tbuckley/cabot-search huggingface dataset:
Effect of neratinib on HER2 mRNA stability via hsa-miR-23a-5p and efficacy of CDK4/6 inhibitors in HER2-low breast cancer.
Authors: Liushan Chen, Lingling Ye, Yuqi Liang, Qian Zuo, Yuyu Hu, Qianqian Guo, Qianjun Chen
Journal: Journal of Clinical Oncology (2024)

e12550 Background: Traditional HER2-negative breast cancer sometimes includes HER2-low components, and CDK4/6 inhibitors are the first- and second-line treatments for advanced HER2-low breast cancer. Nonetheless, little is understood about how the stability of HER2 mRNA in HER2-low breast cancer affects the effectiveness of CDK4/6 inhibitor therapy and the associated intervention techniques. Methods: In order to investigate the impact of HER2-low on the effectiveness of CDK4/6 inhibitor in treating breast cancer, we first used HER2-0 and HER2-low breast cancer cells/mice as the study object and assessed the anti-proliferation effect of CDK4/6 inhibitor using CCK8 technique and monoclonal formation experiment. Second, we increased the treatment of anti-HER2 inhibitor neratinib and assessed its impact on the efficacy of HER2 low breast cancer CDK4/6 inhibitors. By reducing the expression of HER2 in HER2 low breast cancer cells, we analyzed and determined whether HER2 is the primary pathway that influences the poor efficacy of HER2 low breast cancer CDK4/6 inhibitors; At last, actinomycin D was used to detect the mRNA stability of HER2 in the treatment of HER2-low breast cancer by neratinib against CDK4/6 inhibitors, and then microRNA sequencing and luciferase reporter gene detection technology were used. To investigate the specific mechanism of action of neratinib on the mRNA stability of HER2 in the treatment of HER2-low breast cancer by CDK4/6 inhibitors. Results: Our study found that treatment with CDK4/6 inhibitors was significantly less effective against HER2-low breast cancer compared to HER2-0 subtype (P=0.005). Notably, in HER2-low subtype cells, HER2 knockdown significantly inhibited cell proliferation (P&lt;0.001), G1 phase cell cycle arrest (P=0.001), and downregulated cyclin D1 expression and CDK4 protein levels (P=0.007, P=0.003). Second, it was found that in the cell and animal models of HER2-low breast cancer, the addition of the CDK4/6 inhibitor drug neratinib effectively reduced the stability of HER2 mRNA (P=0.001), inhibited the cell cycle of G1 phase (P=0.005). In addition, we observed that lowering the dose of neratinib to 1/2 (20 mg/kg) remained effective and well tolerated (P=0.002). Finally, we found that neratinib can reduce the mRNA stability of HER2 by binding hsa-miR-23a-5p to the 3'UTR region of HER2 (P&lt;0.001), thereby improving the efficacy of CDK4/6 inhibitors in HER2-low breast cancer. Conclusions: We found that low expression of HER2 reduced the efficacy of CDK4/6 inhibitors in HER2-low breast cancer; Neratinib reduces the mRNA stability of HER2 by binding hsa-miR-23a-5p to the 3 'UTR region of HER2, thereby improving the efficacy of CDK4/6 inhibitors in HER2-low breast cancer. These findings provide a tolerable and effective two-drug combination regimen for patients with clinical HER2-low breast cancer.
Investigating the prevalence and correlates of anxiety and depression among patients with COVID-19 with and without concomitant tumor conditions.
