bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of interleukin-enhanced factor 2 (ILF2) expression with prognosis and clinico-genomic features in breast cancer (BC).
Authors: Bustos Matias A. , Yin Jun , Brodskiy Pavel , Kang Irene , Graff Stephanie L. , Sammons Sarah , Dawar Richa , Spetzler David , Hoon Dave S. B. 
Published: June 2022

1030 Background: Novel prognostic and predictive biomarkers beyond traditional histological subtypes are needed to better inform outcomes and enhance therapy guidance in breast cancer (BC). We have previously reported that ILF2 was overexpressed in TNBC cell lines and has a functional role in DNA and RNA metabolism, making it a promising biomarker for risk assessment and treatment decisions. Herein, we aim to leverage a large clinico-genomic dataset to further characterize ILF2 in BC patients (pts). Methods: A total of 9456 BC tissue samples underwent molecular profiling at Caris Life Sciences (Phoenix, AZ). Analyses included next generation sequencing of DNA (592 Gene Panel, or Whole Exome Sequencing), and RNA (Whole Transcriptome Sequencing), and immunohistochemistry (IHC). Wilcoxon and Fisher’s exact were used to determine statistical significance. Overall survival (OS) was obtained from insurance claims and Kaplan-Meier estimates were calculated. Spearman correlation was used to identify highly correlated genes (ρ>0.6) with ILF2 and significant genes that were subsequently analyzed via pathway analysis using STRING. Results: BC pts were grouped into ILF2-High (H, top quartile) and ILF2-Low (L, bottom quartile) based on mRNA expression (TPM). ILF2-H pts were significantly younger (73 vs 80% for pts >50), enriched in ductal histology (90.9 vs 77.7%), TNBC subtype (48.9 vs 18.9%), and had a higher CNS metastases rate (4.3 vs 1.4%) compared to ILF2-L pts (all q<0.0001). ILF2 overexpression was associated with significantly inferior OS in all BC pts (HR 3.38, 95%CI: 2.97 – 3.84); when stratified into known BC hormonal receptor (HR) subtypes, ILF2 was prognostic in both HR+ BC (HR 1.7, 95 CI: 1.34-2.19) and TNBC (HR 3.8, 95 CI: 3.1-4.7), all p<0.0001. In TNBC (n=2468), ILF2-H was associated with a higher frequency of TP53 mutations(mt), lower rate of PIK3CA mt and higher amplification of CCNE1 and FGF23; in HR+/HER2- BC (n = 5071), an association with a higher rate of TP53 mt, PD-L1 expression, NOTCH2 and CCND2 amplification was seen (Table). No significant molecular correlation with ILF2 was seen in HR-/HER2+ BC (n=682). In TNBC, ILF2 expression was significantly correlated with genes involved in spliceosome, cell cycle and RNA transport pathways. In HR+/HER2- BC, ILF2-correlated genes were significantly enriched in mismatch repair and DNA replication pathways (p<0.05 for all factors individually). Conclusions: High expression of ILF2 is associated with a poorer prognosis independent of subtype in BC and our study warrants further investigation on ILF2 as a diagnostic and therapeutic target.[Table: see text]
Survival of elderly patients with HER2+/HR- metastatic breast cancer in clinical practice: SEER-Medicare data 2012-2016.
Authors: Ou Zhonghui , Spring Laura , Nohria Anju , Seeger John D. , Murimi-Worstell Irene 
Published: June 2022

