta at gestational days 12 and 18. Results: At gestational day 12, a time of rapid expansion of the β-cell mass, 189 islet GPCR mRNAs were quantifiable, while 79 of the 126 known islet GPCR ligand mRNAs were detectable in placental extracts. Approximately half of the quantifiable placental GPCR ligand genes were of unknown function in β-cells. The expression of some islet GPCR and placental ligand mRNAs varied during pregnancy, with altered expression of both GPCR and ligand mRNAs by gestational day 18. Conclusion: The current study has revealed numerous potential routes for interaction between the placenta and islets, and offers an atlas to inform further functional studies of their roles in adaptive responses to pregnancy, and in the regulation of the β-cell mass.
Knockdown of MAGEA6 Activates AMP-Activated Protein Kinase (AMPK) Signaling to Inhibit Human Renal Cell Carcinoma Cells
Authors: Ye Xueting , Xie Jing , Huang Hang , Deng Zhexian
Published: February 2018

Background/Aims: Melanoma antigen A6 (MAGEA6) is a cancer-specific ubiquitin ligase of AMP-activated protein kinase (AMPK). The current study tested MAGEA6 expression and potential function in renal cell carcinoma (RCC). Methods: MAGEA6 and AMPK expression in human RCC tissues and RCC cells were tested by Western blotting assay and qRT-PCR assay. shRNA method was applied to knockdown MAGEA6 in human RCC cells. Cell survival and proliferation were tested by MTT assay and BrdU ELISA assay, respectively. Cell apoptosis was tested by the TUNEL assay and single strand DNA ELISA assay. The 786-O xenograft in nude mouse model was established to test RCC cell growth in vivo. Results: MAGEA6 is specifically expressed in RCC tissues as well as in the established (786-O and A498) and primary human RCC cells. MAGEA6 expression is correlated with AMPKα1 downregulation in RCC tissues and cells. It is not detected in normal renal tissues nor in the HK-2 renal epithelial cells. MAGEA6 knockdown by targeted-shRNA induced AMPK stabilization and activation, which led to mTOR complex 1 (mTORC1) in-activation and RCC cell death/apoptosis. AMPK inhibition, by AMPKα1 shRNA or the dominant negative AMPKα1 (T172A), almost reversed MAGEA6 knockdown-induced RCC cell apoptosis. Conversely, expression of the constitutive-active AMPKα1 (T172D) mimicked the actions by MAGEA6 shRNA. In vivo, MAGEA6 shRNA-bearing 786-O tumors grew significantly slower in nude mice than the control tumors. AMPKα1 stabilization and activation as well as mTORC1 in-activation were detected in MAGEA6 shRNA tumor tissues. Conclusion: MAGEA6 knockdown inhibits human RCC cells via activating AMPK signaling.
Treatment of Aortic Stenosis With a Self-Expanding, Resheathable Transcatheter Valve
Authors: Linke Axel , Holzhey David , Möllmann Helge , Manoharan Ganesh , Schäfer Ulrich , Frerker Christian , Worthley Stephen G. , van Boven A.J. , Redwood Simon , Kovac Jan , Butter Christian , Søndergaard Lars , Lauten Alexander , Schymik Gerhard , Walther Thomas
Published: February 2018

Background—

The aim of the Portico TAVI (transcatheter aortic valve implantation) system study was to evaluate outcomes ≤1 year after implantation of a novel resheathable, self-expanding TAVI system in a multicenter patient population with severe aortic stenosis (AS).

Methods and Results—

High-risk patients (n=222) with symptomatic severe AS (mean age, 83.0±4.6 years; 74.3% women) were enrolled across 12 centers in Europe and Australia. The study’s primary end point was all-cause mortality at 30 days. A total of 209 patients who received the Portico TAVI system were available for follow-up after the 30-day visit. Data collection included hemodynamic assessment by echocardiography with core laboratory evaluation and assessment of functional status. Valve Academic Research Consortium–defined adverse events were adjudicated by an independent Clinical Events Committee. TAVI using the Portico valve led to a significant and persistent improvement in aortic valve function at 1 year. More than mild paravalvular leak was present in 5.7% and 7.5% of patients at 30 days and 1 year, respectively. Kaplan–Meier estimates at 30 days and 1 year were 3.6% and 13.8% for all-cause mortality, 3.6% and 9.6% for cardiovascular mortality, and 3.2% and 5.8% for major (disabling) stroke. After 30 days and ≤1 year of follow-up, adverse events included stage 3 acute kidney injury (n=3), major vascular complications (n=5), and life-threatening/disabling bleeding (n=3). Overall permanent pacemaker rate was 14.7%. At 1 year, 74.8% improved ≥1 New York Heart Association class compared with baseline (
P
<0.0001).

