bluuebunny/crossref_metadata_2025_split huggingface dataset:
Doxorubicin, cisplatin, and ifosfamide (API) as first-line therapy for relapsed or metastatic uterine leiomyosarcoma.
Authors: Hadoux Julien , Rey Annie , Duvillard Pierre , Lhomme Catherine , Balleyguier Corinne , Haie Meder Christine , Morice Philippe , Gouy Sebastien , Uzan Catherine , Mazeron Renaud , Larue Christine , Pautier Patricia 
Published: March 2020

10098 Background: Uterine leiomyosarcomas (ULMS) are rare gynecologic malignancies characterized by a poor prognosis due to a high rate of local and metastatic recurrences. Chemotherapy (CT) with doxorubicin or ifosfamide or both is associated with a 10 to 30% objective response rate (ORR) and a cisplatin-based multiCT approach achieved a good response rate (DECAV therapy: API + dacarbazine + vindesine, 54% ORR in uterine sarcomas), though toxic. We aimed to determine efficacy and toxicity of doxorubicin, cisplatin and ifosfamide (API) combination as first line treatment of metastatic or relapsed ULMS (MRULMS). Methods: This monocentric study included MRULMS pts with a physiological age < 65 y. CT consisted in doxorubicin 50 mg/m² d1, ifosfamide 3 g/m²/d d1d2 + mesna, cisplatin 75 mg/m² d3, + G-CSF; q 3 weeks. Results: Results in 38 pts with MRULMS were analyzed; median age was 51 (40-64), median cycles of CT was 5; 8 (21%) pts were treated for local relapse, 21 (55.3%) for metastatic disease and 9 (23.7%) for both. Metastatic sites were: lungs in 16 pts (42.1%), pelvis in 7 pts (18.4%), liver in 7 pts (18.4%), peritoneum in 6 pts (15.8%) and bone in 5 pts (13.2%); 14 pts (36.8%) had a multisite metastatic disease. Main grade 3-4 toxicities in 38 pts were neutropenia (74%), thrombopenia (60%), anemia (55%), fatigue (18%) and vomiting (13%). Febrile neutropenia was observed in 35% of pts and 1 patient died of septic shock after cycle 1. Thirty four pts were evaluable for response (4 pts had complete surgery at relapse) and 16 pts responded (4 CR + 12 PR) (ORR: 47%); 23.5% and 29.4% of the pts had respectively stable and progressive disease. For all pts (38) and evaluable pts (34), median PFS were 9.8 and 9.5 months and OS 27 and 25.3 months respectively. Conclusions: Despite toxicity observed, API is an effective treatment which compares favorably with other first line therapies for MRULMS pts.
The impact of genetic variability on severe toxicity of (neo-) adjuvant chemotherapy in breast cancer patients receiving 5-fluorouracil, epirubicin, and cyclofosfamide (FEC).
