bluuebunny/crossref_metadata_2025 huggingface dataset:
CRDC Program Collaborator Names from NCI Cancer Research Data Commons: Lessons Learned and Future State
Authors: Kim Erika , Davidsen Tanja , Davis-Dusenbery Brandi N , Baumann Alexander , Maggio Angela , Chen Zhaoyi , Meerzaman Daoud , Casas-Silva Esmeralda , Pot David , Pihl Todd , Otridge John , Shalley Eve , Barnholtz-Sloan Jill S. , Kerlavage Anthony R.
Published: May 2024

CRDC Program Collaborators
Supplementary Table 5 from Single-Cell Analysis Identifies NOTCH3-Mediated Interactions between Stromal Cells That Promote Microenvironment Remodeling and Invasion in Lung Adenocarcinoma
Authors: Xiang Handan , Pan Yidan , Sze Marc A. , Wlodarska Marta , Li Ling , van de Mark Karyn Ann , Qamar Haleema , Moure Casey J. , Linn Douglas E. , Hai Josephine , Huo Ying , Clarke James , Tan Tze Guan , Ho Samantha , Teng Karen W. , Ramli Muhammad N. , Nebozhyn Michael , Zhang Chunsheng , Barlow Julianne , Gustafson Corinne E. , Gornisiewicz Savanna , Albertson Thomas P. , Korle Stephanie L. , Bueno Raphael , Moy Lily Y. , Vollmann Elisabeth H. , Chiang Derek Y. , Brandish Philip E. , Loboda Andrey
Published: May 2024

The summary of gene signatures used in the study
CRDC Program Collaborator Names from NCI Cancer Research Data Commons: Resources to Share Key Cancer Data
Authors: Wang Zhining , Davidsen Tanja M. , Kuffel Gina R. , Addepalli KanakaDurga , Bell Amanda , Casas-Silva Esmeralda , Dingerdissen Hayley , Farahani Keyvan , Fedorov Andrey , Gaheen Sharon , Grossman Robert L. , Kikinis Ron , Kim Erika , Otridge John , Pihl Todd , Porter Melissa , Rodriguez Henry , Staudt Louis M. , Thangudu Ratna R. , Venkatachari Sudha , Zenklusen Jean Claude , Zhang Xu , Barnholtz-Sloan Jill S. , Kerlavage Anthony R.
Published: May 2024

CRDC Program Collaborator
Data from Chromoplexy Is a Frequent Early Clonal Event in EWSR1-Rearranged Round Cell Sarcomas That Can Be Detected Using Clinically Validated Targeted Sequencing Panels
Authors: Dermawan Josephine K. , Slotkin Emily , Tap William D. , Meyers Paul , Wexler Leonard , Healey John , Vanoli Fabio , Vanderbilt Chad M. , Antonescu Cristina R.
Published: May 2024

Abstract
Chromoplexy is a phenomenon defined by large-scale chromosomal chained rearrangements. A previous study observed chromoplectic events in a subset of Ewing sarcomas (ES), which was linked to an increased relapse rate. Chromoplexy analysis could potentially facilitate patient risk stratification, particularly if it could be detected with clinically applied targeted next-generation sequencing (NGS) panels. Using DELLY, a structural variant (SV) calling algorithm that is part of the MSK-IMPACT pipeline, we characterized the spectrum of SVs in EWSR1-fused round cell sarcomas, including 173 ES and 104 desmoplastic small round cell tumors (DSRCT), to detect chromoplexy and evaluate its association with clinical and genomic features. Chromoplectic events were detected in 31% of the ES cases and 19% of the DSRCT cases. EWSR1 involvement accounted for 76% to 93% of these events, being rearranged with diverse noncanonical gene partners across the genome, involving mainly translocations but also intrachromosomal deletions and inversions. A major breakpoint cluster was located on EWSR1 exons 8–13. In a subset of cases, the SVs disrupted adjacent loci, forming deletion bridges. Longitudinal sequencing and breakpoint allele fraction analysis showed that chromoplexy is an early event that remains detectable throughout disease progression and likely develops simultaneously with the driver fusion. The presence of chromoplexy was validated in an external ES patient cohort with whole exome sequencing. Chromoplexy was significantly more likely to be present in cases that were metastatic at presentation. Together, this study identifies chromoplexy as a frequent genomic alteration in diverse EWSR1-rearranged tumors that can be captured by targeted NGS panels.
Significance:
Chromoplexy is detectable using targeted NGS in a substantial portion of EWSR1-rearranged round cell sarcomas as an early and persistent clonal event, expanding the genomic complexity of fusion-associated sarcomas.
Figure S1 from A Review of Recent Advances in the Molecular Mechanisms Underlying Brain Metastasis in Lung Cancer
Authors: Guan Chao , Zhang Xiaoye , Yu Li
Published: May 2024

Figure S1 shows factors contributing to EGFR mutation predisposition to BM in lung cancer.
Supplementary Materials and Methods from Differential Distribution of the DNA-PKcs Inhibitor Peposertib Selectively Radiosensitizes Patient-derived Melanoma Brain Metastasis Xenografts
Authors: Ji Jianxiang , Dragojevic Sonja , Callaghan Cameron M. , Smith Emily J. , Talele Surabhi , Zhang Wenjuan , Connors Margaret A. , Mladek Ann C. , Hu Zeng , Bakken Katrina K. , Sarkaria Paige P. , Carlson Brett L. , Burgenske Danielle M. , Decker Paul A. , Rashid Mohammad Abdur , Jang Mi-hyeon , Gupta Shiv K. , Eckel-Passow Jeanette E. , Elmquist William F. , Sarkaria Jann N.
Published: May 2024

