bluuebunny/crossref_metadata_2025_split huggingface dataset:
The age and origin of the South Mountain Batholith (Nova Scotia, Canada) as constrained by zircon U–Pb geochronology, geochemistry, and O–Hf isotopes
Authors: Bickerton Luke , Kontak Daniel J. , Murphy J. Brendan , Kellett Dawn A. , Samson Iain M. , Marsh Jeffrey H. , Dunning Greg , Stern Richard 
Published: March 2022

The South Mountain Batholith (SMB; Nova Scotia, Canada) is the largest composite batholith exposed in the Appalachians and lies entirely within the most outboard Meguma terrane. In situ and CA–TIMS U–Pb dating and in situ isotopes (Lu–Hf, O) and geochemistry for zircon from all phases of the SMB constrain its source as well as its evolution. CA–ID–TIMS for zircon yields emplacement (autocryst) ages, indicating a transition from granodiorite (378.7 ± 1.2 to 375.4 ± 0.8 Ma) to leucogranite (375.4 to 371.8 ± 0.8 Ma) over several million years. Furthermore, in situ SHRIMP, LA–MC–ICP–MS, and SIMS analyses of distinct zircon domains reveal: (1) abundant ancient xenocrysts (∼420 Ma to 2.2 Ga); (2) antecryst ages ca. 3–15 million years older than SMB emplacement; (3) autocryst δ18O values between +7.3‰ and +9.1‰ (V-SMOW); (4) similar isotopes, REE signatures, and derived fO2 values among antecrysts and autocrysts; and (5) εHf values from the 371.8 ± 0.8 Ma Davis Lake Pluton (DLP) autocrysts that are higher (+1.74 to +4.38) than the rest of the SMB (−2.99 to +1.68). Collectively, these data suggest a protracted magmatic evolution for the SMB with melt generation and assembly from ∼390 to 370 Ma via melting of a metasomatized mantle source followed by contamination, first from the structurally underlying Avalonian terrane and later by metasedimentary wall rocks of the Meguma terrane. The most southwesterly part of the SMB (i.e., DLP) represents a petrogenetically distinct magmatic phase that underwent less overall contamination than the rest of the SMB.
Weathering processes and forms
Authors: Trudgill Stephen T. , Goudie Andrew S. , Viles Heather A. 
Published: March 2022

Abstract
This chapter considers the various processes of rock weathering, starting with physical weathering processes (frost, wetting and drying, heating and cooling or insolation weathering, and salt weathering (haloclasty)). It then turns to a consideration of chemical weathering processes and to the remarkable increase of interest in biological (organic) processes. This is followed by a discussion of rates of weathering and the techniques that have been developed to study them, including the analysis of sediment loads and the measurement of surface changes with instruments like the micro-erosion meter. The global carbon cycle and the links between geomorphology and soils are also considered. Progress in the study of weathering forms such as alveoli, pits and tafoni is described. There is also a discussion of materials deposited as a consequence of chemical weathering, such as various types of duricrust. Finally, weathering hazards are addressed together with an assessment of the ways in which humans have accelerated some weathering processes.
Abstract ES1-2: Genomics of HER2+ breast cancer
Authors: Perou C 
Published: March 2022

Abstract
Human epidermal growth factor receptor 2 (HER2) is amplified and overexpressed in about 20% ofall breast cancers and, when untreated, is the most aggressive breast cancer phenotype. The prognosis of patients with HER2-positive breast cancer has been markedly improved thanks to the effectiveness of anti-HER2 therapies. However, we still overtreat a high proportion of patients with toxic chemotherapy +antiHER2 combinations, while others still develop recurrent disease despite these complex regimens. Both the intrinsic complexity of HER2-positive tumors and the properties of its tumor microenvironment likely contribute to differences in response toanti-HER2 targeted therapies. HER2-positive breast cancer is highly heterogeneous, and all the intrinsic molecular subtypes can be identified within HER2-positive tumors by gene expression. HER2-enriched subtype has been systematically associated with higher pCR rates to anti-HER2 targeted therapies across multiple trials in early stages. Genomically, the HER2-enriched subtype is the most HER2 oncogene addicted of the subtypes, which likely explains the high sensitivity to anti-HER2 therapies. However, this may also explain why a HER2-enriched tumor with residual disease after anti-HER2 treatments carries a particularly poor prognosis. Conversely, both tumor-infiltrating lymphocytes (TILs) and RNA-based immune-signatures are significantly and independently associated with a higher likelihood of pCR and better survival outcomes in patients with HER2-positive disease. Thus, integrating the prognostic information provided by clinical factors, genomic subtype, and immune-related signatures is essential to improve the design of future clinical trials and establish new and better treatment algorithms for HER2-positive breast cancer treatment.
Citation Format: C Perou. Genomics of HER2+ breast cancer. [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr ES1-2.
Abstract ES13-1: Targeting EZH2 functions
Authors: Kleer CG 
Published: March 2022

