bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of MiR-1290 and its potential targets with characteristics of estrogen receptor α-positive breast cancer.
Authors: Endo Yumi , Toyama Tatsuya , Takahashi Satoru , Yoshimoto Nobuyasu , Iwasa Mai , Asano Tomoko , Fujii Yoshitaka , Yamashita Hiroko 
Published: March 2020

614 Background: Recent analyses have identified heterogeneity in estrogen receptor (ER) α-positive breast cancer. Subtypes called luminal A and luminal B have been identified, and the tumor characteristics, such as response to endocrine therapy and prognosis are different in these subtypes. However, little is known about how the biological characteristics of ER-positive breast cancer are determined. Methods: In this study, expression profiles of microRNAs (miRNAs) and mRNAs in ER-positive breast cancer tissue were compared between ERhigh Ki67low tumors and ERlow Ki67hightumors by miRNA and mRNA microarrays. Results: Unsupervised hierarchical clustering analyses revealed distinct expression patterns of miRNAs and mRNAs. We identified a down-regulation of miR-1290 and up-regulations of 6 miRNAs in ERhigh Ki67lowtumors. We picked up 11 genes that were potential target genes of the selected miRNAs. Protein expression patterns of the selected target genes were analyzed in ER-positive breast cancer samples by immunohistochemistry: miR-1290 and its 4 putative targets, BCL2, forkhead box A1 (FOXA1), microtubule associated protein tau (MAPT) and N-acetyltransferase-1 (NAT1) were identified. Transfection experiments revealed that introduction of miR-1290 into ER-positive breast cancer cells decreased mRNA and protein expression of NAT1 and FOXA1. Conclusions: Our results suggest that miR-1290 and its potential targets, NAT1 and FOXA1, might be associated with characteristics of ER-positive breast cancer.
Prognostic significance of the chemokine CXCL13 in node-negative breast cancer.
Authors: Schmidt Marcus , van de Sandt Leonie , Boehm Daniel , Sicking Isabel , Battista Marco Johannes , Lebrecht Antje , Solbach Christine , Naumann Gert , Rahnenfuehrer Joerg , Wirtz Ralph M , Hengstler Jan G 
Published: March 2020

615 Background: The chemokine CXCL13 is chemotactic for B cells. We examined the prognostic significance of CXCL13 mRNA expression in node-negative breast cancer. Methods: Microarray based gene-expression data for CXCL13 (205242_at) were analysed in four previously published cohorts (Mainz, Rotterdam, Transbig, Yu) of node-negative breast cancer patients not treated with adjuvant therapy (n=824). A meta-analysis of previously published cohorts was performed using a random effects model. Prognostic significance of CXCL13 on metastasis-free survival (MFS) was examined in the whole cohort and in different molecular subtypes (ER+/HER2-, ER-/HER2-, HER2+). Independent prognostic relevance was analysed using multivariate Cox regression. Results: Higher RNA expression of CXCL13 was related to better MFS in a meta-analysis of the whole cohort (HR 0.88, 95% CI 0.83-0.94, P<0.0001). Prognostic significance was most pronounced in the HER2+ positive molecular subtype (HR 0.72, 95% CI 0.59-0.87, P=0.0009) as compared to ER+/HER2- (HR 0.86, 95% CI 0.76-0.98, P=0.0024) and ER-/HER2- (HR 0.85, 95% CI 0.75-0.98), P=0.02) carcinomas of the breast. CXCL13 showed independent prognostic significance (HR 0.81, 95% CI 0.7336 0.8982, P=0.0001) in multivariate analysis. In addition to CXCL13, only histological grade of differentiation (HR 2.20, 95% CI 1.41-3.42, P=0.0005) and tumor size (HR 1.72, 95% CI 1.13-2.61, P=0.012), but neither age nor HER2 status nor hormone receptor status retained an independent prognostic association with MFS. Conclusions: The chemokine CXCL13 has independent prognostic significance in node-negative breast cancer. Higher expression of CXCL13 is associated with improved outcome.
Phase II study of lapatinib in combination with vinorelbine, as first- or second-line therapy in women with HER2-overexpressing metastatic breast cancer.
Authors: Chew Helen K. , Schwartzberg Lee Steven , Badarinath Suprith , Rubin Peter , Shumaker Grace , Daugherty James P. , DeSilvio Michelle , Mahoney Janine M. 
Published: March 2020

