tbuckley/cabot-search huggingface dataset:
Recurrence rates and long-term survival in women diagnosed with breast cancer at age 40 and younger.
Authors: J. M. Buckley, S. Coopey, S. Samphao, M. C. Specht, K. S. Hughes, M. Gadd, A. G. Taghian, B. L. Smith
Journal: Journal of Clinical Oncology (2011)

70 Background: Young age at diagnosis of breast cancer has been reported to be an independent risk factor for disease recurrence. However, there is little data on long term survival of young patients. We present long term follow up of a large cohort of women diagnosed with breast cancer at age 40 and younger. We determined rates of loco-regional recurrence (LRR), distant recurrence, and overall survival and adjusted for the patient and tumor characteristics which potentially predict outcomes. Methods: Following Institutional Review Board approval, data from the medical records of 628 women diagnosed with breast cancer at age 40 or younger between 1996 and 2008 were collected. Survival curves were estimated using the Kaplan Meier method. Results: Median age was 37 years (range: 21-40) and median follow-up was 72 months (range: 5-177). The rates of LRR as a first site of recurrence were 5.56% at 5 years and 12.11% at 10 years. In the entire population, with median follow-up of 72 months, there was no difference in the rates of loco-regional failure between patients who underwent breast conserving therapy (7.34%) compared to mastectomy (7.40%) (p=0.980). The rates of distant recurrence as a first event were 10.65% at 5 years and 14.58% at 10 years. Overall survival was 93.1% at 5 years and 87.26% at 10 years. 79.1% of patients received systemic therapy. For patients who developed disease recurrence, either LRR or distant, median time to first recurrence was 35 months (range: 3-167). Conclusions: Women aged 40 and younger at diagnosis of breast cancer have a good prognosis, with low overall recurrence rates at 5 and 10 years. Local recurrence in our cohort is lower than in prior studies, suggesting advances in therapy have made breast conservation a safe option in young breast cancer patients.
MSI2 Is Required for Maintaining the Activated Myelodysplastic Syndrome Stem Cell
Authors: Tzu-Chieh Ho, James Taggart, Elianna Amin, Haiming Xu, Trevor Barlowe, Alexander R Perez, Patrick Tivnan, Rachel Okabe, Christopher Lengner, Amit Verma, Gail J Roboz, Monica L. Guzman, Christina S Leslie, Stephen D. Nimer, Michael G. Kharas
Journal: Blood (2015)
Identifying women at increased risk of breast cancer: Can we use genotyping at low penetrance loci?
Authors: C. Merrick, J. Dunlop, L. Baker, E. Gellatly, A. Martin, P. Quinlan, R. Tavendale, A. M. Thompson, C. Palmer, M. Reis, J. N. Berg
Journal: Journal of Clinical Oncology (2011)

162 Background: Most inherited predisposition to breast cancer is attributable to low penetrance susceptibility loci, a number of which have been identified through genome-wide association studies. Although individually each locus has a small effect, combining data from multiple loci would be expected to provide more risk information. We investigated the size of risk determination that can be achieved using genotyping at 18 loci. We then calculated its effect when combined with risk estimated from family history alone in terms of management under UK guidelines, where a woman who has a 10 year risk of 3% or greater requires additional breast screening from a younger age. Methods: Genotyping for 18 loci was carried out in 253 women at increased risk of breast cancer due to a positive family history and 118 matched controls. The relative risks conferred by genotype at the 18 loci were combined under a log-additive model and transformed into a log-polygenic risk. The BOADICEA risk estimation tool was used to calculate breast cancer risk due to family history. Results: Both the increased risk and control groups demonstrated a normal distribution of log-polygenic risk with similar variance. There was a significantly higher mean in the increased risk compared to the control group (mean = 0.1313 and 0.0874 respectively, p = 0.007). No significant correlation was found between polygenic risk calculated from genotype data and the family history risk estimated using BOADICEA. When polygenic risk was combined with family history risk there was significant reclassification of risk for those with a family history. 36.76% moved into a higher risk category while 3.68% moved into a lower risk category. Conclusions: Our data suggests that genotyping will be clinically relevant for estimating breast cancer risk. Individuals with a family history overall have a higher genotype risk than the population. The lack of correlation of genotype risk with BOADICEA risk suggests that the two risk estimates can be considered independently. By combining genotype with family history data, we demonstrated a significant reclassification of risk for individuals with a family history, with better identification of women in this group requiring intervention.