1039 Background: Older patients with human epidermal growth factor 2-positive (HER2+) metastatic breast cancer(mBC) are underrepresented in clinical trials. We aim to assess the overall survival (OS) and breast cancer-specific survival of elderly women with de novo HER2+/hormone receptor-negative (HR-) mBC in a real-world setting. Methods: Elderly women with HER2+/HR- mBC treated with chemotherapy and/or HER2-targeted agents and with continuous Medicare Part A, B, and D coverage 1-year before diagnosis were identified from the SEER-MEDICARE database 2012-2016. Patients were retrospectively followed from metastatic diagnosis until death, disenrollment from Medicare A, B, or D, or end of the observation period. Patients' year and month of diagnosis and death were retrieved from SEER. Death dates were verified with Medicare records reported by the Social Security Administration (SSA). For all-cause deaths, Kaplan-Meier analysis was used to estimate overall survival. The cumulative incidence competing risk (CICR) method based on cumulative incidence function (CIF) was used to estimate breast cancer-specific death incidence. Results: Seventy-three patients (mean age at diagnosis, 75.0±7.7 years) met the inclusion criteria. Among them, 56 were treated with trastuzumab ± pertuzumab /chemotherapy as first-line treatment, and 17 were treated with chemotherapy only. The median time to initiate trastuzumab-based treatment from diagnosis was 2.5 months, and the longest trastuzumab treatment length was over 44 months. The median follow-up for OS was 13 months. One patient developed stomach cancer 6 months after breast cancer diagnosis. In Kaplan-Meier analysis, censoring or not censoring this patient after second cancer development resulted in a median OS of 19 months (95% CI, 9-24 months) and 18 months (95% CI, 9-22 months). The OS at the end of 46 months was approximately 25%. Five patients died from other causes, including lung cancer, cerebrovascular diseases, aortic aneurysm and dissection, pneumonia and influenza, and heart diseases during treatment. Considering these competing risks, 50% (95% CI, 36%-64%) of patients specifically died from breast cancer between 21 and 22 months, estimated by the CICR method. Conclusions: Our study observed a shorter OS among HER2+/HR- mBC elderly patients in clinical practice than the OS of 40.8 and 56.5 months among younger patients in the CLEOPATRA trial, suggesting that age is an important prognostic factor for breast cancer survival. The presence of second cancer and other competing risks led to overestimating the probabilities of breast cancer-specific death and resulted in a shorter OS using the Kaplan-Meier method. The CICR method is more relevant to estimate the breast-cancer-specific death incidence.
Treatment patterns and their impact on the outcome of patients with HR+/HER2+ metastatic breast cancer in a large real-world cohort.
Authors: Carausu Marcela , Carton Matthieu , Dieras Veronique C , Petit Thierry , Guiu Lahaye Severine , Veyret Corinne , Goncalves Anthony , Augereau Paule , Ferrero Jean-Marc , Levy Christelle , Ung Mony , Desmoulins Isabelle , Debled Marc , Bachelot Thomas , Eymard Jean-Christophe , Pistilli Barbara , Frenel Jean-Sebastien , Chevrot Michaël , Mailliez Audrey , Cabel Luc 
Published: June 2022

1043 Background: The place of endocrine therapy (ET) in the treatment of hormone receptor-positive (HR+), HER2+ metastatic breast cancer (MBC) is still not clearly defined. Data suggest that blocking both HR and HER2 signaling pathways could be an efficacious strategy to overcome secondary resistance. Methods: We aimed to retrospectively evaluate the impact of first line (L1) therapy for HR+/HER2+ MBC patients (pts) included between 2008- 2017 in the French real-world ESME MBC database (NCT03275311). Our primary endpoints were median overall survival (mOS) and median first progression-free survival (mPFS1). We used descriptive statistics and the Kaplan-Meier method to report patient characteristics and outcomes. Cox proportional hazards models and a propensity score were constructed to report and adjust for prognostic factors. Results: From the 23,501 female pts in the ESME MBC cohort, 1,790 pts had HR+/HER2+ MBC treated with Trastuzumab (T, n=1,089) or Trastuzumab-Pertuzumab (TP, n=701) during L1. Among them, 1,584 pts received antiHER2 therapy+CT+/-ET and 206 pts, antiHER2+ET only. Pts with antiHER2+CT+/-ET had more often ECOG performance status 0 (29.5% vs 15.8%, p<0.001), grade III tumors (36.6% vs 25.6%, p=0.007), time to MBC < 6 mo (51.6% vs 29.1%, p<0.001), TP as antiHER2 therapy (43.2% vs 9.4%, p<0.001), ≥3 metastatic sites (23.2% vs 14.8%, p=0.007), visceral metastasis (56.5% vs 42.4%, p<0.001), and less often bone-only disease (18.4% vs 35%, p<0.001) than pts with antiHER2+ET. In multivariable analysis, antiHER2+CT+/-ET was not superior to antiHER2+ET (Table), while TP was superior to Trastuzumab, and this result was confirmed by matching pts using a propensity score ( p=0.76 for mOS and p=0.85 for mPFS1). Using the time-dependent ET variable among pts with antiHER2+CT, pts with maintenance ET had significantly better PFS1 and OS than those without (adjusted HR for PFS1=0.70 [95%CI 0.60-0.82], adjusted HR for OS=0.47 [95%CI 0.39-0.57], p<0.001). Conclusions: These data suggest that endocrine therapy could be an interesting less toxic alternative to chemotherapy in combination with antiHER2 therapy as first line treatment for HR+/HER2+ MBC pts.[Table: see text]
Post-recurrence survival in asymptomatic compared with symptomatic metastatic breast cancer: A multicenter retrospective study.
Authors: Kuba Sayaka , Maeda Shigeto , Minami Shigeki , Moriuchi Hiroki , Tanaka Aya , Akashi Momoko , Morita Michi , Sakimura Chika , Baba Masayuki , Otsubo Ryota , Matsumoto Megumi , Yamanouchi Kosho , Yano Hiroshi , Kanetaka Kengo , Nagayasu Takeshi , Eguchi Susumu 
Published: June 2022

