tbuckley/cabot-search huggingface dataset:
Impact of prior anticancer treatments on palbociclib (PAL) clinical outcomes in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−) advanced breast cancer (ABC) in real-world settings.
Authors: Gabrielle Betty Rocque, Joanne Lorraine Blum, Yan Ji, Timothy J. Pluard, John Migas, Shailendra Lakhanpal, Erin Stephany Jepsen, Yao Wang, Monica Z. Montelongo, Zhe Zhang, Eric Roland Gauthier, Debashish Tripathy
Journal: Journal of Clinical Oncology (2024)

1055 Background: Cyclin-dependent kinase 4/6 inhibitors (eg, PAL) combined with endocrine therapy (ET) is a standard of care for patients with HR+/HER2− ABC. The impact of prior anticancer treatments on clinical outcomes of patients with HR+/HER− ABC treated with palbociclib in routine care is not well known and was investigated in the POLARIS study. Methods: POLARIS is a prospective, observational, multicenter, real-world study in the US and Canada. Enrolled patients were adults (≥ 18 y) with HR+/HER2− ABC who received PAL + ET as standard of care. Real-world progression-free survival (rwPFS) and overall survival (OS) were described by prior treatment. Results: A total of 1250 patients were enrolled. Median age was 64 years (range, 22–97), 67.9% had recurrent disease, and 72.1% received PAL as first-line treatment (1LOT) vs 27.9% as ≥ 2LOT. Prior anticancer therapies (1LOT: adjuvant/neoadjuvant setting; ≥ 2LOT: metastatic setting) were received by 912 patients (73.0%), which included ET-alone (n=254), chemotherapy-alone (n=235), chemotherapy + ET (n=338) or other (n=85). The median follow-up duration was 35.7 months for rwPFS and 39.1 months for OS. In 1LOT, both rwPFS and OS were numerically shorter for patients who received prior chemotherapy (either alone or with ET) when compared with patients who received ET-alone or had no prior therapy (Table). In ≥ 2LOT, patients who received prior chemotherapy-alone or ET-alone had comparable rwPFS, which was numerically longer than for patients with prior chemotherapy + ET; OS was comparable regardless of prior treatment. Conclusions: Overall, patients with HR+/HER2− ABC with prior chemotherapy receipt tended to have shorter clinical benefit. Regardless of LOT, numerically longer rwPFS was achieved in patients who received prior ET-alone. In 1LOT, OS was longer in patients who received prior ET-alone while in ≥ 2LOT, OS was comparable across prior treatment subgroups. Small sample sizes of some ≥ 2LOT subgroups as well as observational nature of the study may limit interpretation. [Table: see text]
Demographic Disparities in Lung Cancer Mortality and Trends in the United States From 1999 Through 2020: A Population-Based CDC Database Analysis
Authors: Alexander J. Didier, Logan Roof, James Stevenson
Journal: Journal of the National Comprehensive Cancer Network (2024)

Lung cancer is the leading cause of cancer-related mortality in the United States and is projected to account for 127,070 deaths in 2023. Although the lung cancer mortality rate has been decreasing over the last decade, demographic disparities in mortality still exist. We sought to determine the impact of demographic factors on lung cancer mortality and trends in the United States.
Degradation of estrogen receptor α induced by ionizing radiation contributes to senescence of ER<sup>+</sup> breast cancer cells.
Authors: Jufang Wang, Hongyan Li, Hong Zhang
Journal: Journal of Clinical Oncology (2024)

