bluuebunny/crossref_metadata_2025 huggingface dataset:
Concrete Application of Computer Virtual Image Technology in Modern Sports Training
Authors: Chi YongHui , Li Jun
Published: March 2022

The efficiency of basketball shooting training has always been an urgent problem to be solved in basketball sports. Applying computer virtual image technology to basketball sports training is the key to improve basketball shooting ability and improve the effect of basketball sports training. Therefore, based on the design of basketball shooting automatic recognition system based on the background difference method, this study puts forward the specific application of computer virtual image technology in modern sports training. By analyzing the techniques of image denoising, image detection, and image calibration, a goal detection algorithm for modern sports basketball shooting training is designed. Firstly, the camera is used for image capture, the RGB image is converted into gray image, and the median filter is used to suppress the noise in the image. Then, the background difference method is used to detect the moving region, and the background modeling is combined with the mean method. After obtaining the background reference model, the image is differentiated, the gray image after image difference is binarized, and then the binary image is postprocessed by morphological middle closure operation. Finally, the image calibration technology is used to extract the basketball feature information. Through the region segmentation algorithm, the basketball shooting part is segmented and judged, so as to realize the basketball shooting training goal detection. The experimental results show that the proposed method has a good effect on basketball shooting training goal detection and can effectively improve the detection accuracy and efficiency.
PTBP1 is a Novel Poor Prognostic Factor for Glioma
Authors: Liu Pan , He Guo-Chao , Tan Yu-Zhen , Liu Ge-Xin , Liu An-Min , Zhu Xiao-Peng , Zhou Yang , Hu Wan-Ming
Published: March 2022

Objective. Polypyrimidine tract‐binding protein 1 (PTBP1) is an RNA‐binding protein, which plays a role in pre‐mRNA splicing and in the regulation of alternative splicing events. However, little was known about the correlation between PTBP1 and glioma and its prognostic significance in glioma patients. Our aim was to investigate the expression, functional role, and prognostic value of PTBP1 in glioma. Methods. We explored the expression of PTBP1 protein using immunohistochemistry in 150 adult malignant glioma tissues and 20 normal brain tissues and evaluated its association with clinicopathological parameters by chi‐square test. Kaplan‐Meier method was used to evaluate the prognostic effect of PTBP1 in glioma. Univariate/multivariate Cox analyses were used to identify independent prognostic factors. Transcriptional regulation network was constructed based on differentially expressed genes (DEGs) of PTBP1 from TCGA/CGGA database. GO and KEGG enrichment analyses were used to explore the function and pathways of DEGs. Results. Out of the 150 malignant glioma tissues (60 LGG and 90 GBMs) and 20 normal brain tissues in our cohort, PTBP1 protein was high expressed in glioma tissues (79/150, 52.7%), but no expression was detected in normal brain tissues (0/20, 0%). The expression of PTBP1 was significantly higher in GBMs (P < 0.001). More than half of GBMs (62/90, 68.9%) were PTBP1 high expression. Chi‐square test showed that the expression of PTBP1 was correlated with patient age, WHO grade, Ki‐67 index, and IDH status. High expression of PTBP1 was significantly associated with poor prognosis in glioma, and it was an independent risk factor in glioma patients. Furthermore, we shed light on the underlying mechanism of PTBP1 by constructing a miR‐218‐TCF3‐PTBP1 transcriptional network in glioma. Conclusion. PTBP1 was high expressed in glioma, and it significantly correlated with poor prognosis, suggesting a potential therapeutic target for glioma, particularly for GBM.
TimelikeW-Surfaces in Minkowski 3-Spaceℝ13and the Sinh-Gordon Equation
Authors: Alluhaibi Nadia , Abdel-Baky Rashad A.
Published: March 2022

LetMandM∗be two timelike surfaces in Minkowski 3-spaceℝ13. If there exists a spacelike (timelike) Darboux line congruence between each point ofMandM∗, then the surfaces are timelike Weingarten surfaces. It turns out their Tschebyscheff angles are solutions of the Sinh-Gordon equation, and the surfaces are related to each other by Backlund’s transformation. Finally, a method to construct new timelike Weingarten surface has been found.
Abstract ES1-2: Genomics of HER2+ breast cancer
Authors: Perou C
Published: March 2022

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

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

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

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

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

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

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

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>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<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

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 < 0.001), positive human epidermal growth factor receptor 2 (HER2) status (OR 1.25, p < 0.001), complete response on magnetic resonance imaging (MRI) (OR 1.62, p < 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.
Abstract P2-05-01: Inactivation of LATS1/2 drives luminal-basal plasticity to initiate basal-like mammary carcinomas
Authors: Kern Joseph , Tilston-Lunel Andrew , Federico Anthony , Ning Boting , Peppler Grace , Stampouloglou Eleni , Lenburg Marc , Beane Jennifer , Monti Stefano , Varelas Xaralabos
Published: March 2022

