tbuckley/cabot-search huggingface dataset:
A phase I study of pemetrexed in combination with docetaxel in advanced solid tumor patients.
Authors: Lee D. Cranmer, Sherif S. Morgan, Amy S Bauland, Yrma Burruel, Jeanette S Cardenas, Terry Concannon, Kathy J Schmidt, Robin Snyder-Walker, Linda L. Garland
Journal: Journal of Clinical Oncology (2014)

2567 Background: Pemetrexed is an anti-folate targeting the purine and pyrimidine synthetic pathways. Docetaxel is a third generation cytotoxic that modulates microtubule dynamics, inhibiting cell division. Our primary objective is to determine the MTD for the combination in a biweekly regimen in advanced solid tumors. Secondary endpoints include characterizing the adverse events (AEs) profile, anti-tumor activity, and recommended phase 2 dose (RPTD). Methods: Pemetrexed and docetaxel were administered on days 1 and 15 of a 28-day cycle. The dose escalation scheme consisted of 7 planned dose levels ranging from 300-600 mg/m2 pemetrexed and 30-60 mg/m2 docetaxel. Cohorts of 3-6 patients were enrolled in each dose level using the classical 3+3 dose escalation design. AEs were classified using CTCAE 3.0. Upon determination of MTD, an expansion phase was implemented to include 12 patients treated at the MTD level. Results: 33 advanced solid tumor patients were enrolled; 32 received treatment (1 ineligible). 28/32 patients received at least one prior line of chemotherapy. Three (3) patients were removed from the study before completing one cycle: 1 due to disease progression, 1 refused further treatment, 1 experienced dose-limiting toxicity (grade 3 gastrointestinal AE).Most frequent, treatment-related AEs were fatigue (85%), leukopenia (73%), nausea (69%), elevated aminotransferases (54%–62%), anemia (62%), and neutropenia (62%). MTD was deemed to be 500 mg/m2 pemetrexed and 40 mg/m2 docetaxel. Twenty-six (26) patients were evaluable for response: 19% PR (5: 2 sarcoma, 2 NSCLC, 1 renal cell kidney cancer), 50% SD (13: 7 sarcoma, 4 NSCLC, 1 bladder cancer, 1 thymoma), and 31% PD (8: 6 sarcoma, 2 NSCLC). Conclusions: Administration of pemetrexed and docetaxel was feasible without unexpected toxicities. The combination demonstrated preliminary evidence of significant anti-tumor activity in pretreated patients with advanced solid tumors. It may also be a useful alternative doublet in patients with non-squamous NSCLC unable to tolerate platinum. The RPTD is 500 mg/m2 pemetrexed and 40 mg/m2 docetaxel. Given the preliminary anti-tumor activity, the combination deserves further investigation, particularly in sarcoma. Clinical trial information: NCT01172028.
What factors influence advanced ovarian cancer patient (AOC pt) outcomes to phase I trial treatments?
Authors: Timothy Anthony Yap, Angela George, Caroline O Michie, Mabel Wong, Rebecca Bowen, Saeed Rafii, Vasiliki Michalarea, Tom van Hagen, Liz Y. Han, Grigorios Rallis, L Rhoda Molife, Udai Banerji, Rebecca Sophie Kristeleit, Susana N. Banerjee, Johann Sebastian De Bono, Martin Eric Gore, Stanley B. Kaye
Journal: Journal of Clinical Oncology (2014)