Supplementary Materials and Data show the cell culture and western blot data
Supplementary Figure 2 from Differential Distribution of the DNA-PKcs Inhibitor Peposertib Selectively Radiosensitizes Patient-derived Melanoma Brain Metastasis Xenografts
Authors: Ji Jianxiang , Dragojevic Sonja , Callaghan Cameron M. , Smith Emily J. , Talele Surabhi , Zhang Wenjuan , Connors Margaret A. , Mladek Ann C. , Hu Zeng , Bakken Katrina K. , Sarkaria Paige P. , Carlson Brett L. , Burgenske Danielle M. , Decker Paul A. , Rashid Mohammad Abdur , Jang Mi-hyeon , Gupta Shiv K. , Eckel-Passow Jeanette E. , Elmquist William F. , Sarkaria Jann N.
Published: May 2024

Supplemental Figure 2 shows bar graph of quantification of cells that have >25 gH2Ax foci per cell in M27 cell line, after treatment with peposertib and radiation
Table S4 from Pharmacological Characterization of SDX-7320/Evexomostat: A Novel Methionine Aminopeptidase Type 2 Inhibitor with Anti-tumor and Anti-metastatic Activity
Authors: Cornelius Peter , Mayes Benjamin A. , Petersen John S. , Turnquist David J. , Dufour Pierre J. , Dannenberg Andrew J. , Shanahan James M. , Carver Bradley J.
Published: May 2024

Results of enzyme assays that assessed the potential inhibitory activity of the MetPA2 inhibitor against various enzymes.
Figure S3 from Darolutamide Added to Docetaxel Augments Antitumor Effect in Models of Prostate Cancer through Cell Cycle Arrest at the G1–S Transition
Authors: Buck Stefan A.J. , Van Hemelryk Annelies , de Ridder Corrina , Stuurman Debra , Erkens-Schulze Sigrun , van ’t Geloof Sem , Teubel Wilma J. , Koolen Stijn L.W. , Martens-Uzunova Elena S. , van Royen Martin E. , de Wit Ronald , Mathijssen Ron H.J. , van Weerden Wytske M.
Published: May 2024

Combination of docetaxel and darolutamide in PC346C PDXOs.
A: Dose-response curve with mean normalized viability (+/- SEM) of three separate experiments with technical sextuplicates. Curves were interpolated by non-linear regression analysis and used to determine absolute IC50 value.
B: Logarithmic Combination Index (CI) plot for the combination of docetaxel and darolutamide, identifying synergistic (log(CI) < 0), additive (log(CI) = 0) or antagonistic (log(CI) > 0) effects. Fa: fractional effect. The combination index and corresponding degree of synergism or antagonism is indicated for each combination.(18)
Supplementary Figure Legends from 4′-Ethynyl-2′-Deoxycytidine (EdC) Preferentially Targets Lymphoma and Leukemia Subtypes by Inducing Replicative Stress
Authors: Calbert Marissa L. , Chandramouly Gurushankar , Adams Clare M. , Saez-Ayala Magali , Kent Tatiana , Tyagi Mrityunjay , Ayyadevara V.S.S. Abhinav , Wang Yifan , Krais John J. , Gordon John , Atkins Jessica , Toma Monika M. , Betzi Stéphane , Boghossian Andrew S. , Rees Matthew G. , Ronan Melissa M. , Roth Jennifer A. , Goldman Aaron R. , Gorman Nicole , Mitra Ramkrishna , Childers Wayne E. , Graña Xavier , Skorski Tomasz , Johnson Neil , Hurtz Christian , Morelli Xavier , Eischen Christine M. , Pomerantz Richard T.
Published: May 2024

Supplementary Figure Legends
Supplementary Table S2 from Simvastatin Overcomes Resistance to Tyrosine Kinase Inhibitors in Patient-derived, Oncogene-driven Lung Adenocarcinoma Models
Authors: Ma Weijie , Wei Sixi , Li Qianping , Zeng Jie , Xiao Wenwu , Zhou Chihong , Yoneda Ken Y. , Zeki Amir A. , Li Tianhong
Published: May 2024

Supplementary Table S2
Abstract Db1-01: Anthracyclines …to give or not to give? “For” argument
Authors: Piccart Martine , Nader-Marta Guilherme
Published: May 2024

Anthracyclines have been one of the mainstays of early breast cancer treatment for decades. In a recent patient-level meta-analysis including data from over 18,000 patients, anthracycline-containing regimens were associated with improvements in disease-free survival and overall survival, regardless of estrogen receptor or nodal status. Importantly, trials specifically designed and powered to assess the safety of anthracyclines omission failed to demonstrate the non-inferiority of taxane-based anthracycline-free regimens and confirmed the benefit of these agents, particularly in patients with node-positive and hormone receptor-negative breast cancer. Several therapies incorporated into the management of early breast cancer were studied in populations largely treated with anthracycline-based chemotherapy backbones in both HER2-negative (i.e., perioperative pembrolizumab, post neoadjuvant olaparib and capecitabine) and HER2-positive disease (i.e., dual HER2 blockade, adjuvant T-DM1). It is uncertain whether the benefits demonstrated by these strategies would be maintained if anthracyclines were omitted. While anthracyclines are associated with some long-term toxicities, particularly with an increased risk of lymphoproliferative malignancies and dose-dependent cardiotoxicity, these adverse events are not associated with an increased risk of death (including deaths from cardiovascular causes) when compared to anthracycline-free regimens. The identification of risk factors for cardiotoxicity, combined with improvements in monitoring strategies, allows improvements in patient selection, early detection of myocardial damage and, possibly, implementation of cardioprotective interventions, leading to improved cardiovascular outcomes. Until high-quality evidence demonstrates the safety of omitting anthracyclines in high-risk populations, these agents should continue to be used in carefully selected patients after individual risk versus benefit assessment to be shared with the patient.