Authors: Qiong Luo, Haiyu Liu, Qixian Zheng, Qianyuan Zhang, Suyun Zhang, Guizhen Weng, Xiangqi Chen, Sheng Yang
Journal: Journal of Clinical Oncology (2024)

e24090 Background: This study aims to assess the prevalence of anxiety and depression among patients diagnosed with novel coronavirus pneumonia, with and without concurrent tumor, identifying associated factors to offer empirical data and theoretical foundations for enhancing therapeutic strategies and life quality for this demographic. Methods: 74 patients diagnosed with novel coronavirus pneumonia were randomly selected from the Respiratory and Critical Care Medicine and Oncology departments of Fujian Medical University Affiliated Union Hospital between January 3 and March 18, 2023. Scale scores were employed, including the Hospital Anxiety and Depression Scale, Medical Coping Modes Questionnaire, Social Support Rating Scale, and Type D Personality Scale. Additionally, routine blood analyses at admission were conducted to compute the Neutrophil to Lymphocyte Ratio (NLR). Anxiety and depression prevalence were compared between groups with and without tumors, and correlations were examined with other scale scores and NLR. Results: Among the 74 patients with novel coronavirus pneumonia, 14 with tumors exhibited a 64.29% incidence rate for anxiety and depression, while 60 without tumors presented a 33.33% rate, signifying a statistically significant discrepancy (P &lt; 0.05). Notable differences were observed in social support and NLR between groups (P &lt; 0.05), though coping methodologies and Type D personality distributions showed no statistical variance (P &gt; 0.05). Conclusions: Novel coronavirus pneumonia patients with tumors demonstrate a markedly elevated incidence of anxiety and depression, influenced by social support and NLR. Early implementation of psychological and pharmacological interventions could potentially mitigate these conditions, enhancing life quality and clinical outcomes for this population and meriting further investigative exploration.
Real world outcomes of sequential ADC therapy in metastatic breast cancer: Patients treated with sacituzumab govitecan and trastuzumab deruxtecan.
Authors: Nicholas Mai, Miriam Klar, Emanuela Ferraro, Maria Bromberg, Yuan Chen, Pedram Razavi, Shanu Modi, Sarat Chandarlapaty, Elaine M. Walsh, Joshua Z. Drago
Journal: Journal of Clinical Oncology (2024)

1085 Background: Sacituzumab govitecan (SG) and trastuzumab deruxtecan (TDXd) are antibody drug conjugates (ADCs) that are approved for the treatment of HER2 low metastatic breast cancer (MBC). Both carry payloads which inhibit topoisomerase 1, and it is unknown whether these ADCs retain clinical activity when used sequentially to each other. Here we present a retrospective study of patients treated with both SG and TDXd at our institution and report real world progression free survival (PFS), clinical factors associated with longer PFS, and whether ADC sequence impacts outcome. Methods: All patients with MBC treated at MSKCC who had received both SG and TDXd (in any order) were eligible for inclusion. Clinicopathological and demographic data were obtained from retrospective chart review. PFS was determined clinically and calculated using Kaplan-Meier survival analysis. Univariate and multivariate associations of survival were assessed using Cox proportional hazards models. Results: Eighty-five patients met eligibility per the criteria above: 54 with estrogen receptor positive (ER+) MBC and 31 with triple negative breast cancer (TNBC). 33 patients received SG followed by TDXd (14 ER+, 19 TNBC), and 52 received TDXd followed by SG (40 ER+, 12 TNBC). Median age at time of second ADC treatment (ADC2) was 59 among all patients, 62 among SG first, and 58 among TDXd first. This cohort was heavily pre-treated, with median 5 prior therapies at the time of first ADC (ADC1) and 7 at the time of ADC2. Both the SG first and TDXd first cohorts had median 1 line of intervening therapy between ADCs. In the SG first group, median ADC2 (TDXd) PFS was 3.5 months (95%CI 2.7-7.7), and in the TDXd first group median ADC2 (SG) was 2.8 months (95%CI 2.6-3.7). On multivariate analysis, neither ADC sequence (SG first vs. TDXd first, HR 1.30, 95%CI 0.71-2.37, p=0.4) nor ER status (TNBC vs. ER+, HR 1.21, 95%CI 0.63-2.32, p=0.6) showed statistically significant differences in ADC2 PFS between these groups. Instead, later treatment line at the time of ADC2 was significantly associated with shorter ADC2 PFS (continuous, HR 1.11, 95%CI 1.01-1.23, p=0.03). To separately evaluate differences in PFS for each ADC depending upon whether it was first or follow-up therapy, median ADC1 vs. ADC2 PFS is summarized by ADC (Table). Conclusions: In this heavily pre-treated patient cohort, the clinical activity of both SG and TDXd appear modest in the ADC2 setting. Further studies are needed to confirm these findings and to determine whether payload cross-resistance may undermine the benefit of sequential ADC therapy. [Table: see text]
Receptor expression testing of the synchronous axillary nodal metastasis in early-stage breast cancer: Comparison of primary tumor and its draining nodes.