621 Background: Lapatinib (L), an inhibitor of epidermal growth factor receptor and human epidermal growth factor receptor 2 (HER2) is approved in combination with capecitabine for second-line treatment of HER2+ metastatic breast cancer (MBC). Vinorelbine (V)is a semi-synthetic vinca alkaloid approved for use in patients (pts) with MBC. A previous phase I trial provided a maximum tolerated dose of L plus V. Methods: This was a multicenter, phase II study (LPT111110; NCT00709618) to evaluate the efficacy and safety of L plus V in women with histologically confirmed stage IV HER2+ MBC, ≤1 prior chemotherapeutic regimen (no prior L or V was allowed; prior trastuzumab was permitted) and a Zubrod performance status of 0-2. Pts received L (1500 mg daily) plus V (20 mg/m2IV on Days 1, 8, 15) in a 4-week treatment cycle until disease progression or study withdrawal. Primary endpoint: overall response rate (ORR). Secondary endpoints: progression-free survival (PFS), overall survival, time to response (TTR), duration of response (DOR), time to progression, and safety assessments. Results: The study was terminated after three years due to slow enrollment; 60 pts were planned and 44 enrolled and were treated. The ORR was 41% (95% CI: 26.4%-55.4%; 4 complete responses, 14 partial responses). Investigator-assessed median (95% CI) PFS, TTR, and DOR were 24.1 (16.9-36.7), 7.5 (7.1–8.1), and 32.0 (18.0-42.3) weeks, respectively. Survival data are not available since data collection was terminated after discontinuation of study treatment. All pts experienced at least 1 adverse event (AE). Conclusions: The combination of L plus V resulted in a 41% ORR and was generally well tolerated. However, definitive conclusions could not be drawn as the study was terminated early and not powered for inference testing. Further exploration of L plus V is warranted to clearly define the role of this novel combination in the treatment of HER2+ MBC. Clinical trial information: NCT00709618. [Table: see text]
Prognostic and predictive value of a low estrogen receptor expression in breast cancer: A retrospective study from a reference center.
Authors: Diorio Caroline , Bouchard-Fortier Antoine , Blanchette Caty , Provencher Louise 
Published: March 2020

627 Background: Threshold of estrogen receptors positivity in breast cancer has been lowered to ≥1% of stained cells by immunohistochemistry testing. This change was based on experts’ recommendations from the 2009 St Gallen International Expert Consensus and from the 2010 guidelines of the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP). However few studies support these guidelines and the benefit of treating weakly positive estrogen receptor tumors (1-9%) is unknown. Methods: We identified 2221 breast cancer patients with estrogen receptors tested by ligand-based assay, treated and followed in our institution between 1976 and 2008. Date and cause of death were identified through linkage to Quebec Mortality File. A multivariate Cox proportional-hazards model was used to assess the effect of estrogen receptor levels on breast cancer mortality in patients who received hormonal therapy (tamoxifen). Results: In patients with low estrogen receptors, 17% (383 patients) were within 0-3 fmol/mg of cytosol and 12% (266 patients) were within 4-9 fmol/mg of cytosol. Patients with estrogen receptor levels of 0-3, 4-9, 10-19, 20-49, and ≥50 fmol/mg of cytosol had a 20-year breast cancer survival rate of 56%, 56%, 63%, 71% and 60% respectively. From the 2221 patients, 661 (29.8%) received hormonal therapy. In these patients, estrogen receptor levels of 0-3, 4-9, 10-19, 20-49 and ≥50 fmol/mg of cytosol were associated with lower breast cancer mortality (HR (p-value) of 1.00 (reference), 0.59 (0.09), 0.19 (<0.0001), 0.26 (<0.0001) and 0.31 (<0.0001) respectively); with significant mortality reduction only for estrogen receptor levels ≥10 fmol/mg of cytosol. Conclusions: A weak expression of estrogen receptors (<10 fmol/mg) in breast cancer is associated with increase breast cancer mortality. Our results did not show a significant benefit to treat these patients with hormonal therapy as oppose to those with estrogen receptor levels ≥10 fmol/mg of cytosol. To further support these findings, a similar study should be repeated in patients with estrogen receptors tested by immunohistochemistry.
Lack of efficacy of adjuvant lapatinib in HER2-negative breast cancer (HER2–ve BC): Analysis of patients in the TEACH trial.
Authors: Chavarri Guerra Yanin , Chan Arlene , Finkelstein Dianne M. , Chan Valorie F. , Harvey Vernon J. , Lee Keun Seok , Jain Minish Mahendra , Petrakova Katarina , Raina Vinod , Xu Binghe , Gomez Henry , Rappold Erica , Kaneko Tomomi , Huang Yingjie , Goss Paul E. 
Published: March 2020

