tbuckley/cabot-search huggingface dataset:
Clinicopathological features and prognosis for pregnancy-associated breast cancer: A matched case-control study.
Authors: Aydah Al-Awadhi, Saif Al-Shamsi, Mohammad Hourani, Mawada Hussein, Fatima AlKindi, Lina Wahba, Abla Alagha, Alaa Shoqeir, Tallal Younis
Journal: Journal of Clinical Oncology (2024)

e12573 Background: Pregnancy-Associated Breast Cancer (PABC) is defined as breast cancer diagnosed during pregnancy or within 1 year postpartum. Studies indicate that PABC tends to have poorer prognostic characteristics and often worse outcomes compared to non-PABC. The primary goal of this study is to examine disease characteristics associated with PABC versus non-PABC in the United Arab Emirates (UAE), where breast cancer is characterized by a younger age and more advanced stage compared to North America and Europe. Additionally, the UAE has a younger mean age for first-time mothers and a similar age for all mothers compared to North America and Europe. Methods: Patients with PABC were selected from BC cases of women ≤40 years treated at Tawam Hospital, the largest tertiary cancer center in the UAE between January 2003 – December 2020. Each PABC patient was matched to two non-PABC patients (controls) according to cancer stage, age, and year of diagnosis. The Fisher's exact and Kruskal-Wallis tests were used to compare both study groups. Results: 66 women with PABC were identified, with a median age at diagnosis of 33.0 (interquartile range [IQR]: 30.0-37.0) years. Most presented with stage II (45.5%) or stage III (39.4%) disease and underwent mastectomy and axillary lymph node dissection. Invasive ductal carcinoma was the most frequent histological type in both groups (86.4% for PABC and 85.6% for non-PABC). PABC was associated with higher grade 3 disease compared with non- PABC (53% vs 51.5% p= 0.009). More women with PABC received neoadjuvant chemotherapy (NACT) and radiation therapy (RT) compared with non-PABC (48.5% vs 3%, p &lt;0.001 and 80.3% vs 65.9%, p= 0.046, respectively). There were no statistically significant differences with regards to tumor size, nodal involvement, underlying histologic subtype, ER/PR expression or HER-2 status, rates of breast-conserving surgery and adjuvant chemotherapy receipt between the two groups. The median progression-free survival (PFS) was 3.2 years (IQR: 1.9-7.1) in PABC and 3.4 years (IQR: 1.2-6.2) in non-PABC group (P=0.306). The median overall survival (OS) was 4.5 years in the PABC (IQR: 2.4-7.9) versus 4.5 years (IQR: 1.9-7.9) in the non-PABC group (P = 0.786). Conclusions: PABC in women ≤40 years appears to be associated with grade III tumors and NACT and RT receipt compared to non-PABC. However, there were no significant difference in PSF and OS between PABC and non-PABC. Further analysis is underway to evaluate the prognostic factors and their effect on survival.
Safety and efficacy of low dose versus high dose corticosteroid for graft versus host disease (GVHD): A systematic review.
Authors: Pradeep Khanal, Sangam Shah
Journal: Journal of Clinical Oncology (2024)

e24047 Background: Graft-versus-host disease (GVHD) is an immune-mediated complication of allogeneic hematopoietic stem cell transplantations. Current standard dose of corticosteroids used by the most hospitals for GVHD patients is 1-2 mg/kg/day. The prednisone dose used in the treatment of a GVHD has been a matter of debate. In this systematic review, we aimed to compare low dose prednisone to high/standard dose prednisone in terms of multiple prognostic outcomes of the patients undergoing allogenic hematopoietic stem-cell transplantations. Methods: We searched the databases PubMed, Cochrane library, and clinicaltrials.gov for all studies investigating the efficacy and safety of low dose and high dose steroid for GVHD. We set the search strategy incorporating the search terms, Graft-versus-host disease," "low dose cortico-steroid," and "high dose corticosteroid", and operated using the Boolean operators ‘AND’, and ‘OR’. Thus, retrieved articles were then exported on an Excel sheet, and duplicates were removed. After selecting the study based on inclusion criteria, data on study characteristics and biomarker description was extracted on a pre-determined data extraction table on the Microsoft Excel. Results: The search revealed 547 studies and 3 studies that met the eligibility criteria of this review have been included.During relapse, chronic GVHD, mortality, and malignancy outcomes were generally similar between doses, low-dose prednisone showed benefits for leukemia-free, relapse-free, and overall survival. Overall, the randomized trial by Chang et al. found lower risks of HZV and pulmonary infections with low-dose prednisone compared to standard-dose. (Table 1) Other infections were similar between groups. Conclusions: Low-dose prednisone showed similar efficacy to standard-dose for most GVHD outcomes (relapse risk, mortality), with potential benefits on survival, reduced HZV/pulmonary infections, and reduced adverse effect of higher cumulative dose of corticosteroids. [Table: see text]
Immune subtyping of ER-positive, PR-negative and HER2-negative breast cancers by immunohistochemistry: Molecular basis and clinical relevance.
