bluuebunny/crossref_metadata_2025_split huggingface dataset:
A pilot phase II trial of cabergoline in the treatment of metastatic breast cancer.
Authors: Costa Ricardo Lima Barros , Santa-Maria Cesar Augusto , Scholtens Denise M. , Jain Sarika , Gradishar William John , Clevenger Charles V , Kaklamani Virginia G. 
Published: September 2018

e12568 Background: The prolactin receptor can be overexpressed in breast cancer, and pre-clinical data indicate that it contributes to the pathobiology of breast cancer. Cabergoline is a potent dopamine receptor agonist of D2 receptors and has a direct inhibitory effect on pituitary prolactin secretion resulting in reduced serum prolactin levels. Methods: A pilot phase II study of cabergoline in patients with metastatic breast cancer was conducted with primary end point of best overall response rate (ORR) among patients with measurable disease. Eligible patients had metastatic breast cancer, any receptors status was allowed, and there was no limit of prior lines of therapy. Both measurable and unmeasurable diseases (RECIST 1.1) were allowed. Cabergoline 1mg orally, twice weekly (1 cycle = 4 weeks) was given until disease progression or unacceptable toxicity. Immunohistochemistry prolactin receptor staining was performed on available baseline tumor tissue, and serum prolactin levels were serially assessed. Results: A total of 20 women were enrolled, 19 of whom were evaluable for response (one patient died on C1D7 of unrelated causes). Mean age was 62 (range 42-83); 15 (75%) were Caucasian; mean number of prior lines of therapy 5 (range 0-14). Tumor receptor statuses were distributed as follows: HR+/HER2+ 1(5%), HR+/HER2- 18 (80%), HR-/HER2+ 1 (5%). Analysis was performed after a median follow-up of 6.8 months (0.2-26.2). Best ORR was 8.3% among 12 patients with measurable disease. Results for secondary endpoints were as follows: 4-month CBR = 26% (including patients with measurable and non-measurable disease), median PFS = 1.9 months, and median OS = 10.4 months. Most common treatment related AEs were nausea (30%), fatigue (25%), and elevation in alkaline phosphatase (15%). The highest-grade AE was a single grade 3 treatment-related pain in extremity. Nine patients had sufficient baseline tissue for analysis, there was no correlation between baseline tumor prolactin receptor expression and clinical benefit ( p= 0.24). Additional correlative work is ongoing. Conclusions: Cabergoline was well tolerated and associated with modest anti-tumor activity. Clinical trial information: NCT01730729.
Immunohistochemical (IHC) sub-classification of 105 triple negative breast cancers (TNBC).
Authors: Stacoffe Marion , Vinceneux Armelle , Arbion Flavie , Vegas Helene , Fromont Gaelle , Linassier Claude 
Published: September 2018

e12577 Background: Molecular data have shown that TNBC was a heterogeneous group of tumors. The objective was to evaluate prognosis of IHC sub-classification adapted from molecular model. Methods: We used IHC sub-classification based on positivity for androgen receptor (AR) (Roche, SP 107), cytokeratine 5/6 (CK) (Dako, D5/16B4) and Epidermal growth factor receptor (EGFR) (Biosd, 31G7). Samples with more than 10% AR nuclear immunostaining were considered positive. Threshold for CK and EGFR was 1%. We distinguished 4 groups of tumors: AR phenotype (AR+, EGFR-, CK5/6-), basal-like phenotype (AR-, EGFR+/-, CK5/6 +/-), triple-negative phenotype (AR-, EGFR-, CK5/6-) and mixed group (AR+, EGFR+/-, CK5/6 +/-). Tissue micro-array blocks were constructed with samples from a retrospective cohort treated in adjuvant setting for non metastatic TNBC in a single institution from 2003 to 2013. Survival data were estimated by the Kaplan-Meier method and compared by the log-rank test in univariate analysis. Multivariate analysis including tumor size (T), lymph nodes status (N) and lymphovascular invasion (LVI) was performed using Cox model. Results: 105 patients were followed-up for a median period of 56.3 months [6-155]. Median age was 54 years [29-80]. 57.1% were stage pT1, 41.9% were pN+ and 37,1% presented LVI. 11 patients were classified as AR phenotype, 35 as basal-like, 46 as triple-negative phenotype and 13 as mixed group. 18 patients developed metastases: 3/11 AR, 5/35 basal-like, 6/46 triple-negative and 4/13 mixed group. No difference was observed between TNBC subgroups in terms of disease free survival DFS (p = .98) and overall survival OS (p = .86). T, N and LVI were the only prognostic factors (p = .05, p = .05 and p = .046 respectively). Conclusions: We found no impact of IHC sub-classification of TNBC. Correlation between IHC and molecular biology is in progress.
Efficacy and safety of eribulin in patients with triple negative metastatic breast cancer: Real life experience.
Authors: Manikhas Alexey , Kovalenko Elena , Manzyuk Valentina , Bolotina Larisa V , Zhilyaeva Larisa , Karabina Elena , Ponomarenko Dmitry 
Published: September 2018

