tbuckley/cabot-search huggingface dataset:
Patient-reported outcomes in N1 breast cancer: A phase III trial comparing whole-breast to whole-breast plus regional irradiation after taxane-based chemotherapy (KROG 1701).
Authors: Nalee Kim, Won Park, Haeyoung Kim, Won Kyung Cho, Yeon Hee Park, Sung Ja Ahn, Jinhong Jung, In Young Jo, Kyu Chan Lee, Tae Hyun Kim, Tae Gyu Kim, Kyung Hwan Shin, Jin Hee Kim, Jong Hoon Lee, Hyung-Sik Lee, Hae Jin Park, Ju Hye Lee, Minji Koh, Yong Bae Kim, Ik Jae Lee
Journal: Journal of Clinical Oncology (2024)

577 Background: Recent randomized trials have highlighted the benefits of regional node irradiation (RNI) in high-risk node-positive or pN1 breast cancer, yet its impact in the context of modern taxane-based adjuvant chemotherapy remains unclear. In this multi-center phase III trial, we study to prove the hypothesis that there is no difference in terms of disease-free survival between standard whole-breast irradiation (WBI) with RNI and WBI alone in pN1 breast cancer patients receiving taxane-based adjuvant chemotherapy. Comprehensive patient-reported outcomes (PROs) collected at multiple time points are now reported. Methods: The KROG 17-01 trial (NCT03269981), a prospective, multicenter, non-inferiority study, randomized patients with pN1 breast cancer after breast-conserving surgery and adjuvant taxane-containing chemotherapy to WBI or WBI+RNI. Both conventional and hypofractionated radiotherapy (RT) were allowed. PROs were assessed using the EORTC QLQ-C30 and QLQ-BR23 modules. All data were collected at baseline, during RT, and at follow-up intervals of 3-6 months, 1, 2, 3, 4, and 5 years post-treatment. Linear mixed models were used to compare PROs between treatment arms. Results: From April 2017 to December 2021, 840 patients were enrolled; 777 received intervention as assigned, and 750 completed baseline PRO questionnaires (387 in WBI+RNI, 363 in WBI). Overall, PRO domains improved over time (p&lt;0.001). During RT, the WBI+RNI group experienced more fatigue, nausea, and vomiting (p&lt;0.05), and reported lower global health (p=0.090) and physical functioning (p=0.049) with borderline significance compared to the WBI group. At 3-6 months post-RT, WBI+RNI group also showed higher arm symptom scores (p=0.030). Apart from these specific timepoints, no significant differences were observed in other PRO domain scores, including arm and breast symptoms, between treatment arms. In addition, there was no significant differences in PRO domains according to RT techniques and fractionation, except for breast symptoms during RT, favoring hypofractionation and intensity-modulated RT. Conclusions: In patients with pN1 breast cancer treated with taxane-based adjuvant chemotherapy, adding RNI was associated with minor, transient declines in specific PRO domains. However, these differences were not clinically significant, indicating comparable overall patient experiences between the two treatment arms. Clinical trial information: NCT03269981 .
Effects of plant-based diet (PBD) and exercise therapy (Ex) on weight and body composition in patients with primary hormone receptor (HR) positive breast cancer: A phase 2 randomized controlled trial.
