tbuckley/cabot-search huggingface dataset:
Semi-quantitative protein analysis of HER2 and ER levels in human breast cancer reveals broad expression ranges within HER2+ and ER+ phenotypes
Authors: L. Liotta, M. Pierobon, J. Wulfkuhle, J. Laird, C. Livasy, V. Espina, L. Esserman, E. Petricoin
Journal: Journal of Clinical Oncology (2009)

11014 Background: ER and HER2 measurements underpin a majority of breast cancer clinical testing, yet determination of ER and HER2 protein levels are routinely performed using subjective approaches. We have developed a semi-quantitative calibrated protein microarray, the Reverse Phase Protein Microarray (RPMA), to more adequately determine accurate and precise protein expression levels in clinical tissue specimens. We utilized this method to determine HER2 and ER expression levels and compared the results to those values reported from the clinical laboratory. Methods: Pure tumor epithelium from 149 frozen pre-treatment human breast cancer tissue specimens (from the I-SPY TRIAL: CALGB 150007/150012, ACRIN 6657) were procured via Laser Capture Microdissection and protein pathway mapping was performed whereby the ER (N=112) and HER2 (N= 118) levels were directly measured and compared with reported IHC values. Results: Overall, RPMA measurements of HER2 had excellent correlation with IHC and FISH HER2 determination with no IHC or FISH false positives (88/88). 7 out of 30 of the FISH/IHC+ cases were found by RPMA to have HER2 values as low or lower than the FISH/IHC- cases with the HER2+ population having RPMA expression levels that varied by as much as 10-fold. There was less concordance between RPMA ER values and IHC ER values. Detailed analysis of a more homogeneous ER+ population (Allred =8) revealed a large dynamic range of expression of ER (10–20 fold) by RPMA. The HER2 and ER RPMA results were independently validated by Western Blot using a separate biopsy. Conclusions: Discreet protein expression values obtained by RPMA for ER and HER2 reveal distinctly broad expression values, with as much as 10–20 fold dynamic range in expression, even in a homogeneous (e.g. Allred score of 8) population. Such dynamic differences in protein expression may produce dramatic effects in therapeutic response rate. These findings, if found to be clinically useful, point to a potential need for more fine-tuned protein expression determination by quantitative high-throughput technologies for patient stratification even for standard-of-care FDA approved therapies. [Table: see text]
Effect of Homocysteine Derivatives and Methionine Antagonists on Rat Liver Regeneration<xref ref-type="fn" rid="FN2">2</xref>
Authors: L L Gershbein
Journal: JNCI Journal of the National Cancer Institute (1965)

Rats were submitted to partial hepatectomy, leading to the removal of two thirds of the liver, and placed on various diets containing homocysteine derivatives and methionine antagonists for 10.5 days. The amount of tissue regenerated or the increment was ascertained and compared with the respective controls. In agreement with earlier work, the extent of liver regeneration was markedly depressed by 0,20 percent DL-ethionine, S-benzyl-DL-homocysteine (0.25%), and α-methyl-DL-methionine (0.25%), but, at a comparable molar level (1.1–1.5 mM/kg feed), the decreases with the S-n-propylhomocysteines and S-i-propylhomocysteines were not statistically significant. Pathologically the liver was severely affected by the ethionine group. Both the D and L forms of ethionine at 0.10 percent inhibited restoration of liver weight. These data and the histological impression infer a greater toxicity for the L-enantiomorph. Liver regeneration was greatly inhibited by the methionine antagonists, cycloleucine (0.050%) and allylglycine (0.15%), but essentially unaffected by the sulfoxide and sulfone of methionine (each at 0.50%), by the corresponding derivatives of DL-ethionine (0.15% for both), by DL-methylmethioninesulfonium chloride (0.85%), and by dimethyl sulfoxide (0.75%). A small but definite decrease resulted with DL-methionine-DL-sulfoximine (0.10%).
The Beta-Subunit Of Heterotrimeric G Proteins Harbors Gain-Of-Function Mutations In Multiple Hematologic Malignancies
Authors: Akinori Yoda, Guillaume Adelmant, Nobuaki Shindoh, Bjoern Chapuy, Yuka Yoda, Oliver Weigert, Nadja Kopp, Shuo-Chieh Wu, Sunhee S. Kim, Huiyun Liu, Trevor Tivey, Jeffrey W. Tyner, Jason Gotlib, Michael W. Deininger, Shannon Turley, Jarrod A Marto, Andrew A. Lane, David M. Weinstock
Journal: Blood (2013)
Non-AIDS-related malignancies: expert consensus review and practical applications from the multidisciplinary CANCERVIH Working Group
Authors: J.-P. Spano, I. Poizot-Martin, D. Costagliola, F. Boué, O. Rosmorduc, A. Lavolé, S. Choquet, P.-E. Heudel, V. Leblond, J. Gabarre, M.-A. Valantin, C. Solas, A. Guihot, G. Carcelain, B. Autran, C. Katlama, L. Quéro
Journal: Annals of Oncology (2015)
Breast Cancer Screening and Diagnosis Clinical Practice Guidelines
Authors: Therese B Bevers, Benjamin O Anderson, Ermelinda Bonaccio, Patrick I Borgen, Saundra Buys, Mary B Daly, Peter J Dempsey, William B Farrar, Irving Fleming, Judy E Garber, Randall E Harris, Mark Helvie, Susan Hoover, Helen Krontiras, Sara Shaw, Eva Singletary, Celette Sugg Skinner, Mary Lou Smith, Theodore N Tsangaris, Elizabeth L Wiley, Cheryl Williams
Journal: Journal of the National Comprehensive Cancer Network (2006)