Basal-like breast cancers, an aggressive breast cancer subtype that has poor treatment options, are thought to arise from luminal mammary epithelial cells but undergo plasticity to a basal-like state upon transformation. Identifying cellular mechanisms underlying this luminal-basal plasticity will allow an improved understanding of the pathogenesis of basal-like breast cancers. The Hippo signaling pathway, an important cell fate regulator across many tissues, has been implicated in breast cancer development. Central to Hippo signaling are the tumor suppressor kinases LATS1 and LATS2 (LATS1/2), which function to inhibit the transcriptional regulators YAP and TAZ (YAP/TAZ). In this study, we investigated the roles of LATS1/2 in the maintenance of mammary epithelial homeostasis and tumorigenesis in vivo. Using genetic mouse models, we found that conditional co-deletion of LATS1/2 in adult luminal cells promotes rapid proliferation and acquisition of basal cell traits, leading to early development of basal-like ductal carcinoma in situ and an eventual transition to a metastatic state. Further co-deletion experiments demonstrated that these phenotypes are dependent on YAP/TAZ. Transcriptional analyses of LATS1/2-null cells sorted from mammary glands demonstrated that these cells adopt gene expression signatures that correlate with mammary basal cells and human basal-like breast cancers, and revealed an association with Sox9, a transcription factor implicated in luminal progenitor fate and basal-like carcinomas. Collectively, this study demonstrates that LATS1/2 are important mediators of luminal cell fate in mammary epithelial homeostasis and that dysregulation of Hippo signaling in vivo promotes luminal-basal cell plasticity leading to basal-like mammary carcinoma development.

Citation Format: Joseph Kern, Andrew Tilston-Lunel, Anthony Federico, Boting Ning, Grace Peppler, Eleni Stampouloglou, Marc Lenburg, Jennifer Beane, Stefano Monti, Xaralabos Varelas. Inactivation of LATS1/2 drives luminal-basal plasticity to initiate basal-like mammary carcinomas [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 P2-05-01.
Abstract P2-11-16: Rate of breast biopsy referrals in BRCA mutation carriers: A retrospective comparative study and matched analysis
Authors: Pomerantz Adi , Tsoref Daliah , Grubstein Ahuva , Wadhawker Sonya , Rapson Yael , Gadiel Itay , Goldvaser Hadar , Hammerman Ariel , Shochat Tzipora , Sharon Eran , Yerushalmi Rinat
Published: March 2022

Purpose: To evaluate the total biopsy and positive biopsy rates in women at high risk of breast cancer compared to the general population. Methods: The study group consisted of 330 BRCA mutation carriers attending the dedicated multidisciplinary breast cancer clinic of a tertiary medical center in Israel. Clinical, genetic, and biopsy data were retrieved from the central healthcare database and the medical files. Patients who were at age 50 years or older during follow-up were matched 1:10 to women in the general population referred for routine breast cancer screening at the same age, as recommended in the international guidelines. The groups were compared for rate of biopsy studies performed and percentage of positive biopsy results. Matched analysis was performed to correct for confounders. Results: The matched analysis revealed that the total biopsy rate per 1000 follow-up-years was 61.7 in the study group and 22.7 in the control group (p <0.001). The positive biopsy rates per 1000 follow-up-years were 26.4 and 2.0, correspondingly (p <0.001), and the positive biopsy percentages were 42.9% and 8.7% correspondingly (p <0.0001).Conclusions: BRCA mutation carriers who attend a dedicated clinic, have a 2.7 times higher biopsy rate per 1000 follow-up-years, a 13.2 times higher positive biopsy rate per 1000 follow-up-years, and a 4.9 times higher positive biopsy percentage compared with women in the general population. Keywords: Biopsy, BRCA, breast cancer, screening, high risk

Citation Format: Adi Pomerantz, Daliah Tsoref, Ahuva Grubstein, Sonya Wadhawker, Yael Rapson, Itay Gadiel, Hadar Goldvaser, Ariel Hammerman, Tzipora Shochat, Eran Sharon, Rinat Yerushalmi. Rate of breast biopsy referrals in BRCA mutation carriers: A retrospective comparative study and matched analysis [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 P2-11-16.
Abstract P2-14-15: Timing of the immunization defines immune signature of a peptide cancer vaccine combined with Neoadjuvant chemotherapy in HR+ breast cancer patients
Authors: Makhoul Issam , Ibrahim Saddam M , Abu-Rmaileh Muhammad , Jousheghany Fariba , Siegel Eric , Rogers Lora J , Lee John J , Pina-Oviedo Sergio , Post Ginell R , Beck Thaddeus , Kieber-Emmons Thomas , Monzavi-Karbassi Behjatolah
Published: March 2022