5560 Background: Relapse to approved anticancer treatments is almost inevitable in AOC pt. Novel agents in phase I trials may benefit such pt. Methods: Retrospective study of pt records 6/1998-10/2010 from AOC pt allocated to Phase I trials including efficacy expansion phases of novel therapies in the Drug Development Unit at Royal Marsden Hospital (RMH). Results: 200 AOC pt were allocated to ≥1 trial each (281 allocations). 187 (94%) ECOG PS 0-1; 10 (5%) PS 2-3; 3 (1%) unknown. 51 (24%) platinum (pl) sensitive; 145 (67%) pl resistant; 20 (9%) unknown. 53 (27%) BRCA mutant, 9 (4%) BRCA wildtype and 138 (69%) unknown. 135 (68%) pt started ≥1 trial (mean 1.4 [1-8]; total 216 trials); 63 (32%) pt did not start due to progressive disease (PD). Median time from allocation to start of trial was 23 days. There were 43 (20%) RECIST complete/partial responses (CR/PR), including CR/PR with PARP inhibitors (18/79 [23%]), anti-angiogenics (9/65 [14%]) and pl/taxane chemotherapy combinations (14/43 [33%]). Factors associated with CR/PR versus (v) those who did not start trial due to PD were: fewer prior treatments (mean 3 [1-6] v 4.3 [1-9]; p=0.02), pl sensitive v resistant (<0.001), CR/PR v PD with previous therapy (p<0.0001), better ECOG PS at allocation (mean 0.6 v 0.9; p=0.02), fewer metastatic sites (1.7 v 2.1; p=0.04), higher albumin (38 v 32g/L; p<0.0001) and hemoglobin (12.8 v 11.6g/dL; p<0.0001) levels, lower white cell counts (6.2 v 7.2; p=0.02) and baseline CA125 levels (1049 v 3649; p=0.02), BRCA mutation (p<0.0001), and better RMHPrognostic Score (0.56 v 1.34; p<0.0001). Mean trial duration was 163 days (10-1483 days). Mean survival was 902 days for CR/PR pt v 117 days for pt who did not start treatment due to PD (p<0.0001). Treatments were well tolerated; of 385 adverse events, 351 (91%) Grade (G) 1/2; 34 (9%) G3/4. A substantial proportion of AOC pt (134/200 [67%]) received ≥1 (mean 1.3 [1-8]) subsequent lines of therapy after Phase I trials. Conclusions: Phase I trial treatments provided pt benefit in AOC although 32% of pt allocated to such trials failed to start treatment due to PD. These data suggest that phase I trial referrals should be considered earlier in AOC treatment pathways, particularly with the emergence of promising novel agents.
Comparison of genotyping performance in DNA extracted from matched FFPE tumor, FFPE lymph node, and whole blood for pharmacogenetic analyses.
Authors: Daniel Louis Hertz, Kelley M Kidwell, Jacklyn N Thibert, Christina L Gersch, Meredith M. Regan, Todd C Skaar, Norah Lynn Henry, Daniel Hayes, Catherine Van Poznak, James M. Rae
Journal: Journal of Clinical Oncology (2015)

1528 Background: Pharmacogenetics requires genetic information from patients’ germline DNA.There is concern that DNA extracted from formalin-fixed paraffin embedded (FFPE) tumors may not accurately represent germline DNA due to somatic genetic alterations and technical challenges. Our objective was to compare genotyping performance for DNA isolated from FFPE tumor (T), FFPE non-cancerous lymph node (LN), and whole blood (WB) to determine the extent and source of genotyping inaccuracy in FFPE tumor DNA. Methods: Single nucleotide polymorphisms (SNPs) from genes that affect drug elimination, efficacy, and toxicity were genotyped on Sequenom MassArrays using DNA isolated from matched T, LN, and WB samples obtained from patients with early stage breast cancer. The no-call rate was calculated for each tissue type and the discordant call rate was calculated for T and LN by comparison with the WB genotype. Results: After quality control, matched samples from 114 patients were genotyped for 247 SNPs in 80 genes. The no-call rate in T (4.3%) was greater than LN (3.0%) and both were greater than WB (0.5%). The discordant rate in T (1.1%) was greater than LN (0.3%). Samples with heterozygous genotypes were more likely to be no- or discordantly-called than homozygous samples (all p < 0.001, Table). Conclusions: FFPE T no- and discordant-call rates were acceptable (< 5%), though higher in heterozygous samples, suggesting that somatic genetic alterations and FFPE storage have minimal effect and/or FFPE T samples contain sufficient normal tissue for germline genotyping. FFPE T samples can be used in pharmacogenetic research, however, certain genes that are highly altered in somatic tissue require germline specimens and inaccurate genotyping of heterozygous samples precludes use of FFPE T for clinical pharmacogenetics. No and discordant call rates in each sample type. T LN WB No Calls Overall 4.3% (1221/28158) 3.0% (843/28158) 0.5% (135/28158) Homozygous 1.8% (346/18900) 2.5% (468/18900) - Heterozygous 9.5% (864/9123) 4.0% (363/9123) - Discordant Calls Overall 1.1% (306/26824) 0.3% (84/27204) - Hom. 0.2% (33/18554) 0.2% (32/18432) - Het. 3.3% (273/8259) 0.6% (52/8760) -
Post-transplantation long-term outcomes in 43 HIV-positive patients affected by high-risk or relapsed lymphoma.
Authors: Ernesto Zanet, Pascual Balsalobre, Martina Taborelli, Jose Diez-Martin, Alessandro Re, Josep M. Ribera, Maurizio Rupolo, Philippe Genet, Diego Serraino, Gaelle Guillerm, Mario Mazzucato, Cristina Durante, Ian Gabriel, Kate Cwynarski, Eulogio Conde Garcia, Maria Rosario Varela Gomez, Rosanna Ciancia, Umberto Tirelli, Mariagrazia Michieli
Journal: Journal of Clinical Oncology (2017)