628 Background: Benefit from trastuzumab (T) in patients (pts) with HER2–ve tumors by central laboratory FISH testing was shown in an exploratory analysis of the NSABP B-31trial and confirmed by levels of expression of HER2 mRNA. DNA sequencing studies demonstrate that undetected HER2 mutations may drive tumor growth. It is hypothesized that pts with BC deemed as HER2–ve based on amplification may still benefit from anti-HER2 therapy. We undertook an exploratory analysis of disease free survival (DFS) in pts in TEACH whose tumors were HER2–ve or borderline by central FISH testing. Methods: TEACH, a randomized, double-blind, placebo (P)-controlled trial in 33 countries, evaluated lapatinib (L) in reducing relapse risk in T-naive pts pretreated with chemotherapy for HER2+ BC. L showed a hazard ratio (HR) for DFS compared with P of 0.83 (95% confidence interval [CI] 0.70-1.00); P=.053 in the ITT population (n=3147) and in pts with HER2+ BC by central FISH [HR: 0.82 (0.67-1.00); P=.04]. We conducted an exploratory analysis of DFS in pts with borderline or HER2–ve tumors by central FISH. Estimated DFS times were calculated using a stratified log-rank test. HR was estimated by a stratified Cox regression model. Results: 657 pts (21%) did not have centrally confirmed HER2+ BC (L: 341 and P: 316) in the ITT population: 425 had negative (HER2:CEP-17 ratio <1.8) or borderline (≥1.8–<2.0) FISH testing (L: 218 and P: 207), 216 were unevaluable due to insufficient tissue or sample failed to hybridize (L: 114 and P: 102) and 16 were not centrally tested. In the 425 pts with centrally confirmed HER2–ve or borderline FISH results with 27 events in L and 34 in P, the HR for DFS in L compared with P was 0.94 (0.56-1.57). The percentage of pts with DFS at 4 yrs was 85.0% (79.5%-90.4%) in L and 81% (75.1%-87.1%) in P. Conclusions: Although L showed efficacy in pts with centrally confirmed HER2+ BC in the TEACH trial, our analysis did not show benefit in pts whose tumors were HER2–ve or borderline by central FISH. The TEACH trial shows once again that quality control of HER2 testing is crucial and central laboratory testing should be considered for non-specialized centers worldwide. Clinical trial information: NCT00374322.
Role of HER3 expression and PTEN loss in patients with HER2-overexpressing metastatic breast cancer (MBC) patients who received taxane plus trastuzumab treatment.
Authors: Park Yeon Hee , Jung Hyun Ae , Chang Won Jin , Choi Moon Ki , Hong Jung Yong , Ok Oh-Nam , Seo Jeong Ju , Choi Yoon-La , Do Ingu , Ahn Jin Seok , Im Young-Hyuck 
Published: March 2020

637 Background: The HER3 receptor is a key member of ErbB family and preferentially signals through the PI3K pathway. Formation of dimers between HER3 and HER2 seems to be crucial for HER2-driven signals in HER2 overexpressing tumors. Given the fact that HER2-HER3 is considered the most active signalling dimer of the ErbB system, HER3 activity may contribute to the resistance of trastuzumab. PTEN plays a well-established role in the negative regulation of the PI3K pathway. Our aim of this study was to investigate the role of HER3 and PTEN expression in patients with HER2 overexpressed MBC. Methods: One-hundred twenty-five MBC patients who were treated with taxane plus trastuzumab chemotherapy as the first line therapy were included in this analysis. Immunohistochemical stainings (IHC) with HER3 and PTEN antibody were conducted retrospectively. Results: Median age was 48 years. HER3 IHC was graded from 0 to 3. PTEN IHC was scored as multiplication of intensity and proportion from 0 to 300. The patients who had negative HER3 stain showed better progression free survival (PFS) to taxane plus trastuzumab chemotherapy than those positive HER3 stain (p=0.001, median PFS 21 vs. 11 mo.). The patients who had PTEN score of more than 20 showed longer PFS than those PTEN score of 20 or less than 20 (p=0.006, median PFS 13 vs. 9 mo.). The patients who had PTEN score of more than 20 showed longer overall survival (OS) than those PTEN score of 20 or less than 20 (p=0.005, median OS 48 vs. 25 mo.). HER3 negativity and PTEN loss were identified as independent risk factors for PFS [Hazard Ratio (HR) 0.4 (95% CI 0.3-0.8 for HER3 negativity; HR 2.1 (95% CI 1.2-3.7) for PTEN loss]. However, PTEN loss (HR 3.1 [95% CI 1.6-6.3]) was identified as an independent risk factor for OS. Conclusions: HER3 and PTEN expression may be predictive markers for trastuzumab treatment in HER2-positive MBCs. PTEN expression may have a potential predictive and prognostic biomarker for trastuzumab treatment.
Use of high-intensity surveillance in patients following a diagnosis of stage I-II non-small cell lung cancer.
Authors: Wright Jason Dennis , Neugut Alfred I. , Siddiq Zainab , Glied Sherry A. , Hershman Dawn L. 
Published: March 2020