e12580 Background: Eribulin demonstrates improved overall survival compared to standard treatments, Her2-negative and TNBC patients have the most survival benefit. We sought to describe treatment patterns of eribulin and clinical outcomes among TNBC patients with advanced breast cancer treated in community oncology practices across the Russian Federation. Methods: Patients treated with eribulin anytime between January 1, 2014 and January 1, 2017 with a diagnosis of MBC were identified by providers within the Russia Oncology Research Center. Providers reviewed the health records (electronic or paper-based) and abstracted selected data points into an electronic case report form for each eligible patient. Results: A total 52 TNBC patients were considered by 10 providers. A median of age at start of eribulin was 47,5 (39-55) yrs and ECOG status 0-1 were assessed. Most of the pts (92,3%) had visceral mts, a median number metastatic disease regions was 2 (1-3). Eribulin was administered as the 1st and 2nd line of BC treatment to 14 (26,9%) pts, 3rd line – to 9 (17,3%), the 4thand later lines – to 29 (55,8%) pts. Objective response occurred in 5 (9,6%) pts. Stable disease registered in 24 (46,1%) pts. Median PFS was 3,0 months (95% CI 1,9-8,55). Overall the drug was well tolerated. The most common type of toxicity was hematologic. Neutropenia gr II was observed in 8 (15,4) pts and III-IV gr in 6 (11,5%), two cases of febrile neutropenia were registered. 4 (7,7%) pts experienced fatigue gr II. Peripheral neuropathy gr II was observed in 4 (7,7%) pts. Dose reduction due to toxicity was performed in 8 (15,4%) pts. Treatment was never withdrawn due to toxicity. Conclusions: This is the first real-life study of clinical outcomes, for patients initiating eribulin therapy for TNBC in community oncology practices throughout the Russian Federation. . Our experience with Eribulin in TNBC patients confirms it efficacy and safety in all lines of treatment, including intensively pretreated patients in this hard-to-treat population.
Association of family history and location of BRCA1 and BRCA2 mutations in triple-negative breast cancer patients.
Authors: Tan Yen Yen , Muhr Daniela , Rappaport-Fuerhauser Christine , Gschwantler-Kaulich Daphne , Grimm Christoph , Polterauer Stephan , Pfeiler Georg , Berger Andreas , Tea Muy-Kheng Maria , Singer Christian F. 
Published: September 2018

e12588 Background: We assessed the prevalence of family history and its association with germline BRCA1/2mutation status/location and age at onset in triple-negative breast cancer (TNBC) patients. Methods: 266 patients with TNBC < 60 years unselected for family history of cancer were enrolled and germline DNA was sequenced to identify mutations. Family pedigrees were prospectively collected from these patients. Logistic regression was used to investigate family history and its association with mutation type/location and age at onset. ROC curves were constructed to determine good predictors of BRCAmutations. Results: BRCA mutations were identified in 18.0% of all patients (15.0% BRCA1, 3.0% BRCA2). BRCA1 carriers have a significantly earlier age at onset than non-mutation carriers (40 vs 49 years; p < .001). While 39/124 (31.4%) patients with family history of cancer carried a BRCA1/2 mutation, 9/142 (6.3%) BRCA carriers had no family history of cancer. BRCA1 carriers with ≥1BC in the family are commonly identified in the breast cancer cluster regions (53.1%). BRCA2 carriers more commonly cluster within the ovarian cancer regions. Of note, this difference was not statistically significant. Women with mutations in BRCA1 OCCR are diagnosed at a younger age. TNBC diagnosed ≤45 years with ≥1BC and ≥1OC in the family are good predictors of BRCA1 mutation (AUC 0.867). Conclusions: Young women with TNBC and a family history of BC and OC are likely to have a BRCA mutation. Specific BRCA mutation locations may add to the identification of a subgroup of TNBC patients with a relatively higher risk of subsequent ovarian cancer. Identification of high-risk TNBC patients with BRCA1 mutation will enable clinicians to optimize cancer management for this phenotype, but will require further validation in larger studies.
Parallel mutation screening and methylation quantification improves the molecular diagnostic yield for colorectal cancer.
Authors: Min Jun , Lan Xiaoliang , Qin Zi , Liu Xiaojie , Zhang Sufen , Nguyen John , Gore Athurva , Liu Rui , Liang Li 
Published: September 2018