Authors: Neil M. Iyengar, Erica Salehi, Jessica A Lavery, Olivia Chan, Sarah Lehman, Meghan G. Michalski, Gina Fickera, Adele Carlson, Jenna Harrison, Whitney P. Underwood, Cara Anselmo, Su Chun, Stephanie Cao, Catherine P. Lee, Wendy Demark-Wahnefried, Chaya S. Moskowitz, Lee W. Jones
Journal: Journal of Clinical Oncology (2024)

548 Background: Obesity increases breast cancer recurrence and mortality. Strategies that induce weight loss may improve clinical outcomes. We investigated the feasibility and efficacy of personalized energy restricted PBD plus Ex on weight and body composition in primary HR-positive breast cancer (NCT04298086). Methods: Postmenopausal women with body mass index (BMI) ≥ 27 kg/m 2 on adjuvant endocrine therapy were randomized (1:1) to PBD plus Ex or attention control for 24 weeks. PBD plus Ex received individualized caloric goals adjusted weekly to target 1.5 lbs/week weight loss. PBD targeted 500 kcal/day goal deficit achieved via nutrition coaching and meal delivery. Ex sessions targeted 250 kcal goal expenditure via remotely delivered treadmill walking 3-5 days/week with real-time monitoring. Attention control received a home treadmill and monthly check-in calls. Baseline to post-intervention changes in weight and body composition, measured by dual energy X-ray absorptiometry (DXA), were compared between arms using linear mixed models. Results: 43 women were randomized between 8/2020 and 4/2023. Weight data was available for all participants (35 measured at follow-up, 8 abstracted from clinical documentation); 37 completed post-intervention DXA. At baseline, mean BMI was 34 (SD 4) kg/m 2 . Intention-to-treat results are presented in the Table. Mean weight loss in PBD plus Ex was –13% (SD 6%) compared with –5% (SD 6%) in attention control (mean between group difference –8 kg, 95% CI –11, –4). Mean fat loss in PBD plus Ex was –6 kg compared with –2 kg in attention control (mean between group difference –4 kg, 95% CI –6, –2). Lean mass increases were greater in PBD plus Ex (P&lt;0.001). Weekly energy deficit goal compliance was 95% in month 1 and 64% in month 6. No serious adverse events were observed. Baseline and post-intervention tissue samples were available on 37 (86%) patients, which will undergo biologic correlative analysis. Conclusions: Personalized PBD plus Ex led to substantial weight loss and favorable changes in body composition during endocrine therapy for HR-positive breast cancer. Clinical trial information: NCT04298086 . [Table: see text]
Combination of predicted sensitivity to endocrine therapy (SET2,3 index) and the Recurrence Score in node-positive breast cancer: Independent validation in the PACS-01 trial.
Authors: Frederique Madeleine Penault-Llorca, Amelie Lusque, Thomas Filleron, Kevin Tran, Lili Du, Frederick Baehner, Florence Dalenc, Magali Lacroix-Triki, Thomas Bachelot, Fabrice Andre, Pascal Boucher, Jerome Lemonnier, W. Fraser Fraser Symmans
Journal: Journal of Clinical Oncology (2024)

565 Background: SET2,3 index measures hormone receptor-related transcriptional activity (SET ER/PR ) adjusted for a baseline prognosis index (BPI) derived from tumor size, nodes involved and a 4-gene molecular subtype (RNA4). SET2,3 added prognostic information to the 21-gene Breast Recurrence Score (RS) in the SWOG 8814 trial (1). To confirm this, we independently evaluated both tests performed on node-positive, hormone receptor-positive (HR+) cancers from the PACS-01 trial (Roche et al, JCO 2006, PMID: 17116941) that evaluated the addition of adjuvant docetaxel to anthracycline-based chemotherapy. Adjuvant endocrine therapy became standard for premenopausal patients during PACS-01, justifying a sensitivity analysis in the population who received adjuvant endocrine therapy. Methods: SET2,3 was measured with the QuantiGene Plex bead-based hybridization assay (ThermoFisher) using an aliquot of residual RNA from prior RS testing in 791 HR+ tumor samples. Pre-defined cut points defined higher risk if RS &gt;25 or SET2,3 &lt;2.10. SET ER/PR index and BPI, individual components of SET2,3 index, were evaluated as continuous variables. The primary endpoint was distant recurrence-free interval (DRFI). Multivariable Cox proportional hazards models were used to calculate hazard ratios with 95% confidence interval (HR, 95%CI) adjusted for treatment arm, and the likelihood ratio (LR) of benefit from addition of SET2,3 to RS with LR test for significance at p &lt;0.05. Results: Of 791 tumor samples, 760 (96.1%) passed quality control (QC) for the SET assay; 724 had pathologic information to calculate SET2,3 index; and 659 had results for RS and SET2,3. At a median follow-up of 8 years, distant recurrence occurred in 144 of 659 (21.9%) patients overall, and 94 of 490 (19.2%) patients in the sensitivity population. Overall, high RS status (HR 2.33, 1.60-3.39) and high SET2,3 (HR 0.43, 0.30-0.62) were independently prognostic. SET2,3 was high in 303/377 (80.4%) patients with RS ≤25, with 5-year DRFI of 93.7% [95%CI 90.2;95.9]; and SET2,3 was low in 171/282 (60.6%) patients with RS &gt;25, with 5-year DRFI 64.6% [95%CI 56.9;71.3]. SET ER/PR index of endocrine transcriptional activity and the BPI, each contributed additional prognostic information to RS status in the sensitivity population (Table). Conclusions: SET2,3 index added prognostic information to the Recurrence Score in this independent blinded validation study of the PACS-01 trial for node-positive breast cancer. 1. Speers et al, JCO 2023, PMID: 36649570. [Table: see text]
Long-term oncologic outcome of breast-conserving surgery in breast cancer with BRCA 1/2 mutation (ON-BRCA II, KoREa-BSG 06).
