bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of tumor-infiltrating lymphocytes (TILs) and immune signatures with PAM50 intrinsic subtyping hormone receptor-positive (HR+)/HER2-negative (HER2-) early breast cancer (BC): A translational analysis of two multicentric neoadjuvant trials.
Authors: Griguolo Gaia , Paré Laia , Miglietta Federica , Bottosso Michele , Generali Daniele Giulio , Frassoldati Antonio , Musolino Antonino , Spazzapan Simon , Vernaci Grazia , Giarratano Tommaso , Cappellesso Rocco , Bisagni Giancarlo , Piacentini Federico , Tagliafico Enrico , Cagossi Katia , Pinato Claudia , Schiavi Francesca , Prat Aleix , Dieci Maria Vittoria , Guarneri Valentina 
Published: May 2024

558 Background: HR+/HER2− BCs are generally described as immunologically cold, with low levels of TILs and PD-L1. Nevertheless, the addition of immunotherapy (ICI) to chemo has been reported to increase pCR rates in high-risk early HR+/HER2– BCs. Assessing the interaction between immune features and tumor biology may identify of a subset of patients (pts) with HR+/HER2− BC that would be the ideal candidates for the combination of chemo and ICI. Methods: Gene-expression data from two multicentric neoadjuvant phase II trials (GIADA, LETLOB) enrolling stage II-IIIA HR+HER2- BC pts was retrieved (Dieci, CCR 2022; Guarneri, JCO 2014). In the GIADA trial, 758 genes were assessed on baseline tumor samples by nCounter (N=43). In the LETLOB trial, gene-expression data (Affymetrix platform) from baseline core-biopsies was available for 66 pts. Intrinsic subtype was assigned using a research-based PAM50 predictor. TILs were evaluated following guidelines. Association of TILs and immune signatures with intrinsic subtyping was assessed by Kruskal-Wallis test. Results: PAM50 subtype distribution (N=109) was 44% Luminal B (LumB), 33% Luminal A (LumA), 18% Basal-like, 5% HER2-enriched (HER2-E). TILs were assessed on 101 samples: median 2 (range 0-100). Basal-like BCs showed higher TILs than other subtypes (p=0.008). No significant difference was observed between LumA and LumB BCs (Table). Basal-like tumors showed higher levels of previously published immune signatures associated with CD8 T-cells (p<0.001), Cytotoxic cells (p<0.001), IFN-gamma (p<0.001), and response to ICI in the GeparNuevo trial (p=0.003) (N=109). PD-1 (p=0.002), PD-L1 (p=0.001), and PD-L2 (p=0.001) genes were also more expressed in Basal-like BCs (evaluable in 43 samples). No significant difference was observed between LumA and LumB tumors. A significant weak to moderate positive correlation was observed between continuous TILs and immune signatures and basal-like PAM50 signature (p<0.001, Spearman coefficient=0.372 for TILs, from 0.354 to 0.648 for immune signatures). Conclusions: PAM50 intrinsic subtyping and TILs/immune signatures capture only partially overlapping information on the biology of HR+/HER2- BCs. Pts with HR+/HER2- BCs simultaneously showing features of biological aggressiveness and enhanced immunogenicity may represent the ideal candidates for the combination of ICI and chemo. [Table: see text]
Association of circulating T lymphocytes and their functional states with pathologic complete response (pCR) in breast cancer (BC). A prospective Italian study.