Authors: Huimin Zhang, Yuting Zhao, Peiling Xie, Heyan Chen
Journal: Journal of Clinical Oncology (2024)

e12553 Background: The diversity and plasticity behind ER+/PR−/HER2− breast cancer (BC) remain underexplored. In our previous work, an immune subtype classification for ER+/PR-/HER2- BC with RNA-seq data was established to distinguish between immune-hot and -cold tumors to provide guidance for immune checkpoint inhibitor (ICI) therapy. However, considering the economic costs, the clinical application of sequencing methods is limited. This study aimed to identify biomarkers of the immune subtype classification and develop a diagnostic procedure for ER+/PR-/HER2- BC immune subtyping based on the immunohistochemistry (IHC) technique, thereby identifying candidates of ICI therapy and refining treatment strategies for ER+/PR-/HER2- BC. Methods: RNA-seq data for 411 patients diagnosed with ER+/PR-/HER2- BC were obtained from the METABRIC database (METABRIC cohort). The immune subtype classification was established by consensus clustering with 1480 immune-related genes. Biomarkers for each immune subtype were identified from differentially expressed genes and validated using logistic regression and ROC curve analysis. Validation of the immune classification was conducted using RNA-seq data from the GEO and TCGA databases. Transcriptomic gene chip sequencing was performed on surgical specimens from 15 ER+/PR-/HER2- BC patients in our center (Chip cohort) to classify the immune subtypes. Biomarkers identified were validated and a diagnostic procedure was designed using IHC techniques. Results: In the METABRIC cohort, immune subtypes including Clusters 1-5 were established. Five biomarkers including DCN, SPP1, CXCL9, STC2, and SRGAP1 were identified, with the AUC values of ROC curves being 0.90, 0.82, 0.99, 0.70, and 0.89, respectively. Notably, Cluster 3 exhibited higher infiltration of CD8+ T cells, B cells, and M1 macrophages, with a greater association with immune activation pathways, thus being defined as the immune-hot subtype. Cluster 1, also showing a moderate immune cell infiltration, was characterized by a more pronounced stromal infiltration. In the Chip cohort, IHC revealed that Cluster 3 exhibited the highest levels of CD8+ T cell and B cell infiltration as well as PD-L1 expression, suggesting a potential benefit from ICI therapy. In contrast, Cluster 1 demonstrated the most extensive infiltration of endothelial and fibroblast cells. The other subtypes were characterized by a suppressed immune microenvironment, especially in Cluster 2, where an infiltration of SPP1+ macrophages was observed. A diagnostic procedure was designed with the biomarkers using IHC techniques. Conclusions: This study validated the immune subtype classification for ER+/PR-/HER2- BC. An easy-to-use IHC-based diagnostic procedure was developed, facilitating the identification of potential ICI therapy candidates in clinical practice at a lower cost.
Examining the risk factors for trastuzumab-related cardiotoxicity in a predominantly Hispanic South Texas population: A descriptive study.