The lifetime risk of a woman developing breast cancer has increased over the past 5 years in the United States: of every 7 women, 1 is at risk based on a life expectancy of 85 years. An estimated 214,640 new cases (212,920 women and 1,720 men) of breast cancer and 41,430 deaths (40,970 women and 460 men) from this disease will occur in the United States in 2006. However, mortality from breast cancer has decreased slightly, attributed partly to mammographic screening. Early detection and accurate diagnosis made in a cost-effective manner are critical to a continued reduction in mortality. These practice guidelines are designed to facilitate clinical decision making. For the most recent version of the guidelines, please visit NCCN.org
Qualitative age interactions (or effect modification) suggest divergent pathways for early-onset and late-onset breast cancers
Authors: W. F. Anderson, L. A. Brinton, B. Chen, S. S. Devesa
Journal: Journal of Clinical Oncology (2007)

21036 Background: Notwithstanding some recent declines, breast cancer incidence rates have risen for decades, though not equally for all age groups. We used the National Cancer Institute's SEER program to further explore the effect of aging upon breast cancer incidence. Materials and Methods: The SEER program collected data on n=494,543 in-situ + invasive female breast cancer cases, newly diagnosed during 1974–2003. Temporal trends by race, stage, and grade were stratified by age at diagnosis in decades: 20–29 to 80+ years. Results: We observed age interactions over time. For example, as the specification of grade improved from 1974–2003, temporal trends for high and low grade tumors varied with age. Among women ages &lt;40 years, high grade lesions were more common than low grade tumors for all time periods. Among women ages 40+ years, high grade lesions were more common during the early years, and then rates crossed, after which low-grade tumors were more common than high grade lesions. Conclusion: Age at diagnosis was both a quantitative (non- crossover) and qualitative (crossover) effect modifier. The crossing of rates from high to low grade tumors among women ages 40+ years in the 1980s is consistent with more aggressive breast cancer screening, with mammography preferentially detecting low grade tumors among women targeted for screening, i.e., ages 40–80 years. Though once thought to be rare or artifactual, qualitative interactions or effect modification suggest etiologic heterogeneity in an otherwise homogeneous disease process. Indeed, if true, qualitative age interactions imply divergent pathways for early-onset and late-onset breast cancers. No significant financial relationships to disclose.
A <i>UGT1A1</i> genotype-directed phase I study of irinotecan (CPT-11) combined with fixed dose of capecitabine in patients with metastatic colorectal cancer (mCRC)
Authors: T. Kim, S. Sym, S. Lee, M. Ryu, J. Lee, H. Chang, H. Kim, J. Shin, Y. Kang, J. Lee
Journal: Journal of Clinical Oncology (2009)