Citation Format: Martine Piccart, Guilherme Nader-Marta. Anthracyclines …to give or not to give? “For” argument [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr Db1-01.
Abstract ED02-01: Biological peculiarities of ILC
Authors: Desmedt C.
Published: May 2024

One in 8 women will be diagnosed with breast cancer in her lifetime and approximately 15% of them have invasive lobular breast cancer (ILC). ILC differs in many ways from the most common BC subtype, called non-special type (NST) (Van Baelen et al. Ann Oncol 2022). The microscopic hallmark of ILC is the presence of single files of relatively small discohesive tumor cells, which stems from a dysfunctional E-cadherin-catenins complex at the intercellular junctions, a feature that is uncommon in NST. More than 90% of ILC express the estrogen (ER) and/or progesterone receptor (PR) and lack HER2 amplification, while this is only the case in ~65% of NST. Patients with ILC also show a distinct clinical behavior as compared to NST: generally, a poor response to chemotherapy, more late recurrences, and a peculiar metastatic pattern. The first part of the presentation will focus on presenting the biological knowledge we have accumulated over the years about primary ILC. We will review the studies which compared ILC and NST at the genomic, transcriptomic and immune level. The second part of the presentation will be focused on metastatic breast cancer. Here we will review the published evidence regarding the metastatic dissemination of ILC, its genomic landscape and the contribution of the local tumor microenvironment. We will also dedicate attention to the important biological and clinical knowledge which can be gained by studying samples collected from patients with metastatic ILC who consented to post-mortem tissue donation. Finally, the last part of the presentation will be dedicated to mixed NST/ILC tumors. These tumors account for up to 18% of all invasive breast cancers and represent an even more under investigated area of research as pure ILC.

Citation Format: C. Desmedt. Biological peculiarities of ILC [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr ED02-01.
Abstract ED05-01: Demystifying the Axilla: Challenging scenarios in the upfront surgery setting and after NAC
Authors: Barrio A.
Published: May 2024

Management of the axilla has evolved significantly over time, with a trend toward less extensive axillary surgery. While historically, all patients underwent axillary lymph node dissection (ALND) due to the Halstedian belief that ALND was essential for the cure of breast cancer, advances in systemic therapy, radiotherapy, and understanding of tumor biology have resulted in the abandonment of ALND for a large proportion of patients having upfront surgery with limited nodal disease, and in those with no residual nodal disease after neoadjuvant systemic therapy. Over time, axillary management has become increasingly complicated, with significant variability in real-world management for different clinical scenarios. In this talk, we will address challenging scenarios in axillary management, both in the upfront surgery setting and after neoadjuvant chemotherapy (NAC). In the upfront surgery setting, we will address management of a positive sentinel node in patients treated with mastectomy, management of ≥ 3 positive sentinel nodes after lumpectomy or mastectomy, and the use of sentinel lymph node biopsy for patients with clinically node-positive hormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2) negative breast cancer. In the setting of patients receiving NAC, we will discuss the optimal approach to the axilla in patients with residual disease after NAC, and in those with locally advanced breast cancer. As we move away from ALND in low-risk scenarios where data from randomized and prospective trials have demonstrated oncologic safety, we await results from ongoing clinical trials to provide us with high-level evidence regarding the safety of omission of ALND in high-risk patients with more extensive nodal disease.

Citation Format: A. Barrio. Demystifying the Axilla: Challenging scenarios in the upfront surgery setting and after NAC [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr ED05-01.
Abstract ED05-02: When less is more: Patient-friendly radiation courses with WBI and PBI
Authors: Meattini I.
Published: May 2024

Over the past few decades, remarkable progress has been made in understanding the biology and pathology of breast cancer. A personalized conservative approach has been currently adopted addressing the patient's individual risk of relapse. After postoperative whole breast irradiation for early-stage breast cancer, a rate of recurrences outside the initial tumour bed lower than 4% at 5 years was observed. Thus, the highest benefits of breast irradiation seem to result from the dose delivered to the tissue neighbouring the tumour bed. Nonetheless, reducing treatment morbidity while maintaining radiation therapy's ability to decrease local recurrences is an important challenge in treating patients with radiation therapy.

In this regard, strategies such as partial-breast irradiation and whole breast hypofractionation have been developed to reduce toxicity without compromising oncologic outcomes. According to the national and international published guidelines, clinical oncologists can refer to specific dose/fractionation schedules and eligible criteria. However, there are still some areas of open questions.

Breast cancer represents a multidisciplinary paradigm; it should be considered a heterogeneous disease where a "one-treatment-fits-all" approach cannot be considered an appropriate option.

A wide overview on the main partial and whole breast irradiation advantages, risks, timings, techniques, and available recommendations is presented, providing practical findings to support clinical decision-making, exploring future perspectives, towards a balance for optimisation of breast cancer.