Conclusions—

The Portico TAVI system is safe and effective at 1 year, yielding low mortality and stroke rates in high-risk patients with severe AS.

Clinical Trial Registration—

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01493284.
Preliminary assessment of genetic diversity and population connectivity of the Mugger Crocodile in Iran
Authors: Campos João Carlos , Mobaraki Asghar , Abtin Elham , Godinho Raquel , Brito José Carlos
Published: February 2018

The Mugger Crocodile (Crocodylus palustris) is a threatened reptile inhabiting the Indian Sub-continent and Western Asia. Despite its “Vulnerable” conservation status, data about population genetic structure and connectivity are unavailable. This study makes a preliminary assessment of the genetic diversity, population structure and habitat connectivity of C. palustris in Iran. Ten tissue samples collected along the Sarbaz-Bahukalat basins were analysed and a set of 12 microsatellites was genotyped. Genetic diversity indices were estimated and population substructuring was assessed through Bayesian clustering analysis. Potential connectivity was verified through Remote Sensing water indexes, further implemented in a circuit analysis. Low genetic diversity was observed (mean observed heterozygosity = 0.35; mean expected heterozygosity = 0.43) and no population structure was found (K = 1). Water index and circuit analysis suggested possible connection among sites. This study highlights the potential vulnerability of crocodile populations and the importance of habitat connectivity for their persistence in the arid regions of Iran.
Political Drama in the Ming-Qing Transition: A Study of Four Plays
Authors: Hardie Alison
Published: February 2018

In the late Ming dynasty, a new genre of drama arose, which presented on stage recent political events, featuring real historical persons; this genre continued across the Ming-Qing transition. The earliest and one of the best known examples is The Cry of the Phoenix (Ming feng ji), dramatising the conflict between corrupt minister Yan Song (1481-1568) and upright official Yang Jisheng (1516-1555), and probably written by someone in the literary circle of Wang Shizhen (1526-1590). The genre reached its apogee in Kong Shangren’s (1648-1718) The Peach Blossom Fan (Taohua shan). Around the Ming-Qing transition, in the Chongzhen and Shunzhi reigns, a considerable number of plays focused on the conflict during the preceding Tianqi reign between the Eastern Grove (Donglin) faction and the chief eunuch Wei Zhongxian (1568-1627). Eleven plays on this subject are known, of which three survive: Fan Shiyan’s Eunuch Wei Grinds Down the Loyal (Wei jian mo zhong ji), the Clear-Whistling Scholar’s (Qingxiaosheng) A Happy Encounter with Spring (Xi feng chun), and Li Yu’s 李玉 A Roster of the Pure and Loyal (Qing zhong pu). Basing my argument on an examination of these plays and of another play by Li Yu, Reunion across Ten Thousand Miles (Wan li yuan), also based on contemporary events, I suggest that the lively version of events given by these political dramas both reflected and helped to develop and spread the popularly accepted view of late-Ming and Southern Ming factional conflict leading to the fall of the Ming dynasty. According to this view, broadly following the Eastern Grove and Revival Society (Fushe) narrative, the decline and fall of the Ming dynasty was the fault of corrupt officials and evil palace eunuchs who misled the Emperor and were bravely resisted by righteous and incorruptible officials who fell as martyrs to their unprincipled opponents. This simplistic view, endorsed to a great extent in the official Ming History (Ming shi), which was mostly written by former Eastern Grove and Revival Society adherents, has persisted in the popular mind to the present day. I also argue that, after the establishment of the Qing, political drama could serve as a vehicle for the covert expression of Ming loyalism.
Inter-Subjectivity and Imagined Sovereignty: John Fryer’s New-Age Novel Contest in 1895 and the Rise of Modern Chinese Novel
Authors: Yao Dadui
Published: February 2018

