bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimization of protein extraction for proteomic analysis of formalin-fixed and paraffin-embedding (FFPE) biopsy specimens from males with breast cancer.
Authors: Bezerra Maria Júlia Barbosa , Silva Jackeline Almeida , Sant'Ana Rosane Oliveira , Picanço-Albuquerque Clarissa Gondim , Luciano Maria Claudia dos Santos , Bastos Jose Fernando , Barbosa Oliveira Francisca Fernanda , Freire Italo Aguiar , Bitencourt Flávio da Silveira , Hirth Carlos Gustavo , Silva Paulo Goberlanio de Barros , Silva-Fernandes Isabelle Joyce de Lima 
Published: June 2023

e13119 Background: Male breast cancer corresponds to 1% of breast cancer diagnoses. Given this low incidence, the tumors detected have a worse prognosis and lethality. Formalin fixation and paraffin-embedding (FFPE) methods are the most common to maintain biopsied samples. It is a low-cost procedure and is a valuable resource for the study of pathological molecular mechanisms and research of potential biomarkers and therapeutic target molecules. However, in this technique cross-links are formed compromising protein extraction, resulting in low yield and quality for mass spectrometry analysis. Objective: To present an optimized method of protein extraction from male breast FFPE samples for proteomic analysis. Methods: Four protein extraction protocols were optimized and tested in female breast cancer FFPE samples from Haroldo Juaçaba Hospital/Cancer Institute of Ceará to preserve the male sample. Each protocol was performed using a total of eight 5uM tumor slides. Different deparaffinization processes were tested followed by distinct extraction buffers and variable incubation time. The characteristics of each of the protocols and optimizations are presented in the table. The quantification of the protein profile was carried out in nanodrop 2000. The protocol with the highest yield was used in the male breast cancer sample FFPE. Analysis of the protein profile in polyacrylamide gel (SDS PAGE) was performed. Results: Protocol IV presented the highest yield of protein (16.9 mg/mL) and protocols I, II, and III presented, 0.46 mg/mL and 0.28 mg/ml, and 2.3 mg/mL, respectively. Protocol IV was selected to be used in the male breast cancer sample and the yield was 14.26 mg/mL, similar to the female sample. Protein bands from male and female samples using protocol IV were detected on the SDS-PAGE gel. Conclusions: Protocol IV performed a satisfactory protein yield in breast cancer samples FFPE. [Table: see text]
Clinical and molecular characterization of a cohort with breast cancer brain metastases.
Authors: Oyogoa Emmanuella , Chun Brie , Sandow Lyndsey , Rice Douglas , Goodyear Shaun , Zimmer Alexandra Dos Santos 
Published: June 2023

e13122 Background: Breast cancer (BC) is the most common cancer in Women in the United States, it is the second most frequent cause of brain metastases (BM). Despite steady improvement in BC treatment (tx) and prognosis, BM continues to be an unmet need. With most BM patients excluded from clinical trials, the study of cohorts remains an important source of information regarding this aspect of the disease. We aim to characterize incidence, disease course, tx, and molecular profile of BM for BC subtypes. Methods: In this single-center retrospective analysis, we identified all adult patients (>18 years) diagnosed (dx) with BC as well as secondary malignant neoplasm of the brain from 1/1/15 to 10/1/22 using database query from EMR. Baseline characteristics were obtained through chart review. Molecular profiling was performed in a total of 41 patients, 8 of which was from brain tissue. Next generation sequencing (NGS) was the most used method. Results were generated using descriptive statistics. Results: We identified 304 BC patients with BM (median age = 60 years [range: 24 to 88]). Baseline characteristics are described in table 1. Hormone receptor positive/HER2-neu negative (HR+/HER2-) was the most commonly observed BC subtype (41.4%), and triple negative BC (TNBC) was the least frequent (16.8%). On primary tissue biopsy, five patients with recurrent BC had a subtype shift that differed from their initial disease: 2 patients with HR +/HER2 – BC subtype recurred with TNBC, 2 patients with a HR+/HER2- recurred with HR+/HER2+ BC, and 1 patient with TNBC at initial dx had their disease shift to HR+/HER 2- BC at first metastatic recurrence then back to TNBC 4 years after initial dx. NGS was available for 41 patients, with TP53, MSS, PIK3CA and ERBB2 being the most frequently observed mutations. On average, 3 lines of therapy were used before dx of BM. In the metastatic setting, capecitabine was one the most commonly used drugs. Targeted central nervous system (CNS) tx used in this study population include WBRT, SRS, SBRT and surgical resection. Conclusions: Studying patterns of disease presentation, progression during standard tx, and the molecular characteristics accompanying BM will enable us to develop more effective tx for patients. Our cohort includes a spectrum of BC subtypes and natural histories. Further characterization of this cohort with tx interactions, progression and survival timeline is ongoing and will be reported at the meeting. [Table: see text]
Clinical outcomes of patients with metastatic breast cancer treated with eribulin: A real-world evidence study from China.