Abstract
Anaplasia, or loss of mature specialized features, is a characteristic of malignant cells. Thus, it is not surprising that deregulation of proteins that govern cell type identity may lead to cancer. EZH2, a Polycomb group protein which regulates transcriptional memory in normal cells through H3K27 trimethylation, is overexpressed in breast cancer compared to normal breast, and is a tissue-based biomarker of survival in patients with breast cancer. EZH2 enhances breast cancer initiation and progression, making it a desirable therapeutic target with several inhibitors already in clinical trials. While the main mechanism of EZH2 oncogenic function has been ascribed to trimethylation of H3K27, mounting evidence supports that EZH2 also functions through non-canonical H3K27me3-independent mechanisms, especially in triple negative breast carcinomas (TNBC). These include transcriptional activation through direct binding to the NOTCH1 promoter to regulate cancer stem cells, and EZH2 phosphorylation at specific sites to either reduce affinity for histone H3 and/or increase binding to nonhistone proteins to promote metastasis. This body of work highlights the importance of blocking EZH2 H3K27me3-dependent as well as non-canonical functions in TNBC to improve outcomes. In this Educational Session, I will discuss current insights into EZH2 oncogenic mechanisms in TNBC including metaplastic carcinomas, an aggressive and chemoresistant TNBC subtype. We will also discuss how the discovery of novel EZH2 mechanisms may set the stage for the development of previously unconsidered therapeutic opportunities.
Citation Format: CG Kleer. Targeting EZH2 functions [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr ES13-1.
Abstract ES6-3: Immunotherapy vs Capecitabine for Triple Negative Breast Cancer
Authors: Loi S 
Published: March 2022

Abstract
Immunotherapy vs capecitabine for triple negative breast cancer. Educational session. Sherene Loi, MD, PhDPeter MacCallum Cancer Centre, Melbourne, Australia. Neoadjuvant treatment is now standard of care for the majority of early stage triple negative breast cancer (TNBC), with the achievement of non-pathological complete response (pCR) the main indicator to escalate treatment. Until recently only capecitabine was used in this setting. 2021 has seen reporting of the OlympiA adjuvant study, which reports major benefits for olaparib in germline BRCA positive TNBC patients, though a minority. KEYNOTE522 has now set the scene for incorporating neoadjuvant pembrolizumab with chemotherapy in early stage TNBC, with significantly improved event free survival, particularly those that do not achieve pCR. In this talk I will examine how we can rationally think about treating these patients with the available options.
Citation Format: S Loi. Immunotherapy vs Capecitabine for Triple Negative Breast Cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr ES6-3.
Abstract ES8-4: Axillary management in upfront surgery - staging, local control or both?
Authors: Wong S 
Published: March 2022