Authors: Aditi Sharma, Maria Elena Fierro, Aishwarya Kothare, Samuel B. Governor, Zuha Alam, Karen Liu, Stella Pak, Prince Otchere
Journal: Journal of Clinical Oncology (2024)

e24000 Background: Trastuzumab, a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2), stands as first line treatment for HER2 positive breast cancer. Despite its efficacy, trastuzumab’s association with cardiotoxicity requires monitoring via serial transthoracic echocardiograms (TTEs). We aimed to evaluate the risk factors for trastuzumab related cardiotoxicity in a South Texas population that is uniquely a majority-minority Hispanic population. Methods: A retrospective chart review study was conducted of all female patients with HER2-positive breast cancer who received trastuzumab treatment from 2015-2021. A total of 180 patients were identified. Patients without baseline TTE or a baseline left ventricle ejection fraction (LVEF) less than 53% were excluded. The final sample size included 132 patients. Cardiotoxicity was defined as a decrease in LVEF of more than 10% during the 1-year study period. Results: The mean age at the time of diagnosis in the study population was 54.2 years. The average BMI of the study participants was 30.89. The incidence of cardiotoxicity in this study population was 6%. Among those who developed cardiotoxicity, 50% had hypertension, 25% had hyperlipidemia, 12.5% had type 2 diabetes mellitus, and 12.5% had previous coronary artery bypass surgery (CABG). In terms of cancer treatment, 12.5% of patients had a history of radiation, 25% had a history of anthracycline therapy, and 12.5% had their trastuzumab treatment ended prematurely. Of the cardiotoxicity population, 37.5% patients were former smokers and 25% were former alcohol users. Hispanic/Latino patients composed 58% of the study population and represented 50% of patients who experienced cardiotoxicity. Conclusions: The incidence of trastuzumab-related cardiotoxicity in this Hispanic/Latino majority-minority population was 6%, lower than the 9% observed in a predominantly white population in our previous study. However, further studies are needed to determine the factors contributing to this reduced cardiotoxicity rate in this population.
Cardiovascular toxicity of fluoropyrimidines: Experience from a quaternary referral center.
Authors: Michel Chedid El Helou, Bahar Laderian, Abdel Hadi El Hajjar, Ali Mushtaq, Diego Sadler, Rohit Moudgil, Brian Griffin, Patrick Collier
Journal: Journal of Clinical Oncology (2024)

e24028 Background: Fluoropyrimidines, including 5-fluorouracil (5-FU) and capecitabine, are widely used chemotherapeutic agents. Their use has been linked to various forms of cardiovascular (CV) toxicity. We sought to analyze the rate of CV events and associated factors in patients receiving fluoropyrimidines at our institution. Methods: We included all patients who received intravenous 5-FU or oral capecitabine at the Cleveland Clinic since 2000. Diagnosis data was obtained based on ICD-10 Codes. CV events included chest pain/angina, myocardial infarction, chronic ischemic heart disease, arrhythmias, conduction disorders, cardiac arrest, cardiomyopathy, and heart failure. CV events were accounted for if they occurred during treatment or within 30 days following the latest administration of the agent. Logistic regression was performed to identify predictors of CV events. Results: A total of 17,236 patients were included, of which 9,386 (54.5) received 5-FU and 7,850 (45.5) received capecitabine. Median age at treatment was 63. The most frequent malignancies were gastrointestinal (70%) and breast cancer (12.3%). A total of 2,283 patients (13.2%) experienced at least one CV event either during treatment or within 30 days following drug administration. The most frequent CV events were chest pain/angina (35.7% of all events). On multivariable logistic regression, factors associated with increased risk of CV events were black race, smoking history, hypertension, and obesity (Table). A prior history of CV disease was also associated with increased risk of CV events (OR 1.22; 95% CI [1.09 - 1.33]). Finally, intravenous 5-FU was linked to higher odds of CV events compared to oral capecitabine (OR 1.48; 95% CI [1.34 - 1.63]). Conclusions: This large-scale cohort study provides pivotal insights into the cardiovascular risks associated with fluoropyrimidine therapy. Besides traditional risk factors, black patients were more likely to suffer from CV events. Additionally, capecitabine may offer better CV outcomes compared to 5-FU. These findings underscore the need for refined risk assessment and enhanced cardiovascular monitoring in patients treated with fluoropyrimidines. [Table: see text]
Utility of axillary surgery in patients with de novo metastatic breast cancer undergoing surgery of the primary site.