Authors: Ben Ayed Rahma , Conte Benedetta , Martini Veronica , Boldorini Renzo , Gobbato Simone , Ruffilli Beatrice , Vezzoli Francesca , Alsati Rami , Negrini Letizia , Sala Nicole , Matera Letizia , Branni Carmen , Dodaro Ivan , Gambaro Anna , Rossi Valentina , D'Avanzo Francesca , Gennari Alessandra 
Published: May 2024

559 Background: In BC, pCR is associated with substantial survival benefit. Hence, escalated neoadjuvant treatments (NATs) are being increasingly employed to improve pCR rates, warranting biomarkers for better patients’ selection. T-cell exhaustion and senescence are dysfunctional states that coexist in patients with cancer, impairing antitumor immunity and sustaining a suppressive immune microenvironment. Here, we assessed the impact of such states on pCR across different BC subtypes and NATs. Methods: This is a prospective study on patients undergoing NAT for BC at the Maggiore Hospital of Novara, Italy. Blood was collected at baseline and after NAT. Circulating T lymphocytes were characterized with exhausted (CD28, PD1, LAG3) and senescent (CD57, KLRG-1) biomarkers utilizing flow cytometry. Neutrophiles/lymphocytes ratio (NLR) and lymphocytes/monocytes ratio (LMR) were also retrieved. Subpopulations with frequency <1% were normalized for total CD3+ cells. Results: From October 2020 to January 2024, 134 patients were enrolled and 115 completed NAT (85.8%). Fifty-one (38,1%) had adequate samples for analysis, 16 (31,4%) with hormone receptor positive HER2 negative BC (HR+HER2-), 15 (29,4%) with HER2+, and 20 (39,2%) with triple negative BC (TN). At baseline, patients with TNBC had the lowest NLR (p=0.018) and lowest senescent CD4+CD28- (p=0.042). Associations with pCR are shown in the Table. Overall, LMR associated with increased pCR (OR 1.34 [95% CIs 1.00-1.89]), and NLR with decreased pCR (OR 0.67 [0.39-1.04]). Both associations were driven by HR+ status (interaction p = 0.061 and 0.060). Senescent CD4+ predicted lower pCR in both HR-HER2+ (OR 0.10 [0.01-0.36]) and TNBC (OR 0.10 [0.01-0.5]). In TNBC, exhausted CD8+ predicted higher pCR (OR 1.78 [1.08-3.79]). When assessed separately in patients who received NAT with or without pembrolizumab, exhausted CD8+ remained predictor of pCR in chemotherapy + pembrolizumab (OR 1.84 [1.03-5.00]), but not with chemotherapy alone (p=0.203). The dynamics of paired pre-NAT and post-NAT TNBC samples revealed significant differences. Senescent CD4+ increased after chemotherapy, but not with chemotherapy + pembrolizumab (p=0.007). Pembrolizumab was associated with depletion of PD1-positive CD8+, while chemotherapy alone was not (p=0.020). Conclusions: The characterization of circulating T lymphocytes could help identify patients who benefit more in terms of pCR from specific NATs, including chemoimmunotherapy. [Table: see text]
The landscape of the intestinal microbiome amongst patients with newly diagnosed invasive breast cancer (BC) and ductal carcinoma in situ (DCIS).
Authors: Sammons Sarah L , Kuntz Thomas , Hughes Melissa E. , Morgan Xochitl , Waks Adrienne Gropper , Garrido-Castro Ana Christina , DiLullo Molly , Ligibel Jennifer A. , Ogayo Esther R. , Giordano Julia , Ryan Sean , Rahman Tasnim , BARROSO-SOUSA ROMUALDO , Martin Alyssa R. , O'Quinn Casey , Parker Tonia , Lin Nancy U. , Mittendorf Elizabeth A. , Tolaney Sara M. 