Authors: Vulsteke Christof , Lambrechts Diether , Dieudonné Anne-Sophie , Hatse Sigrid , Brouwers Barbara , Van Brussel Thomas , Neven Patrick , Belmans Ann , Schoffski Patrick , Paridaens Robert , Wildiers Hans 
Published: March 2020

1020 Background: We assessed the impact of single nucleotide polymorphisms (SNP) of potential genes of interest in germline DNA on severe adverse events in breast cancer (bc) patients receiving (neo-) adjuvant FEC chemotherapy. Methods: Cases were retrospectively evaluated through electronic chart review for febrile neutropenia (primary endpoint), febrile neutropenia first cycle, prolonged grade 4 or deep (<100/µl) neutropenia, anemia grade 3-4, thrombocytopenia grade 3-4 and non-hematological grade 3-4 events. The panel of genes, genotyped using iPLEX technology on a MALDI-TOF based MassARRAY Compact Analyser (Sequenom Inc., CA, USA), included ABCBI, ABCC1, ABCC2, ABCG2, ALDH3A1, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP3A4, CYP3A5, DPYD, FGFR4, GPX4, GSTA1, GSTP1, MTHFR, NQ01, TYMS, XPD/ERCC2, XRCC1, UGT1A1, UGT1A6 and UGT2B7. These genes are involved in the metabolization of the studied chemotherapeutics. Because of multiple testing the false discovery rate (FDR) was calculated. Results: We identified 1089 patients treated between 2000-2010 with 3-6 cycles of FEC, for whom germline DNA was available.Homozygous (TT, 0.5%) and heterozygous (GT,11%) genotypes for rs4148350 in the Multi Drug Resistance Protein I (ABCC1/MRP1), compared to wild-type (GG, 88.5%), were associated with febrile neutropenia, febrile neutropenia in first cycle, prolonged grade 4 or deep neutropenia and thrombocytopenia (80 vs 25 vs 15.7%, 40 vs 17.6 vs 9.5%, 100 vs 41.7 vs 33.8% and 20 vs 2.8 vs 0.34% respectively; p 0.0006, 0.01, 0.002 and 0.008 FDR 0.03, 0.65, 0.06 and 0.2). Variant genotypes for rs45511401 (GT/TT, 12%) in ABCC1, compared to wild-type (GG, 88%), were associated with febrile neutropenia, febrile neutropenia in first cycle and thrombocytopenia (26.5 vs 15,8%, 17.1 vs 9.7% and 3.4 vs 0.3%, respectively; p 0.007, 0.03 and 0.005, FDR 0.2, 0.75 and 0.2). Conclusions: Genetic variation in the ABCC1 gene was strongly associated with severe hematological toxicity of FEC. Other previously described SNP were not validated. This is the largest bc study in which the impact of genetic variability on the adverse events of FEC chemotherapy was investigated.
Are mastectomy rates really increasing? Experiences from a single institution and a population-based database.
Authors: Yi Min , Mittendorf Elizabeth Ann , Hwang Rosa F. , Babiera Gildy , Kuerer Henry Mark , Crow Jaime , Lange Georgia , Shah Ruchita R. , Hunt Kelly 
Published: March 2020

1028 Background: Recent studies have reported increased mastectomy rates for the treatment of early stage breast cancer during the last decade. The aims of this study were to examine trends in mastectomy rates at a single institution and in a population-based database and to compare differences between the two cohorts. Methods: Patients with stage 0-II breast cancer diagnosed from 2000 to 2008 were identified from our cancer center institutional database (CC cohort, n=8,915) and the Surveillance, Epidemiology and End Results database (SEER cohort, n=359,572). Patients without primary surgery or unknown surgery type were excluded. Mastectomy rates by the year of diagnosis were evaluated and multivariable logistic regression models were built to identify clinicopathologic factors that predicted mastectomy as the treatment choice. Results: The proportion of patients treated with mastectomy decreased from 44.5% to 37.8% between 2000 and 2005 in the CC cohort (P=0.003) and from 42.8% to 36.6% in the SEER cohort (P<0.0001). Subsequently, the mastectomy rate increased to 48.6% in the CC cohort (P<0.0001) and to 40.1% in the SEER cohort by 2008 (P<0.0001). Multivariable analysis found that patients with younger age (<50), stage 0 or II cancer vs. stage I, high grade tumor, low median household income, and lobular histology were more likely to choose mastectomy in both the SEER and CC cohorts. In the CC cohort, patients with preoperative breast MRI were also more likely to undergo mastectomy. The percentages of patients receiving preoperative MRI and choosing prophylactic contralateral mastectomy increased each year in the CC cohort. The rate of preoperative breast MRI increased from 4.7% in 2005 to 9.6% in 2008 (P<0.0001). Patients choosing prophylactic contralateral mastectomy increased from 8.4% in 2005 to 11.8% in 2008 (P=0.06). Conclusions: Our study shows that there was a decrease in mastectomy rates from 2000 to 2005 and a subsequent increase in mastectomy rates from 2005-2008 in both the CC and SEER cohorts. Increased use of preoperative breast MRI and the decision to undergo contralateral prophylactic mastectomy likely contributed to the increased mastectomy rates in the CC cohort.