e12544 Background: According to the clinical and pathological characteristics, breast cancer is usually classified into estrogen receptor positive (ER + ), human epidermal growth factor receptor 2 positive and triple negative. Among them, ER + breast cancer accounts for more than two-thirds of total breast cancer. Nowadays, both ionizing radiation and endocrine therapy are used for the treatment of ER + breast cancer. In our previous studies, it was found that significant cellular senescence and reduction of endogenous estradiol (E2) were induced by carbon ion or X-ray exposure in ER + breast cancer cells. However, the underlying mechanism remains unclear. Methods: Two human ER + breast cancer cell lines, MCF7 and T47D, were chosen to investigate the senescence-associated indications after 1-10 Gy of X-ray exposure. Since the elevated estrogen receptor α (ERα) is the most significant characteristic of ER + breast cancer, the levels of ERα were detected by qRT-PCR and West Blotting analysis. In addition, MCF7 tumors were established in BALB/C nude mice and discerned using immunohistochemistry after local exposure of tumors to 2 Gy of X-rays. Results: It was confirmed that the cell survival decreased in a dose-dependent manner after 1-10 Gy of X-ray exposure in both cell lines. Increased p21 protein expression which was considered as a senescence biomarker and enhanced senescence-associated β-galactosidase activity were also observed after X-ray exposure. Meanwhile, distinct cell cycle arrest was induced by 2 Gy of X-rays in T47D cells or by 8 Gy of X-rays in MCF7 cells, implying that T47D cells were prone to enter senescence. Furthermore, both the mRNA levels and protein levels of ERα were significantly decreased at 24 hours in the two cell lines when the exposure dose was up to 4 Gy of X-rays. Reduction of glucocorticoid-regulated kinase 3 (SGK3), a transcriptional target for ERα, was also observed in both cell lines, in according with the reported SGK3-dependent survival mediated by ERα/E2 dimer in ER + breast cancer cells. In vitro experiments, the results verified the ERα degradation and the proliferating inhibition indicated by suppression of Ki67 protein in MCF7 tumor after 2 Gy exposure. Conclusions: These findings reveal that the degradation of estrogen receptor α induced by ionizing radiation contributes to the senescence of ER + breast cancer cells and thereby inhibits the tumor growth. The results provide a potential therapeutic strategy to enhance the radiosensitivity of ER + breast cancer cells through regulations of ERα or ERα-regulated kinase SGK3 in radiotherapy.
Expanding multiple features of extracranial metastasis to predict survival for patients with breast cancer brain metastasis: A population-based retrospective analysis.
Authors: Hangcheng Xu, Yan Wang, Qiang Sa, Yun Wu, Yiran Zhou, Jiayu Wang, Binghe Xu
Journal: Journal of Clinical Oncology (2024)

e13038 Background: Breast cancer brain metastasis (BCBM) is associated with poor survival outcomes and reduced quality of life. The Graded Prognostic Assessment (GPA) score model serves as a well-established tool for predicting the prognosis of BCBM. Notably, the presence of extracranial metastasis (ECM) is considered as a significant prognostic factor in the breast GPA. This study aims to further refine this factor to enhance the prognostic prediction for BCBM. Methods: This study included all inpatients diagnosed with BCBM at the Cancer Hospital, Chinese Academy of Medical Sciences (CHCAMS), from January 2010 to July 2021. The subsets were categorized by the presence, number, location, and control status of ECM. Baseline clinicopathological characteristics were documented and compared among subgroups. The primary endpoint was overall survival (OS) after the diagnosis of BCBM. We used the Kaplan–Meier method with log-rank test to compare the survival outcomes. Cox regression analyses were conducted to identify significant prognostic factors, which were then incorporated into a new Breast-GPA model. Results: A total of 286 patients with BCBM were included in the study. Kaplan–Meier survival curves suggested that patients without ECM when diagnosed with BCBM showed better survival (p=0.0068). In the subgroups with ECM, more than 3 organs involved, both bone and visceral metastasis and progressive ECM portended dismal OS (p=0.0032, 0.0014 and 0.00054). Multivariate analysis (MVA) demonstrated that the presence, number, and control status of ECM significantly influenced OS after BCBM (p=0.01, 0.03, and 0.048, respectively). The specific location of ECM also had a significant impact on the long-term survival (p=0.0014). By modifying the current GPA model to include categories for '3 or fewer controlled ECM', the predictive accuracy of the newly established GPA model was further enhanced. Conclusions: More extracranial sites, both bone and visceral invasion and uncontrolled ECM were independent prognostic factors for dismal survival outcomes of BCBM patients.
Preliminary safety and efficacy of TQB2930, a HER2-targeted bispecific antibody in patients with advanced breast cancer: Results from a phase 1b study.
Authors: Qingyuan Zhang, Jingxuan Wang, Liru Li, Xiaohua Zeng, Han Zhang, Ying Song, Dabei Tang, Xingjian Niu, Wenjie Ma, Lifan Tu, Shuang Fu, Zoucheng Pan
Journal: Journal of Clinical Oncology (2024)