Published: May 2024

563 Background: The gut microbiota has been recognized as a master modulator of the immune system and has been associated with outcomes among cancer patients. There is a paucity of knowledge surrounding the landscape of the gut microbiome in BC pts with invasive and non-invasive disease or how it can affect response to systemic therapy. We sought to define the landscape of the gut microbiome in invasive BC and DCIS patients and evaluate differences by subtype. Methods: Prospective clinical trials (NCT04425018 and NCT02752685) and institutional registries enrolling patients with DCIS and stage I-III invasive BC at a single institution collected baseline stool samples prior to initiation to systemic therapy. Samples underwent whole-genome metagenomic sequencing (2 x 150 bp, Illumina NovaSeq) and data were processed into taxonomic (species) abundances using MetaPhlAn4. Associations between metadata and ecological features (alpha and beta diversity) were tested with ANOVA and PERMANOVA. Individual species were tested for association as univariable linear models on normalized, log-transformed relative abundances, with p-values FDR adjusted for multiple comparisons, using MaAsLin2. Results: 278 baseline samples were analyzed: 43 DCIS, 101 TNBC, 54 HR+/HER2-, 24 HR-/ HER2+, 37 HR+/HER2+. Most patients were age >50 (71%) and white (83%). No significant differences were observed in baseline stool microbiomes between invasive BC and DCIS pts for alpha (p = 0.185) or beta (p= 0.476) diversity, nor for individual microbial species. HR+/HER2+ BC had a unique microbiome profile with significantly different beta diversity (p = 0.005), with six associated species (q < 0.25). No other associations with invasive BC subtype were observed. Bacteroides ovatusabundance was significantly different between Stage I and III BC pts (p = 0.0003, q = 0.116). Several taxa were associated with age at diagnosis. Conclusions: No significant differences were observed in baseline stool microbiome composition between patients with invasive breast cancer and DCIS. HR+/HER2+ BC microbiome composition was distinct from other subtypes, and a significant difference in Bacteroides ovatus abundance emerged between Stage I and III pts, suggesting potential microbial associations with cancer subtypes and progression.
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: Penault-Llorca Frederique Madeleine , Lusque Amelie , Filleron Thomas , Tran Kevin , Du Lili , Baehner Frederick , Dalenc Florence , Lacroix-Triki Magali , Bachelot Thomas , Andre Fabrice , Boucher Pascal , Lemonnier Jerome , Symmans W. Fraser Fraser 
Published: May 2024

565 Background: SET2,3 index measures hormone receptor-related transcriptional activity (SETER/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 >25 or SET2,3 <2.10. SETER/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 <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 >25, with 5-year DRFI 64.6% [95%CI 56.9;71.3]. SETER/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]
Clinical application of novel mobile AI solution for real-time detection and differential diagnosis in breast ultrasound: The first prospective feasibility study.
Authors: Lee Jeeyeon , Cheng Tsui-Fen Fiona 
Published: May 2024

574 Background: Existing artificial intelligence (AI) solutions for breast ultrasound faced limitations due to their non-real-time detection and server dependency. However, novel mobile real-time AI solution now enable on-device detection and differential diagnosis, aiding in immediate decision-making. This study aims to evaluate the feasibility and effectiveness of such a mobile AI solution in clinical settings, by comparing it against expert breast imaging diagnoses. Methods: From August to December 2023, a feasibility study was conducted in tertiary medical center of Taiwan using mobile AI solution (CadAI-B for breast, BeamWorks Inc., Korea). CadAI-B is connected via HDMI or DVI to an ultrasound equipment using tablet PC. It supports healthcare providers to detect suspicious breast lesions by highlighting suspicious area during breast ultrasound scanning, and to make a differential diagnosis by providing BI-RADS categories and malignancy score (0-100%). The rate of real-time detection in malignancies and area under the receiver operating characteristic curve (AUC) was calculated. Distribution of BI-RADS categorized by CadAI-B were compared with those by breast imaging experts on independent review. Results: The analysis included 33 patients with an average age of 47 years (IQR, 44 – 62). There were 14 malignancies, 17 benign lesions, and 2 normal cases, and 30 patients (90.9%) underwent biopsy. For patients with malignancies, CadAI-B successfully identified all malignancies. Overall diagnostic performance, as AUCs calculated by the malignancy score and BI-RADS, was 0.835 and 0.850, respectively. The per-patient sensitivity of CadAI-B was 100.0%, while the specificity was 52.6%. The BI-RADS distribution between CadAI-B and expert was the same in malignant cases. In benign cases, CadAI-B categorized 9 cases (50.0%) as C4A or C4B, while experts classified 13 cases (72.2%), indicating a potential reduction in the need for biopsy. Conclusions: This study demonstrates that real-time processing capabilities of CadAI-B enable the identification of critical lesions during breast ultrasound, helping to reduce unnecessary biopsy. These findings may be helpful in diagnostic decisions and training of non-experts in clinical settings and offer the potential to improve workflow efficiency. [Table: see text]
Radiofrequency ablation without excision for breast cancer: 5-year results of ipsilateral breast tumor recurrence-free survival in the RAFAELO study (NCCH1409).