Authors: Mahmoud Abdallah, Maria Tria Tirona, Kemnasom Nwanwene, Jai Kumar Khatri, Adarsh Sidda, Layana Roslyn Biglow, Howide Eldib, Ahmad Mahdi
Journal: Journal of Clinical Oncology (2024)

e12542 Background: Early stage (Stage I-III) human epidermal receptor -2 (HER2) positive and triple negative breast cancers (TNBC) tend to behave more aggressively than hormone positive breast cancers with higher and earlier incidences of recurrences. Oftentimes, testing for receptor subtypes is done only on the primary tumor and not on the synchronous axillary metastasis, with the assumption that the axillary metastasis is congruous to the primary lesion. Current guidelines also do not specify a requisite to do this testing. Information about the receptor expression types is fundamental for the treatment of breast cancer. We aimed to determine if there is significant discordance between the primary and ipsilateral axillary metastasis in early-stage breast cancer. Methods: We conducted a retrospective analysis via electronic medical record review of a large institutional database from 2008 to 2020. Sample for this study included all patients with a diagnosis of early-stage breast cancer (Stage I - III) with triple negative or HER2 positive tumors. Data on demographics, comorbidities, receptor status, staging, and mortality were collected. Results: Electronic charts from 448 patients were reviewed. 140 patients had axillary node positive disease. 40 (29%) of the 140 patients underwent testing for receptors subtypes on both primary and axillary nodal metastasis. 8 (20%) of the 40 patients had discordance in their receptor subtype expressed in their respective axillary nodal metastasis. 32 (80%) of the 40 patients had axillary receptor expression congruous to the primary tumor. At the time of our review, there was no statistically significant mortality between discordant compared to concordant group (13% vs 20%; p=0.54). 2 patients were lost to follow up. Conclusions: Our data suggests that one in every five axillary metastatic breast cancers can have receptor subtypes discordant compared to the receptors expressed on the primary tumor. Knowledge about any such discordance between the primary and respective axillary metastasis has a consequential impact on the treatment approach for early-stage breast cancer. This is especially true if the patient’s nodal metastatic lesions indeed prove HER2 receptor positivity or do not express any receptors (TNBC). Consequently, patients may be being deprived of benefits from advances in treatment of these cancers, such as targeted therapies towards HER2 receptor, hormonal treatments when indicated, or the utilization of neoadjuvant chemotherapy. A strong case can be thus made to revise current standards to include receptor testing on all primary and synchronous axillary metastasis. Further testing is needed to validate our findings.
RNASEH2B loss and PARP inhibition in advanced prostate cancer
Authors: Juliet Carmichael, Ines Figueiredo, Bora Gurel, Nick Beije, Wei Yuan, Jan Rekowski, George Seed, Suzanne Carreira, Claudia Bertan, Maria de Los Dolores Fenor de la Maza, Khobe Chandran, Antje Neeb, Jon Welti, Lewis Gallagher, Denisa Bogdan, Mateus Crespo, Ruth Riisnaes, Ana Ferreira, Susana Miranda, Jinqiu Lu, Michael M. Shen, Emma Hall, Nuria Porta, Daniel Westaby, Christina Guo, Rafael Grochot, Christopher J. Lord, Joaquin Mateo, Adam Sharp, Johann de Bono
Journal: Journal of Clinical Investigation (2024)

BACKGROUND. Clinical trials have suggested antitumor activity from PARP inhibition beyond homologous recombination deficiency (HRD). RNASEH2B loss is unrelated to HRD and preclinically sensitizes to PARP inhibition. The current study reports on RNASEH2B protein loss in advanced prostate cancer and its association with RB1 protein loss, clinical outcome and clonal dynamics during treatment with PARP inhibition in a prospective clinical trial.