1026 Background: TQB2930 is a HER2-targeted bispecific antibody, binding to two distinct HER2 epitopes, the same domain as trastuzumab (ECD4) and pertuzumab (ECD2). This study aims to evaluate the safety and efficacy of TQB2930 for patients with advanced breast cancer after failure of standard therapy. Methods: This phase 1b, dose-escalation and expansion trial included patients preferred HER2-expressing or HER2-amplified breast cancer who had received standard therapy. In the dose-escalation phase, TQB2930 was given weekly (10mg/kg, QW), biweekly (20mg/kg, Q2W), or triweekly (30mg/kg, Q3W). After the dose-escalation phase, eligible patients were enrolled and dosed biweekly or triweekly in the expansion cohort. The primary endpoints were safety, maximum tolerated or maximum administered dose, and the secondary endpoints were immunogenicity, pharmacokinetics, and tumor response per RECIST v1.1. Results: As of Dec 20, 2023, 34 patients(pts) have received TQB2930 weekly (n=3), biweekly (n=16), and triweekly (n=15). All pts were female, the median age was 59. 22 pts had HER2 expression of ICH3+ or ICH2+ with FISH+, and the others had ICH2+ with FISH- or ICH1+. The median prior lines of therapies were 3 (range: 0-8), with one pt intolerance to first-line treatment enrolled, and the median prior lines of HER2-targeted therapies were 2 (range: 0-8). No dose-limited toxicity was observed. The main treatment-related adverse events (TRAEs) were infusion reaction, occult blood of urine, leukopenia, and neutropenia. 3 pts were reported grade≥3 TRAEs, including neutropenia, anemia, and hypokalemia. Of 31 response-evaluable pts, the objective response rate (ORR) was 25.8% with 8 partial responses (PRs) were observed (including 5 confirmed PRs and 3 PRs awaiting confirmation). The disease control rate was 80.6%. Moreover, 5 pts achieved PR at 30mg/kg (ORR 41.7%), including one with prior exposure to trastuzumab, pyrotinib, tucatinib, ARX788, and the other one prior to trastuzumab, pertuzumab, lapatinib, MRG002. The median progression-free survival for all pts was 5.5 months (95%CI 3.58-NE). Additionally, Pharmacokinetic analysis showed exposure (C max and AUC 0-t ) of TQB2930 increased linearly with doses within 10~30mg/kg. After dosing, the mean peak concentration reached at 2.5-4.3 h, and the elimination half-life of TQB2930 was 109-161 h. Conclusions: TQB2930 is well tolerated and has demonstrated promising single-agent anti-tumor activity in HER2-positive breast cancer who have failed standard anti-HER2 therapies, including multiple lines of prior HER2 targeted agents. These early signs of activity support the further exploration of combination therapy of TQB2930 and the study is ongoing. Clinical trial information: NCT06202261 .
Impact of HER2 low status on genomic signatures in triple negative breast cancer (TNBC).
Authors: Melissa Taylor, Shilpa Reddy, Prashanth Ashok Kumar, Dana Hariri, Ethan Sokol, Smruthy Sivakumar, Julia Quintanilha, Dean Pavlick, Mia Alyce Levy, Jeffrey S. Ross, Maryam B. Lustberg
Journal: Journal of Clinical Oncology (2024)