Citation Format: I. Meattini. When less is more: Patient-friendly radiation courses with WBI and PBI [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr ED05-02.
Abstract ED05-03: Surgical management of Stage I TN and HER2+ breast cancer
Authors: Mamtani A.
Published: May 2024

The management of early-stage triple-negative (TN) and HER2-positive (HER2+) breast cancer has evolved significantly with continually improving systemic therapies. The use of neoadjuvant chemotherapy (NAC) has become standard for stage II disease, for both surgical downstaging and assessment of response to treatment, allowing for tailoring of systemic therapy in the adjuvant setting. However, the optimal treatment approach for stage I TN and HER2+ disease remains controversial, given the limited burden of disease at presentation with most patients considered candidates for limited surgery, and the excellent overall outcomes with de-escalated systemic therapy regimens in the adjuvant setting. This presentation will discuss the evolving landscape and current standards for stage I TN and HER2+ disease.

Citation Format: A. Mamtani. Surgical management of Stage I TN and HER2+ breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr ED05-03.
Abstract ED11-01: Is inflammatory breast cancer a genomically different type of breast cancer?
Authors: Howard F.
Published: May 2024

Inflammatory Breast Cancer (IBC) is a unique and aggressive disease, constituting 2 - 4% of breast cancer diagnoses yet responsible for up to 10% of breast cancer related deaths. IBC remains a clinical diagnosis, without highly specific molecular markers, and the genomic drivers of the disease are incompletely characterized. The overrepresentation of human epidermal growth factor 2 amplification and triple-negative disease within IBC have confounded comparisons between IBC and non-IBC. Nonetheless, some consistent genomic observations have emerged that may begin to explain the characteristic behavior of IBC, supported by both comparative clinical studies and preclinical models. This session will review mutational analysis, gene expression profiling, and epigenetic findings that highlight similarities as well as subtle differences between IBC and non-IBC.

Citation Format: F. Howard. Is inflammatory breast cancer a genomically different type of breast cancer? [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr ED11-01.
Abstract PO1-04-04: Inetetamab combined with pyrotinib and oral vinorelbine for patients with HER2-positive metastatic breast cancer: a single-arm phase 2 trial
Authors: Huang Xiang , Jin Nan , Sun Chunxiao , Yan Xueqi , Yang Fan , Liang Yan , Li Wei , Yin Yongmei
Published: May 2024

Aim: The efficacy and safety of inetetamab in combination with pyrotinib and oral vinorelbine was investigated in patients with human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer. Methods: In this prospective, single-arm, phase 2 trial, patients with HER2-positive metastatic breast cancer after progression on trastuzumab were recruited. Patients received combined treatment of inetetamab (loading dose of 8 mg/kg, subsequent doses 6 mg/kg, intravenously once every 3 weeks) plus pyrotinib (400 mg orally once daily) plus vinorelbine (60 mg/m2 orally once weekly) until disease progression or intolerable toxicity. The primary endpoint was progression free survival (PFS). Secondary endpoints included objective response rate (ORR), overall survival (OS), disease control rate (DCR) and safety. The study was retrospectively registered in ClinicalTrials.gov on March 23rd, 2023. The registration number is NCT05823623. Results: Between Jan 1, 2022, and Dec 31, 2022, thirty patients were screened and enrolled to this study. The patients’ median age at enrollment was 54 years, twelve patients (40.0%) had hormone receptor-positive disease and 23 patients (76.7%) had visceral metastasis. The median PFS was 8.63 months (95% confidence interval [CI] 4.15 to 13.12 months). ORR was 53.3% (16/30) and DCR reached 96.7% (29/30). The most common grade III/IV adverse events included leukopenia (5[16.7%]), neutropenia (4[13.3%]) and diarrhea (3[10%]). No treatment-related serious adverse events or treatment-related deaths occurred. Conclusions: The combination regimen of inetetamab plus pyrotinib plus oral vinorelbine showed an encouraging efficacy and favorable safety in patients with HER2 positive metastatic breast cancer.

Citation Format: Xiang Huang, Nan Jin, Chunxiao Sun, Xueqi Yan, Fan Yang, Yan Liang, Wei Li, Yongmei Yin. Inetetamab combined with pyrotinib and oral vinorelbine for patients with HER2-positive metastatic breast cancer: a single-arm phase 2 trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-04-04.
Abstract PO1-07-04: Multiomics analysis reveals the landscape of PD-L1 expression in triple-negative breast cancer
Authors: Wang Han , Ding Xiao-Hong , Liu Cheng-Lin , Xiao Yi , Shui Ruo-Hong , Li Yan-Ping , Chen Chen , Yang Wen-Tao , Shao Zhi-Ming , Jiang Yi-Zhou
Published: May 2024