Background: We have developed P10s-PADRE, a carbohydrate-mimetic-based peptide, cancer vaccine and demonstrated its safety and immunogenicity in a Phase I clinical trial performed in stage IV breast cancer patients. HR+/HER2- breast cancer is the most common form of breast cancer diagnosed in the United States. These patients face a persistent risk of distant recurrence long after completion of their treatment and new strategies to activate anti-tumor immune responses can improve outcomes of standard therapies. The current study was performed to examine the feasibility, safety and immunogenicity of adding P10s-PADRE to standard-of-care chemotherapy in HR+/HER2− early-stage breast cancer patients. Methods: Five combination schedules were designed based on the timing of immunizations relative to a standard-of-care neoadjuvant chemotherapy regimen. Induction of on-treatment antibody and cellular responses, including T-cells, natural killer (NK) cells, and cytokines was determined. Tumor-infiltrating lymphocytes were quantified in core and surgical biopsies. The data were used to define the treatment effect in general and the vaccine contribution in particular. Results: Combination of P10s-PADRE with chemotherapy was safe and immunogenic. Antibody response was superior in a particular combination schedule, called schedule C, where 3 weekly immunizations preceded the first dose of chemotherapy. We observed that the schedule C, relative to other schedules, displayed an increase in CD16 expression on NK cells, a drop in serum IFN-γ, and an increase in quantity of stromal TILs in residual tumors. Subjects demonstrated a significant reduction in the size of their primary tumor and three subjects achieved pCR. Conclusions: The timing of the immunization relative to the chemotherapy seems to define the type and strength of the immune responses elicited. A particular combination schedule, schedule C, appears promising and the results warrant the conduct of randomized phase II trials.

Citation Format: Issam Makhoul, Saddam M Ibrahim, Muhammad Abu-Rmaileh, Fariba Jousheghany, Eric Siegel, Lora J Rogers, John J Lee, Sergio Pina-Oviedo, Ginell R Post, Thaddeus Beck, Thomas Kieber-Emmons, Behjatolah Monzavi-Karbassi. Timing of the immunization defines immune signature of a peptide cancer vaccine combined with Neoadjuvant chemotherapy in HR+ breast cancer patients [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 P2-14-15.
Abstract P3-09-10: NTRK1/2/3 fusions are observed in both secretory and non-secretory breast cancers
Authors: Sokol Ethan , Maund Sophia , Ross Jeffrey , Wilson Timothy
Published: March 2022

Background NTRK1/2/3 kinase fusions are rare oncogenic drivers found in <1% of solid tumors. NTRK fusion-positive (NTRK+) solid tumors have shown meaningful clinical response to small molecule NTRK inhibitors such as entrectinib and larotrectinib, and broad genomic testing will help identify patients (pts) with these rare alterations. NTRK fusions occur more frequently in some cancers than others. For example, NTRK fusions are characteristic of secretory breast cancers (BCa), and it has been posited that non-secretory BCa lack druggable NTRK fusions (PMID: 30707464). However, these conclusions were drawn on limited patient populations. Here we show evidence of NTRK fusions in both secretory and non-secretory breast tumors in the largest real-world cohort of NTRK+ breast tumors reported to date. Methods Comprehensive genomic profiling of at least 324 cancer-related genes, including NTRK1/2/3, was done at Foundation Medicine on de-identified all-comer BCa pts during the course of routine clinical care. Pathology reports and hematoxylin and eosin (H&E) images of NTRK+ breast tumor tissue were examined by a board-certified pathologist for designation of secretory vs. non-secretory phenotype. Results NTRK fusions were identified in 23 BCa specimens. H&E images were available for review in 22 cases, and another was confirmed as secretory via the pathology report. Pathologist review of those 23 cases revealed that NTRK fusions were present in 11 with secretory phenotypes, 11 with non-secretory phenotypes, and 1 with a mixed secretory phenotype. Secretory cases most often harbored a ETV6-NTRK3 fusion (n=7) with additional recurrent fusions seen in TPM3-NTRK1 (n=2) and LMNA-NTRK1 (n=2). Non-secretory breast cancers also harbored ETV6-NTRK3 (n=2), TPM3-NTRK1 (n=1), and LMNA-NTRK1 (n=1) fusions, as well as several unique fusion events that retain the NTRK kinase domain. Conclusions While rare, NTRK fusions occur in a wide variety of tumor types. Within BCa, this includes both secretory and non-secretory phenotypes, with half of the identified alterations occurring in non-secretory BCa. Recurrent events, including ETV6-NTRK3, were observed in both populations. These data support NTRK fusion testing for all BCa pts with both secretory and non-secretory histologic subtypes.