1049 Background: Asymptomatic metastatic breast cancer (mBC) is often detected using tumor marker or imaging tests in Japan. At the ASCO 2019, we reported on mBC detection, the distribution of symptomatic and asymptomatic disease by subtype (abstract e12568). We aimed to determine whether there are differences in post-recurrence survival (PRS), and treatment between asymptomatic and symptomatic MBCs, and identify factors associated with PRS. Methods: We performed a multicenter, retrospective analysis of patients with mBC treated in our hospitals from 2008 to 2018. Patients were divided into asymptomatic and symptomatic MBCs to compare their prognosis by breast cancer (BC) subtypes: luminal (hormone receptor positive/human epidermal growth factor 2 [HER2] negative), HER2 (any hormone receptor/HER2 positive), and triple-negative (TN) (hormone receptor negative/HER2 negative). Results: Of 204 patients with mBC (114 asymptomatic, 90 symptomatic), PRS was longer in asymptomatic mBC than in symptomatic mBC (median survival: 55 months vs. 29 months; p < 0.001) and tended to have longer overall survival (OS) (110 months vs 72 months, respectively; p = 0.09). In multivariate analysis, TN, recurrence-free survival (RFS), multiple metastasis sites, and symptomatic disease were independently predictive of PRS (Table). In luminal and HER2, PRS trended higher in the asymptomatic group than in the symptomatic group (luminal: 54 months vs. 41 months; p = 0.08, HER2: 71 months vs. 27 months; p = 0.09), but without significant difference in OS (luminal: 112 months vs. 124 months; p = 0.91, HER2: 113 months vs. 72 months; p = 0.40). In the luminal group, 13 patients (11%) were treated with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. The median PRS was 80 months for luminal patients with three factors — longer than 4 years of RFS, a single metastasis site, and asymptomatic disease. The duration of endocrine therapy did not differ between groups; however, the patients with luminal BC in the asymptomatic group had longer chemotherapy than those in the symptomatic group. In TN, PRS was very short (asymptomatic, 28 months; symptomatic, 10.5 months; p = 0.01). Conclusions: We demonstrated that asymptomatic MBC and symptomatic MBC differed in terms of subtypes, prognosis, and duration of chemotherapy in the luminal group. Therefore, unique treatment strategy for asymptomatic or symptomatic MBC should be developed. [Table: see text]
The frequency of second primary malignancies and colonic polyps in Lynch syndrome with MSI tumors following immune checkpoint blockade.
Authors: Harrold Emily , Patel Zalak , Maio Anna , Cercek Andrea , Yaeger Rona , Segal Neil Howard , Reidy Diane Lauren , O'Reilly Eileen Mary , Desai Avni Mukund , Carlo Maria Isabel , Latham Alicia , Liu Ying L , Mandelker Diana , Markowitz Arnold , Offit Kenneth , Shia Jinru , Diaz Luis A. , Stadler Zsofia Kinga 
Published: June 2022