1092 Background: HER2 status has become more important with new treatment regimens subcategorizing HER2 to into low (1+or 2+ FISH-) or absent HER2 expression. Through comprehensive genomic profiling (CGP), we aim to identify distinctive molecular features associated with various immunohistochemistry (IHC) categories of HER2 low tumors. Methods: Retrospective review of pathology specimens submitted to Foundation Medicine were done and 514 TNBC (ER-/PR-/HER20,1+,2+FISH-) and 191 3+/HER2 amplified clinically advanced BC underwent hybrid capture-based CGP to evaluate genomic alterations (GA) in 324 genes, MSI status and tumor mutational burden (TMB, mutations/Mb). PD-L1 expression was determined by IHC (Dako 22C3 TPS). Chi-square test and Mann Whitney U test were used in the statistical comparisons of the 2 groups. Statistical significance was defined as p &lt; 0.05. Results: 53.5% were HER2 IHC 0+, 31.5% were HER2 IHC 1+ and 15.0% were IHC 2+/FISH negative. The HER2 3+/amplified BC were 59% ER+ and 41% ER-. Notable differences in GA frequencies included a significant increase in PIK3CA GA in the HER2 2+ vs the HER 0+ and 1+ groups (p=.0003). A lower frequency in BRCA1 GA in the HER2 2+ (5.2%) vs the HER2 0+ (9.8%) was significant when compared to the 1.0% in the HER2 3+/amplified cases (p&lt;.0001). BRCA2 GA frequencies did not show statistically significant differences among the TNBC HER2 IHC score groups. TP53 and RB1 had the highest frequency in HER2 0+ samples, with decreasing prevalence in the HER2 1+, 2+ and 3+/amplified cases (p&lt;.0001 for both). There was also a trend towards higher frequency of CDH1 GA as the HER2 IHC score increased from 0 to 2+ among TNBC. There were no significant differences in immunotherapy biomarkers (MSI, TMB and PD-L1) based on HER2 status among the TNBC groups. TMB &gt;= 10 mutations/Mb was significantly higher in the HER2 3+/amplified group (p=.004). Conclusions: We found that TNBC HER2 2+ positive FISH show key molecular differences from their HER2 low (1+) or absent (0+) counterparts. The most substantial difference was an increase in GA in PIK3CA. While this is targetable in the hormone positive setting, its potential role as a target in the hormone negative setting is uncertain. Also noted but did not reach significance was a decrease in GA within BRCA1/2 and a positive linear relationship with CDH1 and HER2 IHC expression. These GA differences may indicate potential treatment options for different HER2 subgroups and warrant further investigation. Limitations of our study include the retrospective nature and the lack of clinical data. [Table: see text]
On-treatment (tx) dynamic circulating tumor DNA changes (∆ctDNA) associated with progression-free survival (PFS) and overall survival (OS) of patients (pts) with HR+/HER2− advanced breast cancer (ABC) in MONALEESA-3 (ML-3).
Authors: Stephen K. L. Chia, Nadia Solovieff, Mukta Joshi, Seock-Ah Im, Giulia Valeria Bianchi, Luis de la Cruz-Merino, Guy Heinrich Maria Jerusalem, Gabe S. Sonke, Arnd Nusch, J. Thaddeus Beck, Dennis J. Slamon, Craig Wang, Juan Pablo Zarate, Fei Su, Patrick Neven
Journal: Journal of Clinical Oncology (2024)

1012 Background: In ML-3, ribociclib (RIB) demonstrated a significant PFS/OS benefit over placebo (PBO) in pts with HR+/HER2− ABC. We report associations of on-tx ∆ctDNA with OS/PFS and tumor size and of ctDNA detectability with radiological progression. Methods: Pts were randomized 2:1 to RIB or PBO + fulvestrant as 1 st - or 2 nd -line tx. ctDNA levels were measured by NGS at cycle 1 day 1 (C1D1), C4D1, C8D1, and every 8 cycles until end of tx. Analyses included: Wilcoxon rank sum text to compare ∆ctDNA from C1D1 to C4D1; Kaplan-Meier method to visualize relationship of ctDNA with PFS/OS; Cox proportional hazards model for associations of ctDNA and tumor metrics (objective response rate, best % change, % change at 1 st tumor evaluation); Fisher’s exact test to compare ctDNA detectability between arms; and ∆ctDNA across time points to assess lead time between ctDNA level-based and radiological progression. Results: Overall, 534/726 (73.6%) pts had paired C1/C4 measurements. Rates of detectable (+) and undetectable (−) ctDNA at C1 and C4 were: C1+/C4+, 33.0%; C1+/C4−, 34.5%; C1−/C4−, 27.5%; and C1−/C4+, 5.1%. RIB vs PBO had a larger % decrease in ctDNA level from C1 to C4 (P=0.003). Pts with better best overall response also had larger ctDNA decreases from C1 to C4 (P&lt;0.0001). On-tx ∆ctDNA from C1 to C4 correlated with PFS/OS (P&lt;0.0001; Table). C1-/C4-, C1+/C4-, and C1+/C4+ strongly correlated with PFS within response categories (PR, SD, NCRNPD). C1-to-C4 % ∆ctDNA was only moderately correlated with tumor size change (best % change, r=0.41; change at 1 st evaluation, r=0.32; both P&lt;0.001). Univariate/multivariate analyses showed significant correlations between ctDNA metrics (% change, detection pattern at C4D1) and PFS/OS. ctDNA detection and % change generally remained significantly associated with PFS/OS even after adjusting for change in tumor size. In a longitudinal analysis of pts who cleared ctDNA at C4D1 (C4–), the median lead time between ctDNA progression and radiological progression was 8.2 mo (IQR 4.5–15.6). Conclusions: On-tx ∆ctDNA from C1 to C4 was correlated with PFS/OS even after adjusting for tumor size changes, suggesting that ctDNA and tumor dynamics capture distinct aspects of tumor tx responses. Decreases in ctDNA were greater with RIB vs PBO, mirroring ML-3 efficacy readouts but at a much earlier timepoint. This longitudinal analysis of ctDNA in ML-3 suggests that detecting ∆ctDNA is a sensitive way to monitor progression and may be a potential surrogate for efficacy in HR+/HER2− ABC. Clinical trial information: NCT02422615 . [Table: see text]
Comparative analysis of genomic tests for the prediction for late recurrence risk in hormone receptor–positive invasive breast cancer in a sample of Colombian patients.
Authors: Jose Joaquin Caicedo
Journal: Journal of Clinical Oncology (2024)