121 Background: The advent of highly active antiretroviral therapy (HAART) allowed to extend autologous stem cell transplantation (ASCT) to HIV-positive patients affected by lymphoma. In the literature, data are lacking on long-term events developed by this population. Methods: Herein we are reporting the preliminary analysis of long-term data of 43 pts out of 61 pts, affected by high-risk or relapsed lymphoma and treated by ASCT in different European countries. These 61 pts reached a complete response after ASCT and received HAART concomitantly to chemotherapy. We considered the following events after ASCT: lymphoma relapses, second cancers, opportunistic infections (OIs) and cardiovascular events. Results: Thirteen pts experienced OIs, after 0.36 years from ASCT (IQR: 0.12 -2.91). Twelve pts had a secondary malignancy and 6 pts had a lymphoma relapse, at a median time of 4.90 years (IQR: 2.56 – 9.90) and 2.88 years (IQR: 0.57 – 4.27) from ASCT, respectively. Six pts developed a cardiovascular event at 6.29 years (IQR: 4.84 – 9.32) from ASCT. Eight pts died: 3 of lymphoma relapse, 3 of second malignancy, 1 of acute myocardial infarction and 1 of car accident. With a median of 9.18 years of follow-up, (IQR: 5.99-12.43) the OS, PFS and EFS of the entire sample of pts were 82%, 75% and 35% at 10 years, respectively. Conclusions: Thirty-five out of 43 pts are still alive and in long-term complete remission after ASCT. These data confirm the long-term dramatic efficacy of ASCT. We support surveillance of OIs early after ASCT and of second cancers, lymphoma relapses and cardiovascular events from ASCT. Secondary malignancies developed by our pts are non-AIDS-defining cancers and a majority are linked to a viral pathogenesis or lifestyle behaviours (i.e. smoking). Secondary cancers and lymphoma relapses are the main causes of death in this population. Cardiovascular events may represent a cause of death but also a major reason of disability.
Gemcitabine (G) and vinorelbine (V) in patients (pts) with recurrent advanced non-small cell lung cancer (NSCLC): Sequence of administration matters
Authors: R. Juergens, J. R. Brahmer, D. Ettinger
Journal: Journal of Clinical Oncology (2006)