6505 Background: The incidence of stage I and II lung cancer has been increasing due to the reported benefits of CT screening in high risk individuals. Guidelines suggest continued surveillance following diagnosis, however the extent to which this is done is unclear. We examined the patterns and predictors of surveillance imaging in patients following a diagnosis of stage I-II non-small cell lung cancer (NSCLC). Methods: The SEER-Medicare database was used to identify patients with stage I-II, NSCLC who underwent curative intent surgical resection from 2000-2006.Three surveillance periods (6-18, 18-30, 30-42 months) after diagnosis were identified. Use of imaging was quantified for each period and logistic regression models developed to examine predictors of thoracic imaging during all 3 surveillance periods. Results: Between 2000-2006 5269 patients were identified. During the first year of surveillance use of chest CT (48% in 2000 to 78% in 2006) and PET (2% to 23%) increased while use of bone scan (12% to 6%) and chest radiography (87% to 71%) decreased over time. Similar trends were noted for surveillance periods 2 and 3. During the study, surveillance imaging was performed in all 3 surveillance periods in 38% of the cohort. Yearly surveillance imaging increased with time; 21% of patients diagnosed in 2000 vs. 78% diagnosed in 2006 underwent testing in the first 3 years of follow-up (P<0.0001). In a multivariable model, in addition to year of diagnosis, patients with high socioeconomic status (OR=1.96; 95% CI, 1.51-2.55 compared to low SES) were more likely to undergo yearly surveillance imaging, while Hispanics (OR=0.42; 95% CI, 0.21-0.85) and older patients (OR=0.52; 95% CI, 0.43-0.63) were less likely to undergo testing. Conclusions: The use of costly diagnostic imaging of uncertain value is increasing rapidly for patients with localized NSCLC. Non-clinical factors including high socioeconomic status and white race are among the strongest predictors of use of high intensity surveillance.
Choosing mastectomy over lumpectomy: Factors associated with surgical decisions in young women with breast cancer.
Authors: Rosenberg Shoshana M. , Sepucha Karen , Ruddy Kathryn Jean , Tamimi Rulla M. , Gelber Shari I. , Meyer Meghan E , Schapira Lidia , Come Steven E. , Borges Virginia F. , Winer Eric P. , Partridge Ann H. 
Published: March 2020

6507 Background: Few studies have comprehensively evaluated surgical decisions in young women with breast cancer. Young women have unique medical and psychosocial concerns, and identifying factors associated with surgical choices in this population can inform their decision-making process. Methods: As part of an ongoing multi-center cohort study enrolling women diagnosed with breast cancer at age 40 or younger, we evaluated 277 women with stage I-III disease who indicated they had a choice between mastectomy and breast conserving surgery (BCS). Logistic regression was used to identify predictors of choosing mastectomy vs. BCS. Independent variables with a p-value ≤ 0.15 in bi-variate analyses were included in the final multivariable model. Results: 172/277 women (62%) had either a single or bilateral mastectomy as their definitive surgery. Median age at diagnosis was 37 (range: 17-40). Most women were married (75%), had stage I or II disease (90%), and estrogen receptor (ER) positive tumors (65%); approximately 14% were carriers of a BRCA 1 or 2 mutation. In the multivariable analysis (Table), having a mutation, nodal involvement, HER2-positivity, tumor grade, lower BMI, having 2 or more children, anxiety, and decisional involvement by the patient were all associated with mastectomy. Age, race, marital status, tumor size, having a first degree relative with breast or ovarian cancer, ER status, fear of recurrence, and depression were not significantly associated with having a mastectomy. Conclusions: Despite being candidates for BCS, many young women choose to have a mastectomy. Our results suggest potential targets for interventions such as anxiety reduction and fostering fully informed shared decision-making. [Table: see text]
For-profit hospital ownership status and use of brachytherapy after breast-conserving surgery.
Authors: Sen Sounok , Soulos Pamela R. , Herrin Jeph , Roberts Kenneth B , Yu James B. , Lesnikoski Beth-Ann , Ross Joseph S. , Krumholz Harlan , Gross Cary Philip 
Published: March 2020