e13003 Background: Recurrent somatic mutations and methylation patterns have previously been identified as biomarkers for non-invasive screening of colorectal cancer (CRC). However, most clinical screening assays have focused on a limited number of genomic loci, potentially reducing sensitivity and specificity. Here, we examined the potential utility of using an expanded set of mutation and methylation markers to improve screening accuracy of CRC. Methods: Pairs of colorectal tumor and tumor-adjacent tissues were resected from 41 CRC patients in Nanfang Hospital (NFH), China. The DNA was extracted, processed, and sequenced with Singlera Genomics’ OncoAim assay, which detects mutations across 59 genes implicated in cancer and quantifies the methylation level for key CRC genes. Matched pre- or post-surgery plasma samples were also collected and processed in parallel. Results: Thirty-eight tumor samples (93%) contained somatic mutations with greater than 5% allele frequency, while twenty-nine tumor samples (71%) contained aberrant methylation patterns. Among the tumor-adjacent samples, six contained somatic mutations and eight contained epigenetic abnormalities. Out of three tumor samples without any detectable somatic mutations, one showed an aberrant methylation pattern. Importantly, aberrant methylation patterns in tumor samples were also detected in matched plasma samples. Conclusions: Parallel mutation screening and methylation analysis not only improves the diagnostic yield, but also paves the way for non-invasive monitoring on patients with no common mutations.
Pcarrier: Individual and family distributions of a susceptibility gene for breast and ovarian cancer based on family history.
Authors: Lefebvre Alexandra , de Pauw Antoine , Stoppa-Lyonnet Dominique , Nuel Gregory 
Published: September 2018

e13005 Background: Most of the BRCA1/2 and PALB2 analyses performed in patients with a personal and familial history (FH) of breast/ovarian cancer are negative. In this context, there is no targeted analysis available to identify relatives at high risk (carrier of the causal hypothetical mutated gene). Thus, the recommendations of surveillance to all relatives are based only on the FH of cancer. At the Institut Curie we assess the degree of severity of the FH by calculating the probability of carrying a single autosomal dominant susceptibility gene without taking into account genotyping results but using the LINKAGE software with the parameters of the Claus-Easton model (1993). This reliable but old tool has a slow console interactive interface (roughly 15 min of clinicians time for each assessed family). Methods: We rewrite the model as a Bayesian network combining Mendelian genetics with classical survival analysis. All probabilistic computations are performed through belief propagation (sum-product algorithm) over real numbers or polynomials. The programming language is C++. Results: pCarrier is a modern and efficient implementation of the Claus-Easton model for clinicians with the following features: 1) fast non-interactive command line ( < 1s to process a previously registered family) combined with a graphical user-friendly interface; 2) computations dealing with monozygotic twins or loops without any human intervention (ex: loop breaking); 3) choice between the original discretized model (individual FH into 14 classes) and its continuous version (piecewise constant hazard); 4) marginal individual carrier distribution for all individuals in the pedigree; 5) joint distribution of the number of carriers among any group of individuals (ex: in the entire family, among the living only). Conclusions: pCarrier is experimented since January 2017 in the Institut Curie as a replacement of the existing tool and appears so far to be dramatically faster and easier to use for the clinicians, highly reliable (consistence with the existing tool), and able to provide new useful decision-making probabilities using the distribution of the number of carriers.
Oncologists’ use of tumor sequencing findings and patient derived benefit.
Authors: Gornick Michele Caroline , Cobain Erin Frances , Le Lan Q. , Stoffel Elena Martinez , Chinnaiyan Arul M. , Roberts J. Scott 
Published: September 2018