Emerging therapeutic agents for lung cancer
Authors: Bhagirathbhai Dholaria, William Hammond, Amanda Shreders, Yanyan Lou
Journal: Journal of Hematology & Oncology (2016)

Lung cancer continues to be the most common cause of cancer-related mortality worldwide. Recent advances in molecular diagnostics and immunotherapeutics have propelled the rapid development of novel treatment agents across all cancer subtypes, including lung cancer. Additionally, more pharmaceutical therapies for lung cancer have been approved by the US Food and Drug Administration in the last 5 years than in previous two decades. These drugs have ushered in a new era of lung cancer managements that have promising efficacy and safety and also provide treatment opportunities to patients who otherwise would have no conventional chemotherapy available. In this review, we summarize recent advances in lung cancer therapeutics with a specific focus on first in-human or early-phase I/II clinical trials. These drugs either offer better alternatives to drugs in their class or are a completely new class of drugs with novel mechanisms of action. We have divided our discussion into targeted agents, immunotherapies, and antibody drug conjugates for small cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). We briefly review the emerging agents and ongoing clinical studies. We have attempted to provide the most current review on emerging therapeutic agents on horizon for lung cancer.
Targeting BH3-Domain Anti-Apoptotic Proteins with ABT-737 Decreases DNA Synthesis, Induces Cell Death and Sensitizes Rituximab-Sensitive and Rituximab-Resistant Non-Hodgkin’s Lymphoma Cell Lines to the Anti-Tumor Activity of Chemotherapy Agents.
Authors: Sanjay Vinjamaram, Francisco J. Hernandez-Ilizaliturri, Steve Retke, Joy Knight, Myron S. Czuczman
Journal: Blood (2007)
Interleukin-33-induced expression of PIBF1 by decidual B cells protects against preterm labor
Authors: Bihui Huang, Azure N Faucette, Michael D Pawlitz, Bo Pei, Joshua W Goyert, Jordan Zheng Zhou, Nadim G El-Hage, Jie Deng, Jason Lin, Fayi Yao, Robert S Dewar, Japnam S Jassal, Maxwell L Sandberg, Jing Dai, Montserrat Cols, Cong Shen, Lisa A Polin, Ronald A Nichols, Theodore B Jones, Martin H Bluth, Karoline S Puder, Bernard Gonik, Nihar R Nayak, Elizabeth Puscheck, Wei-Zen Wei, Andrea Cerutti, Marco Colonna, Kang Chen
Journal: Nature Medicine (2016)
Gene Expression Profile (GEP) Analysis as a Tool to Control the Efficacy Dasatinib Treatment in Relapsed Imatinib-Resistant CML Patients Previously Undergone to Allogeneic Stem Cell Transplantation. Preliminary Data of a Single Institution
Authors: Bruno Martino, Maria Cuzzola, Carmela Rigolino, Domenica Ielo, Antonio Marino, Francesco Nobile, Pasquale Iacopino
Journal: Blood (2008)
Detection of Low Level Nilotinib or Dasatinib Resistant BCR-ABL Mutations by Mass Spectrometry In CML Patients Who Fail Imatinib Is Highly Predictive of Their Subsequent Clonal Expansion When Treated with the Drug for Which Their Mutation Confers Resistance
Authors: Wendy T Parker, Musei Ho, Rebecca M Lawrence, Darryl L Irwin, Hamish S Scott, Timothy Hughes, Susan Branford
Journal: Blood (2010)
Rechallenging taxanes in recurrent breast cancer in patients treated with (neo-) adjuvant taxane-based therapy.