Authors: Janghee Lee, Jai Min Ryu, Hong-Kyu Kim, Hyung Seok Park, Byeongju Kang, Sung Gwe Ahn, Min Sung Chung, Seon-Hi Shin, Junwon Go, Sanghwa Kim, Eun Young Kim, Young-Joon Kang, Sun Young Min, Moo Hyun Lee, Eunju Shin, Jisoo Shin, Sae Byul Lee, CHIHWAN CHA
Journal: Journal of Clinical Oncology (2024)

552 Background: Among patients with sporadic breast cancer, it is well known that prognoses are similar following breast-conserving surgery (BCS) versus mastectomy. However, previous data assessing oncologic outcomes between BCS and mastectomy in patients with BRCA mutation are limited and inconsistent. Thus, this study aims to compare the oncologic outcomes including locoregional recurrence (LRR), distant recurrence (DR), and overall survival (OS) among this population. Methods: Patients with BRCA mutation and index breast cancer who underwent BCS or mastectomy between January 2008 and December 2015 were retrospectively screened from 13 institutions. We included patients aged from 20-80 with invasive breast cancer (pT1-3 N0-3). Patients with de novo metastasis were excluded. To minimize selection bias from retrospective nature, the propensity score matching (PSM) with Greedy nearest neighbor method was performed for covariates including age, molecular subtype, and tumor stage. Results: A total of 553 patients with BRCA mutation were identified. Among them, 367 (66.2%) patients received BCS and 186 (33.8%) were treated with mastectomy. After 1:1 PSM, there was no significant differences in age, molecular subtype, tumor size, nodal status, and histologic tumor grade between patients undergoing BCS versus mastectomy. At 8.3 years of median follow up, LRR, DR, and OS rates did not differ between groups (all p &gt; 0.05). On multivariate analysis, type of breast surgery (BCS vs. mastectomy) was not significantly associated with the oncologic outcomes after adjusting covariates including age, molecular subtype, tumor stage, and histologic grade (all p &gt; 0.05). Additionally, we performed subgroup analysis in matched patients based on tumor size, LN metastasis, HG, and subtype. In all subgroup, the type of breast surgery was not a significant risk factor influencing disease recurrence. Conclusions: Our findings suggest that there was no difference in oncologic outcomes among BRCA mutation carriers who underwent BCS or mastectomy. Breast conservation with close surveillance is a reasonable treatment option for BRCA mutation carriers. Further studies combined with prospectively collected data are warranted to validate our findings.
Evaluating the association between radiomic features on breast MRI and dormant tumor cell presence in the SURMOUNT trial.
Authors: Kalina Polet Slavkova, Elizabeth S. McDonald, Eric A. Cohen, Lauren Pantalone, Lauren Bayne, Isoris Nivar, Pauleen Sanchez, Walter C. Mankowski, Melanie Brown, Amy Sanders Clark, Killian Rohn, Lewis A. Chodosh, Despina Kontos, Angela DeMichele
Journal: Journal of Clinical Oncology (2024)

561 Background: While breast cancer treatment is effective at eradicating primary disease, approximately 20% of patients will ultimately recur at a distant site. Recurrence has been linked to the presence of minimal residual disease (MRD) after treatment, which presents as circulating micrometastases and dormant tumor cells (DTCs) located primarily in the bone marrow. Radiomic features on MRI are imaging biomarkers that have been linked with lesion heterogeneity, which in turn has been associated with disease aggressiveness. Here, we examine the association between radiomic features from the primary lesion on MRI and the presence of post-treatment DTCs. Noninvasively identifying patients at high risk of MRD would facilitate optimized treatment strategies to reduce recurrence risk. Methods: Dynamic contrast-enhanced MRI data from breast cancer survivors enrolled in the SURMOUNT trial (N=104) were retrospectively analyzed. Participants with MRIs collected within 90 days of diagnosis who consented to provide a bone marrow aspirate (BMA) sample were eligible. Working with a board-certified radiologist, we successfully identified and segmented the primary lesion for N=70 patients with BMA outcomes. Using the publicly available CaPTk software, we computed 33 radiomic features for each segmented lesion based on pixel intensity, morphology, and grey level textures. To reduce the dimensionality of the feature space, we used these feature values to group the participants into clusters—termed radiomic phenotypes — via agglomerative hierarchical clustering with significance testing. Fisher’s exact test was applied to test the statistical significance of the association between radiomic phenotype and BMA outcome (± DTC). For all statistical tests, p&lt;0.05 was considered significant. Results: Of the N=70 participants analyzed, 58 were negative and 12 were positive for DTCs present in the bone marrow. Two statistically significant radiomic phenotypes ( p&lt;0.05) were identified that were strongly associated with BMA outcome ( p=0.0251). 11 out of 12 positive outcomes were grouped into the second radiomic phenotype (Table). Conclusions: We found a statistically significant association between DTC presence and radiomic phenotypes derived from MRI data. Given the large percentage of positive outcomes assigned to the second radiomic phenotype, the radiomic phenotypes may indicate low and high risk of MRD, respectively. Importantly, this analysis shows promise for the ability to predict MRD from noninvasive imaging features. These results motivate continued data collection to increase sample size and identify a robust set of radiomic features, which may ultimately be used as predictors in potential models of MRD risk. [Table: see text]
Artificial intelligence (AI) –powered H&amp;E whole-slide image (WSI) analysis to predict recurrence in hormone receptor positive (HR+) early breast cancer (EBC).