e13016 Background: Despite increasing use of tumor genomic sequencing in clinical oncology, there is currently limited understanding of how oncologists interpret and apply this information to a patient’s clinical management. Methods: We surveyed oncologists who referred patients with refractory cancers to the Michigan Oncology Sequencing (MI-ONCOSEQ) program which uses integrative clinical sequencing to detect multiple classes of somatic and germline molecular aberrations including point mutations, amplifications, insertions/deletions, gene fusions, and outlier gene expression from June 2014-February 2015. Patients were also surveyed approximately 2 weeks after notification of completion of sequencing. In addition, we conducted chart reviews to ascertain how many patients’ clinical management was changed or derived clinical benefit as a result of sequencing. Results: Forty-three oncologists (37% female, 98% academic medical center practice), referring 112 patients ( M = 2, range: 1-9) completed the survey (response rate = 93%). Oncologists reported an intention to change 22% of patients’ treatment plans on the basis of sequencing results, with referral to a clinical trial (N = 12; 50%) as the most frequently endorsed intended change. However, few patients (N = 9, 38%) had an actual change in clinical management. Barriers identified included patient factors, ineligibility for identified treatment, and loss to follow-up/deceased. Of the 57 patients who completed post-sequencing surveys, 34 (60%) reported that results of sequencing had not been disclosed. However, patient records had documentation that results disclosure had indeed taken place in 41% of cases. Conclusions: Although expectation of enrollment in clinical trials is frequently proposed as the indication for genomic sequencing, practice barriers remain. These include lack of access to studies, severity of patient illness and challenges to effective communication of results.
A closer look at next generation sequencing (NGS) in breast cancer: A retrospective analysis.
Authors: Laderian Bahar , Sandoval Leon ANA CRISTINA , Alsharhan Loulwa , El Ashry Dorraya , Lippman Marc E. 
Published: September 2018

e13023 Background: Targeted cancer therapy has been posited to revolutionize treatment paradigms in oncology. There are, a paucity of data regarding the use of NGS in breast cancer (BC). Herein we report our experience with NGS in a consecutive series of BC patients. Methods: Using an IRB approved protocol, we retrospectively identified patients with BC treated at the Sylvester Comprehensive Cancer Center (UMMSOM) who underwent NGS. Data were collected on demographics, tumor characteristics, genomic mutation profiles, and subsequent response to targeted therapy after 3 months. Results: Between January 2013 and April 2016, 101 BC patients underwent NGS. The mean age at diagnosis was 49. Ninety-one percent were stage IV, 6% were stage III, 2% were stage II, and 1% were stage I. Fifty percent had estrogen receptor (ER)+, HER2- tumors, 31% had triple-negative tumors, 13% had HER2+, ER+ tumors, and 6% had HER2+, ER- tumors. Ninety-six percent had at least one mutation, of which 78% had a targetable mutation. Sixteen patients received targeted therapy (TT). The average time between NGS and TT was 5 months ranging 0-22 months, during which seven patients received other systemic therapy. The most common reasons for not receiving TT were no actionable mutations (24%), not meeting criteria for an available clinical trial (14%), stable disease (SD) (13% ), lost to follow up (11%), physician decision (11%). Of the 16 patients who received TT, 7 patients had progression of disease, 3 died before response could be evaluated and presumably had no benefit, 2 discontinued TT due to side effects, 1 had SD, 1 had a partial response, and 2 were too early to be assessed. Conclusions: The majority of BC patients in our series had actionable mutations. However, TT was not offered to a significant number of patients for a multiplicity of reasons and the clinical benefit in those patients treated according to NGS findings was dismal. While NGS is surely a promising technology that should be utilized in combination with molecular tumor board, a host of reasons limit its usefulness at this time and its expense may well not justify its use outside of clinical trials.
A prospective study of stress, anxiety and depression response to undergoing genetic assessment at the time of ovarian cancer diagnosis.
Authors: Frey Melissa Kristen , Lee Sarah S. , Schwartz Zachary , Gerber Deanna , Martineau Jessica , Lutz Kathleen , Reese Erin , Dalton Emily , Pothuri Bhavana , Curtin John P , Blank Stephanie V. 
Published: September 2018