Authors: Mahtab Vasigh, Karen J Ruth, Richard J. Bleicher, Allison A. Aggon, Mary Pronovost, Andrea S Porpiglia, Austin D. Williams
Journal: Journal of Clinical Oncology (2024)

1086 Background: Approximately 6% of patients have de novo metastatic breast cancer (MBC) for whom surgery is reserved for special circumstances since it confers no survival benefit. The prospective studies evaluating surgery of the primary site in MBC recommended standard surgical management of the axilla. However, it is unclear whether axillary surgery is of any utility among these patients. We sought to evaluate the survival benefit of axillary surgery in MBC patients undergoing primary site surgery. Methods: From the National Cancer Database (2012-2020), we identified patients aged 18-79 with MBC undergoing surgery of the primary site and grouped patients according to axillary surgery performed: none, sentinel lymphadenectomy (SLNB), or axillary lymph node dissection (ALND) with or without SLNB. We performed a landmark analysis beginning 12 months after diagnosis to assess overall survival (OS) and used Cox regression to adjust for clinicodemographic characteristics. Results: We identified 7,808 patients, 20.2% of whom had no axillary surgery, 16.3% had SLNB, and 63.5% had ALND. Of the patients who had axillary surgery, 26.3% were pN0. Patients who had no axillary surgery, were older (mean 57.2 vs 60.3 years), more likely to have tumor histology other than ductal or lobular (8% vs. 4%), be cN0 (28% vs. 20%), less likely to have bone-only metastases (36% vs. 44%) and undergo breast-conserving surgery (49% vs. 24%) [all p&lt;0.001]. The mean and median number of positive nodes was 1.3±2.3 in the SLNB, and 5.9±6.8 in the ALND group. 36-month adjusted survival estimates were 71.4%, 66.5%, and 58.0% for SLNB, ALND, and no axillary surgery groups, respectively. On univariate analysis and after adjusting for clinicodemographic features, both SLNB and ALND remained independently associated with improved OS when compared with no surgery (Table). Conclusions: As in prior retrospective analyses of surgery for the primary site, we found that the performance of axillary surgery in MBC patients was associated with improved OS. Selection bias is likely a contributing factor as surgeons are more likely to recommend axillary surgery for patients with a better functional status. Of concern is the number of MBC patients being exposed to the morbidity of ALND who are ultimately pN0, and thus derived no benefit. These findings highlight the need to carefully weigh the risks and benefits before performing axillary surgery. Prospective studies evaluating axillary surgery are needed to validate these results. [Table: see text]
Assessment of chemotherapy-induced nausea and vomiting in adult patients with hematopoietic stem-cell transplant at a tertiary care hospital.
Authors: Ahmed Alanazi, Abdullah M. AlRajhi, Adel Alnakhli, Mohammed Salman Bashir, Fouad Alnajjar
Journal: Journal of Clinical Oncology (2024)

e24098 Background: Chemotherapy induced nausea and vomiting (CINV) is prevalent and potentially treatment-limiting side effects in cancer patients.1 Nausea and vomiting are frequent and significantly affect cancer patients' daily functioning and health-related quality of life (HRQL). A patient who experienced nausea and vomiting showed to be affected by worse physical, cognitive, social functioning, and global quality of life in comparison to patients who don’t have nausea and vomiting. Methods: We conducted a prospective cohort observational study to assess the complete response (CR) and risk factor associated with nausea and vomiting among HSCT patients at King Fahad Medical City (KFMC). All adult patient underwent Bone Morrow Transplant (BMT) were included in the study. Data was collected prospectively during admission to the hospital and receive the conditioning regimen. Patients was interviewed by clinical pharmacist and assessed using MASCC Antiemesis Tool© (MAT) to assess the effectiveness of our regimen used to prevent nausea and vomiting during active chemotherapy days and delayed phase. Results: A total of 30 patients were enrolled in the study during a one year follow up from April 2021 to April 2022. Data analysis was done and revealed as follows; out of 30 patients enrolled 18 (60%) patients were female while 12 (40%) were male. Lymphomas including (Non-Hodgkin, and Hodgkin lymphomas) were the most common diagnosis included among patients 17 (56.6%). BEAM protocol was the most common conditioning regimen protocol used 13 (43.3%). Complete response (CR) was achieved in 13 (43.3%) patients during acute nausea and vomiting, while 17 (56.7%) patients weren’t being able to achieve CR. Furthermore, out of the 30 patients observed, 6 (20.0%) experienced delayed vomiting, while 19 (63.3%) experienced delayed nausea. Similarly, Complete response (CR) was achieved in 11 (36.7%) patients during delayed nausea and vomiting, while 19 (63.3%) patients weren’t being able to achieve Complete response (CR) respectively. Breakthrough medication for nausea and vomiting was needed in all patients who didn’t have to achieve CR 19 (63.3%) patients. There was no association between age, gender, conditioning regimen, and type of transplant and achieved CR among patients (P- value; &gt; 0.05). However, more breakthrough medication is needed when CR is not achieved (P- value; &lt; 0.05). Conclusions: At our institution, among hematopoietic transplant recipients receiving appropriate antiemetics, approximately half (50%) achieved complete response (CR) in preventing chemotherapy-induced vomiting (CINV). Age, gender, and transplant type were not significantly associated with increased CR failure, while the specific conditioning regimen did not show a statistically significant impact.