Background: Tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) remain controversial in predicting clinical outcomes of triple-negative breast cancer (TNBC), as outcomes do not always correlate with the expression of these biomarkers. Genomic and transcriptomic alterations that might contribute to the expression of these biomarkers remain incompletely uncovered. Methods: We evaluated PD-L1 immunohistochemistry (IHC) scores (SP142 and 28-8) and TILs in our TNBC multiomics dataset and two immunotherapy clinical trial cohorts. Then, we analyzed genomic and transcriptomic alterations correlated with TILs, PD-L1 expression and patient outcomes. Results: Despite TILs serving as a decent predictor for TNBC clinical outcomes, there remained exceptions. Our study revealed that several genomic alterations were correlated with unexpected events. Particularly, PD-L1 expression may cause a paradoxical relationship between TILs and prognosis in certain patients. Consequently, we classified TNBCs into four groups based on PD-L1 and TIL levels. The TIL-PD-L1+ and TIL+PD-L1- groups were not typical “hot” tumors; both were associated with worse prognoses and lower immunotherapy efficacy than TIL+PD-L1+ tumors. Copy number variation of PD-L1 and oncogenic signaling activation were correlated with PD-L1 expression in the TIL-PD-L1+ group, whereas GSK3B-induced degradation might cause undetectable PD-L1 expression in the TIL+PD-L1- group. These factors have the potential to affect the predictive function of both PD-L1 and TILs. Conclusions: Several genomic and transcriptomic alterations may cause paradoxical effects among TILs, PD-L1 expression and prognosis in TNBC. Investigating and targeting these factors will advance precision immunotherapy for TNBC patients. Keywords: Triple-negative breast cancer, PD-L1 expression, Tumor-infiltrating lymphocytes, Multiomics, Immunotherapy

Citation Format: Han Wang, Xiao-Hong Ding, Cheng-Lin Liu, Yi Xiao, Ruo-Hong Shui, Yan-Ping Li, Chen Chen, Wen-Tao Yang, Zhi-Ming Shao, Yi-Zhou Jiang. Multiomics analysis reveals the landscape of PD-L1 expression in triple-negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-07-04.
Abstract PO1-07-08: Value of high resolution full field optical coherence tomography and dynamic cell imaging (D-FFOCT) for one-stop rapid diagnosis breast clinic
Authors: Simon Alexis , Badachi Yasmina , Ropers Jacques , Laurent Isaura , Dong Lida , Da Maia Elisabeth , Bourcier Agnes , Canlorbe Geoffroy , Uzan Catherine
Published: May 2024

BACKGROUND: Full field optical coherence tomography combined to dynamic cell imaging (D-FFOCT) is a new, simple to use, nondestructive, quick technique than can provide sufficient spatial resolution to mimic histopathological analysis. The objective of this study was to evaluate diagnostic performance of D-FFOCT for one-stop rapid diagnosis breast clinic. METHODS: D-FFOCT was applied to fresh untreated breast and nodes biopsies. Four different readers (senior and junior radiologist, surgeon and pathologist) analyzed the samples without knowing final histological diagnosis or ACR classification. The results were compared to conventional processing and staining (Hematoxylin-eosin). RESULTS: A total of 217 biopsies were performed on 152 patients. There were 144 breast biopsies and 61 lymph nodes with 101 infiltrative cancers (49,27%), 99 benign lesions (48,29%), 3 ductal in situ carcinoma (1,46%) and 2 atypias (0,98%). The diagnostic performances results were as follow: sensitivity: 77% [0.7;0.82], specificity: 64% [0.58;0.71], PPV: 74% [0.68;0.78] and NPV: 75% [0.72;0.78]. A large images atlas was created as well as a diagnosis algorithm from the readers experience. CONCLUSION: D-FFOCT provides interesting results defining malignancy on fresh breast and nodes samples. By training with the diagnosis algorithm and the images atlas or by using machine learning, radiologists could obtain even better outcomes allowing quick detection of breast cancer and lymph node involvement.

diagnosis algorithm

Figure 1 Images in DCI and FFOCT

Two infiltrating cancer diagnosed on pathology (A,B). Focusing on cells (C). Normal galactophoric duct (D). Adenofibroma (E)

Citation Format: Alexis Simon, Yasmina Badachi, Jacques Ropers, Isaura Laurent, Lida Dong, Elisabeth Da Maia, Agnes Bourcier, Geoffroy Canlorbe, Catherine Uzan. Value of high resolution full field optical coherence tomography and dynamic cell imaging (D-FFOCT) for one-stop rapid diagnosis breast clinic [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-07-08.
Abstract PO1-08-05: Using the CTS5 Score to Predict Late Recurrence in Male and Female Estrogen Receptor-Positive Breast Cancer Patients: a SEER database analysis of 65,729 cases
Authors: Wang Fenhua , Ren Fang , Qian Jian , Xu Yunxia , Wu Jiayi , Zong Yu , Gu Xidong
Published: May 2024

Purpose: The Clinical Treatment Score post-5 years (CTS5) score is a prognostic prediction tool to predict the risk of late distant recurrence in postmenopausal women with estrogen receptor-positive (ER+) breast cancer. Here we aimed to evaluate the prediction role of CTS5 in male breast cancer patients using the Surveillance, Epidemiology, and End Results (SEER) database. Methods: ER+ early male and female breast cancer patients from the SEER database 2010-2013 were included. Clinicopathological features and the CTS5 score between the gender groups were compared using chi-square test. Overall survival (OS) and breast cancer-specific survival (BCSS) were estimated by Kaplan-Meier plots and compared between the groups with Log-rank test and multivariate cox proportional hazard regression models was used to determine the relationship between the CTS5 score and breast cancer survival outcomes in different gender cohorts. Results: A total of 65,729 ER+ breast cancer patients were included in the study and 611 were men. Male breast cancer was more likely to be diagnosed later in life (>50 years old, 87.1% vs 73.6%, p < 0.001), with more aggressive biological features (grade Ⅱ 51.6% vs 47.2%, p < 0.001; grade Ⅲ 37.8% vs 28.3%, p < 0.001) , and higher tumor burden (stage Ⅱ 45.8% vs 32.9%, p < 0.001, stage Ⅲ 17.5% vs 10.5%, p < 0.001) when compared to female counterparts. More male patients were CTS5 intermediate- or high-risk than female patients (high 7.9% vs 6.3%, intermediate 41.1% vs 24.6%, low 51.1% vs 69.1%, p < 0.001). Patients were divided into 0-5 year and >5 year cohorts based on whether they had a BCSS event within 5 years. In the >5 year cohort, patients with CTS5 high- or intermediate- risk had worse survival outcomes compared with low-risk cases in male and postmenopausal female patients but not in premenopausal female patients. In the 0-5 year cohort, the CTS5 score was not predictive for disease recurrence in male or postmenopausal patients. Conclusion: Male breast cancer patients were more likely to have aggressive tumors and worse survival outcomes. The CTS5 score could be applied to predict breast cancer-specific mortality risk beyond 5 years in male ER+ breast cancer patients.