2554 Background: The risk of severe toxicity of CPT-11 can be in part explained by polymorphism of UGT1A1. The most common polymorphism in Whites is UGT1A1*28. UGT1A1*6 is another common polymorphism in Asians. We designed a phase I study to investigate UGT1A1 genotype-directed maximum tolerated dose (MTD) of CPT-11 plus fixed dose of capecitabine in patients (pts) with Korean mCRC. Methods: Pts with mCRC screened UGT1A1 genotyping (*28 and *6) and were stratified into one of 3 groups according to the number of defective allele (DA): 0 (none of *28 or *6 allele), 1(only one of *28 or *6 allele), and 2 (*28/*28, *6/*6, or double heterozygous for *28 and *6). The dose of CPT-11 was escalated as following: Level -I:200, I:240, II:280, III:320, IV: 350, V: 380 mg/m 2 (IV, once every 3 weeks). Capecitabine (1,000 mg/m 2 PO BID) was administered on days 2–15 every 3 weeks. Dose limiting toxicity (DLT) and pharmacokinetic analyses was determined at cycle 1. Results: Forty-two pts, median age 50 years, EOOG performance ≤1 were recruited: 0 DA group (18 pts), 1 DA (18), and 2 DA (6). In 0 DA group, two of six pts experienced DLT at 380 mg/m 2 with grade III asthenia (1 pts) and febrile neutropenia (1). In 1 DA group, all of two pts experienced DLT at 380 mg/m 2 with grade III asthenia. In 2 DA group, two of three pts experienced DLT at 240 mg/m 2 with febrile neutropenia (1) and grade IV neutropenia (1). The MTD was defined as CPT-11 350 mg/m 2 for pts with 0 and 1 DA group and CPT-11 200 mg/m 2 for pts with 2 DA group, with capecitabine. Median SN-38G/SN-38 AUC was 10.45, 8.78, and 1.66 in pts with 0, 1, and 2 DA group, respectively. Conclusions: CPT-11 dosing by UGT1A1*28 and *6 genotypes is feasible in Korean pts with mCRC. A dose of CPT-11 350 mg/m 2 IV for pts with 0 and 1 DA group and CPT-11 200 mg/m 2 for pts with 2 DA group, with capecitabine every 3 weeks, is recommended for further study. [Table: see text] No significant financial relationships to disclose.
Disruption of CD9 Expression Affects Adhesion, Migration, and Actin Polymerization through RAC1 Signalling Pathway in ETV6/RUNX1 Pre-B Lymphocytes
Authors: Marie-Pierre Arnaud, Audrey Vallée, Guillaume Robert, Jacinthe Bonneau, Elisabetta Dondi, Christine Le Roy, Nadine Varin-Blank, Marie-Dominique Galibert, Marie-Bérengère Troadec, Virginie Gandemer
Journal: Blood (2014)
Assessment of performance measures for patients with the myelodysplastic syndrome (MDS) in the United States.
Authors: G. A. Abel, B. A. Neville, J. C. Weeks, R. M. Stone
Journal: Journal of Clinical Oncology (2010)

6002 Background: Although baseline bone marrow examination and assessment of iron stores before initiating an erythropoiesis-stimulating agent (ESA) are nationally endorsed performance measures for patients with MDS, it is not known to what extent clinicians adhere to them. Methods: We used the SEER-Medicare database to identify Medicare enrollees diagnosed with MDS from 2001-2005. Inpatient and outpatient claims through 2007 were analyzed for evidence of bone marrow examination, iron assessment (bone marrow iron stain, or serum ferritin, iron or transferrin), erythropoietin level, and ESA use through CPT, HCPCS, and ICD-9 procedure codes. Descriptive statistics were performed, and multivariable logistic regression was used to characterize covariates. Results: 6753 MDS patients met eligibility criteria. Median age at diagnosis was 79.8 (IQR 74.6-84.5); 45.0% were female. 5495 subjects (81.4%) had a claim for bone marrow biopsy within 3 months before to 3 months after their SEER diagnosis date. 4,108 (60.8%) had at least one claim for an ESA during the study period; of those, 1,754 (42.7%) had evidence of iron assessment within 3 months before their first ESA treatment, and 839 (20.4%) had pre-ESA assessment of erythropoietin level. In a multivariable model, age < 75 (OR 1.66 [1.42- 1.94]), metropolitan residence (OR 1.41 [1.18-1.68]), being married (OR 1.22 [1.07-1.38]), residence in the Midwest (OR 1.38 [1.12-1.70]), and highest vs. lowest socioeconomic quintile based on census tract (OR 1.42 [1.16-1.75]) were associated with bone marrow examination (p < 0.005 for all); notably, year of diagnosis and Charlson Comorbidity Score were not. There were no multivariable associations with pre-ESA iron assessment, except for residence in the West (OR 1.26 [1.07-1.49]). Conclusions: The majority of patients in our cohort received baseline bone marrow examination, although performance varied with several nonclinical characteristics. In contrast, less than half of patients undergoing ESA treatment had evidence of pretreatment assessment of iron status, and even fewer of pretreatment erythropoietin assessment. Given the high cost of ESA therapy, these findings may have important policy implications. No significant financial relationships to disclose.
Racial/ethnic disparities and geographic differences in lung cancer incidence - 38 States and the District of Columbia, 1998-2006.
Authors: T. L. Fairley, E. Tai, J. S. Townsend, S. L. Stewart, C. B. Steele, S. P. Davis, J. M. Underwood
Journal: MMWR Morbidity and Mortality Weekly Report (2010)
Phase I dose escalation study to determine the safety, pharmacokinetics and pharmacodynamics of BMS-582664, a VEGFR/FGFR inhibitor in patients with advanced/metastatic solid tumors
Authors: L. S. Rosen, G. Wilding, C. Sweeney, D. Casale, G. Kollia, C. Wu, M. Ayers, C. Hill, S. M. Galbraith
Journal: Journal of Clinical Oncology (2006)