Authors: X. Guo, S. Loibl, M. Untch, V. Möbus, K. Schwedler, P. A. Fasching, J. Barinoff, F. Holms, C. Thomssen, D. M. Zahm, R. Kreienberg, M. Hauschild, H. Eidtmann, S. Tauchert, K. Mehta, G. Von Minckwitz
Journal: Journal of Clinical Oncology (2011)

1055 Background: Docetaxel and paclitaxel are among the most active substances for the treatment of breast cancer. As they are today used in adjuvant regimen, efficacy data from pivotal trials in the metastatic setting in taxane-naïve populations cannot still reliably been used as reference. Methods: The Taxane Re-challenge Cohort Study identified participants from 6 prospective (neo-)adjuvant taxane-based studies with recurrent disease and collected data about their subsequent treatment. Out of 381 recurrent patients, 106 (27.8%) were re-challenged with a taxane-based treatment as first- or later-line therapy for recurrent disease. Results: Taxanes were used as first-line therapy in 74 patients and showed an overall response rate of 48.6% (including complete responses in 27.0%). Response rate was dependent on the disease-free interval (<1 year: 34.8%, 1−2 years: 42.9%, >2 years: 63.3%; P=0.04) and presence of visceral metastasis (present: 62.5%; not present 32.4%; P=0.01). Patients without visceral metastasis and disease-free interval >2 years achieved the longest overall survival. Hormone- and HER2 receptor status was not predictive, however triple-negative tumors responded in 50.0%. Overall response rate of later-line taxane-based treatment was 28.2%. Conclusions: Re-challenging taxanes appears to be effective and therefore represents a reasonable option in this population.
Report of a Phase II Study of Proteasome Inhibitor Bortezomib (Velcade) in Patients with Relapsed or Refractory T-Cell Lymphoma.
Authors: Pier Luigi Zinzani, Monica Tani, Vittorio Stefoni, Lapo Alinari, Enrica Marchi, Mariapaola Fina, Michele Baccarani
Journal: Blood (2005)
Methodology to screen and evaluate cost/survival of anticancer drugs in advanced/metastatic gastrointestinal cancers.
Authors: Helmy M. Guirgis
Journal: Journal of Clinical Oncology (2012)

196 Background: There is a paucity of methods to screen cost/survival of anticancer drugs in 1 st -line advanced/metastatic (adv/met) gastrointestinal (GI) cancers. Methods: Average whole prices (AWP) in United States dollars (US $) of evaluated drugs for the entire course were divided by previously reported median survival gain in days. Generic drugs were given flat total costs of up to $750. A 100% crude score was assigned to cost/survival/day &lt; $25 and 0% to cost/survival/day $750. Results were expressed as % scores of cost/progression-free-survival (cost/PFS) or cost/overall survival (cost/OS). Guidelines were suggested for corrections; lack of OS - 10%, adverse effects (AEs) - 0 -15%, Quality of life (QoL) - 0-10% and administration and preparation (A and P) - 0-10%. Results: Generic drugs scored 80%-90% in pancreatic and biliary followed by Trastuzumam 60% in gastric and Bevacizumab 0-40% in colon cancers (Table 1). Conclusions: Methodology based on limits on cost/survival/day was developed to screen anticancer drugs in GI cancers. Generic drugs in bilary and pancreatic cancers scored the highest. [Table: see text]
Factors associated with mortality after breast cancer metastasis.