Citation Format: Fenhua Wang, Fang Ren, Jian Qian, Yunxia Xu, Jiayi Wu, Yu Zong, Xidong Gu. Using the CTS5 Score to Predict Late Recurrence in Male and Female Estrogen Receptor-Positive Breast Cancer Patients: a SEER database analysis of 65,729 cases [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-08-05.
Abstract PO1-08-11: The survival rate of hereditary breast cancer in young women of Kazakh population
Authors: Kaidarova Dilyara , Omarbayeva Nazgul , Abdrakhmanova Aliya , Shatkovskaya Oxana , Omarov Dilyar
Published: May 2024

Background

The study focused on determining survival rates between breast cancer patients with various germinal mutations and those without mutations among Kazakh women. Methods

The study included 222 female patients of Kazakh ethnic group diagnosed with stage I-IV stage breast cancer at the age up to 40 years old. DNA samples were tested by next-generation sequencing on the MiSeq Illumina platform using Trusight Cancer kit for the analysis of 94 genes and 287SNPs. Information about dates of diagnosis and death retried from cancer registry system. Survival analyses were performed and compared mutation carriers and non-carriers subgroups. The 5-year survival was calculated using the Kaplan-Meier method. Results

Next generation sequencing test identified 11 various pathogenic mutations in 57(25.7%) of overall 222 patients. The 5-year survival analysis for mutation carriers were 72.1%and 82.1% for non-carriers, with no statistically significant difference(P0.232). When stratified by mutational type, the 5-year survival rates were 71.8% for BRCA1 carriers, 81.3% for BRCA2, 53.35% for TP53 and 50% for moderate risk gene PALB2 mutation. These findings suggest that mutations in certain genes may be associated with differences in survival outcomes. Conclusions

In breast cancer patients of Kazakh population similar to the world prevalence and predictive value of germline mutations have been found. A subcohort of mutation carriers and non-carriers demonstrated no significant difference in 5-year survival rate which may be associated with an early onset of disease, high-risk predictor of poor prognosis. Long-term survival and detailed PFS will be published according to information of follow-up visits and the cancer register system.

Citation Format: Dilyara Kaidarova, Nazgul Omarbayeva, Aliya Abdrakhmanova, Oxana Shatkovskaya, Dilyar Omarov. The survival rate of hereditary breast cancer in young women of Kazakh population [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-08-11.
Abstract PO1-12-01: 'Not even my husband knows that I have this [breast cancer]': Survivors’ Experiences in Accessing, Navigating and Coping with Treatment
Authors: Chidebe Runcie C.W. , Orjiakor Tochukwu C. , Okwu Gloria C. , Orji Mary-Gloria A. , Nwosu-Zita THEODORA , Agha Agha A. , Aruah Simeon C. , Okem-Akwiwu Chika , Nwakasi Candidus C. , Gyimah Akwasi Adjei , Shinkafi-Bagudu Zainab , Okoye Ifeoma J. , Esiaka Darlingtina K.
Published: May 2024

Purpose: Nigeria has the highest breast cancer (BC) burden in Africa. While the survival rates for BC are over 90% in many high-income countries; low-and middle-income countries like Nigeria have 40% BC survival rates. Prior studies show that the burden and poor BC survival rates are exacerbated by both health system and individual level factors, yet there is a paucity of literature on the experiences of BC survivors in Nigeria. Hence, this study explored BC survivors' divergent and convergent experiences in accessing, navigating, and coping with treatment.

Methods: Participants (N=24, aged 35 to 73 years) were recruited and engaged in focus group discussions (Group 1, n = 11; Group 2, n = 13 participants). Transcripts were transcribed verbatim and analyzed with inductive thematic analysis.

Results: Four themes were identified: “I am carrying this [breast cancer] alone”, “Living my life”, “‘God’ helped me”, and “A very painful journey”. Participants described how they concealed their BC diagnosis from family and significant others while accessing and navigating BC treatment. Also, they adopted spiritual beliefs as a coping mechanism while sticking to their treatment and acknowledging the burden of BC on their wellbeing.

Conclusions: Our findings point to the urgent need for improved BC treatment facilities in Nigeria.

Implications for Breast Cancer Survivors: Nigeria BC survivors are navigating both limited treatment facilities and coping with the personal challenges of BC diagnosis. There is a need for the government and clinicians to explore innovative technologies in improving BC treatment experiences in Nigeria.