3051 Background: This is the first multiple-dose study with BMS-582664, an oral VEGFR/FGFR tyrosine kinase inhibitor (IC50 34, 10, 145, 125 nM for VEGFR2, VEGFR3, FGFR1 and FGFR2 respectively). Patients (pts) with metastatic solid tumors refractory to standard therapy were enrolled. Part A of this study has completed. Part B is ongoing to evaluate the effect of BMS-582664 on dynamic contrast enhanced MRI (DCE-MRI) parameters. Methods: Part A: Open label dose escalation, continuous qd schedule, 3 patients per cohort. The starting dose was 180 mg. Dose escalation continued until dose limiting toxicities (DLTs) at 1000 mg in 2/3 pts were observed. The next lower dose level (800 mg) was expanded to 6 pts. Blood sampling for pharmacodynamic [circulating endothelial cells (CECs) and Collagen IV ELISA] and PK analysis was performed on Days 1, 8 and 26. BMS-582664 (prodrug) and its active metabolite, BMS-540215 were analyzed using an LC/MS/MS assay. DCE-MRI was performed at 320 mg, 600 mg and 800 mg at baseline ×2, Days 2, 8 and 26. Results: Negligible BMS-582664 was detected. BMS-540215 AUC increased proportionally to dose increase across 180 mg to 1000 mg. The accumulation ratio (Day 26:Day 1) of C 24hr, C max and AUC was 4.8, 2.0 and 2.1 respectively at 1000 mg, but close to 1 at lower doses. The median time on study for all patients in Part A was 84 days. Conclusions: DLT was dizziness/fatigue. BMS-582664 has pharmacodynamic and anti-tumor activity and was well tolerated at ≤ 800 mg qd. [Table: see text] [Table: see text]
Atypical variant of hypereosinophilic syndrome responsive to imatinib mesylate: A case report
Authors: J. N. Kuruvilla
Journal: Journal of Clinical Oncology (2006)

16530 Background: Idiopathic hypereosinophilic syndrome (HES) was first described by Chusid et al in 1975. The diagnosis of HES rests on three features: A persistent eosinophil count of greater than &gt;1500 cells/μL for more than 6 months, no other etiologies for eosinophilia, and symptoms of organ involvement. The requirement of end organ damage differentiates HES from benign eosinophilia, in which there is no organ damage, in spite of years of eosinophilia. Methods: We present a case of a 28-year-old African American male, admitted for shortness of breath and leg swelling. Past medical history was significant only for asthma. Results: Laboratory investigation demonstrated an average white blood cell count of 15,900 U/L and eosinophilia of 29.6% over a 6-month period. Stool studies for ova and parasite, Rheumatoid factor, antinuclear antibody, pANCA, cANCA and complements were within normal limits. Thyroid stimulating hormone, liver function studies, and erythrocyte sedimentation rate were within normal limits. IgE level was 158 (mildly high). Peripheral smear showed only mature eosinophils. A bone marrow biopsy showed a hypercellular marrow consistent with an atypical variant of HES. Cytogenetic studies did not reveal any clonal abnormalities. Trans-esophageal echocardiogram showed severe mitral regurgitation. During the hospital course the patient had a mitral valve replacement with a St. Jude’s mechanical valve and mitral valve pathology showed post inflammatory changes and ventricular myocardial biopsy staining for eosinophilic major basic protein confirmed eosinophilic changes. The patient remained refractory to aggressive steroid therapy, and was started on imatinib mesylate, which lead to a complete remission. Conclusions: HES is a very rare and often fatal condition. A 1989 French study showed a 5-year survival of 80%, and a 15-year survival of 42%. HES has three known variants: The atypical myeloproliferative variant of HES is often refractory to glucocorticosteroid therapy, but responds to treatment with the tyrosine kinase inhibitor, imatinib mesylate. No significant financial relationships to disclose.
Bevacizumab plus irinotecan/5-FU/leucovorin for treatment of metastatic colorectal cancer results in survival benefit in all pre-specified patient subgroups
Authors: G. A. Fyfe, H. Hurwitz, L. Fehrenbacher, T. Cartwright, J. Hainsworth, W. Heim, J. Berlin, F. Kabbinavar, E. Holmgren, W. Novotny
Journal: Journal of Clinical Oncology (2004)