e13092 Background: Approximately 70% of invasive breast cancers are hormone receptor-positive, requiring 5 years of endocrine therapy as the gold standard treatment. However, extended endocrine therapy (EET) may be needed, considering the late recurrence risk up to 15 years post-diagnosis. Different genomic tests predict the risk of recurrence. The 70-gene signature classifies patients as low or high risk during the first 5-years after diagnosis. The 12-gene test identifies high and low-risk patients for distant relapse up to 15 years, while a third test, based on 7-gene expression, assesses distant relapse risk up to 10 years. These tests assist clinicians in defining the need for EET. This study aims to compare the results of these genomic tests to determine late recurrence and distant relapse risks after 5 years, guiding EET indications. Methods: This is a retrospective descriptive transversal study involving 27 female patients diagnosed with hormone receptor-positive invasive breast cancer, treated in the same oncologic center in Colombia. All patients were first tested with the 70-gene genomic profile, with 15 patients undergoing the 12-gene test and 12 cases undergoing the 7-gene assay approximately 5 years later. Concordance between test results was assessed, and socio-demographic variables were descriptively analyzed. Results: The mean age was 54.4 years (SD=11.7). Invasive ductal carcinoma comprised 77.7% and invasive lobular carcinoma 22.22%. The 70-gene profile identified 21 cases (77.7%) as low-risk. Among those, 87.5% had a high-risk result with the 12-gene test, and 60% had a high-risk score with the 7-gene test. Conclusions: The findings support the utility observed in the sub-analysis of the NSABP-B42 study, showing that a low-risk result in the 70-genes signature, means high risk of late recurrence and the need for EET, emphasizing the importance of further evaluation and validation of genomic tests in predicting breast cancer recurrence risks. Larger sample sizes are necessary to confirm these results and establish their clinical relevance in oncology practice.
Acceptance and usability testing of a visual care-navigation tool for patients, survivors, caregivers, nurses, and oncologists.
Authors: Samira Daswani, Douglas W. Blayney, Molly Lindquist, Arko Dasgupta, Stephanie Finley, Celeste Leung
Journal: Journal of Clinical Oncology (2024)

e13064 Background: Breast cancer patients (BCP) and family caregivers (CG) describe their experience as a difficult hike, without access to a map, relevant gear, or a guide. The shrinking oncologist workforce has ~24 minutes per patient to communicate the condition, treatment plan and answer questions. Many use hand-drawn visuals – analogous to a map or process flow diagrams. 97% of BCP use Dr. Google™, which results in “Cancer Information Overload” and non-evidence-based activities. A team of survivors, cartographers, and oncologists developed an interactive cancer map and self-management platform to coach BCP to navigate treatment. Using equitable design, features include: (a) 7th grade reading level; (b) written content and audio/video assets; (c) supporting the user from diagnosis through survivorship to make the platform accessible to a diverse population. After acceptance testing showed high willingness to use &amp; recommend (ASCO Quality 2023;552), we tested the platform’s usability through observed use and task-analysis. Methods: A convenience sample of BCP, CG and oncology HCP [including advanced practice providers (APP)] underwent a usability test in two waves. We defined a set of tasks the users should be able to accomplish. We observed the users during a 30-minute virtual session and recorded the session, noted the task accomplishments, and any issues. Issues from wave 1 were addressed and incorporated into the test for wave 2. Results: We tested two waves of users between November 30, 2023 and February 1, 2024. The results are shown in the table. After wave 1, we modified the platform and tested the maps with wave 2 users. Two core usability features were added between waves: (a) user drill down to access a more detailed level of the map; (b) a product tour guiding the user through the tool, which addressed qualitative user observations that showed initial confusion as to how to begin navigation. Conclusions: Cartographically represented maps of the cancer journey and the self-management tools are acceptable to BCP, survivors, and CG and are usable. Per the ASCO Quality 2023;552 poster, the platform is acceptable to HCPs and not perceived to increase work, and APPs found value in the platform to enable education. Features have been added to ensure a diverse population can easily use the platform including guided walk through and welcome videos. [Table: see text]