Short-term complications and use of breast brachytherapy in the national Medicare population in 2008-2009.
Authors: Presley Carolyn J. , Soulos Pamela R. , Herrin Jeph , Roberts Kenneth B , Yu James B. , Killelea Brigid K. , Lesnikoski Beth-Ann , Long Jessica B. , Gross Cary P. 
Published: March 2020

1030 Background: Brachytherapy as an alternative to whole-breast irradiation (WBI) for early-stage breast cancer has disseminated into clinical practice; however, current national treatment patterns and associated complications remain unknown. Methods: We constructed a national sample of Medicare beneficiares aged 66 to 94 who underwent breast conserving surgery in 2008-2009 and who were treated with brachytherapy or WBI. We used hospital referral regions to assess national treatment variation and an instrumental variable analysis to compare complication rates between treatment groups, adjusting for patient and clinical characteristics such as age, number of comorbidities, receipt of chemotherapy or screening mammogram, and type of radiation facility. We compared one-year overall, wound and skin, and deep tissue and bone complications between brachytherapy and WBI using specific procedure and diagnosis codes identified in Medicare claims. Results: Of the 29,648 women in our sample, 4,671 (15.8%) received brachytherapy. The median percent of patients receiving brachytherapy varied substantially across hospital referral regions (interquartile range: 7.5%-23.3%). In the bivariate analysis, 34.3% of women treated with brachytherapy had a complication compared to 27.3% of those who received WBI (P<0.001). After adjusting for patient and clinical characteristics, 35.3% (95% CI: 34.7, 35.8) of women treated with brachytherapy had a complication compared to 18.7% (95% CI: 18.2,19.2) treated with WBI (average predicted difference: 16.5%, 95% CI: 15.8, 17.3, P<0.001). While brachytherapy was associated with a 16.9% (95% CI: 10.0, 23.8, P<0.001) higher absolute percentage of wound and skin complications compared to WBI, there was no difference in deep tissue and bone complications. Conclusions: Brachytherapy is commonly used among Medicare beneficiaries; in some regions nearly one in four women who underwent adjuvant radiation received brachytherapy. After one year, wound and skin complications were significantly more common among women who received brachytherapy compared to those receiving WBI, but there was no difference in deep tissue and bone complications.
Frequency of TLE3 overexpression in breast carcinoma subtypes including a large cohort of triple-negative patients.
Authors: Basu Gargi D. , Ghazalpour Anatole , Arguello David , Ashfaq Raheela , Gatalica Zoran , McGinniss Matthew Jerome , Blevins Richard , Danenberg Kathleen D 
Published: March 2020

1040 Background: The taxanes are an important class of agents for the treatment of a broad range of malignancies including breast cancer. They improve survival in patients with early stage and metastatic breast cancer. Transducin-like enhancer of split 3 (TLE3) is a transcriptional repressor which influences growth and microtubule stability and its expression has been implicated in response to taxane therapy in breast cancer. We investigated the tumor expression of TLE3 in breast cancer patients, including a large cohort of the triple negative subtype. Methods: We analyzed TLE3 (M-201), ER(1D5), PR(PgR636) and HER2/neu(Polyclonal) expression by immunohistochemistry in 978 breast cancer patients. Immunoreactivity was assessed by scoring the percentage of cells stained in each field and by the intensity of staining. Results: To sub-classify the 978 breast cancer patients, we utilized hormone receptors (ER and PR) and HER2 expression/amplification. Overall, 36% of the total breast cancer patients were hormone receptor positive, 15% were HER2 positive and 49% were triple negative. The percentage of triple negative patients was higher in our cohort, given the fact that molecular profiling services are used more frequently for this subtype. A total of 477 patients were triple negative of which 61% stained positive for TLE3 expression. Of the 150 HER2 positive patients, 73% stained positive for TLE3 expression as compared with 82% TLE3 positivity in the 351 hormone receptor positive patients. By pairwise comparison, the hormone receptor positive vs triple-negative subtype showed the highest statistical significance in ratios of TLE3 positives (p =2.5e-10). Conclusions: Our results show that TLE3 is over-expressed in the majority of HER2 positive and hormone receptor positive breast cancer patients. Interestingly, the frequency of over-expression of TLE3 was lowest in the triple negative subtype thereby making it more important to identify those patients in this group who are most likely to respond to taxanes prior to therapy. To our knowledge, this is the first study providing a comprehensive review of TLE expression in breast cancer subtypes.