3617 Background. Bevacizumab [Avastin (BV)], a recombinant, humanized monoclonal antibody against VEGF, has demonstrated efficacy and safety when added to irinotecan/5-fluorouracil/leucovorin (IFL) chemotherapy as first-line therapy for metastatic colorectal cancer (CRC). The results of the primary analysis of a randomized phase III trial demonstrated that the addition of BV to IFL resulted in significant improvement in survival compared with IFL alone (p=0.00004; median survival increased from 15.61 to 20.34 months). Additional sub-group analyses were performed to evaluate the effects of baseline risk factors on survival. Methods. The effects of demographic and baseline prognostic characteristics and selected baseline laboratory values on duration of survival, PFS, and objective response rate were examined. Patient characteristics included baseline ECOG performance status, number of organ sites with metastases, site of primary tumor, age, sex, race, prior adjuvant chemotherapy, prior radiotherapy, duration of metastatic disease, years since diagnosis of CRC, baseline sum of longest diameters of target lesions, baseline levels of albumin, alkaline phosphatase, and LDH. Descriptive summaries of duration of survival and PFS were produced for each level of the categorical variables listed above for each treatment arm. These descriptive summaries consisted of the hazard ratio from unstratified Cox regression and Kaplan-Meier estimates of median time to the event. Results. 815 patients were randomized to receive either IFL + placebo or IFL + BV. A survival benefit in the IFL/BV arm was seen across all patient subgroups compared with the IFL/placebo arm (see table). Conclusion. The addition of Bevacizumab to IFL chemotherapy results in prolonged survival in multiple sub-groups. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech Genentech Genentech Genentech
Phase II study of clinical benefit of oral tegafur (T), levofolinic acid (L) and megestrol acetate (M) in patients with symptomatic hormone-refractory metastatic carcinoma of the prostate (HRMCP) final results
Authors: E. Batiste-Alentorn, E. Gallardo, A. Balil, F. Gili, J. Carles, O. Juan, M. Nogue, M. Boleda, I. Anton, A. Arrivi
Journal: Journal of Clinical Oncology (2004)

4677 Background: Continuous infusion of Tegafur (Fluorouracil) has shown activity in HRMPC and T+L is a safe alternative in breast and colon adenocarcinomas. M has shown antiandrogen activity and is useful in advanced cancer patients. This study aimed to evaluate the efficacy and safety of oral T+L+M in HRMPC, together with overall survival. Methods: Between June 1999 and September 2001, 12 centers enrolled 44 symptomatic patients with progressive metastatic disease who had been withdrawn from hormonal and antiandrogen therapy. Patients received oral T 400mg BID +L 12.5mg BID +M 160mg/day. Primary efficacy endpoints were changes in symptom severity and quality of life (QOL). Decrease in 50% PSA values, measurable disease and toxicity were also evaluated. Survival analysis was performed using the Kaplan-Meier method. Results: Mean age was 71, baseline Karnofsky index was 77% and baseline PSA was 256 ng/ml (8–1230). Efficacy was assessed in 27/44 patients with at least 12 weeks (mean: 20.6 weeks) of treatment. 70.4% of these patients improved on the main symptom (48% of patients reported a >2 point improvement on the VAS). 33% reported improvements on the QLQ-C30. 6 patients (22%) showed improvements on PSA, disease progression occurred in 12 patients (44%), and disease stabilized in 9 patients (33%). In these patients, 50% life expectancy was 382 days (95%CI: 282–684), and 25% life expectancy was 864 days (95%CI: 388–995). 44 patients receiving treatment were included in the toxicity analysis. Grade 3 –4 toxicity by cycle was 13%. The most frequent adverse events were diarrhea (4 patients, 9%) and vomiting (3 patients, 6.8%). Asthenia, anemia, anorexia, infections, and ataxia each occurred in 1 patient (4.5%). Conclusions: In these patients, the treatment schedule studied proved to be effective in improving symptoms and, to a lesser degree, QOL. Toxicity was low and survival rates were acceptable. No significant financial relationships to disclose.