Authors: Yan Xi , Chen Lan , He Ping , Tian Ting-Lun , Zhong Xiaorong , Luo Ting 
Published: June 2023

e13126 Background: Eribulin is a novel synthetic analog of halichondrin B that acts as a microtubule inhibitor and inhibits the G2-M growth phase. Eribulin was approved for metastatic breast cancer (MBC) based on the landmark phase 3 EMBRACE trial (Cortes et al, Lancet 2011; NCT00388726); however, only a small number of Asian patients were included in that trial. Therefore, in this real-world study, we retrospectively assessed the clinical outcomes of Chinese patients with MBC who received eribulin. Methods: Adult patients with MBC who received eribulin as several lines of therapy were retrospectively analyzed. Socio-demographic, clinical, pathology, imaging, and therapy records were reviewed. Progression-free survival (PFS) and tumor response were evaluated. Results: A total of 85 patients were included. The median age was 45 years (range, 21–63). Eribulin was used as a first, second, third, and fourth or more chemotherapy agent in 13 (15.3%), 16 (18.8%), 11 (12.9%) and 45 (52.9%) of patients with MBC, respectively. Eribulin was monotherapy in 32.9% of patients; eribulin plus anti-HER2 targeted therapy was used in 9.4% of patients; eribulin plus immunotherapy was used in 5.9% of patients; eribulin plus other chemotherapy was used in 36.5% of patients, and eribulin plus antiangiogenic therapy was used in 9.4% of patients. The objective response rate (ORR) was 28.2% overall. By number of lines of therapy, the first-line ORR was 38.5% and the second-line ORR was 37.5%. On subgroup analysis, ORR of patients with liver metastasis and lung metastasis was 43.9% and 38.6 %, respectively. By molecular classification, the ORR of patients with HR+/HER2− disease was 66.7%; among patients with HER2+ disease, 32.6%; and among patients with triple-negative BC, 13.3%. The 6-month PFS rate was 33.6% overall. By number of lines of therapy, the 6-month PFS rate among patients who received eribulin as first-line treatment was 67.7% and among patients who received eribulin as second-line treatment, 38.3%. Among patients who received eribulin monotherapy, the 6-month PFS rate was 21.4% and among patients who received eribulin combination therapy, 41.2%. No adverse reactions related to neutrophils were reported. Conclusions: This real-world retrospective study suggests that eribulin was effective in Chinese patients with MBC with a range of prior lines of chemotherapy, supporting the use of eribulin in the treatment of Chinese patients with MBC.
Therapeutic strategies for metaplastic breast cancer: A clinicopathologic analysis of a single institution cohort.