Molecular characteristics and metastasis predictor genes of triple-negative breast cancer.
Authors: Kuo Wen-Hung , Chang Yao-Yin , Hou Ming-Feng , Chuang Eric Y , Chang King-Jen 
Published: March 2020

1043 Background: Triple-negative breast cancer(TNBC) is a subtype of breast cancer with aggressive tumor behavior and distinct disease etiology. Due to the lack of an effective targeted medicine, treatment options for triple-negative breast cancer are few and recurrence rates are high. Although various multi-gene prognostic markers have been proposed for the prediction of breast cancer outcome, most of them were proven clinically useful only for estrogen receptor-positive breast cancers. Reliable identification of triple-negative patients with a favorable prognosis is not yet possible. Methods: Clinicopathological information and microarray data from 157 invasive breast carcinomas were collected at National Taiwan University Hospital from 1995 to 2008. Gene expression data of 51 triple-negative and 106 luminal breast cancers were generated with oligonucleotide microarrays. A prognostic 45-gene signature for triple-negative breast cancer was identified using Student’s t test and receiver operating characteristic analysis. Results: Hierarchical clustering analysis revealed that the majority (94%) of triple-negative breast cancers were tightly clustered together carrying strong basal-like characteristics. A novel 45-gene signature giving 98% predictive accuracy in distant metastasis recurrence was identified in our triple-negative patient cohort. External validation of the prognostic signature in an independent microarray dataset of 59 early-stage triple-negative patients also obtained statistical significance (hazard ratio 2.29, 95% CI 1.04-5.06, Cox P = 0.04), outperforming five other published breast cancer prognostic signatures. The prognostic signature was statistically predictive with the node-negative triple-negative patients in the validation cohort. Conclusions: The 45-gene prognostic signature identified in this study revealed that TGF-β signaling in immune/inflammatory regulation may be critically involved in distant metastatic invasion of TNBC. The 45-gene signature, if further validated, may be a clinically useful tool in risk assessment of metastasis recurrence for early-stage triple-negative patients.
Racial differences in outcomes of triple-negative breast cancer.
Authors: Pacheco Jose , Gao Feng , Bumb Caroline , Ellis Matthew J. , Ma Cynthia X. 