17101 Background: G and V have demonstrated clinical efficacy as single agents and in combination in pts with metastatic NSCLC. Methods: This single-institution, prospective, phase II trial evaluated a biweekly combination of G and V in NSCLC pts who had received 1 prior chemotherapeutic regimen and had disease progression. Eligibility criteria included: Age ≥ 18; PS ≤ 2; and adequate organ function. Pts with stable brain metastases were allowed. A Simon two-stage design specified enrollment of 15 evaluable pts in stage I. If 1 response was seen, 20 more pts would be enrolled. The power of this study to detect an increase in response from 10% to 30% was 90% with a two-sided alpha of 5%. G (1200 mg/m 2 IV over 30 min.) was followed by V (30 mg/m 2 IV over 6–10 min.) on days 1 and 15 of each 28 day cycle. Chemotherapy was given for 6 cycles unless disease progression or unacceptable toxicity was seen. Results: From 11/1998 to 10/2000, 15 of 20 pts enrolled (6 males, 9 females) were evaluable for response. Two pts had grade 4 neutropenia, and 1 pt had grade 4 thrombocytopenia. The only non-hematologic grade 3 toxicities were fatigue, phlebitis, and arthralgias. No objective responses were observed, but 11 pts had stable disease for a mean of 6 mos. The median survival time was 9.4 mos (95% CI = 4.2, 14.8), with a median time to progression of 4.2 mos (95% CI = 1.9, 5.6). The one year survival was 47%. Conclusions: While this schedule of GV was well tolerated, it was felt to be inactive. In vitro and pharmacokinetic studies published after the completion of our trial, suggest G followed by V may have antagonistic effects leading to lower dose delivery of both drugs. Our study was the only study of GV in 2 nd -line NSCLC in the literature (n = 6) without an objective response. Our study, as well, was the only 2 nd -line study that administered G prior to V. 1 st -line studies in the literature (n = 12) that administered V prior to G had, on average, a 1.7 month higher median survival (10.0 vs 8.3 mos) which was statistically significant (p-value &lt; 0.001). Based on this data, sequence of GV should be a consideration in future clinical trials. Because of the lack of response, further studies using this drug sequence, dose, and schedule for GV are not recommended. [Table: see text]
Multicenter phase 2: Capecitabine (CAP) + oxaliplatin (OX) + bevacizumab (BEV) + trastuzumab (TRAS) for patients (pts) with metastatic esophagogastric cancer (MEGCA).
Authors: Peter C. Enzinger, Thomas Adam Abrams, Jennifer A. Chan, Nadine Jackson McCleary, Hui Zheng, Eunice Lee Kwak, Matthew Yurgelun, Lawrence Scott Blaszkowsky, James M. Cleary, Brian M. Wolpin, Jeffrey A. Meyerhardt, Eileen Regan, Christopher Graham, Katharine Straw, Charles S. Fuchs, Ronan Joseph Kelly
Journal: Journal of Clinical Oncology (2015)

4038 Background: In MEGCA, cisplatin+CAP has RR 46% and OS 12.1 mos with BEV (AVAGAST) and RR 47% and OS 13.8 mos with TRAS (ToGA). We sought to improve these results by combining CAPOX with both BEV and TRAS. Methods: Pts with HER2/neu IHC 3+ or FISH+ MEGCA, with 0-1 prior chemo, received a loading dose of TRAS 4mg/kg, day (d) 1. One week later, pts received BEV 7.5mg/kg/d1, TRAS 6mg/kg/d1, OX 130mg/m2/d1 and then q21d. CAP d1-14/q21d was decreased from 1700mg/m2/d to 1200mg/m2/d after 4 of the first 5pts developed G3 diarrhea. Consenting pts underwent identical research biopsies prior to and 7 days after TRAS loading dose. Primary endpoint was RR by RECIST 1.1, scored by independent Harvard Tumor Imaging Metrics Core. Results: Of 35 pts enrolled, median age 58 (32-80), 4F/31M, HER2/neu IHC3+: 25/FISH+: 10, ECOG PS 0: 18/ 1: 17, prior chemo 10, primary: esophagus 16/GEJ 10/gastric 9, sites of mets: LN 26, liver 19, lungs 9, bone 2, other 6. Pts have received mean 16 cycles (2-50+). Of 34 pts (1 too early), PR 24 + CR 2 = 76.5% RR (95% CI, 0.59 – 0.88) by blinded review. For all 35pts, median PFS = 13.93 mos (95%CI, 8.5 - 22.33); median OS = 26.92 mos (95%CI, 11.31 – 36.36). Safety for 30pts (enrolled after CAP dose change): 16 pts required dose modification: CAP 12, OX 14, BEV 2, TRAS 0. Pts w grade 3-4 AE: periph neuropathy 3, bleeding 3, thromboembolic event 2, hypertriglyceridemia 2, ANC 2, HTN 1, plts 1, diarrhea 1. One pt died of cardiac arrest after 3yrs on tx. Conclusions: CAPOX+BEV+TRAS is well tolerated in pts with MEGCA. There appears to be at least additive effect between BEV and TRAS. Combinations of anti-VEGF and anti-HER2/neu agents should be considered in future randomized studies of HER2/neu+ MEGCA. Clinical trial information: NCT01191697.
Cyclooxygenase-2 (COX-2) expression after neoadjuvant chemoradiotherapy and response to platinum/taxanes containing adjuvant chemotherapy in esophageal cancer
Authors: Y. Fujiwara, R. Yoshikawa, K. Koishi, T. Matsumoto, S. Kojima, T. Hashimoto-Tamaoki, T. Tsujimura
Journal: Journal of Clinical Oncology (2007)