Abstract
Axillary management in women undergoing upfront surgery for operable breast cancer has changed dramatically over the last several decades. Axillary lymph node dissection (ALND), a procedure that was historically used in both clinically node negative and node positive patients to stage the axilla and optimize locoregional control, is associated with the potential for significant long-term morbidity in the form of upper extremity lymphedema, paresthesia, and shoulder dysfunction. Efforts to minimize the morbidity associated with ALND, as well as the recognition that only a minority of patients with clinically node negative disease are found to have nodal metastases at the time of axillary surgery, prompted the development and validation of sentinel lymph node biopsy (SLNB). In women who are clinically node negative, SLNB has been shown to accurately stage the axilla without compromising oncologic outcomes, identifying nodal disease in up to 30% of cases. The application of clinical trial data from Z0011 and AMAROS in T1-T2 breast cancer with 1-2 positive lymph nodes undergoing breast conservation allow for omission of completion ALND with no impact on locoregional control or survival. The ongoing POSNOC trial (NCT02401685) will further determine whether women with T1-T2 disease undergoing breast conservation or mastectomy require directed axillary treatment in the form of ALND or axillary radiation to minimize the risk of axillary failure. An altogether omission of axillary staging in clinically node negative breast cancer remains an area of evolving interest, with CALGB 9343 trial data supporting this approach in older women with stage I estrogen-receptor positive (ER+) HER2- breast cancer. Trials examining the omission of SLNB in other select patient populations with negative axillary imaging are the subject of ongoing investigation. At present, prognostic information derived from SLNB for clinically node negative women undergoing upfront surgery for early-stage triple negative and HER2+ breast cancer, premenopausal ER+HER2- breast cancer, and BRCA1/2-associated breast cancer remain important for adjuvant systemic therapy decision-making.
Citation Format: S Wong. Axillary management in upfront surgery - staging, local control or both? [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr ES8-4.
Abstract MS1-1: CRISPR screens to identify novel DNA repair defects synthetic lethal therapies
Authors: Durocher D 
Published: March 2022

Abstract
The orchestration of DNA repair is of fundamental importance to the maintenance of genomic integrity and tumor suppression. DNA damage must be detected in the context of the varied chromatin landscape, its presence must be communicated throughout the cell to alter many ongoing processes, and the machinery that will mend the lesion must be recruited to the damage site. In my presentation, I will discuss our recent efforts in mapping genome maintenance pathways using genome-scale CRISPR/Cas9 screens in human cells. I will highlight how these screens can also identify potentially actionable synthetic lethal genetic interactions that could form the basis of new oncology drug discovery efforts. I will focus particularly on our efforts to uncover and characterize the synthetic lethal interaction network surrounding BRCA1 and BRCA2 deficiency, as well as our work that led to the discovery that inhibition of the PKMYT1 kinase is lethal in cells with amplification in the cyclin E-coding gene, CCNE1.
Citation Format: D Durocher. CRISPR screens to identify novel DNA repair defects synthetic lethal therapies [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr MS1-1.
Abstract OT1-12-02: Trial in progress: Phase 2, open-label study to evaluate the safety and efficacy of praluzatamab ravtansine in metastatic HER2 non-amplified breast cancer as monotherapy and combination with pacmilimab
Authors: Miller Kathy , Emens Leisha A. , Tolaney Sara M. , Hurvitz Sara A. , Hamilton Erika , Paton Virginia , Hannah Alison , Boni Valentina 
Published: March 2022