Authors: Jimin Moon, Hyunwoo Lee, Yoon Ah Cho, Gahee Park, Wonkyung Jung, Seulki Kim, Jiwon Shin, Jiyoung Park, Jongchan Park, Donggeun Yoo, Sergio Pereira, Chang Ho Ahn, Eun Yoon Cho
Journal: Journal of Clinical Oncology (2024)

571 Background: The recurrence risk (RS) based on transcriptomic profiles or Ki-67 level of HR+ EBC has been used for adjuvant treatment decisions and may also aid selecting patients who could benefit from novel treatments including CDK4/6 inhibitor or oral selective estrogen receptor degraders (SERDs). Artificial intelligence-powered H&amp;E whole slide image (WSI) models can be a practical approach for this biomarker without the need of additional tissue samples. We developed ML-based models of histopathologic features from an H&amp;E WSI to approximate RS of 21-gene assay (OncotypeDx) using various algorithms of different complexities. Methods: The development dataset was composed of 1,009 cases from TCGA-BRCA with gene expression profiles and 483 EBC cases from Samsung Medical Center with RS results. The prediction model was developed in two-stages. First, Lunit SCOPE, an AI-powered H&amp;E WSI analyzer, detects various cell types and segments tissue areas resulting in various cell densities in tissue regions of interest. Next, four traditional ML models were applied on top of the first stage results. In addition, a deep learning model based on multiple instance learning (DL-MIL) was developed using three features: a supervised convolutional neural network, a supervised cell detection model, and an AI-based pathology profiling analyzer, for extracting semantic contents. The model performance was validated using two independent EBC test sets: 248 cases for comparison with the RS results (set 1), and 708 cases with DFS (set 2). Results: The cross-validation performance of the four traditional ML algorithms had area under the curve of receiver operating characteristics curve (AUROC) ranging from 0.728 to 0.779, where mitotic cell density, tumor cell density, and fibroblast density in cancer area were the variables with the highest importance for all four models. The DL-MIL model had cross validation performance of AUROC 0.831. In test set 1, DL-MIL model showed the highest discrimination with AUROC of 0.828 compared to traditional ML models where logistic regression showed the highest discrimination with AUROC of 0.786 (Table). The DL-MIL model showed the highest performance among the models to predict DFS with hazard ratio (HR) of 2.48 (1.47-4.18). Conclusions: Histopathomic models can accurately predict the RS of high risk as well as poor DFS from only H&amp;E WSIs. These AI models can be a practical tool for treatment selection including emerging drugs such as SERDs. [Table: see text]
Deep learning-based quantitative assessment of tumor-infiltrating lymphocytes from hematoxylin and eosin-stained slides in triple-negative breast cancer: A prognostic study.