Citation Format: Runcie C.W. Chidebe, Tochukwu C. Orjiakor, Gloria C. Okwu, Mary-Gloria A. Orji, THEODORA Nwosu-Zita, Agha A. Agha, Simeon C. Aruah, Chika Okem-Akwiwu, Candidus C. Nwakasi, Akwasi Adjei Gyimah, Zainab Shinkafi-Bagudu, Ifeoma J. Okoye, Darlingtina K. Esiaka. 'Not even my husband knows that I have this [breast cancer]': Survivors’ Experiences in Accessing, Navigating and Coping with Treatment [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-12-01.
Abstract PO1-15-08: Genomic characterization of triple-negative breast cancer metastases reveals PKD1 as a novel biomarker for immunotherapy
Authors: Zhu Xiu-Zhi , Zhou Yi-Fan , Wang Yun-Yi , Ding Xiao-Hong , Jin Xi , Shao Zhi-Ming , Jiang Yi-Zhou , Wang Zhong-Hua
Published: May 2024

Background: While primary triple-negative breast cancer (TNBC) garners significant research attention, the genomic alterations that occur in metastasis remain insufficiently understood, especially within Asian populations. Furthermore, the genomic information obtained from the primary tumor inadequately guides metastatic cancer treatment, highlighting the critical need for in-depth investigations into metastatic TNBC. Methods: We constructed the largest cohort of TNBC metastases (n = 296) among advanced TNBC patients treated at Fudan University Shanghai Cancer Center (FUSCC) between October 2018 and December 2020. Comprehensive DNA sequencing was conducted on the collected metastatic samples to analyze genomic alterations associated with treatment response. The underlying mechanisms of specific biomarkers were also explored. Results: We presented the genomic landscape of 296 TNBC metastases, encompassing mutant genes, mutation sites and copy number variations. Through multidimensional analysis, significant disparities in TNBC were observed between Western and Asian populations, primary and metastatic tumors, as well as different metastatic sites. Notably, our findings underscore the importance of sequencing TNBC metastases to guide precision therapy, which was associated with longer progression-free survival compared to physician-chosen treatments, shedding light on the pivotal clinical value of genomic studies in metastatic settings. Furthermore, efficacy analysis suggested that PKD1 mutations enriched in metastases mediated resistance to immunotherapy. These findings were further validated through three clinical trials (NCT03805399, NCT04129996, and NCT04395989). Mechanistic studies unveiled the involvement of PKD1 in TNBC immune evasion by upregulating CCL2, thereby facilitating the recruitment of M2-type tumor-associated macrophages. Conclusion: Our study emphasizes the critical significance and necessity of genomic profiling of metastases in guiding precision therapy for TNBC. Moreover, our findings reveal PKD1 as a novel and promising biomarker for immunotherapy.

Citation Format: Xiu-Zhi Zhu, Yi-Fan Zhou, Yun-Yi Wang, Xiao-Hong Ding, Xi Jin, Zhi-Ming Shao, Yi-Zhou Jiang, Zhong-Hua Wang. Genomic characterization of triple-negative breast cancer metastases reveals PKD1 as a novel biomarker for immunotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-15-08.
Abstract PO1-18-02: Histologic grade is a better predictor of specific survival than Ki67 in localized ER+/HER2- breast cancer: a real-world study
Authors: SÁNCHEZ Cesar , Alejandro Cataldo , Walbaum Benjamin , ACEVEDO FRANCISCO , Constabel Christine , Saure Antoine , Rey Pablo
Published: May 2024

Introduction: Breast cancer (BC) is the most common cancer in women. The determination of prognostic factors is relevant for the decision of systemic therapy. Objective: To determine, in the real world, the prognostic role of Ki67 and histologic grade (HG) in patients with non-metastatic BC in two cancer centers; an academic and a community hospital. Methodology: Retrospective analysis of a longitudinal BC patients registry. Clinicopathological characteristics and disease specific survival (DSS) of women diagnosed in stages I/II/III between the years 2012-2021 were analyzed. Results: We evaluated 3,969 cases that met the inclusion criteria. In the univariate analysis, prognostic factors significantly associated with DSS were: reason for consultation (screening vs symptoms), stage, hormone receptor status, HG and Ki67. On multivariate analysis, stage III, Ki67 ≥20%, and GH3 were significantly associated with a risk of death of 4.41, 2.52, and 1.92; respectively, regardless of the treatment center and BC subtype. However, in the hormone receptor positive (HR+)/HER2 + group the HG presented greater discriminatory power than Ki67. Hazard ratio 2.0 for both, but not statistically significant for Ki67. The ROC-AUC curves for Ki67 indicated that the best cut-off point for DSS was 20%, for the entire cohort and also for the HR+/HER2- group. Conclusions: The behavior of the prognostic variables was expected and coincided with the literature. HG seems to be a better predictor of specific mortality in HR+ BC. Ki67 showed a cut-off value consistent with that suggested by expert consensus.

