bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of KRAS G12D vs. G12V circulating tumor DNA variant allele fraction and real-world overall survival in metastatic non-small cell lung and colorectal cancers.
Authors: Till Jacob Edward , Bucheit Leslie A , Zhang Nicole , Clemens Keelia M. , Carpenter Erica L. 
Published: July 2024

3041 Background: We previously reported KRAS G12D but not G12V variant allele fraction (VAF), as measured in circulating tumor DNA (ctDNA), was associated with overall survival (OS) in metastatic treatment-naïve pancreatic cancer (mPDAC). However, this has not been examined in other RAS-driven cancers. Here we assessed association of real-world OS (rwOS) with KRAS G12D and G12V VAF in metastatic colorectal cancer (mCRC) and non-small cell lung cancer (mNSCLC). Methods: We queriedGuardantINFORM, a real-world evidence database of aggregated commercial payer health claims and de-identified results from Guardant360 (G360) ctDNA testing from 2014 to 2023, to identify mNSCLC/mCRC patients who were treatment-naive and had KRAS G12D or G12V mutations identified < 30 days prior to first-line therapy initiation. Those with co-occurring KRAS alterations, KRAS amplifications, and/or MSI-H were excluded. Outcomes were assessed as above vs. below median VAF and stratified by treatment type. The Cox regression model was run for continuous VAF, adjusting for age, gender, summary comorbidity score [Elixhauser Comorbidity Index (ECI)], and year of G360. Results: For mCRC, KRAS VAF above median was significantly associated with shorter rwOS for both G12D and G12V (Table 1); subgroup analysis of the predominant standard-of-care chemotherapy, FOLFOX, showed similar findings. For mNSCLC, KRAS VAF above median was associated with shorter rwOS for G12V, but not G12D (Table). Subgroup analysis by first-line treatment type revealed this association to be similar for chemotherapy-containing regimens but not immunotherapy (IO) alone. Conclusions: While a variant-specific association of KRAS VAF with rwOS was observed in mNSCLC overall (G12V associated, G12D not), above vs below median VAF was not associated with rwOS for the subset of patients receiving IO only. In contrast, for mCRC both G12D and G12V VAF were associated with rwOS, including for the subset of patients who received chemotherapy. These data suggest a complex interplay between KRAS variant, ctDNA shedding, first-line treatment, and OS that will be important in the interpretation of the prognostic implications of ctDNA-identified KRAS alterations. [Table: see text]
Ethnic and clinical differences in gBRCA and HRD mutated breast and ovarian cancers and their response to PARP inhibitors.
Authors: Uttamchandani Ashok , Syed Naveed , Chintakuntlawar Ashish Vittalrao , Afrooz Imrana , Uttam Chandani Kanishka , Hasan Riad Al , Vilasini Deepthi , Salami Aisha Mohamed Al , Chehal Aref Ahmad 
Published: July 2024

e13102 Background: Hereditary mutations of the homologous recombination (HR), the key DNA double-strand break repair pathway, are one of the well-known causes of breast and ovarian cancers. Few reports exist on these mutations and the utilization of PARP inhibitors in the Middle Eastern region. Methods: This is a single-center retrospective study of breast and ovarian cancer patients who underwent genetic testing for g BRCA and HR defects (HRD) respectively between August 2021 and May 2023. Data was summarized using descriptive statistics and compared using counts and percentages. Response to treatment was assessed using RECIST criteria. Results: The prevalence of pathogenic mutations was 22.8%, with 26.3% of breast cancers harboring g BRCA mutations and 24% of ovarian cancers showing HRD positivity. Middle Eastern patients comprised 40% of the g BRCA-positive breast cancer group, while Asians accounted for 66% of the HRD-positive ovarian cancer patients. In mutated breast cancer, 53.3% had a positive family history of cancer. 33.3% of mutated breast cancer group and 66.6% of the ovarian cancer group received PARPis. Objective response to PARPi was 40% and 100% in breast and ovarian cancers, respectively. Conclusions: Our study revealed a high prevalence of g BRCA mutations (26.3%) in breast cancer and HRD positivity (24%) in ovarian cancer). Ethnic profiles differed between these cancers, with Middle Eastern and Southeast Asian patients dominating the breast and ovarian groups, respectively. Interestingly, the TNBC rate in breast cancer remained around 20% regardless of g BRCA status. While disparities between HRD groups were more pronounced in ovarian cancer, as expected, unexpected trends emerged in breast cancer. Further research with larger cohorts is needed to confirm these findings. [Table: see text]
Percutaneous cryoablation of breast cancer metastases: Analysis of long-term single center experience, efficacy and outcomes.