Published: March 2020

1048 Background: The incidence and mortality of breast cancer can differ significantly among racial and ethnic groups. African American (AA) women have a lower incidence of breast cancer, but higher mortality compared to other racial groups. Triple negative breast cancer (TNBC: negative for the expression of estrogen receptor, progesterone receptor and HER2), which is an aggressive type of breast cancer, occurs more frequently in AA women. The few studies addressing whether racial differences exist in the outcomes of patients with TNBC have yielded inconsistent results. Methods: The Washington University Medical Oncology Database captures the clinical information for all new patients (pts) seen at the Breast Oncology Clinic. Most of these pts reside in the St. Louis metropolitan area. Using this database, we performed a retrospective analysis to examine the association of race with the clinical presentation and outcome of TNBC in this geographically defined patient population. Results: Between May 2006 and March 2011, 506 pts with TNBC were entered in the database. Analysis was done on 499 patients for whom follow up data is available. The median follow up (F/U) time was 24.5 months and the median age at diagnosis was 53 (24 to 98) years. Thirty percent of pts were AA. Only 5% presented with stage IV at diagnosis and the majority of tumors (86%) were high grade. Neoadjuvant chemotherapy was administered in 151 pts, 22% of whom achieved a pathologic complete response (pCR). There was no significant difference between races in the age of diagnosis, F/U time, tumor stage, grade, frequency of receiving neo/adjuvant chemotherapy and pCR rate to neoadjuvant chemotherapy. There was no difference in disease free survival (DFS) and overall survival (OS) between AA and other racial groups by either univariate or multivariate analysis that took into account tumor stage, grade, patient age and menopausal status. The HR for OS was 1.154 (CI 0.772 – 1.725, p value 0.4860) and for DFS it was 0.947 (CI 0.650 – 1.380, p value 0.7764) in AA compared to other races. In the 92 pts who recurred, there was no racial difference in time from recurrence to death. Conclusions: Race does not significantly affect the clinical presentation or outcome of TNBC in the St. Louis metropolitan area.
A prognostic model for predicting breast cancer (BC)-related survival in operable triple-negative (TN) patients (pts).
Authors: Munzone Elisabetta , Botteri Edoardo , Bagnardi Vincenzo , Sciandivasci Angela , Aurilio Gaetano , Adamoli Laura , Esposito Angela , Rotmensz Nicole , Goldhirsch Aron , Nole Franco 
Published: March 2020

1049 Background: TNBC represent a heterogeneous disease in terms of biology, prognosis, and treatment response. We propose a prognostic model to identify homogeneous subgroups of patients and tailor risk-adapted adjuvant therapies indications. Methods: We analyzed 1,049 pts operated in our institute from 1997 to 2007 for early TNBC. Pts who received neoadjuvant chemotherapy (CT), with T4 tumors or previous history of cancer were excluded. Death from BC was the primary endpoint of the study. We calculated an individual predicted risk using a multivariable Cox regression model, with age, tumor size, number of positive lymph nodes and Ki-67 analyzed as continuous covariates, and tumor grade and perivascular invasion as categorical covariates. Results: Median age was 52 years, 562 (53.4%) and 670 (65.1%) pts had a pT1 and pN0 TNBC, respectively. Median Ki-67 was 48%. Adjuvant CT regimens were distributed as follows: classical CMF 388 (37.0%), anthracycline containing regimens 455 (43.4%), taxanes 12 (1.1%), other regimens 66 (6.3%) and no CT 128 (12.2%). After a median follow-up of 6 years, 131 deaths from BC were observed (5-year cumulative incidence 11.9%). At multivariable analysis, age, tumor size, number of positive lymph nodes, Ki-67, tumor grade and perivascular invasion were associated with the risk of death and were included in the prognostic model. Its predictive accuracy was good (C-index 0.73). We subsequently identified three homogeneous prognostic subgroups - low, medium and high-risk - according to the tertiles values of the predicted risk. The outcomes are shown in the table. Conclusions: We could identify homogeneous prognostic subgroups of TNBC pts according to clinical-pathological features. This prognostic model suggests that the use of CT in TN low-risk pts might be questionable. We are currently externally validating this model on a different series of pts. [Table: see text]
A heuristic platform for clinical interpretation of cancer genome sequencing data.
Authors: Van Allen Eliezer Mendel , Wagle Nikhil , Kryukov Gregory , Ramos Alexis , Getz Gad , Garraway Levi A. 