Abstract
Background: Probody® therapeutic candidates (Pb-Tx) are masked antibodies designed to be conditionally activated in the tumor microenvironment by tumor-associated proteases. This allows Pb-Tx to address previously undruggable targets that are highly expressed in both tumor and normal tissues. Praluzatamab ravtansine is a masked antibody-drug conjugate targeting CD166 with a DM4 payload. A phase 1 monotherapy study showed safety and durable clinical activity (clinical benefit rate at 24 weeks [CBR24] 28%) in patients (pts) with metastatic HR-positive/HER2 non–amplified breast cancer (mHR+/HER2− BC) or metastatic triple-negative breast cancer (mTNBC). Pacmilimab, a masked PD-L1 inhibitor, demonstrated monotherapy activity in pts with TNBC with an acceptable tolerability profile.Trial design: This phase 2, open-label study with 3 parallel arms (~40 evaluable/arm) will evaluate praluzatamab ravtansine monotherapy (7 mg/kg Q3W) in pts with mHR+/HER2− BC or mTNBC, and praluzatamab ravtansine (7 mg/kg Q3W) combined with pacmilimab (1200 mg Q3W) in pts with mTNBC. Adult pts with an ECOG PS 0–1, measurable disease, and willingness to receive ocular prophylaxis for DM4-related toxicities will be enrolled. Key eligibility criteria for the mHR+/HER2− BC cohort include 2–4 prior regimens in the metastatic setting (excluding single-agent endocrine therapy). No CD166 screening required for HR+/HER2− BC but mTNBC must be CD166+. Pts with mTNBC must have received 1–3 prior metastatic regimens. For mTNBC pts who receive the doublet, key exclusion criteria include known PDL1 negative tumor, history of autoimmune disease, and progression within 120 days of 1st dose of an immuno-oncology agent. Pts with corneal disorders will be excluded. Primary endpoint is overall response rate (ORR) assessed by an independent radiology committee per RECIST v1.1. Secondary endpoints include ORR by investigator, duration of response, CBR16 & 24, progression-free survival, and overall survival. This study will also evaluate safety and tolerability, pharmacokinetics, and antidrug antibodies with praluzatamab ravtansine as monotherapy and in combination with pacmilimab. This trial is enrolling (NCT04596150).
Citation Format: Kathy Miller, Leisha A. Emens, Sara M. Tolaney, Sara A. Hurvitz, Erika Hamilton, Virginia Paton, Alison Hannah, Valentina Boni. Trial in progress: Phase 2, open-label study to evaluate the safety and efficacy of praluzatamab ravtansine in metastatic HER2 non-amplified breast cancer as monotherapy and combination with pacmilimab [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-12-02.
Abstract OT2-28-01: A phase 2 study of sitravatinib in metastatic, pre-treated, triple negative breast cancer, NCT # 04123704
Authors: Shafaee Maryam Nemati , Otte Kristen , Neill Nicholas J , Osborne Kent C , Westbrook Thomas F , Hilseneck Susan , Ellis Matthew J 
Published: March 2022

Abstract
Background:Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer, disproportionally affecting African American and Hispanic patients, and germline BRCA1/2 mutation carriers. Prognosis of relapsed, metastatic disease is extremely poor and effective well-tolerated therapies are urgently needed. Our collaborators have discovered that TNBCs often lose feedback control of receptor tyrosine kinases (RTKs) including PDGFR and MET, locking these receptors in a chronically active state. These receptors share a common negative regulator called Protein Tyrosine Phosphatase, Non-Receptor Type 12 (PTPN12). Baylor investigators have shown that PTPN12- deficient TNBCs may be responsive to combined RTK inhibition. Sitravatinib is a spectrum selective RTK inhibitor that has shown strong antitumor activity in patient derived xenografts (PDXs) of TNBC with low levels of PTPN12. We have therefore designed a phase II, multi-institution, two cohort trials to evaluate the efficacy of sitravatinib in patients with metastatic TNBC (mTNBC). Methods: Patients with diagnosis of mTNBC who have received at least one line of chemotherapy +/- atezolizumab for advanced disease would be considered for enrollment. Patients would need to have tissue from metastatic site available for evaluation or agree to undergo biopsy if banked tumor tissue is not available. Sitravatinib at 100 mg daily, the recommended phase 2 dose for sitravatinib monotherapy, will be started at the initiation of the study and continued until progression or unacceptable toxicity. The study will employ a modified optimal Simon’s two stage design. Patients will be recruited into two cohorts: PTPN12 low or PTPN12 high/normal cohorts simultaneously and independently. Seven patients will be enrolled to each arm during the first stage. After the first stage, depending on the observed number of responses, the study will proceed to the 2nd stage. The primary endpoint is progression-free survival status at 24 weeks (PFS24). Current Trial status: The trial is funded by Mirati Therapeutics and opened to enrollment at Dan L Duncan Comprehensive Cancer Center (DLDCCC) clinics as of 6/8/21. Trial is due to open at UT Southwestern Dallas by 11/2021. The correlative science is funded by an institutional SPORE grant. Conclusion: This trial aims to show that sitravatinib is safe and to investigate whether it could be a treatment option in mTNBC.
Citation Format: Maryam Nemati Shafaee, Kristen Otte, Nicholas J Neill, Kent C Osborne, Thomas F Westbrook, Susan Hilseneck, Matthew J Ellis. A phase 2 study of sitravatinib in metastatic, pre-treated, triple negative breast cancer, NCT # 04123704 [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-28-01.
Abstract P1-01-13: A prospective self-controlled study of indocyanine green instead of radioisotope for axillary sentinel lymph nodes in breast cancer
Authors: Jin Yuting , Yuan Long , Jiang Jun , Qi Xiaowei 
Published: March 2022