Citation Format: Cesar SÁNCHEZ, Cataldo Alejandro, Benjamin Walbaum, FRANCISCO ACEVEDO, Christine Constabel, Antoine Saure, Pablo Rey. Histologic grade is a better predictor of specific survival than Ki67 in localized ER+/HER2- breast cancer: a real-world study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-18-02.
Abstract PO1-20-11: Delay in Diagnosis of Locally Advanced Breast Cancer during Lactation “Case Report”
Authors: Banda Jesus Flores , Donthireddy Kavitha
Published: May 2024

A 38-year-old breastfeeding female with no family history of breast or gynecological cancer presented to her PCP with a 4-month history of galactorrhea and enlarged left-sided breast mass. On physical exam, a 4-inch round complex, nonmobile, non-tender mass in the left breast and bloody-to-pink discharge from the nipple was present on the exam. Diagnostic mammogram and US revealed BIRADS 5, microcalcifications consistent with DCIS, 4-cm mass, with a positive lymph node (LN), and needle core biopsy of both breast and LN, showed DCIS and metastatic carcinoma, respectively. Further workup did not show distant or skeletal metastatic disease. Therefore, a diagnosis was made, and the patient was provided a clinical-stage cT3, cN2, cM0, ER+, PR-, and HER2+. The patient completed neoadjuvant therapy with TCHP and underwent a left lumpectomy with sentinel LN biopsy. Additionally, pathology diagnosis showed scant residual DCIS (10mm) and no metastatic disease in the LN. After that, the patient completed adjuvant radiotherapy and was placed on adjuvant therapy with trastuzumab and pertuzumab. In conclusion, any breast abnormality reported by a pregnant or breastfeeding woman should not be neglected and assumed that it is a regular and physiological change until proven otherwise. Future proposals include guidelines for managing abnormal breast findings during pregnancy.

Citation Format: Jesus Flores Banda, Kavitha Donthireddy. Delay in Diagnosis of Locally Advanced Breast Cancer during Lactation “Case Report” [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-20-11.
Abstract PO1-22-04: Cosmetic results of the breast in patients treated with Five Fraction Accelerated Partial Breast Irradiation for early stage breast cancer: retrospective review comparing Daily versus Every Other Day Treatment
Authors: Goss Alex , Haroz Ellaine , Voltura Anna , McGrath Jennifer , Sloan Olivia , Jackson Matthew , Morris Savvas , Goss Bryan
Published: May 2024

Introduction: Breast cosmesis results using Accelerated Partial Breast Irradiation (APBI) with IMRT external beam in 5 fractions (6Gy x 5 fractions) has been reported as good to excellent in the literature. This retrospective review compares breast cosmesis in patients treated with Daily versus Every Other Day APBI in the community practice setting. Methods: The patient electronic medical records (EMR) were used to identify APBI patients treated at the community cancer center with the 6Gy x 5 fraction regimen. Harvard breast cosmesis four point scale results (poor, fair, good, excellent results) were extracted for each treated APBI patient from clinical notes in the EMR to rate breast cosmesis. For many patients in this review, provider reporting of cosmesis in the EMR overlapped good and excellent categories and so a “good to excellent” score was assigned. Therefore, a three point scale was utilized in statistical analysis (poor-1, fair-2, good to excellent-3). Results: There were 62 patients treated with APBI at a single institution with greater than 6 months follow up (18 patients treated daily and 44 patients treated every other day). Median follow up was 12 months (range 6- 32 months). Of all patients treated there were 0 with poor cosmesis, 3 with fair (1 every other day treatment, 2 every day treatment), 59 with good to excellent cosmesis. Univariate logistical regression analysis revealed no significant difference between daily and every other day treatment (p=0.457) Conclusion: With careful patient selection, quality planning and treatment delivery, good to excellent cosmesis is achievable in the great majority of patients undergoing breast APBI (6Gy x 5 fractions) using IMRT in the community radiation oncology clinic with either daily or every other day treatment. More study is needed, but in this review cosmetic differences seem to be minimal between daily and every other day treatment schedules.

Citation Format: Alex Goss, Ellaine Haroz, Anna Voltura, Jennifer McGrath, Olivia Sloan, Matthew Jackson, Savvas Morris, Bryan Goss. Cosmetic results of the breast in patients treated with Five Fraction Accelerated Partial Breast Irradiation for early stage breast cancer: retrospective review comparing Daily versus Every Other Day Treatment [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-22-04.
Abstract PO1-25-09: A new generation of breast cancer modeling has been achieved through somatic precision gene editing, offering high flexibility and efficiency
Authors: Bu Wen , li Yi
Published: May 2024

Breast cancer, along with many other cancers, is primarily caused by genetic mutations, typically involving the alteration of nucleotides (A, G, C, T) within genes (with a total of 12 possible mutations). Gene sequencing advancements have facilitated the identification of numerous gene mutations in tumor samples. However, comprehending the precise mechanisms through which these gene mutations contribute to tumor initiation, development, and their impact on tumor characteristics cannot be solely determined from these findings. Therefore, it is crucial to observe the influence of mutations on tumor initiation and development from the moment they occur. Since conducting such observations in human subjects is impractical, animal models with simulated gene mutations have become essential for studying tumor initiation and development.

Mice, with a genome comprising approximately 2.7 billion nucleotides, are commonly used as animal models in cancer research due to their cost-effectiveness and high similarity to humans. About 90% of their genes share similar functions, particularly those associated with cancer development. However, achieving precise alterations to specific nucleotides among the 2.7 billion nucleotides within live mouse cells (with a total of 12 possible changes) has presented significant technical challenges. In this study, we present modifications to the CRISPR/Cas9 vector system, enabling homology-directed repair-mediated precise editing of any proto-oncogene in murine somatic mammary epithelial cells, thereby generating mammary tumor models with exceptional flexibility and efficiency. The resulting tumors exhibit significant advantages over traditional mouse models. This technological breakthrough bridges the gap between the potential of CRISPR technology and the accuracy of mouse models, facilitating the study of human tumor evolution and preclinical drug testing.

Citation Format: Wen Bu, Yi li. A new generation of breast cancer modeling has been achieved through somatic precision gene editing, offering high flexibility and efficiency [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-25-09.