10505 Background: Lynch syndrome (LS) is caused by germline mutations in DNA mismatch repair genes and is characterized by microsatellite instability (MSI) status of associated tumors. MSI sensitizes tumors to immune checkpoint inhibition (ICI). The incidence of second primary malignancies and colonic polyps in LS patients with MSI tumors following ICI has not been evaluated. Methods: The Memorial Sloan Kettering LS database was queried for all patients with cancer who received ≥1 cycle of ICI using an IRB approved protocol. LS was confirmed by presence of a germline pathogenic/likely pathogenic alteration in a DNA mismatch repair gene ( MLH1, MSH2, MSH6, PMS2, EPCAM). Tumor and matched normal DNA sequencing was performed via MSK-IMPACT, an IRB approved protocol (NCT01775072). MSI status was assessed using MSIsensor. Results: At our center, 131 patients with LS received ICI mostly (73.3%) in the context of metastatic cancer. While 108 patients received ICI for an MSI tumor, 23 LS patients received ICI for a MSS (Microsatellite Stable) tumor (4 hepatobiliary, 3 colorectal, 3 CNS, 2 endometrial, 2 gastroesophageal, 2 renal, 2 sarcoma, 5 other). Five patients (3.8%) developed ≥1 second primary malignancy while on or following ICI comprised of an MSI small bowel adenocarcinoma, MSI upper tract urothelial cancer, 2 MSS prostate cancers, MSS HCC and MSI sebaceous neoplasm; 1 patient developed both MSS prostate cancer and MSI urothelial cancer on ICI. All five patients’ primary malignancy was MSI. Only a minority of patients underwent surveillance colonoscopies post completion of ICI (31.3%, (41/131)). Of these 41, nine (22%, (9/41)) were identified to have polyps including 8 tubular adenomas and 1 tubulo-villous adenoma. Median time to development of a polyp was 22 months (95% CI 16.82-27.18) from last colonoscopy and 13 months (95% CI 4-25 months) from last ICI. Notably amongst the 23 LS patients whose tumors were MSS, 14 had progression on ICI. Conclusions: Herein, we demonstrate that in LS-patients in receipt of ICI for cancer treatment, the risk of a second primary cancer and polyps remain high following treatment with ICI. Biological mechanisms underlying immune escape warrant further investigation. Surveillance strategies should be continued for LS patients post ICI.
Aromatase inhibitors for breast cancer therapy: Analysis of real-world FAERS data.
Authors: Findakly Dawood , Shi Runhua , Burton Gary Von , Master Samip R. 
Published: June 2022

1051 Background: Aromatase inhibitors (AIs) are extremely effective adjuvant treatment in postmenopausal women with hormone receptor-positive breast cancer (HRPBC). We utilized the Food and Drug Administration Adverse Event Reporting System (FAERS) database to evaluate the musculoskeletal (MSK), fractures, and ischemic heart disease (IHD) adverse events (AEs) caused by AIs. Methods: We conducted a retrospective FAERS public database review to assess the MSK, fracture, and IHD AEs for the three AIs (anastrozole, letrozole, and exemestane) from 2001 through 2021. Chi-square was used to compare categorical variables. Results: A total of 31,683 AEs reports were identified, out of which, 15,140 (47.8%) were MSK, 13,311 (42.0%) were fracture, and 3,232 (10.2%) were IHD. The differences in AEs distributions among the three drug classes were statistically significant for MSK and fracture AEs (P < 0.001) but not reached statistical significance for IHD AEs (P = 0.140). MSK AEs were mostly reported with anastrozole, followed by exemestane, and letrozole in 35.23%, 33.97%, and 32.06%, respectively (P < 0.001). Compared to older individuals, younger adults (≤65 years) had higher rates of MSK AEs—mostly with anastrozole (38.43%, P < 0.001), followed by exemestane (36.37%, P = 0.006) and letrozole (34.28%, P < 0.001). Fracture AEs were mostly reported, in descending order, with letrozole, exemestane, and anastrozole in 12.07%, 11.41%, and 9.34% respectively (P < 0.001). Older adults (> 65 years) had higher rates of fracture AEs with letrozole (16.77%, P < 0.001) and anastrozole (10.37%, P < 0.001), while unable to demonstrate statistical significance with exemestane (13.48%, P = 0.108). Among older adults (> 65 years), IHD AEs were significantly reported with anastrozole (21.56%, P < 0.001) and exemestane (14.18%, P = 0.016) but no statistical significance reached for letrozole (14.12%, P = 0.528). Conclusions: The findings in this study highlight trends for selected AEs with various AI regimens, provide further insights, and help guide therapeutic decisions for patients with HRPBC.
Whole genome germline sequencing: Its role in general health screening in family practice, the first study in the UK.
Authors: Eeles Ros A. , Sandberg Michael , Pichert Gabriella C. , Side Lucy , Homfray Tessa , Jones Ann-Britt , Hicks Sophie , Bancroft Elizabeth 
Published: June 2022