Authors: Chi Jie , Aoun Hussein , Chen Wei , Zong Yu , Ristic Gorica , Jang Hyejeong , Simon Michael S. , Assad Hadeel 
Published: July 2024

e13105 Background: Percutaneous image-guided cryoablation is a minimally invasive loco-regional treatment modality with wide availability and advantages of minimal sedation, short recovery, and ability to continue concurrent systemic therapy. However, there is a paucity of data about its long-term effects in the treatment of metastatic breast cancer despite evidence suggesting a potential survival advantage with loco-regional therapy for oligo-metastatic disease. Methods: We conducted retrospective analysis of patients who underwent CT-guided percutaneous cryoablation for metastatic breast cancer and had at least 1 follow up post cryoablation. Patient data including demographics, cancer treatment history and outcomes were extracted by chart review after IRB approval. Descriptive analyses of overall survival (OS), progression-free survival (PFS), and time to next-line treatment (TTNL) was performed. Results: The study encompassed 37 metastatic breast cancer patients who underwent cryotherapy between 2004-2021. These ablation procedures targeted various metastatic sites, which included the liver, lung, renal, lymph nodes, subcutaneous nodules, and bone. Their median age at the time of cryoablation was 58 years (range: 34-90). Among them, 46% had triple-negative breast cancer (TNBC), 41% were HR+/HER2-, and 8% were HER2+. Prior to first cryoablation procedure, 59% of patients had received more than one line of systemic therapy, and 73% were actively undergoing systemic treatment. The median size of the metastatic lesions treated with cryoablation was 1.8 cm (range: 0.4-6.5 cm). The most frequent site for cryotherapy was the liver (38%), followed by lymph nodes (30%). For the entire cohort, median PFS, TTNL, and OS were 7.1, 14, and 65.7 months, respectively. Subgroup analysis revealed mPFS of 3.1, 7.4 and 14.2 months for TNBC, Her2+ and HR+/Her2- cohorts respectively. Subgroup analysis for OS was not reported due to the small number of events and premature follow up time. Among the 27 patients who experienced disease progression, the majority (74%) had distant progression, with 22% occurring within the same organ but outside the ablation zone. Local recurrence within the ablation zone was rare, observed in only 4% of cases. Conclusions: Percutaneous image-guided cryoablation of metastatic breast cancer lesions demonstrated durable local response, prolonged PFS, TTNL and OS. Future studies investigating cryoablation as part of a multidisciplinary treatment approach for patients with metastatic breast cancer are worthwhile to confirm disease control rate and improvement in survival.
Effect of tumorspheres cultured from circulating cancer stem cells on the innate checkpoint CD47 in patients with breast cancer.