The concept of inter-subjectivity serves as a starting point to discuss a book-writing competition sponsored by John Fryer in 1895 and the rise of modern Chinese fiction. His departure from China the following year had two possible reasons: money and the expectations. The money issue was related to the prompt initiation and excessive expences of this contest; besides, the contest specific requirements contributed greatly to the identity awareness of the Chinese writers. The horizon of one’s expectations touches the problem of subjectivities. A fusion of the expectations of the missionary and those of Chinese literati manifested itself in The New-Age Novel as inter-subjectivity. Nevertheless, the expression of imagined sovereignty of Chinese literati in the works presented at the contest went beyond Fryer’s expectations and gave birth to not only simply a Western impact and Chinese response and a Sino-centric pattern both which served as a spur to the rise of modern Chinese novel.
Self-government and 1911 in China: Revolution or Continuity in the Political Participation in Sichuan Province?
Authors: Togni Monica de
Published: February 2018

The process that led to the creation of self-government organs, and their activities in the first years of their existence, shows a consistent continuity between the imperial and the republican institutions, but also some changes in the institutional behaviour of the representatives of the local communities before and after the 1911’s revolution. The different meaning attributed to the institutional reforms as they appear to have been interpreted by the Qing Court, from the interpretations by the local society - a tools to control the political activism of the local notables vs a means to play a more active role in the local policy -, did not interfere with the creation of the organs of self-government, a part of the new structure to be built for the constitutional monarchy scheduled through imperial edicts on 27th August, 1908. The local activism and activities, as they are illustrated for Sichuan province through provincial and county archive documents, local gazetteers and reviews, show contradictory tendencies even as relates to some officials, and part of local communities anticipating sometimes the dispositions by the central government for the implementations of self-government, and some resistance by the people who had the right to vote in the participation to the preparatory process for the poll. However, the flourishing of self-government councils of the lower level and the fields of their interventions as representatives of the local communities show a very positive attitude on part of the local communities that continued until Yuan Shikai closed them down in 1914. This study will be concentrating on this aspect and will include, among other things, the case-study of Xuanhan county in north-western Sichuan, where a powerful local lineage played a very relevant role, taking advantage of the disruption of the provincial institutional order.
The Influence of Song and Qing Antiquarianism on Modern Chinese Archaeology
Authors: Visconti Chiara
Published: February 2018

Archaeology has been introduced to China in the early twentieth century thanks to the crucial theoretical and methodological contribution of the Western world. Though the emergence of archaeology as a field of study reflected a growing interest among Chinese scholars in empirically based science it is also true that the interest for ancient artefacts and the material traces of the past has been a salient characteristic of Chinese historical accounts since antiquity. Indeed, what scholars termed antiquarianism can be traced to two key works of the Northern Song period, the Kaogu tu by Lü Dalin and the Bogu tu by Wang Fu. The influence of both works is still very visible in the classification of ritual bronze vessels. The other key moment in collecting culture and antiquarian studies was the very long reign of Qianlong, whose art collections exceeded any previous one. Though the investigation methods of Song and Qing literati were certainly different from modern ones it is also true that their cultural tradition remains in many ways a characteristic trait of Chinese archaeology.
The Story of Diaochan: From Chinese fiction to English drama — on the Romance of the Three Kingdoms and G.G. Alexander’s Teaou-Shin
Authors: Lijuan Song
Published: February 2018

This is a descriptive case study which attempts to explain how the story of Diaochan 貂蟬, the famous episode in Romance of the Three Kingdoms, gained its afterlife in the western milieu by being translated and rewritten. This article focuses on the analysis of G.G. Alexander’s Teaou-shin, A Drama from the Chinese, in five Acts, and proposes that during the transformation of a Chinese fictional script to an English theatrical text, the themes and spiritual entity of the story were shifted in order to appeal to the European audiences in the nineteenth century. Furthermore, it argues that the differences between Chinese fiction and English drama are generated from distinct literary genre as well as heterogeneous cultural background.
Separation of monophyletic groups into distinct genera should consider phenotypic discontinuities: the case of Lasiurini (Chiroptera: Vespertilionidae)
Authors: NOVAES ROBERTO LEONAN M. , GARBINO GUILHERME S. T. , CLÁUDIO VINÍCIUS C. , MORATELLI RICARDO
Published: February 2018

Baird et al. (2015) split Lasiurus into three distinct genera (Aeorestes, Dasypterus and Lasiurus) based on tree topology and divergence times for the tribe Lasiurini. This arrangement has not been widely adopted by the scientific community and was criticized by Ziegler et al. (2016). More recently, Baird et al. (2017) reinforced the taxonomic arrangement of Lasiurini comprised by three genera. Baird et al. (2015, 2017) provided the most comprehensive phylogenetic analyses of Lasiurus and offer important insights on the phylogeny and alpha-taxonomy of the group. However, we disagree with the taxonomic arrangement proposed at the genus level and explain our point below.
The larvae of Sericostoma sasbaddes Malicky 2010, S. maclachlanianum Costa 1884, S. clypeatum Hagen 1864, and S. siculum McLachlan 1876 (Trichoptera: Sericostomatidae), including a preliminary key to the Sericostomatidae larvae of European Ecoregion 3 (Italy, Corsica, and Malta)
Authors: WARINGER JOHANN , MALICKY HANS
Published: February 2018