Authors: S. Y. Jung, M. Q. Rosenzweig, S. M. Sereika, F. Linkov, A. Brufsky, J. L. Weissfeld
Journal: Journal of Clinical Oncology (2011)

174 Background: It is generally accepted that patients with breast cancer metastases have poor survival. Metastatic breast cancer patients can be considered a heterogeneous population with a varied clinical course, which underscores the need for accurate prediction of survival based on prognostic factors. The purpose of the present study was to identify factors related to survival in breast cancer patients after diagnosis with metastatic disease. Methods: A total of 557 patients with breast cancer metastasis diagnosis seen at one large urban practice have been followed up between January 1, 1999 and June 30, 2008. Demographic, tumor characteristics, clinical factors as predictors of survival were analyzed using Cox regression model. Results: The median survival length was 40 months (range 1-114 months) with 269 (48.3%) alive and 288 (51.7%) dead. This study demonstrated that hypertension, estrogen receptor (ER) and/or progesterone receptor (PR) status, human epidermal growth factor receptor-2 (HER2) status, number of metastatic sites, and body mass index (BMI) at diagnosis with metastatic breast cancer were the most relevant prognostic factors for survival after metastasis. Conclusions: Findings of this study may form a foundation for the corpus of knowledge explaining the outcome differences in treatment of patients with metastatic breast cancer, potentially helping to create tailored counseling and personalized treatment approaches for this vulnerable group. [Table: see text]
Substantial Variation in Nlv-Specific T Cells Phenotype and Activation Ability upon Antigen Stimulation May Have Implications for Virus-Specific Adoptive Therapy
Authors: Grigory A. Efimov, Alexander S. Vdovin, Filkin Y. Sergei, Polina R. Yefimova, Savely A. Sheetikov, Mikhail Yu. Drokov, Larisa A. Kuzmina, Elena N. Parovichnikova, Valery G. Savchenko
Journal: Blood (2016)
Hematopoietic Precursor Cell Cultures (CFU-C) in Diagnosis and Prognosis of Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML).
Authors: Michael Pierre Bernimoulin, Martine Jotterand, Andre Tichelli, Sandrine Meyer-Monard, Dominik Heim, Alois Gratwohl, Catherine Nissen
Journal: Blood (2005)
Event-Free Survival According to Age in Patients with Chronic Myeloid Leukemia Receiving Imatinib Frontline: The Younger, the Later, the Worse?
Authors: Roberto Latagliata, Massimo Breccia, Ida Carmosino, Federico Vozella, Federico De Angelis, Chiara Montagna, Maria Lucia De Luca, Gioia Colafigli, Luisa Quattrocchi, Giovanna Loglisci, Angela Romano, Paola Volpicelli, Daniela Diverio, Marco Mancini, Giuliana Alimena
Journal: Blood (2015)
Wnt3 Augments Adhesion Mediated Drug Resistance of Myeloma Cells Via Wnt/RhoA Pathway.
Authors: Hiroki Chiba, Masayoshi Kobune, Kazunori Kato, Kiminori Nakamura, Yutaka Kawano, Rishu Takimoto, Takuya Matsunaga, Junji Kato, Yoshiro Niitsu, Hirofumi Hamada
Journal: Blood (2005)
Clinical significance of time to relapse and the distinction between breast cancer recurrences and new primary tumors.
Authors: A. Patt, T. Li, M. Cristofanilli, G. M. Freedman, E. R. Sigurdson, R. J. Bleicher
Journal: Journal of Clinical Oncology (2011)

1071 Background: Longer disease-free interval (DFI) between primary (1°) tumor treatment and relapse correlates with better outcomes. Breast cancer relapses are divided into true local recurrences (LR) and new 1° tumors (NP). Arbitrary cutoff times to relapse are sometimes used to distinguish LR vs NP, but like LR vs NP distinction, this is poorly defined. This study assessed whether histologic phenotypes shifted significantly at any particular DFI help distinguish a LR from a NP. Methods: An IRB-approved, prospective database of >4,300 breast cancer patients (pts) was reviewed. Demographics, histologic and treatment-related characteristics were correlated between initial disease and 1st recurrence for 235 (5.4%) Stage I–III pts who relapsed in the ipsilateral breast between 11/1976 – 9/2008. Results: Pt median age was 51 y. Median time to relapse was 60.5 mos. A shift between 1° tumor and relapse phenotypes was noted in histology (p<.0001), ER expression (p<.0001), PR expression (p<.0001), EIC (p=.0003), and method of presentation (p<.0001, McNemar’s). Time to relapse was not predictive of any of these. HER2/neu (p=.20) and lymphovascular invasion (p=.22) did not vary between 1° tumor and relapse. Sixty % of relapses differed from their 1° tumor by ≥2 characteristics. Among 25 tumors without any phenotypic change, 56% were all T1/T2, N0, receiving only local therapy with surgery and radiotherapy. Factors correlating with a phenotypic shift between 1° tumor and relapse included: T stage (p=.006) on histology shift; chemotherapy (p=.04) on shift in grade; BMI (ER, p=.02; PR, p=.40) and hormonal therapy (ER, p=.02; PR, p=.05) on shift in receptor status; hormonal therapy (p=.01) on shift in EIC; and chemotherapy (p=.001) on shift in method of relapse presentation (logistic regression). Conclusions: Time to relapse is not predictive of change in relapse characteristics, suggesting that DFI should not be considered when defining a relapse as a NP or LR. Frequent change in relapse characteristics makes LR vs NP distinction difficult. As genetic analysis plays a greater role in characterization of tumor behavior, NP vs. LR clinical distinctions will likely become less significant.