Published: March 2020

10502 Background: The ability to identify and effectively sort the full spectrum of biologically and therapeutically relevant genetic alterations identified by massively parallel sequencing may improve cancer care. A major challenge involves rapid and rational categorization of data-intensive output, including somatic mutations, insertions/deletions, copy number alterations, and rearrangements into ranked categories for clinician review. Methods: A database of clinically actionable alterations was created, consisting of over 100 annotated genes known to undergo somatic genomic alterations in cancer that may impact clinical decision-making. A heuristic algorithm was developed, which selectively identifies somatic alterations based on the clinically actionable alterations database. Remaining variants are sorted based on additional heuristics, including high priority alterations based on presence in the Cancer Gene Census, biologically significant cancer genes based on presence in COSMIC or MSigDB, and low priority alterations in the same gene family as biologically significant cancer genes. The heuristic algorithm was applied to whole exome sequencing data of clinical samples and whole genome sequencing data from a cohort of prostate cancer samples processed using established Broad Institute pipelines. Results: Application of the heuristic algorithm to the prostate cancer whole genome rearrangement data identified 172 (out of 5978) rearrangements involving actionable genes (averaging 2-3 events per tumor). Furthermore, two clinical samples processed prospectively were analyzed, yielding three potentially actionable alterations for clinical review. Conclusions: The heuristic model for clinical interpretation of next generation sequencing data may facilitate rapid analysis of tumor genomic information for clinician review by identifying and prioritizing alterations that can directly impact care. Our platform can also be applied to research data to prospectively explore clinically relevant findings from existing cohorts. Future analytical approaches using heuristic or probabilistic algorithms should underpin a robust prospective assessment of clinical cancer genome data.
Rare epidermal growth factor receptor (EGFR) mutations in 10,117 patients with non-small cell lung cancer (NSCLC) evaluated by the French ERMETIC IFCT network: Clinical, molecular, and survival data.
Authors: Beau-Faller Michele , Prim Nathalie , Ruppert Anne-Marie , Nanni Isabelle , Besse Benjamin , Escande Fabienne , Lizard Sarab , Pretet Jean-Luc , DE Cremoux Patricia , DE Fraipont Florence , Rouquette Isabelle , Solassol Jerome , Bieche Yvan , Cayre Anne , Voegeli Anne-Claire , Quoix Elisabeth , Morin Franck , Blons Helene , Cadranel Jacques 
Published: March 2020

10507 Background: The EGFR exon 19 deletion and exon 21 L858R mutation are associated with response to EGFR-TKI. However, the correlation with response to EGFR-TKI remains unclear for rare exon 18 and 20 EGFR mutations. We investigated the clinical features of NSCLC patients with exon 18 and exon 20 EGFR mutations, analyzed response to EGFR-TKI and patient's survival. Methods: Between 2005 and 2011, all rare exon 18 and 20 EGFR mutations were collected from 10117 cases of NSCLC in 15 of 28 French NCI molecular genetic laboratories. Results: During the study period, EGFR mutations were identified in 1048 (10.35%) out of the 10117 performed tests and 108 rare mutations (10.3%) were identified in 103 patients, including 25 never identified mutations. Among them, 48 mutations were localized at exon 18 and 60 at exon 20, with 3 out of the 4 identified T790M exon 20 mutations associated with L858R mutation. Only 5 other rare mutations were associated with EGFR 19 or 21 mutations. 38 patients received EGFR-TKI (erlotinib, n=32; gefitinib, n=6). Among the 36 evaluable patients, best response on TKI was progression in 18 patients (50%), stabilization in 11 (30.5%) and partial response in 7 (19.4%). Tumor control rate observed in exon 18 mutations was 61% (8/13) and 50% (13/26) in exon 20 mutations. For the EGFR-TKI treated patients, the median PFS was 6 months (2-53). Median OS was 15 months (1-92), with no difference between the EGFR-TKI treated patients or not. Conclusions: Prevalence of rare EGFR mutations was 1.06% of all tested NSCLC and 10.35% of all EGFR mutations. Tumor control on TKI was observed in half of the patients. Reports of NSCLC harboring rare mutations are important to help the decision-making process in this subset of patients.