15032 Background: Cyclooxygenase-2 (COX-2) is an inducible enzyme linked to the conversion of arachidonic acid to prostaglandin H 2 . Recent reports have indicated that tumor with high COX-2 expression are refractory to chemotherapy and associated with poor outcome. In this study, we investigated the relationship of COX-2 expressive tumor with response to platinum/taxanes chemotherapy and its clinical significance in esophageal cancer patients undergoing chemoradiotherapy (CRT). Methods: COX-2 expressions were evaluated in 53 patients with histologically confirmed esophageal squamous cell carcinoma (ESCC) undergoing preoperative CRT, by immunohistochemical staining. Preoperative CRT was consisted of 5-FU plus cisplatin chemotherapy and total 40Gy irradiation. Platinum/taxanes treatment was chosen for the first-line adjuvant chemotherapy. Results: 17 patients showed a pathological CR in the resected specimens. COX-2 expression was absent from 14 tumors (38.9%), and positive in other 22 tumors (61.1%). Recurrences were found in 15 patients in COX-2 (+) group, and in 5 patients in COX-2 (-) group (p=0.0874). There were significant associations between OS and effect of CRT, Lymph nodes metastasis, and distant metastasis (p=0.00004, p=0.0095, and p=0.0277, respectively). COX-2 expression showed a significant prognostic value for DFS (p=0.0401), but not for the OS with univariate analysis. Intriguingly, platinum/taxanes chemotherapy succeeded in improving OS in the recurrence group (p=0.0188). Conclusions: Our data suggests that positive COX-2 expression after CRT correlates with early recurrence of ESCC patient after CRT and possible prognostic factor in disease-free survival. Adjuvant chemotherapy after surgery is much more influential for prognosis in the ESCC patients than the status of COX-2 expression after CRT. COX-2 status might provide a preferable choice for platinum/taxanes in postoperative adjuvant setting. No significant financial relationships to disclose.
Methylomic classifiers of anal cancer outcomes: An NRG Oncology / RTOG 98-11 tissue study.
Authors: Erin M. Siegel, Steven A. Eschrich, Anders E. Berglund, Abidemi O. Ajidahun, Anthony Martin Magliocco, Ryan Putney, Bridget Riggs, Jennifer Moughan, Sarah E. Hoffe, Jeff Simko, Jaffer A. Ajani, Chandan Guha, Gordon S. Okawara, John W. Clouse, Mark J. Becker, Joseph F. Pizzolato, Christopher H. Crane, David Shibata
Journal: Journal of Clinical Oncology (2017)

588 Background: Genome-wide epigenetic events appear to play a role in the development and behavior of HPV+ cancers. The value of adjuvant therapy following chemoradiation for localized anal cancer (AC) remains unclear. Molecular prognostication to identify patients (pts) who may be at higher risk for recurrence would be valuable. The goal was to define methylomic profiles predictive of disease-free (DFS) and overall (OS) survival in pts with AC. Methods: Genomic DNA was extracted, processed and methylation status at ~450,000 CpG loci examined (Illumina HumanMethylation450 Array). A multistep bioinformatics methodology was applied to develop a prognostic methylomic classifier for OS and DFS: (1) feature selection for methylated regions (β-value interquartile range ≥ 0.2, ≥ 2 adjacent significant probes within a CpG Island and p &lt; 0.05 by univariate Cox proportional hazards) (2) selected features were entered into a supervised principal component analysis (PCA) and 3 components (PC1, PC2, PC3) were derived (3) classifier was built using forward selection multivariate regression models [PC1, PC2, PC3 alone and in combination with clinical features (size: &gt; T2 vs. ≤ T2, nodal status: N0 vs N+)] using a 10-fold cross-validation (4) final model prediction risk score was generated, dichotomized and evaluated for prognostic values in Cox regression analysis. Results: 121 AC specimens from RTOG 98-11 were examined. The methylomic-only classifier model trended towards statistical significance (log-rank p = 0.05; HR = 1.96; 95% CI 0.99-3.88) in DFS (PC1, PC3 selected). In the combined model with clinical features, the final classifier included T status and epigenetic features (PC1, PC3) and was strongly predictive for DFS (p &lt; 0.0001, HR = 4.45; 2.02-9.76). Final OS classifier models [methylomic-only (p = 0.28 HR = 1.55; 0.70-3.44) or combined (p = 0.013 HR = 2.88; 1.20-6.89)] were not as accurate. Conclusions: Methylomic and clinical features synergize to predict DFS in AC. Multivariate modeling reveal independent contributions from clinical and methylomic variables. Epigenomic profiling may contribute to identification of high-risk pts who may benefit from adjuvant strategies. Support: U10CA180822, U10CA180868, U24CA196067
The social neuroscience of biases in in-and-out-group face processing
Authors: Sylvia Terbeck
Journal: Behavioral and Brain Sciences (2017)