Overall survival in patients with HER2-low breast cancer at a reference hospital in Mexico.
Authors: Brenda Lorena Rubio-Anguiano, Raquel Valencia-Cedillo, Rocio Grajales
Journal: Journal of Clinical Oncology (2024)

e12578 Background: Breast cancer is the most diagnosed cancer in women. The 5-year overall survival (OS) rate in early-stage disease is 97% while in advanced disease is 36%. HER2 is a growth receptor involved in cell survival and proliferation. An overexpression of this protein leads to a more aggressive behavior; however, with targeted therapies, OS has improved. Recently, a new classification has been developed for tumors previously known as HER2-negative: HER2-low; which are those with IHC 1+ or 2+/ISH negative. It is believed that in these types of tumors, the signaling pathways of the HER2-positive subtype are also activated. There are conflicting studies on the prognostic impact of this subgroup. Currently, there is availability of anti-HER2 treatment for patients in advanced stages, as described in the DESTINY-Breast04 study, which changes the treatment paradigm for this pathology. Methods: The aim of this study is to determine overall survival in patients with HER2-low breast cancer. A retrospective, analytical, observational cohort was performed. Patients diagnosed with HER2-negative/low breast cancer, treated at the UMAE Oncology Hospital of the CMN Siglo XXI, from January 2018 to December 2022, were included. OS and disease-free survival (DFS) were calculated using Kaplan-Meier curves, and the impact of HER2-low expression on OS and DFS was assessed using log-rank analysis. The prognostic analysis of the complete model was performed using a Cox proportional hazards model. Results: We included 213 patients. The median age was 57 years. Ninety-five patients were HER2-low (44.6%), and 118 were HER2-negative (55.4%). Seventy-six percent had positive hormone receptor (HR) status. Patients with HR+/HER2-negative were 84 (52.2%), and HR+/HER2-low were 77 (47.8%). Among HR-negative status, the majority were HER2-negative (65.4%). When comparing HER2-negative and HER2-low, no statistically significant differences were found, with a 48-month overall survival of 70% for HER2-negative compared to 87.1% for HER2-low (p= 0.5700). OS analysis in the HER2-low group, comparing HR+ vs. HR-, a statistically significant difference at 48 months of 98.31% vs. 49.17% (p &lt;0.0001), respectively, was found. Regarding DFS, a comparison between HR+ against HR-, it was 79.53% vs. 37.14%, respectively (p= 0.0002). The DFS analysis revealed that, among the variables studied, lymphovascular invasion (LVI) and HR+ status showed a statistically significant association with time to recurrence. Particularly, the presence of HR positivity was associated with a significant 82.6% reduction in the risk of recurrence. Conclusions: HER2 status alone (negative or low) did not offer a clear distinction in terms of OS or DFS. Nevertheless, it was observed a difference in OS and DFS outcomes favoring the HR-positive group when examining HR status among individuals with HER2-low, though this finding requires validation in a larger population.
Chemotherapy in the last 30 days of life, correlation with age and palliative care referral: A 1-year retrospective gastrointestinal program experience at SQCCCRC.