Authors: Batra-Sharma Hemali , Yeung Kay T , Shatsky Rebecca Arielle 
Published: June 2023

e13128 Background: Metaplastic breast cancer (MpBC) is a rare, aggressive, and histologically diverse subtype, which is associated with worse survival outcomes than other triple-negative breast cancers. Methods: This study is a single-institution retrospective analysis of 30 patients with MpBC, focused on response to therapies in the context of histologic subtype, molecular alterations, and PD-L1 expression. Patients with MpBC who received treatment at our institution consented to share clinical information with a research biorepository. Clinicopathologic and next generation sequencing (NGS) data were obtained from patients’ electronic health records. The primary outcomes are overall survival (OS) and event-free survival (EFS), and the secondary outcomes are responses to neoadjuvant therapy, tumor growth on taxane and/or anthracycline, and responses to systemic therapy in the relapsed/metastatic setting. Results: Among the 30 MpBC patients, the median age at diagnosis was 47.5 years. 86.7% were diagnosed with early-stage disease, 36.7% with squamous cell MpBC, 93.3% with triple-negative disease, and 30% with HER2-low disease. Of the patients diagnosed with early-stage disease, 88.5% received neoadjuvant systemic therapy, 96.2% underwent breast surgery, 92.3% received definitive/adjuvant radiation, and 76.9% received adjuvant systemic therapy. 61.5% of patients with localized disease experienced local and/or distant relapse. Median EFS was 14.0 months (95% CI, 10 to 20 months). Median OS was 26.5 months (95% CI, 20 to 32 months). There was no clearly superior neoadjuvant regimen based on MpBC subtype, but more patients with squamous MpBC experienced tumor growth on taxane-containing therapy compared to those with growth on anthracycline-containing regimens. In the relapsed/metastatic setting, patients with squamous cell MpBC and somatic mutations in the PI3K/Akt/mTOR pathway had prolonged partial responses to combination treatment with an anthracycline, mTOR inhibitor, and VEGF inhibitor. Median treatment duration with sacituzumab govitecan in the 1st or 2nd line metastatic setting was 1.5 months (95% CI, 1 to 4 months) before disease progression. Low tumor mutational burden was seen across all MpBC subtypes (median 2.1, 95% CI 1.6-4.0). 75% of the cases were PD-L1 positive by Immune Cell expression. There was no clear association between PD-L1 expression and response to immunotherapy-containing treatments in the neoadjuvant or relapsed/metastatic setting. Conclusions: Our findings on the presentation of MpBC correlate with other clinicopathologic studies. For squamous MpBC, we noted trends on the utility of anthracycline-containing regimens. Chemoimmunotherapy and antibody-drug conjugates have changed management of triple-negative and HER2-low breast cancer, but more prospective data are needed to determine the optimal therapeutic strategies for MpBC.
Validation of a 56 gene panel for the detection of somatic variants in metastatic breast cancer.
Authors: Blankfard Martin , Christiansen Jason H. , Dharajiya Nilesh , Lam Ernest , Wenstrup Rick 
Published: June 2023

e13131 Background: The use of ctDNA and next generation sequencing has unprecedented potential to improve genomic profiling and predicting actionable drug treatment in patients with metastatic breast cancer (MBC). Liquid biopsy is uniquely suited for patients where tissue biopsy is not feasible. We specifically focus on actionable variants found in liquid biopsy for MBC including bTMB and MSI. Here we report on the validation of a 56 gene sub panel for the determination of somatic mutations in MBC. Methods: Commercially available, well-characterized, biological ctDNA reference samples with allele frequency ranging from 0.5 -2.5% and bTMB scores (7 – 20) were obtained to analytically evaluate sensitivity, specificity and precision of a range of clinically significant variants (SNV, indels, fusions and copy number variants) in the TSO-500 ctDNA NGS assay. Additionally, 48 Whole blood samples from well characterized metastatic breast cancer patients and 13 healthy donors were obtained from commercial sources. cfDNA was extracted from the plasma separated from whole blood and analyzed on both TS0-500 ctDNA assay and PGDx Elio Complete. TSO-500 ctDNA sequencing data was further analyzed with the DRAGEN pipeline for variant calling and all variants were annotated and curated with the Clinical Genomic Workspace from PierianDx. PGDx utilized a proprietary pipeline and reporting of all variants detected. Results: Analytical validation determined excellent sensitivity (PPA: 99.4 – 100%), specificity (NPA: 99.6 -99.8%) and reproducibility (95 – 98.6%) for SNV, indels, fusions and Copy number variants. bTMB, with a cutoff for bTMB high as >20 mut/Mb, exhibited a sensitivity of 75% and specificity of 93.3%. Limit of detection (LOD) was established at 0.5 % VAF for SNV, Indels and fusions at a minimum read depth of 1000x. LOD for Copy number amplifications was established at 1.26-fold change or 3 copies. Clinical samples also exhibited excellent concordance across both TS0-500 ctDNA and PGDx Elo Complete. SNV, indels and copy number variants exhibited 100% (PPA) sensitivity and 99-100% Specificity (NPA). bTMB exhibited 87.5 % sensitivity and 96.22% specificity. As expected, fusions and microsatellite instability were observed in the clinical population but were rare. No reportable mutations were found in the healthy donors. Actionable mutations were reported for PIK3CA, ESR1, BRCA1 and BRCA2, TP53 and ERBB2 variants. Rare mutations in ATM, CHEC2, PALB2, FGFR1 and CCND1 were also observed. Conclusions: Clinical utility of liquid biopsy assays requires excellent sensitivity, specificity and precision. The Epic 56 gene panel has established clinical validity and high sensitivity and specificity across all relevant variants including bTMB in MBC. This clinically available NGS panel for metastatic breast cancer allows for routine genomic profiling, specifically in patients where tissue biopsy cannot be obtained.