Abstract
Objective: This self-controlled study aimed to investigate the feasibility of substituting indocyanine green (ICG) for radioisotope (RI) for combined imaging of axillary sentinel lymph node (SLN) in breast cancer. Study Design: Primary breast cancer, clinically axillary node-negative patients (n = 182) were prospectively enrolled from March 2015 to November 2020. ICG, methylene blue (MB), and RI were used to perform axillary SLNB. The main observation indices was the positivity of ICG + MB vs. RI + MB in axillary SLNB; the secondary observation indices were the axillary SLN detection rate, mean number of axillary SLN detected, mean number of metastatic axillary SLN detected and safety.Result: All 182 patients had axillary SLNs; a total of 925 axillary SLNs were detected. Pathological examination confirmed metastatic axillary SLN in 42 patients (total of 79 metastatic SLNs). Positivity, detection rate of SLNs, detection rate of metastatic SLNs, and the number of metastatic SLNs detected were comparable with RI+MB and ICG+MB (P&gt;0.05). The mean number of axillary SLN detected was significantly higher with ICG+MB than with RI+MB (4.99±2.42 vs. 4.02±2.33, P&lt;0.001). No tracer-related adverse events occurred.Conclusion: ICG appears to be a safe and effective axillary SLN tracer, and a feasible alternative to RI in combined imaging for axillary SLN of breast cancer.
Citation Format: Yuting Jin, Long Yuan, Jun Jiang, Xiaowei Qi. A prospective self-controlled study of indocyanine green instead of radioisotope for axillary sentinel lymph nodes in breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-01-13.
Abstract P1-08-06: Development of an aritifical neural network model and comparison with nomogram for prediction of pathological complete response after neoadjuvant chemotherapy in breast cancer
Authors: Shin Hee-Chul , Jung Ji-Jung , Kim Eun-Kyu , Kang Eunyoung 
Published: March 2022

Abstract
Purpose: Identifying patients who may benefit from neoadjuvant chemotherapy will facilitate personalized treatment regarding chemotherapy and surgery. This study compares the predictive performance of an artificial neural network algorithm with nomogram to predict pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in patients with advanced breast cancer.. Methods: Medical records of 359 patients with advanced breast cancer who received NAC prior to surgical resection between January 2017 and December 2019 were retrospectively reviewed. Random over sampling method was used to overcome data imbalance and random sampling method to divide patients into training and test sets at a split ratio of 7:3. Univariate and multivariate regression analyses were used to develop a nomogram and a machine learning model based on artificial neural network. Performance of the two models were evaluated using the validation sets in terms of area under the receiver operating characteristic curve (AUC).. Results: Multivariate logistic regression analysis showed that high level of estrogen receptor (ER) (OR 0.84, p &lt; 0.001), positive human epidermal growth factor receptor 2 (HER2) status (OR 1.25, p &lt; 0.001), complete response on magnetic resonance imaging (MRI) (OR 1.62, p &lt; 0.001), abnormal CEA level after NAC (OR 0.86, p = 0.051), and abnormal CA15-3 level after NAC (OR 0.87, p = 0.074) were independent predictors of pCR. A nomogram and a neural network model to predict pCR were developed using the five predictors. Validation test showed AUCs of 0.789 [95 % confidence interval (CI), 0.707-0.871] for the nomogram and 0.876 [95 % CI, 0.808-0.943] for the neural network model.. Conclusion: We developed a nomogram and an artificial neural network (ANN)-based machine learning model to predict pCR after NAC. Both models showed excellent performance, but the ANN model performed better in terms of accuracy and discrimination. Machine-learning algorithms hold promise in medical application and provide better prediction than nomogram.
Citation Format: Hee-Chul Shin, Ji-Jung Jung, Eun-Kyu Kim, Eunyoung Kang. Development of an aritifical neural network model and comparison with nomogram for prediction of pathological complete response after neoadjuvant chemotherapy in breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-08-06.