Authors: Pizon Monika , Schott Dorothea , Pachmann Ulrich A. , Pachmann Katharina 
Published: July 2024

e13113 Background: Circulating cancer cells, and in particular their very rare subpopulation, circulating cancer stem cells (cCSCs), are responsible for recurrence and metastasis. The exact role of cCSCs in escape of cancer from immunosurveillance is still unknown, but recent studies reported that increased expression of CD47 enable cancer cells to evade phagocytosis by macrophages and promote the cancer stem cell phenotype. Understanding the mechanisms behind this CD47 overexpression in cancer stem cells is critical for developing more effective immunotherapy. Therefore, in the current study, we evaluated the incidence and clinical relevance of tumorspheres cultured from cCSCs expressing CD47 in breast cancer patients. Methods: 110 patients with breast cancer in different stages of disease were included in this study. The determination of cCSCs was performed using the sphere-forming assay. Additionally, anti-CD47 antibody staining was applied to examine CD47 expression on breast tumorspheres. Results: We have developed an innovative in vitro platform for detection of cCSCs from peripheral blood of cancer patients. The number of tumorspheres was associated with disease progression and aggressiveness of primary tumor. Patients with metastatic disease had statistically more tumorspheres as compared to patients without metastasis (30 vs 10/100µl blood, p<0.05). Patients with multiple metastasis had more tumorspheres compared to patients with single metastases (60 vs 30/100µl blood, p<0.05). CD47 was highly expressed in tumorspheres, which are enriched from circulating cancer stem cells and associated with triple-negative tumors. We also observed high heterogeneity of CD47 expression between the tumorspheres of a patient and between the patients. Conclusions: The number of tumorspheres cultured from peripheral blood directly reflects aggressiveness and proliferation capacity of primary tumor. The presence of tumorspheres with high expression of CD47 might suggest their immunoregulatory potential. Better understanding of the interaction between cCSCs and tumor immunology may improve outcome especially in high-risk patients in part by attacking cCSCs and disinhibiting innate immunity.
Are we ready to use PSMA as a theranostic biomarker in clinical practice for patients with breast cancer?
Authors: Bravaccini Sara , Virga Alessandra , Foca Flavia , Cortecchia Stefania , Martinelli Giovanni , Ravaioli Sara , Tumedei Maria Maddalena , Matteucci Federica , Maltoni Roberta , Paganelli Giovanni , Poli Francesca , Mazza Massimiliano , Nicolini Fabio , Ulivi Paola , Sansovini Maddalena , Caroli Paola , Puccetti Maurizio 
Published: July 2024

e13114 Background: Subtype classification for breast cancer (BC) patients is important for risk-stratification. Unfortunately, this parameter is not able to discriminate perfectly between high- and low-risk disease and the identification of an accurate biomarker to determine aggressiveness is still a clinical need. Prostate-specific membrane antigen (PSMA) could be important given that it has been reported to be expressed in BC tumor cells and even more in endothelial cells of tumor vessels. Methods: We analyzed 101 BCs of whom 22 luminal A, 34 Luminal B, 22 HER2 positive and 23 triple negative (TN) BC to assess whether PSMA expression by immunohistochemistry was different in tumor subtypes and was related to ki67 expression and stromal (tumour-infiltrating lymphocytes) TILs. PSMA positivity was calculated as the number of positive vessels on 10 fields at 40X magnifications. Kruskal Wallis’s test was used to assess difference in PSMA positivity among BC subgroups and Dunn’s test was performed for post-hoc comparisons; Spearman’s rho coefficient was calculated to analyze the correlation among PSMA, KI67 and TILs. Results: The median age at diagnosis of BC patients was 66 (min-max: 25-87 years). Seventy (69.3%) patients had ER>0 and 64 (63.4%) had PgR>0. The ductal histotype was present in 92 patients (91%). The majority of the patients had grade 3 tumors (55.4%). Considering the number of positive vessels, our results showed that median PSMA was higher in TNBC compared to Luminal A, Luminal B and HER2 positive tumors (p<0.001, p=0.001 and p=0.041, respectively). Ki67 was higher in TNBC compared to Luminal A, Luminal B and HER2 positive tumors (p<0.001, p<0.001 and p=0.001, respectively). We saw a correlation between PSMA and ki67, especially in HER2 positive tumors (p<0.001), while a correlation between PSMA and TILs was observed in Luminal A (p=0.028). The analysis of PSMA expression on the lymph nodes showed the same trend observed for the primary tumors given that it was higher in TNBC compared to HER2 positive and luminal cancers. Conclusions: Our results suggest that PSMA could be used as a theranostic biomarker in BC considering that it is highly expressed in more aggressive tumors and the possibility to treat PSMA expressing patients for anti-angiogenesis and/or radionuclide treatment.
A genetically engineered epothilone analog as a novel oral microtubule inhibitor: A clinical study of utidelone capsule for advanced breast cancer.