Improving multidisciplinary patient-centered care for adolescents and young adults with cancer.
Authors: Elliott Leighton Andrew , Lagmay Joanne P. , Scott Daimian Holiday , Staley Lauren 
Published: June 2023

e13503 Background: Approximately 90,000 adolescents and young adults (AYA) are diagnosed with cancer annually. Poor outcomes are associated with decreased access to specialized care, limited opportunities for clinical trial participation, treatment protocol variations, and limited psychosocial resources. Fortunately, there has been an increased awareness of the unique challenges faced by AYA patients with the establishment of AYA programs around the world. In order to maximize management opportunities for this marginalized population, our academic healthcare system embarked to establish an effective AYA Oncology Program to serve within the continuum of Pediatric and Medical Oncology and survivorship. Herein, we report the outcomes from this important quality improvement initiative. Methods: In May 2018, the AYA program was established within Pediatric Oncology. We were able to hire a dedicated social worker in March 2020. At this time, growth of the program was limited due to the COVID pandemic. In January 2021, the consult order was updated to enhance tracking metrics. We aimed to increase AYA program consult orders by 20% from 2021 to 2022. In June 2021, we presented the AYA program to Medical Oncology and Malignant Hematology to increase program awareness. We implemented several other educational activities with the Department of Pediatrics, Department of Medicine (including Medical Oncology and Malignant Hematology), and the community via multiple Plan-Do-Study-Act (PDSA) cycles. Results: Since 2020, the AYA program has tracked 91 answered consults – 86 in the last 2 years. In 2022, there were 50 total consults placed compared to 36 in 2021, a 38.9% increase. Since 2021, the AYA program was consulted on 17.2% of newly diagnosed AYA patients. Inpatient consults were more common at 62.6%. Thirteen total consults were ordered for patients ≥30yo, of which only 2 were for patients older than 32. The AYA program was consulted on only 3.5% of newly diagnosed adults ≥30yo compared to 28.7% for the younger AYA patients. Upon surveying medical oncologists at our institution, most providers simply forget to order consults to the AYA program. Conclusions: Total AYA program consult numbers are increasing, however, there is opportunity for growth, especially in reaching the older AYA patients. Our healthcare system has recently approved the establishment of a Best Practice Advisory (BPA) in our electronic medical record to remind providers to order AYA program consults, if appropriate. Once the BPA is established, subsequent PDSA cycles will emphasize reaching older AYA patients by re-circulating educational resources and activities to providers and social workers in Medical Oncology and Malignant Hematology. Future objectives will evaluate outcomes in quality of life, overall survival, healthcare utilization, and clinical trial enrollment amongst other metrics.
Clinical pathways utilization and characteristics of non-adherence at Sidney Kimmel Cancer Center.
Authors: Houtmann Sarah , Manobianco Steven , Hansinger Emily , Binder Adam F. 