10510 Background: Whole genome sequencing (WGS) is now possible due to improvements in next generation sequencing technology. This gives the opportunity to incorporate genetic data into family practice health screening. The fulfilment of the potential of WGS lies in its future implementation into family practice. This study aimed to set up a model pathway to undertake WGS for actionable findings and assess its potential role in enhancing health screening. Methods: A pilot study comprised of 100 healthy participants from 2020-2022, recruited from a family practice, consented to routine baseline blood tests, cardiac assessment (ECG and echocardiogram), abdominopelvic ultrasound, all performed at the practice. Review of past medical, and family history was done from electronic health records (EHR). Germline genetic testing consisted of 84 cancer and 77 cardiac genes and whole genome sequencing (566 actionable genes reported), including higher penetrance monogenic mutations, recessive carrier alterations and pharmacogenomics. A multidisciplinary clinical team reviewed integrated results through an iterative process, which fed back to participants. Results: Twenty of 100 individuals (20%) had an actionable genetic variant in either cancer (10 individuals), thrombophilia (8) or cardiac rhythm disorder genes (2). Eighty percent of the participants had a variant in an autosomal recessive gene. Pharmacogenomics results yielded significant variants in 30%. Conclusions: The majority of patients had a significant change in management for themselves or their families. Whole genome sequencing as part of health screening in family practice is feasible and is likely to have significant beneficial health management implications. This study is the first of its kind in family practice and shows how this can be implemented.
Cascade testing of first-degree relatives of patients with pancreatic cancer with confirmed germline genetic mutations: A simulation modeling study.
Authors: Peters Mary Linton Bounetheau , Davidi Barak , Seguin Claudia L. , Eckel Andrew , Pandharipande Pari 
Published: June 2022

10513 Background: Universal germline genetic testing is recommended for all patients with pancreatic ductal adenocarcinoma (PDAC). In addition to treatment implications for the patient, it is valuable for family members of the PDAC patient to undertake germline testing to understand their familial cancer risk. We evaluated the potential effectiveness of cascade testing of first-degree relatives (FDRs) of PDAC patients to guide MRI-based screening for PDAC. Methods: We used a microsimulation model of PDAC to estimate the potential life expectancy (LE) benefit of cascade genetic testing of FDRs of PDAC patients. Analysis was performed for eight mutations of interest (ATM, BRCA1, BRCA2, PALB2, Lynch, TP53, CDKN2A, STK11) with relative risk of PDAC ranging from 1.6 – 24. FDRs were defined by their sex, age, and information state (not informed, informed but not tested, test negative, or test positive). Family size and composition, communication of genetic testing results, and uptake of cascade testing were based on published studies. For each FDR group, we simulated multiple MRI-based screening strategies, defined by starting age (FDR age at patient diagnosis to age 75) and frequency (once or annual until age 75), and identified the strategy that resulted in the highest LE. Results: Each PDAC patient would have an average of 4.35 living FDRs. 1.32 of these living FDRs would be informed of the patient’s test results but not undergo testing themselves, and 1.03 would test positive for the mutation of interest. For lower risk mutations (ATM, BRCA2, PALB2), FDRs would only undergo screening if they test positive. For Lynch syndrome, not tested FDRs would undergo screening starting at age 65 or 70, whereas FDRs who test positive would start at 50 or 55. For STK11, the highest risk mutation, FDRs would start screening annually as soon as they are informed of the patient’s test results. The total LE gain for cascade testing of FDRs ranged from 0 (BRCA1) to 1.05 years (STK11). Conclusions: For each PDAC patient identified to have a germline genetic mutation, cascade testing of FDRs could add up to a year life expectancy for the family, in addition to the value of the germline information to the PDAC patient’s care. [Table: see text]
Rates of pathogenic variants in common cancer genes among different racial/ethnic groups.
Authors: Beitsch Peter D. , Wernecke Chloe , Cai Steven , Brown Eric Allen , Ortega Krista , Zhu Vicky , Patel Rakesh 
Published: June 2022

10515 Withdrawal Notice: Abstract 10151 by Beitsch et al, entitled "Rates of pathogenic variants in common cancer genes among different racial/ethnic groups," was withdrawn by the authors from presentation and publication. As they were preparing for presentation at the meeting, the authors discovered additional data that potentially altered the abstract's conclusions. The abstract was withdrawn on May 13, 2022.