Authors: Zhang Pin , Wang Wenna , Chen Xi , Tang Li , Qiu Rongguo , Gong Zheng , Xu Binghe 
Published: July 2024

e13115 Background: Utidelone, a genetically engineered epothilone analog, is a potential best-in-class novel microtubule stabilizing agent. Utidelone injection was approved for advanced breast cancer in China in 2021. Utidelone is not susceptible to P-glycoprotein, leading to better oral bioavailability and successful development of an oral formulation-Utidelone Capsule (UTD2). As of now, there has been no oral microtubule stabilizing agent approved in China and the United States. UTD2 may benefit patients in various aspects including effectiveness, safety, better compliance, reduced medical cost, and facilitation of combination therapy, especially with other oral anti-cancer drugs. This is the first clinical study in China to investigate the efficacy and safety of UTD2 monotherapy for treatment of advanced breast cancer. Methods: This is an ongoing open-label, multi-center study (NCT05700084) consisting of three parts: dose escalation, bioavailability and food effect, and in combination with capecitabine for treatment of metastatic breast cancer. Here we report the preliminary results from single center for part I with determination of DLT and MTD as the primary objective, and efficacy, PK profile and safety in patients with pretreated metastatic breast cancer as the secondary objectives. Eligible patients are aged 18-70 years with confirmed advanced breast cancer refractory to prior standard therapies, and have an ECOG PS of 0-1, life expectancy ≥12weeks. Patients are treated with UTD2 monotherapy, at starting dose of 50 mg/m2/d-5day for two patients, with planned escalation (3+3) to 75 mg/m2/d-5day and 75 mg/m2/d-7day, then to 85 mg/m2/d-7day or down to 70 mg/m2/d-7day in a 21-day cycle. Results: As of 25th January 2024, 5 advanced breast cancer patients were enrolled, who had received prior treatment in advanced settings. Dose escalation is ongoing, and 75mg/m2/d-7day cohort is under evaluation. Four patients were evaluated for efficacy with an outcome of 2 PR (each for 50 and 75mg/m2/d-5day dose) and 2 SD (75mg/m2/d-5day dose) with treatment durations of 2 to 8 cycles. Most treatment-emergent adverse events (TEAEs) were Grade 1/2, manageable, and included peripheral sensory neuropathy (PN), dizziness and loss of appetite. There were two patients encountered Grade 3 TEAEs including one with PN and one with diarrhea/insomnia, that recovered through dose reduction or supportive treatment. No grade 4/5 adverse events and no treatment discontinuations due to AE were reported. There have been no DLTs and the MTD is not yet reached. Conclusions: These preliminary results suggested promising efficacy with a manageable safety profile of UTD2 in pretreated metastatic breast cancer patients. This study is still actively enrolling; further data will be provided at the time of presentation. Clinical trial information: NCT05700084 .
Treatment (Tx) patterns, efficacy and safety of eribulin for advanced and heavily pretreated breast cancer (ABC): Updated results from a single-center, real-world study.