Authors: Kinoshita Takayuki , Takayama Shin , Takahashi Masato , Fujisawa Tomomi , Yamamoto Naohito , Shien Tadahiko , Futamura Manabu , Ito Mitsuya , Takahashi Mina , Aogi Kenjiro , Watanabe Kenichi , Onishi Tatsuya , Yoshida Masayuki , Tsuda Hitoshi , Shibata Taro , Yorikane EIko , Ohata Keiko 
Published: May 2024

578 Background: The RAFAELO study is designed to evaluate the safety and efficacy of breast radiofrequency ablation, enabling women between 20 and 79 years of age with small breast cancers to benefit from a nonsurgical treatment and to avoid the associated surgical risks. Methods: The RAFAELO study is a prospective, multi-center, single-arm, confirmatory trial including women between 20 and 79 years of age with unifocal, MRI and ultrasound-visible invasive ductal carcinoma or ductal carcinoma in situ size 1.5 cm or smaller diagnosed by preoperative core-needle biopsy, and classified as any grade, any hormone receptor (HR) status, and any human epidermal growth factor receptor 2 (HER2) status. The primary endpoint was Ipsilateral breast tumor recurrence (IBTR) -free survival at 5 years. e planned sample size was set at 372 considering patients lost to follow-up to achieve the power of 80% with the one-sided alpha of 5%, the expected 5-year IBTR-free survival of 93.7%, and the threshold of 90%. The IBTR-free survival time was estimated using the Kaplan-Meier method. Results: Between August 2013 and November 2017, 372 patients were enrolled in this study. A total of 370 patients received successful radiofrequency ablation per protocol and 353 patients were included for the efficacy analysis. The median age was 55 years (range, 32-78 years). With median follow-up period of 5 years, IBTR was observed in 2 patients among 353 patients. The 5-year IBTR-free survival was 98.6% (90% CI 97.1%-99.3%) and the primary endpoint was met as its lower limit of 90% CI exceeded the threshold (90%). As device-related adverse events during radiofrequency ablation, burns were observed in 4 (1.1%) for Grade 1 and 3 (0.8%) for Grade 2 among 370 patients. No severe device-related adverse events were reported. Conclusions: Breast radiofrequency ablation presents a promising alternative to surgery while offering the benefits of a minimally invasive procedure with minimal risks. Breast cancer patients in Japan can now avail themselves of this minimally invasive treatment that’s subsidized by public insurance. Further analysis within this clinical trial or registry is needed to confirm radiofrequency ablation as a viable alternative to surgical excision for breast cancer patients in the point of cosmetic results and patient’s satisfaction. Clinical trial information: jRCTs032180229 .
Automated digital oncologic data review for breast cancer research: AI-enabled mCODE and field-of-interest extraction framework.