e13024 Background: Genetic assessment (GA) is recommended for all women with ovarian cancer however little is known about the psychological implications of this intervention. We sought to evaluate the psychological response to GA in newly diagnosed ovarian cancer patients as part of our facilitated genetics referral pathway. Methods: English-speaking patients with ovarian cancer undergoing GA at the time of cancer diagnosis completed three validated anxiety, stress and depression survey instruments immediately prior to and following GA and again 6-9 months after GA. Results: Forty-eight English-speaking patients underwent GA; 43 (90%) completed the pre-GA survey, 32 (67%) post-GA survey and 11 (23%) 6-9 months follow-up survey. Eight patients (17%) had documented psychiatric diagnoses (5 anxiety, 2 depression, 1 anxiety+depression) prior to cancer diagnosis. Overall, patients demonstrated mild to moderate stress, clinically significant anxiety and borderline depression (Table 1). There was no change in depression, anxiety or stress scores when comparing pre- to post-GA surveys. Age, stage, method of treatment, performance status at enrollment and history of psychiatric disorders were not associated with anxiety, stress or depression. Conclusions: A genetic testing pathway whereby GA is encouraged and facilitated at the time of diagnosis has not increased patient depression, anxiety or stress in our cohort. Concern about causing additional emotional distress should not deter clinicians from early genetics referral. [Table: see text]
Molecular profiling of cancer outliers.
Authors: Jung Kyungsuk , Bilusic Marijo , Pei Jianming , Slifker Michael , Zhou Yan , Flieder Douglas B , Gray Phillip , Plimack Elizabeth R. 
Published: September 2018

e13025 Background: A few patients with metastatic cancer survive exceptionally longer than others under the same treatment. We hypothesized that there is a specific biologic signature in genetic profiles of long-term survivors that plays a key role in sensitivity to systemic treatment. Methods: Twenty-six patients with metastatic cancer treated at Fox Chase cancer center with exceptional response were included in the study. Exceptional response was defined as complete response > 1 year or stable disease/partial response > 2 years at any time during the disease course. Archived tumor specimens of 16 patients were sequenced and analyzed using Ambry Genetics 142 gene panel. In addition, genes expressions in tumor tissues from 23 exceptional responders and 23 matched controls (age, sex and tumor type) were analyzed using two NanoString nCounter PanCancer panels (Pathway and Immune Profiling). Results: See Table. Conclusions: Multiple common mutations of NOTCH2, NF1, FANCD2, PIK3CB and EPHA5 were found in tumors that responded exceptionally well to treatments. Additionally, certain genes were significantly over-expressed or under-expressed in these tumors compared to matched controls. Underlying mechanisms that these genetic alterations foster, leading to susceptibility to treatment and prolonged patient survival, should be further studied. [Table: see text]
Differences in the immune microenvironment and genomic characteristics of TNBC in African American women compared to other races.
Authors: Szekely Borbala , Safonov Anton Mikhailovich , Karn Thomas , Bhagwagar Sanaea , Killelea Brigid K. , Silber Andrea , Hatzis Christos , Pusztai Lajos 
Published: September 2018

e13028 Background: African American (AA) women are more likely to be diagnosed with triple negative breast cancer (TNBC) compared to other races and have lower pathologic complete response rate to neoadjuvant therapy. Our goal was to assess differences in the immune microenvironment and genomic characteristics of TNBC by race using the TCGA data set. Methods: We compared the expression levels of 13 previously reported immune metagenes (CTL, Mphages, MHC1, Tregs, IF1, NK, STAT1, MHC2, Giam, Tfh, Tinh, Tstim, LCK), histologic tumor infiltrating lymphocyte (TIL) count and overall mutational load, neoantigen load, clonal heterogeneity assessed using the MATH score, amplification and deletion loads of between AA (n = 58) and non-AA TNBC (n = 114). Data was downloaded from the TCGA website, immune metagene expression and MATH scores were calculated as previously reported. Distributions between cohorts were compared using the Mann-Whitney U-test. Results: Among the immune metagenes only the cytotoxic T cell (CTL) metagene showed lower expression in AA patients (3.64 versus 4.08, unadjusted p = 0.046). TIL count was available in 51 of 58 AA and 91 of 114 of non-AA cases, and no significant difference was observed between the racial groups (p = 0.55). We also did not observe statistically significant differences in the mutational load (p = 0.36), neoantigen load (p = 0.38), clonal heterogeneity represented by the MATH score (p = 0.54), and amplification and deletion loads (p = 0.23 and 0.83 respectively) between the two TNBC race groups. We also assess the expression distribution of the immune signatures in an independent Affymetrix gene expression dataset including 40 AA and 323 non-AA patients with TNBC. Similar to the TCGA, there were no significant race differences in the immune signatures, including in the CTL metagene. Conclusions: These results suggest that the differences in prevalence and treatment response seen between TNBC in AA and non-AA patients are unlikely to be due to differences in the immune microenvironment and the genomic landscape of TNBC. However, more subtle comparison in the immune biology of these cancers can only be studies with more focused methods.