Use of the monoclonal antibody PAM4 to differentiate pancreatic ductal adenocarcinoma (PDAC) from chronic pancreatitis and benign nonmucinous cysts of the pancreas.
Authors: Chanjuan Shi, David M. Goldenberg, David V. Gold
Journal: Journal of Clinical Oncology (2012)

188 Background: Previous studies have demonstrated that anti-mucin monoclonal antibody (mAb) PAM4 is highly specific for PDAC and its precursor lesions. To investigate specificity further, we examined the expression of PAM4-reactive mucin in chronic pancreatitis and benign non-mucinous cystic lesions of the pancreas. Methods: A tissue microarray of PDAC (N=14), as well as surgical specimens from chronic pancreatitis (N=32) and benign non-mucinous cystic lesions of the pancreas (N=19), were assessed by immunohistochemistry for expression of the PAM4-reactive mucin, as well as MUC1 (mAb-MA5), MUC4 (mAb-8G7), and CEACAM6 (mAb-MN-15). Results: PAM4-reactive mucin, MUC1, MUC4 and CEACAM6 were expressed in 79% (11/14), 100% (14/14), 86% (12/14) and 100% (14/14) of invasive pancreatic adenocarcinoma. PAM4 only weakly labeled 6% (1/19) of benign non-mucinous cystic lesions, 1 of 15 serous cystadenomas (SCAs) and 0 of 4 cysts with squamous epithelial lining (2 lymphoepithelial cysts, and 2 retention cysts with squamous metaplasia). However, the expression of MUC1, MUC4 and CEACAM6 was detected in 53% (8/15), 0% (0/15) and 13% (2/15) of SCAs, and in 4, 3 and 3 of the 4 cysts with squamous epithelial lining, respectively. PAM4 labeled 19% (6/32) of chronic pancreatitis specimens; however, this PAM4 reactivity was restricted to the PanIN precursor lesions associated with chronic pancreatitis. Inflamed tissue was negative. The expression of MUC1, MUC4 and CEACAM6 was detected in 90% (27/30), 78% (25/32), and 97% (31/32) of chronic pancreatitis. In all of the positively-labeled specimens, the reactivity was present in non-neoplastic inflamed pancreatic tissue in addition to PanIN. Conclusions: The expression of PAM4 was detected in only 6% of benign non-mucinous cystic lesions and in the precursor lesions associated with chronic pancreatitis. These results suggest that PAM4, in contrast to MUC1, MUC4, and CEACAM6, may be useful to differentiate benign non-mucinous cystic lesions of the pancreas and chronic pancreatitis from PDAC. (Supported in part by NIH grant CA096924.)