6511 Background: Because the benefits of adjuvant radiation therapy (RT) for breast cancer decrease with increasing age, the use of newer and more expensive RT modalities such as brachytherapy in the treatment of older women has been questioned. In particular, patients and policy makers may be concerned that for-profit hospitals might be more likely to use therapies with higher reimbursements. Among both younger and older Medicare beneficiaries with breast cancer, we examined whether hospital ownership status is associated with use of adjuvant brachytherapy. Methods: Using the Centers for Medicare and Medicaid Services Chronic Condition Warehouse database, we conducted a retrospective study of female Medicare beneficiaries aged 66-94 years old receiving breast-conserving surgery for invasive breast cancer in 2008 and 2009. We assessed the relationship between hospital ownership and receipt of brachytherapy, as well as overall RT (i.e. brachytherapy or whole breast irradiation) using hierarchical generalized linear models. Results: The sample consisted of 35,118 women, 8.0% of whom had undergone surgery at for-profit hospitals.Among patients who received RT, those who underwent surgery at for-profit hospitals were significantly more likely to receive brachytherapy (20.2%) than patients treated at not-for-profit hospitals (15.2%; OR for profit vs. not-for profit: 1.50; 95% CI: 1.23-1.84; p<0.001). Among women 66-79 years old, there was no relation between hospital profit status and overall RT use. However, among women age 80-94 years old, receipt of surgery at a for-profit hospital was significantly associated with higher overall RT use (OR: 1.22; 95% CI: 1.03-1.45, p=0.03) and brachytherapy use (OR: 1.66; 95% CI: 1.18-2.34, p=0.003), but not whole breast irradiation use (OR: 1.14; 95% CI: 0.96-1.36, p=0.13) Conclusions: Medicare beneficiaries undergoing breast-conserving surgery at for-profit hospitals were more likely to receive brachytherapy, a newer, less proven, and more expensive technology. Among the oldest women, who are least likely to benefit from RT, care at a for-profit hospital was associated with higher overall RT use, with this difference largely driven by the use of brachytherapy.
Multitrial evaluation of longitudinal tumor measurement (TM)-based metrics for predicting overall survival (OS) using the RECIST 1.1 data warehouse.
Authors: Mandrekar Sumithra J. , An Ming-Wen , Dong XinXin , Grothey Axel , Bogaerts Jan , Sargent Daniel J. 
Published: March 2020

6520 Background: We previously reported that alternative cutpoints and alternate categorical metrics to RECIST standards provided no meaningful improvement in OS prediction. Here, we sought to identify and validate continuous, longitudinal TM-based metrics for predicting OS. Methods: Data from 13 trials (1739 patients with sufficient imaging-based measurements from breast, lung or colon cancer) were randomly split (60:40) into training and validation datasets and landmarked at 12-weeks (w). Multiple candidate metrics that capture tumor curve trajectory were considered: first slope (or % change) from baseline to 6 w, last slope (or % change) from 6 w to 12 w, and indicator of increase (<5% (includes no increase or a decrease) vs. ≥5%) from the prior assessment (baseline to 6 w, 6 w to 12 w). Multivariable Cox models stratified by study and number of baseline target lesions (<3 vs. >3) and adjusted for baseline tumor burden (ratio of the sum of lesions/number of lesions) were fit for each tumor type. Predictive ability was assessed via concordance (c)-index (0.5: no association to 1.0: perfect association), and hazard ratios/p-values (HR/p). Results: Patients whose tumor size increased by at least 5% from the prior assessment, as well as whose tumors showed a positive slope (or % change) from 6 to 12 w (indicating tumor growth) had worse OS. The first slope (or % change) metric was less consistent, with an initial decrease in slope suggesting worse OS in some cases. Predictive ability of these metrics varied across tumor type with poorest prediction in Breast (Table). Conclusions: Continuous TM-based metrics performed no better than categorical RECIST metrics for OS prediction. [Table: see text]