Authors: Yang Jiao , Ma Xinyue , Zhao Shidi , Zhao Xiaoai , Wang Le , Dong Danfeng , Yang Jin 
Published: July 2024

e13118 Background: We evaluated the Tx patterns, efficacy and safety of eribulin for heavily pretreated ABC in real-world practice. Previous results were reported at the 2023 ASCO (e13118), updated results for longer follow-up and additional enrollment are presented here. Methods: Patients (pts) with ABC who had progression on anthracycline taxane Tx and received eribulin (1.4 mg/m2 IV on Days 1 and 8 of a 21-day cycle) between April 2020 and October 2023 were enrolled. Response was evaluated using RECIST v1.1. Pts were considered as taxanes sensitive if taxanes treatment duration of last line use exceeds 6 months, otherwise were considered as taxanes resistant. Results: 89 pts were enrolled. Median (range) age was 54 (30–79) years; 80.9% had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0–1, and 40.4% pts had a median of 3 prior lines of chemotherapy. 67.4% of pts had Ki67 >30% and 46.0% had HR+/HER2− disease. 88.7% of pts had visceral metastasis. Eribulin was monotherapy in 30.3% of pts, and combined with bevacizumab, capecitabine, bevacizumab + capecitabine, and anti-HER2 agents in 28.1%, 9.0%, 3.4%, and 25.8%, respectively. The objective response rate was 22.5%; disease control rate was 84.3%. Median progression-free survival (PFS) overall was 6.0 (95% CI, [3.5–8.5]) months (mo). Univariate analysis indicated pts with HER2+ disease had longer PFS than pts with HR+/HER2− or triple-negative BC (median, 13.5, 4.5, and 3.7 mo, respectively; P = 0.011; Table). Pts with Ki67 expression ≤30% had longer PFS than pts with Ki67 >30% (median, 8.0 vs. 4.0 mo; P = 0.02). Pts with grade I-II had longer PFS than pts with grade III (median, 10.5 vs. 4.0 mo; P = 0.003). Pts sensitive to Taxane had longer PFS than pts resistant to Taxane (median, 8.0 vs. 4.0 mo; P = 0.007). Among the 18 pts with a partial response, median PFS was 11.4 mo. The most common adverse events were leukopenia (44.9%), neutropenia (37.1%) and anemia (36.0%). Neurotoxicity was rare (6.7%). Conclusions: In this single-center study of pts with heavily pre-treated ABC in China, eribulin Tx resulted in favorable PFS irrespective of molecular subtype, with a manageable safety profile. In pts with a large tumor burden and a good PS, eribulin-based combinations may further improve outcomes. [Table: see text]
DNA methylation-based biological age and time to relapse in triple negative breast cancer.
Authors: Nannini Drew Robert , Nandu Nitish , Hildebrandt Gerhard , Cortese Rene 
Published: July 2024

e13126 Background: Triple negative breast cancer (TNBC) represents 15% of all breast cancer cases and is one of the most aggressive forms of breast cancer with a poorer prognosis. Due to the lack of receptors, TNBC is not amendable to hormonal or anti-HER2 therapies and current gene expression arrays have limited clinical utility in TNBC. The identification of biomarkers associated with TNBC may aid in elucidating the underlying biological mechanisms of this disease and may also have implications for risk stratification, diagnosis, and prognosis of TNBC. The purpose of this study was to investigate the association between markers of biological aging and time to relapse in TNBC. Methods: DNA methylation and clinical data from a publicly available dataset (GSE141441) were used in this analysis. Breast tissue specimens in female TNBC patients who received (n=56) and who did not receive (n=110) chemotherapy underwent DNA methylation profiling using the Illumina Infinium HumanMethylation450K BeadChip. Five DNA methylation-based biological age metrics were calculated: intrinsic epigenetic age acceleration (IEAA), extrinsic epigenetic age acceleration (EEAA), PhenoAge acceleration (PhenoAA), GrimAge acceleration (GrimAA), and DunedinPACE (Pace of Aging Calculated from the Epigenome). Multiple linear and quantile regression analyses were performed to examine the association between the aging metrics and time to TNBC relapse. Interaction and stratified analyses by Ki-67 was additionally performed. Results: After adjusting for chronological age, GrimAA ( P=0.024) and DunedinPACE ( P=0.019) were negatively associated with time to relapse among patients who did not receive chemotherapy. Specifically, a 1-year increase in GrimAA and 1 unit increase in the pace of aging were associated with a 1.77-month and a 53.62-month shorter relapse of TNBC, respectively. Additionally, Ki-67 significantly modified the association between IEAA ( P=0.023) and DunedinPACE ( P=0.035) among patients who received chemotherapy with a 2.75- and a 42.17-month shorter relapse of TNBC among those with a Ki-67 index greater than 50% per unit increase in IEAA and DunedinPACE, respectively. Conclusions: We observed DNA methylation markers of biological age were associated with time to relapse in TNBC patients and these associations were modified by Ki-67. These biomarkers may have prognostic utility in TNBC relapse and potentially, may aid in oncological precision medicine efforts for personalized treatment regimens and surveillance. [Table: see text]