Caddisfly samples collected from Corsica, Sardinia, and the Italian mainland included the adults of Sericostoma sasbaddes Malicky 2010, S. maclachlanianum Costa 1884, S. clypeatum Hagen 1864, and S. siculum McLachlan 1876. This material, combined with the unique distribution patterns of the four species, enabled the association of the final instar Sericostoma larvae collected at the same locations. Larvae of the two species from Sardinia (S. sasbaddes, S. maclachlanianum) can be separated by the number of bifurcate setae on each pleuron VIII. The two other species are geographically well separated: S. clypeatum is the only Sericostoma species present in Corsica, whereas S. siculum is confined to the Southern Italian Provinces including Sicily. Morphological characters from the larval descriptions have been used for constructing a preliminary larval key to the hitherto known Sericostomatidae species from European Ecoregion 3 (Italy, Corsica, and Malta).
Congenital Ocular Abnormalities in Free-Ranging White-Tailed Deer
Authors: Clarke Lorelei L. , Niedringhaus Kevin D. , Carmichael K. Paige , Keel M. Kevin , Fenton Heather
Published: February 2018

Congenital ocular abnormalities in cervids have been previously reported as individual cases from various regions of the United States and include microphthalmia, anophthalmia, congenital cataracts, dermoids, and colobomata. A common underlying cause for these abnormalities, such as nutritional deficiencies, environmental toxin exposures, or genetic mutations, has not been established. This retrospective study summarized and compared cases of suspected congenital ocular abnormalities in free-ranging white-tailed deer ( Odocoileus virginianus) submitted to the Southeastern Cooperative Wildlife Disease Study (SCWDS) in Athens, Georgia, to the preexisting literature. Of 3645 accessions of white-tailed deer submitted to SCWDS, 15 qualifying case records were found. An additional 15 cases were reported previously in the literature. Conditions described in SCWDS cases included microphthalmia (8/15), congenital cataracts (3/15), anophthalmia (2/15), colobomata (1/15), anterior segment dysgenesis (1/15), ectopic lacrimal gland tissue (1/15), and congenital blindness with corneal opacity (1/15). Most (11/15; 73%) of the SCWDS cases were male fawns with an average age of 4 months at presentation, consistent with previously described cases. Most animals had bilateral abnormalities with few extraocular congenital abnormalities, also consistent with existing reports. Cases were variably tested for various infectious agents at the time of submission; 2 cases were seropositive for bluetongue virus. Spatiotemporal clustering of cases was not evident. This study provided a concise and systematic summary of known existing cases of congenital ocular defects in fawns but did not identify a cause.
The Effects of System Justifying Beliefs on Skin-Tone Surveillance, Skin-Color Dissatisfaction, and Skin-Bleaching Behavior
Authors: Choma Becky L. , Prusaczyk Elvira
Published: February 2018

In two studies with women living in India (Study 1, n = 177) and African American women in the United States (Study 2, n = 120), we investigated whether skin-tone surveillance, which theoretically is a manifestation of self-objectification, predicted greater skin-color dissatisfaction and greater skin-bleaching behavior. Given the existence of colorism in Indian and American societies, we expected that ideologies that rationalize and perpetuate the status quo would moderate the proposed relations. Results were consistent with objectification theory and system justification theory. The positive relation between skin-tone surveillance and skin-color dissatisfaction was weaker among women of color who more strongly (vs. weakly) endorsed system justifying ideologies, and the positive relation between skin-tone surveillance and skin-bleaching behavior was stronger among women of color who more strongly (vs. weakly) endorsed system justifying ideologies. Our results suggest that self-objectification theorists and researchers should consider culturally specific manifestations of self-objectification as well as protective and legitimating effects of system justifying ideologies. We encourage clinicians and policy makers to use public campaigns and individual-level interventions to target the norms and motivations underlying skin-bleaching. Online slides for instructors who want to use this article for teaching are available on PWQ's website at http://journals.sagepub.com/page/pwq/suppl/index