Phase 2 Study of Decitabine in Combination with Tretinoin in Myelodysplastic Syndromes and Acute Myelogenous Leukemia: Interim Results
Authors: Virginia M. Klimek, Emily K Dolezal, Joseph G. Jurcic, Sean Devlin, Kevin Zikaras, Jae H. Park, Todd L. Rosenblat, Stephen Nimer
Journal: Blood (2012)
Statins reduce the burden of ambient particulate matter and inflammatory cells within the lung tissues of smokers with and without COPD
Authors: Kunihiko Hiraiwa, Sally Miller, David A. Ngan, Dragoş M. Vasilescu, Tillie-Louise Hackett, Daisuke Kinose, Jui Chih Cheng, Stephan F. van Eeden
Journal: European Respiratory Journal (2016)

Previous studies from our laboratories have shown retention of particulate matter (PM) in lung tissues of subjects with chronic obstructive pulmonary disease (COPD), with increased retention in more severe COPD, potentially contributing to the persistent lung inflammation and remodelling of lung tissue in COPD [1]. Epidemiological studies have shown that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) reduce morbidity and mortality in subjects with COPD [2], possibly via their well-known pleiotropic anti-inflammatory properties [3, 4]. In an animal model we have shown that statins reduce lung inflammation induced by ambient PM exposure in part by reducing the retention of PM in lung tissues by promoting their removal via the lymphatic system to regional lymph nodes [5, 6]. We postulated that statins reduce the burden of PM retention in the lung tissues of subjects with COPD, and thereby reduce downstream lung inflammatory responses. Statins promote the processing and removal of inhaled particles from lung tissues, thereby reducing lung inflammation <http://ow.ly/Zx68305bv3k> We would like to thank all the laboratory technicians and summer students who contributed to this work.
Phase II trial combining nab-paclitaxel (NP), gemcitabine (G), and bevacizumab (B) in patients (pts) with metastatic breast cancer (MBC): NCCTG N0735.
Authors: D. W. Northfelt, A. C. Dueck, T. P. Flynn, P. J. Zander, P. J. Stella, M. Melnik, E. S. Pavey, E. A. Perez
Journal: Journal of Clinical Oncology (2011)

1126 Background: In N0531 (Roy et al, Ann Oncol 2009) NP+G was effective and tolerable in MBC, with complete + partial response rate (CR+PR) 50%, proportion with 6-month progression free survival (6-mo PFS) 60%, median PFS 7.9 mo, 14% with grade (gr) 4 adverse events (AE). N0735 studied addition of B to NP+G to improve response rate and PFS without reducing tolerability. Methods: Single stage phase II study enrolled pts with measurable MBC eligible for 1st line chemotherapy (chemo). Pts received NP 125 mg/m2 followed by G 1000 mg/m2 days 1 and 8; followed by B 15 mg/kg day 1 of 21 day cycles. Dose modifications allowed for NP and G. Primary endpoint was proportion of pts with PFS 6 months from registration. 47 evaluable pts required to test null hypothesis that 6-mo PFS was at most 60% against alternative of at least 77.5%. Results: 48 evaluable pts enrolled 11/08 - 3/10. Median age 56 (27-77). 30 pts (63%) ER- and 25 (52%) PgR-positive, 2 (4%) HER2 positive. 29 (60%) had prior neoadjuvant or adjuvant chemo. Median follow-up 10.6 mos (5-19.6). Median of 9.5 cycles completed (1-27). 39 pts discontinued, due to progression (36%), pt refusal (26%), adverse events (31%), alternate therapy (3%). 6-mo PFS was 81% (95% CI: 67-91%). Confirmed CR+PR was 69% (95% CI: 54-81%): 2 CR, 31 PR. Median duration of response was 9.9 mos (95% CI: 7.3-12.6). Median PFS was 11.7 mos (95% CI: 8.9-13.1); median overall survival (OS) was not reached. 12-mo OS rate was 84% (95% CI: 73-97%). Gr 4 AE occurred in 18 pts (38%), gr 3/4 AE in 43 (90%). Most common gr 3/4 AEs: neutropenia (71%), fatigue (21%), thrombocytopenia (19%), anemia (15%), leukopenia (10%), dyspnea (10%). Four pts had gr 3 neuropathy. Conclusions: The combination of NP+G+B is active in patients with MBC, and met study's prespecified endpoint (6-mo PFS >60%) to warrant further study of this regimen. Toxicities were manageable, permitting long duration therapy to achieve high response and PFS rates. This regimen should be further evaluated in phase III trials comparing regimens of chemotherapy + targeted agents in MBC.