Abstract The validity and reliability of stereotypes in social perception confirms traditional early social psychological research. Already in 1954 Gordon Allport stated that stereotypes might have a “kernel of truth.” Recent research in social neuroscience, however, contradicts Lee Jussims’ (2012) claim that the application of stereotypes increases accuracy in person perception. Person perception is inaccurate as it is insufficient when it involves only one factor (even if that factor was a reliable predictor).
In the era of genomics should tumor size be reconsidered as a criterion for neoadjuvant chemotherapy?
Authors: Xavier B. Pivot, Laura Mansi, Loic Chaigneau, Philippe Montcuquet, Antoine Thiery-Vuillemin, Fernando Bazan, Erion Dobi, Jean-Loup Sautiere, Marie-Paule Algros, Steven M. Butler, Farid Jamshidian, Phillip G. Febbo, Christer Svedman, Sophie Paget-Bailly, Franck Bonnetain, Cristian Villanueva
Journal: Journal of Clinical Oncology (2014)

e22085 Background: The Oncotype DX Recurrence Score (RS) assay has been validated for prediction of 10-year risk of distant recurrence and likelihood of benefit from chemotherapy in patients with ER-positive, HER2-negative early breast cancer. Patients with high RS tumours have substantial benefit, and patients with low RS tumours have minimal if any benefit from chemotherapy. Tumour size is used as a key parameter when selecting patients for neo-adjuvant chemotherapy. The aim of this study was to assess the distribution of RS in patients selected for neo-adjuvant chemotherapy primarily due to tumour size. Methods: Patients with ER-positive and HER2-negative tumours, with node negative or no more than 1 positive node from three trials were included in this study. Oncotype DX was performed at Genomic Health blinded to the clinical data. Descriptive statistics were calculated for distribution of RS for all cases. Results: Of 277 patients, 96 met eligibility criteria and 81 had sufficient material for analysis. Median tumour size was 40 mm (IQR 30-50 mm). Grade I, II and III were observed in 13, 49 and 17 cases, respectively. There was a wide distribution of RS with a median of 21.4 (IQR 16.05-26.75). In total, 23(28.3%) had high, 28(34.6%) intermediate and 30 (37%) low RS results. Conclusions: The RS may provide relevant information for neo-adjuvant treatment decisions in select patients both in clinical practice but also in studies. Inclusion of low RS disease patients in neo-adjuvant trials will likely only dilute the ability to look at treatment effects.
Expression of cyclin D3 confers resistance to erlotinib
Authors: W. J. Petty, W. R. Voelzke, V. A. Memoli, K. H. Dragnev, J. J. Urbanic, J. R. Rigas, E. Dmitrovsky
Journal: Journal of Clinical Oncology (2007)

18054 Background: Transcriptional repression of cyclin D1 occurs during responses to erlotinib (E) both in vitro and in vivo. Cyclin D3 has overlapping function with cyclin D1 but has distinct transcriptional regulation. Methods: The expression of cyclin D3 was compared in E sensitive cell lines (H358, H441) and an E resistant cell line (A549). Cyclins D1, D2, and D3 were independently overexpressed in E sensitive NIH 3T3 cells by plasmid transfection. Biopsy tissues from a proof-of-principal clinical trial of E were assessed for cyclin D3 expression. Results: A549 cells were resistant to E and expressed high levels of cyclin D3 RNA and protein compared to E sensitive cell lines. Overexpression of cyclin D1 and cyclin D3 conferred partial resistance to E in NIH 3T3 cells while cyclin D2 had no significant effect. Comparison of cyclin D3 immunostaining in tumor biopsies from patients before and after treatment with E revealed an increase in the percentage of cyclin D3 expressing cells following treatment with E. Conclusions: Cyclin D3 confers resistance to E in vitro and in vivo. Drugs such as retinoids and rexinoids that target cyclin D3 expression may prove useful for enhancing sensitivity to E. No significant financial relationships to disclose.