Mechanism study on fig exosome-like nanoparticles inhibiting the progression of bone metastasis in breast cancer.
Authors: Dandan Wang, Hao Tian, Jin Qian, Tingting Zhao, Na Sun, Zifan Mei, Zaihui Peng, Yi Zhang, Xia Kang, Xiaowei Qi
Journal: Journal of Clinical Oncology (2024)

e12562 Background: Breast cancer has overtaken lung cancer as the most common cancer worldwide. Breast cancer bone metastases can lead to death. How to inhibit the progression of bone metastasis of breast cancer is the key to improve the quality of life of breast cancer patients. In recent years, there have been increasing studies on the therapeutic significance of plant-derived extracellular vesicles (PDEVs), which play an important role in anti-tumor and anti-inflammatory. It is a new potential anti-tumor therapy. According to the Chinese medicine classics, figs have anti-cancer effect, but the main active ingredients are not clear yet. Methods: The exosomes were extracted by differential ultracentrifugation. The breast cancer cells (MDA-MB-231, MCF-7, 4T1, E0771) were treated with 0.1 ug/ml and 0.5 ug/ml fig exosome-like nanoparticles (FELNs) for 48 hours. The proliferation rate was measured by BrdU kit and verified by RT-qPCR. The total RNA from MDA-MB-231 cells treated by FELNs was sequenced to screen the differential genes. Key genes were differentially expressed in MDA-MB-231 and MCF-7 cells and further verified. Animal models of breast cancer in situ and bone metastasis were constructed in mice. FELNs were injected intraperitoneally twice a week, live imaging of small animals was performed on the 14th and 21st day to observe the tumor size and progression of breast cancer, and tibia samples were collected for Trap staining. The bone marrow macrophages of mice were extracted and treated by FELNs. The polarization was detected by RT-qPCR. After the removal of the proteins and nucleic acids in FELNs by protease, DNase and RNase, FELNs intervened in breast cancer cells and macrophages to determine the effective components of the FELNs. Results: After breast cancer cells were treated with FELNs, the proliferation rate was significantly decreased, especially MDA-MB-231 (from 70.3% to 17.7%) and MCF-7 (from 7.32% to 1.63%), and the RNA level of proliferation-related gene were significantly down-regulated. The key gene RN7SL1 was screened by sequencing. Overexpression of RN7SL1 significantly promoted the proliferation of MDA-MB-231 and MCF-7 cells, while the level of proliferation-related gene RNA was significantly up-regulated. FELNs significantly inhibited the tumor size and bone metastasis of breast cancer, and the tibial osteolysis was significantly abated by the treatment of FELNs in tibial Trap staining. After the intervention of FELNs in mouse macrophages, the polarization of M1 macrophages was significantly promoted. The proliferation rate of breast cancer cells increased and the polarization of M1 macrophages disappeared by treatment with protein-free FELNs. Conclusions: The protein components in FELNs inhibit the proliferation of breast cancer cells through RN7SL1, thereby inhibiting the progression of breast cancer bone metastasis.