Authors: Ahmad Ghoche, Rami Abu Omar, Amani Ismail Mahmoud, Mansour Al-Moundhri
Journal: Journal of Clinical Oncology (2024)

e24038 Background: Chemotherapy in the last days of life can carry unnecessary toxicities to the patient with no significant impact on survival and disease outcome. This is becoming of greater interest with the involvement of palliative care in patient’s management along with the advent of new therapeutic options with progressively increased cost of treatment. Methods: In our retrospective study, we aimed to analyze retrospectively the data of GI tumors treated at SQCCCRC over one year, by looking at the possible factors influencing the time from last treatment to death. We conducted chart review of all death that occurred between January 2023 and December 2023 in the GI cancer program at SQCCCRC. Information on demographics, type of GI cancer, type, intent and route of chemotherapy, line of chemotherapy and referral to palliative care were collected. Results: A total of 65 patients died within the GI cancer program between January 1st, 2023, to dec 31 st , 2023. Most (72.7%) of the patients died of disease progression. Intent for chemotherapy was palliative in 90.9% of cases. Chemotherapy was parenteral (Intravenous) for the majority (60%, 38/63) of the patients. From all the recovered deaths, a total of 52 patients (82%) were referred to palliative team before death whereas palliative team was involved in the journey of all patients. 12 deaths out of 65 occurred in ICU. Only 11 out of 65 patients died within last 30 days of treatment: 81.8% of them were under palliative care at the time of death. For this group, the median age at diagnosis was 50 yo. Median age at death was 61 yo. 72.7% were male. Primary site of disease was colon followed by stomach. Median time from diagnosis to palliative referral was 13.5 months. 8 patients died within 3.5 days of referral to palliative care. In the logistic regression models, only age at diagnosis was a significant predictor for receiving chemotherapy in the last 30 days of life (p = 0.019). Older age was associated with lower odds of receiving chemotherapy in this period (OR = 0.94, 95% CI = 0.89-0.99). Referral to palliative chemotherapy was not associated with decreased rate of treatment administration within last 30 days of life. Conclusions: While some real-world data suggested correlation between shifting to palliative care and administration of chemotherapy in the last 30 days of life, this was not the case in our collected sample, and only the age of the patient played a role in the chemotherapy timing before death. Further studies are needed to study the reasons behind and the best way to improve patient’s centered approach.
A qualitative analysis of religious coping and participation in patients with head and neck cancer.
Authors: Nosayaba Osazuwa-Peters, Jeehye Rose Lee, Maia Kotelanski, Leslie Ballew, Colton Ortiz, Madeline Garcia, Alexandra Bennion, Sarah Jean Barton, Kimberly Monroe, Walter T. Lee, Monica Himaani Bodd
Journal: Journal of Clinical Oncology (2024)

e24093 Background: Head and neck cancer (HNC) and its treatment sequelae result in substantial disfigurement, depression, and isolation. Though up to 7 out of 10 cancer patients lean on prayer or other forms of spirituality for support, little is known about the significance of prayer and religious communities for patients with HNC. There is also a dearth of literature on the role of clergy as spiritual support for patients with HNC. In this qualitative study, we explore religious coping and barriers to community engagement both from a patient and clergy perspective. Methods: We purposively sampled ten patients with HNC from a single, comprehensive cancer center and twelve clergy for interviews. Patients were selected from a larger study of religious engagement and symptomatic distress. Clergy were recruited from a network of churches near the cancer center. Both patients and clergy completed semi-structured interviews, which were then transcribed and analyzed by descriptive content analysis. Results: Four main themes emerged from patient interviews: 1) HNC-related physical symptoms (dysphagia, stoma, impaired speech) hindered relationship-building with others and structured religious groups. 2) Most patients used positive religious coping, citing frequent prayer to God for strength during treatment and peace regardless of disease outcome. Few patients used negative religious coping, describing feelings of doubt and abandonment by God. 3) Patients predominantly found spiritual (prayer) and practical comfort (encouragement, phone calls) outside of religious communities through family, physicians, and support groups. 4) Barriers to religious community involvement included physical disability, satisfaction with individual spirituality, and religious community politics. Among clergy, barriers to patient engagement in religious communities included: lack of health literacy to understand patient needs, resource limitations, insufficient hospital emphasis on holistic health, and little awareness of opportunities for aid apart from psychosocial support. Overall, most clergy and patients believed faith to be an integral part of coping with head and neck cancer. Conclusions: Though patients with HNC experienced some isolation due to physical symptoms, many found spiritual support through private practices of prayer or individual relationships. Patient and clergy views on barriers to religious community involvement diverged; many patients felt satisfied with personal practices, and clergy felt distanced from patients. While future research should focus on clinical elicitation of religious coping strategies, our patients suggest the successful adaptation of such strategies to private contexts when faced with physically debilitating cancer diagnoses.