Authors: Choi JI-Woo , Park Seho , Sohn Joohyuk , Lew Dae Hyun , Sung Sihyun , Choi Ye-Lim , Lee Sarang , Yang Eun-Jung 
Published: May 2024

e12647 Background: Enhancing outcomes in cancer care and research can be optimally achieved by accelerating data extraction from unstructured electronic health resources. Understanding the association between treatment response markers and long-term outcomes is crucial for refining cancer therapeutic approaches and improving patient prognosis. In this study, we explore the association of oncologic outcomes with pathologic complete response (pCR) in high-risk early-stage breast cancer treated with neoadjuvant chemotherapy (NACT) using automated oncologic data extraction framework. Methods: Patients with primary stage I-III breast cancer who received NACT followed by mastectomy, with or without immediate breast reconstruction from January 2010 to August 2023 were retrospectively analyzed. We extracted pCR results and data on clinical and pathological stage, tumor subtype, grade, and treatment regimens and factors affecting postoperative complications from electronic medical records based on the AI enabled-mCODE (Minimal Common Oncology Data Elements) and fields of interest extraction framework. Employing mixed-effects Cox models, we explored the association between pCR and event-free survival (EFS), distant recurrence free Survival (DRFS) and overall survival (OS). Survival curves of patients were estimated using Kaplan-Meier method. Multivariate analysis was performed to evaluate the predictive factors for pCR. Results: Overall, 2725 patients were analyzed. The median age was 50.6 years. The median follow-up was 67 months. pCR was achieved in 31.0%. Hazard ratio for pCR vs. non-pCR were 0.34 for EFS (95% CI, 0.25-0.45), 0.32 for DRFS (95% CI, 0.23-0.43), 0.21 for OS (95% CI, 0.13-0.34), varying from 0.13 to 0.56 for EFS, 0.12 to 0.48 for DRFS and 0.07 to 0.40 for OS. The presence of pCR remained prognostic for event-free survival in multivariate models adjusted for age, tumor size, and nodal status at baseline. Conclusions: This study confirms that patients achieving pCR after NACT have better long-term survival outcomes that patients who do not. Oncologic data extraction from unstructured electronic medical records using AI-enabled extraction framework can be expected to enhance robust cancer research and generate valuable insights from real-world practice settings for tailored therapeutic decision-making. [Table: see text]
Predictors of response and surgical approach after neoadjuvant chemotherapy in receptor-positive/HER2-negative stage II-III breast cancer patients treated in two private cancer care centers in Lima, Peru: Real-world data.
Authors: Aldecoa-Bedoya Franklin , Aldecoa-Falcon Sebastian , Falcon Silvia Gabriela 
Published: May 2024

e12659 Background: The role of neoadjuvant chemotherapy (NAC) in hormone receptor-positive HER2-negative breast cancer (BC) is controversial, its main benefit being to improve the surgical outcome in both breast and axilla. The aim of this study was to evaluate the response to NAC, as well as possible predictors and the type surgery performed after primary treatment. Methods: Observational, retrospective study from a database of 1356 consecutive cases of BC between 2016 and 2022 in two private oncology centers in Lima Metropolitana. There were 726 new cases of hormone receptor-positive HER2-negative BC (53.5%), of which those patients with clinical stage II-III who received NAC were considered (n=122, 16.8 % of luminal HER2-negative). Results: The average age of the sample was 46.6 years (range 25-72) with a predominance of luminal B subtype (60.7%) and clinical stage II disease (51.6%), as well as an average delay time to treatment of 33.9 days. Chemotherapy choice was AC every 3 weeks followed by weekly paclitaxel (98.4%). The pathological complete response (pCR) rate was of 16.4% in the breast, 29.1% in the lymph nodes and 13.9% in both. None of the variables studied (age, histologic grade and type, clinical stage, tumor size, number of nodes, hormone receptors, Ki-67 and HER2 low) were predictors of pCR. According to RECIST criteria, tumor shrinking in the breast occurred in the majority of patients (partial and complete response: 86.1%) and eight out of ten patients achieved a tumor size reduction of more than 50%. The rate of mastectomy was 67.2% and radical axillary dissection, 70.5%. Conclusions: In our cohort, we found a pCR rate similar to that reported in the world literature. No predictors of pCR were found. Despite the high proportion of tumor response at breast and node level, the surgical approach was mostly radical. The multidisciplinary BC committee in our setting should be strengthened in order to make better decisions on the surgical approach for patients with hormone receptor-positive HER2-negative stage II-III BC who receive NAC.