Published: June 2023

e13505 Background: Clinical pathways are utilized by many oncology practices with goal to deliver high quality, consistent care across health systems. In pathway tools, evidence-based treatments are recommended using the following hierarchy 1) efficacy, 2) adverse events, 3) cost. Previous research has shown that increasing adherence to pathways delivers evidenced based care at reduced cost. However, this comes at the expense of increased “clicks” and inefficiencies in workflow. We hypothesized that at a large academic center with subspecialty oncologists that lack of adherence to pathway utilization did not result in decrease adherence to evidence-based medicine. Methods: At our institution’s main academic hub, all breast, genitourinary (GU), and gastrointestinal (GI) chemotherapy encounters ordered from July 2020 through June 2021 were identified. A subset of these encounters, those ordered without use of Elsevier’s ClinPath, “pathway-independent,” were identified. Chart review was performed to identify clinical characteristics, ordering physicians, and line of treatment. Treatment choice was compared to ClinPath pathways to determine if treatment was “on-pathway” or “off-pathway.” Treatment was also compared to NCCN guidelines, to determine if aligns with standard of care. Results: 1,111 breast, GU, and GI total chemotherapy ordering encounters were identified. Only 103 (9.3%) were pathway-independent orders. 41 were hepatobiliary orders, which do not have a ClinPath pathway at our institution, leaving 62 pathway-independent orders despite a pathway available. 87% of the pathway-independent encounters were on-pathway, just not utilizing the ClinPath tool, and 91.9% align with standard of care. Only 8 of the 62 (12.9%) pathway-independent encounters were off-pathway. Of these 8 encounters, 4 (50%) were GI and 4 (50%) GU chemotherapy. 5 were 1st line treatment, 2 were 2nd line, and 1 was 3rd line. 3 of 8 off-pathway encounters were in accordance with NCCN guidelines. There were justifications for 2 of the 8 off-pathway treatments: prohibitive hepatic dysfunction and patient preference to continue treatment ordered by outside institution. The remainder were by physician preference. Conclusions: At our academic institution, there was high utilization of ClinPath when ordering GI, GU, and breast chemotherapy, with 94.4% total encounters utilizing ClinPath. The vast majority of chemotherapy ordered at our center, even when ordered without ClinPath, aligns with standard of care. While the number of pathway-independent decisions was very small in this sample, it suggests that the clinical pathway tool may not influence clinical decision making as much as suggested in other studies, but likely adds administrative burden to physicians who practice in highly subspecialized areas.
Overcoming barriers to adoption of precision medicine in community oncology centers in the rural southeastern United States using novel informatics tools and academic collaborations.
Authors: Caughey Bennett Adam , Kumar Anivarya , Owen Jennifer R. , Sloat Nicholette , Maynard Elizabeth , Hill Vanessa , Hubbard Christopher , Neely Benjamin , McKinney Matthew Stuart , Sutton Linda , McCall Shannon J. , Datto Michael , Strickler John H. , Green Michelle 
Published: June 2023

e13514 Background: Comprehensive genomic profiling (CGP) is an important tool to identify actionable biomarkers and guide cancer therapy. However, patient (pt) race, socioeconomic status, and clinical setting are associated with lower access to CGP, targeted therapies, and clinical trials. To address this, we expanded a novel framework for genomic data management and clinical decision support developed at a large academic medical center to a network of affiliated community cancer centers located in rural, traditionally underserved communities. Methods: The Duke Precision Cancer Medicine Initiative (PCMI) developed a centralized database to aggregate and normalize CGP results. This database enables CGP review by a multi-disciplinary Molecular Tumor Board (MTB). PCMI established a protocol that allows the MTB to review CGP results and relevant clinical data for consented patients. This protocol opened enrollment at four DCN-affiliated cancer centers in rural North Carolina. Clinical recommendations are captured in a standard note and returned to DCN providers following each review. Our protocol also includes an anonymous survey sent to oncology providers asking about barriers to access and utilization of CGP. Results: Between Jan 2022 and Jan 2023, 62 pts were enrolled and had CGP results reviewed by the MTB; 13 pts (21.0%) were Native American and 20 (32.3%) were Black. 61 actionable genomic alterations were identified from 38 pts, including 16 (25.6%) that molecularly matched clinical trial inclusion criteria. Most DCN providers reported being comfortable ordering (14/20) CGP though fewer expressed comfort with interpretation (9/20) CGP; provider-reported barriers included cost/insurance for targeted therapies (12/20) and distance to clinical trials (14/20). Conclusions: Successful academic-community partnerships to expand access to CGP, clinical trials, and targeted therapies are feasible when supported by fit-for-purpose informatics tools and scalable workflows. Additional work is required to develop comprehensive solutions that ensure equal access to CGP and precision medicine for all patients. [Table: see text]