Authors: Takuma Kobayashi, Kanako C Hatanaka, Nobumoto Tomioka, Teppei Konishi, Mateusz Grynkiewicz, Daisuke Komura, Shumpei Ishikawa, Kenichi Watanabe, Masato Takahashi, Yutaka Hatanaka
Journal: Journal of Clinical Oncology (2024)

553 Background: Tumor-infiltrating lymphocytes (TILs) are pivotal in predicting responses to preoperative chemotherapy in triple-negative breast cancer. Yet, their clinical adoption as a diagnostic marker is limited by the challenge of achieving high accuracy with objective measures. This study introduces a novel AI-based method to quantitatively assess stromal TILs within the tumor bed using hematoxylin and eosin (H&amp;E)-stained slides, examining their correlation with disease-free survival (DFS) and overall survival (OS). Methods: In this study, 68 cases of breast cancer with axillary lymph node metastasis at the time of resection were selected from a total of 3,902 resections conducted between 2002 and 2016. We then developed an AI-based model to detect the epithelium and lymphocytes (CD3/CD20) from H&amp;E-stained slides. This model was trained using annotated datasets, which included 26,509 images of the epithelium and 12,273 images of lymphocytes. The tumor bed areas were precisely defined by pathologists. Subsequently, the AI model identified epithelial and lymphocyte regions within these predefined areas. The TILs score was then calculated as the ratio of the lymphocyte area to the total stromal area within the tumor bed, excluding the epithelial areas identified by the AI model. Finally, we assessed the prognostic significance of the TILs score for DFS and OS through ROC analysis and log-rank tests. Results: ROC analysis identified an optimal TILs score threshold of 0.0042 for both DFS and OS, with an AUC of 0.743 (95% CI, 0.622-0.864) for DFS and 0.686 (95% CI, 0.559-0.812) for OS. This threshold significantly stratified patients into groups with distinct DFS and OS outcomes (P=0.003 and P=0.008, respectively). Conclusions: AI quantification of TILs offers a promising prognostic tool in triple-negative breast cancer, enhancing the objectivity and clinical utility of pathological analyses. Accurate TILs measurement could revolutionize prognostication and treatment planning.
Updated SEER database study of 21-gene assay to assess breast cancer–specific mortality and benefit of chemotherapy by race and ethnicity.
Authors: Emilia Diego, John P. Bennett, Gong Tang, Charles E. Geyer, Jennifer M. Racz, Christy A Russell, Frederick Baehner, Steven Shak, Valentina I. Petkov
Journal: Journal of Clinical Oncology (2024)

533 Background: In randomized studies (NSABP B-20, SWOG 8814, TAILORx, RxPONDER), the predictive effect of the 21-gene Breast Recurrence Score assay (RS) on chemotherapy (CT) benefit has been evaluated in patients with node-negative (N0) and node-positive (N+) breast cancer. Retrospective analyses of TAILORx and RxPONDER demonstrated differences in outcome by racial/ethnic groups (RG); however, there were no differences in CT benefit for any of the clinical outcome measures. In this study we characterized the association between the RS result and breast cancer-specific mortality (BCSM) and chemotherapy benefit in BCSM in RG in the recently updated, population-based SEER registries. Methods: Eligible patients were from the SEER 17 registries, November 2022 submission, and had non-metastatic, hormone receptor-positive, HER2-negative, node negative (N0) breast cancer diagnosed between 2006 and 2019 with a RS result. Analyses were weighted using the inverse of estimated propensity of using CT (yes vs. none/unknown). Prognosis was ascertained by estimating breast cancer specific survival (BCSS) at 9 years among patients with CT recorded as none/unknown by RG. The log-rank test was used to compare BCSM by RG. Multivariable Cox models, including RS result (26-100 vs. 0-25) x CT interaction, were used to assess whether RS result was predictive of CT benefit. Analyses were performed in the overall cohort and in Hispanic (H), non-Hispanic Asian and Pacific Islander (NHAPI), non-Hispanic Black (NHB), and non-Hispanic White (NHW) RGs. Results: There were 145,642 eligible patients and 3,212 breast cancer deaths. Median follow-up was 68 months. NHB patients had higher median RS result and CT usage than other groups (p &lt; .001). In N0 patients, higher RS result was associated with lower 9-year BCSS, both overall and by race/ethnicity (p &lt; .001). In Cox multivariable models (Table), the interaction between RS result by CT was significant among all N0 patients (p &lt; .001) and in NHB patients (p = 0.005), NHW patients (p = 0.002), and H patients (p = 0.019), but not in NHAPI patients (p = 0.766). Analyses of patients with N+ disease and more detailed analysis of CT benefit according to RS results by RG are underway and will also be presented. Conclusions: Real-world evidence from the SEER registries in over 145,000 patients confirms the 21-gene assay is prognostic for BCSS in all groups by race and ethnicity. The RS result was predictive of CT benefit in N0 patients overall and in Hispanic, NHB, and NHW patients, but not in NHAPI patients in this analysis. [Table: see text]