Citation Format: Ethan Sokol, Sophia Maund, Jeffrey Ross, Timothy Wilson. NTRK1/2/3 fusions are observed in both secretory and non-secretory breast cancers [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 P3-09-10.
Abstract P3-12-33: Breast cancer incidence rates in Japan showed unimodal age distribution
Authors: Uchida Ken , Ohashi Hitoshi , Nogi Hiroko
Published: March 2022

Purpose: Breast cancer incidence rates in Japan have been increasing recently. The incidence rates show bimodal age distribution in the developed countries. The latest studies have thrown new light on a close association between etiologic subtypes and the bimodal age distribution. To determine whether bimodal age distributions are also present in Japanese breast cancer, we investigated Japanese breast cancer incidence rates by age and biological features involved in incidence rates.Methods: Using Japanese breast Cancer Registry data, we examined age-at-diagnosis frequency distributions of breast cancer for 2017 and their hormone receptors (estrogen and progesterone) and HER2 status. Japanese female population data were referred to the registry of Statistics Bureau of Japan. Results: We included 94,612 breast cancer cases for 2017 in Japan. The number of breast cancer cases showed bimodal age distributions at 45-49 years and 65-69 years. However, the age distributions altered to unimodal age distribution with slight peaked at 45-49 years by adjusting with Japanese female population. Estrogen and progesterone receptor rates showed higher level at 45-49 years than other age groups (92.3% and 86.8%, respectively). HER2 expression rates showed lower rates (12.2%) at 45-49 years than other age groups.Conclusions: Japanese breast cancer incidence rates showed unimodal age distribution with slight peaks at 45-49 years. Luminal type breast cancer accounted for younger ages at 45-49 than elderly. Etiology of Japanese female breast cancer was different from the developed countries represented as bimodal age distribution.

Citation Format: Ken Uchida, Hitoshi Ohashi, Hiroko Nogi. Breast cancer incidence rates in Japan showed unimodal age distribution [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 P3-12-33.
Abstract P3-19-24: Long-term follow-up results of intensity modulated radiotherapy in early-stage breast cancer patients
Authors: Zolcsák Zita , Loap Pierre , Fourquet Alain , Henry Alexandre Arsene , Landherr László , Hamar Péter , Kirova Youlia
Published: March 2022

Introduction: Early breast cancer patients with complex anatomy received adjuvant intensity modulated radiotherapy with helical tomotherapy (IMRT-HT) in our Institute. The aim of this study was to evaluate our results in terms of local control, overall survival, progression free survival and adverse events. Materials and methods: This study is a retrospective data analysis, enrolling patients treated with helical tomotherapy irradiation technique. Overall survival (OS) and progression free survival (PFS) curves were plotted with Kaplan-Meier method. We also analyzed the OS and PFS data by molecular subgroups. Long-term toxicities were evaluated using Common Terminology Criteria of Adverse Events (CTCAE) version 4.0. Multivariable analysis was performed to determine the predictors of the toxicities. Results: Between 2009 and 2015, 174 patients with 194 treated breasts were irradiated with helical tomotherapy. The median follow-up was 65 months. The 8-year OS was 89,2 % (IC95: 83.5% - 95.4 %), the 8-year PFS was 85,4% (IC95: 80.2%- 91%). The best therapeutic response shown by the 5 year OS data was in the HER2 receptor positive subroup 95% (IC95: 85.9% - 100%). Long-term skin toxicity was the most common long-term side effect, seen in 20.7% of the patients. 5 patients had second primary breast cancer, always located at the contralateral breast. In multivariant analysis, BMI>25 kg/m2 was found to be a predictor of skin toxicity, and pre-existing cardiovascular disease was independently associated with the risk of cardiovascular toxicity. Conclusion: HT can be safely used for adjuvant breast cancer irradiation. In patients with complex anatomy, HT improves clinical target volume coverage and reduces the dose to OARs. Further prospective studies with long follow-up are needed to confirm and validate these results.

Citation Format: Zita Zolcsák, Pierre Loap, Alain Fourquet, Alexandre Arsene Henry, László Landherr, Péter Hamar, Youlia Kirova. Long-term follow-up results of intensity modulated radiotherapy in early-stage breast cancer patients [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 P3-19-24.
Abstract P3-19-26: The impact of post-mastectomy radiotherapy on the survival of breast cancer patients aged 70 years or older: A study based on SEER database
Authors: Lin Jingyi , Luo Shiping , Zhang Jie , Song Chuangui
Published: March 2022

The impact of post-mastectomy radiotherapy on the survival of breast cancer patients aged 70 years or older: a study based on SEER databaseIntroduction: This study aimed to investigate the role of post-mastectomy radiotherapy (PMRT) in the female aged 70 years or older diagnosed with breast cancer, which is still controversial.Methods: This retrospective study extracted data from the Surveillance, Epidemiology, and End Results (SEER) database. Women aged 70 years or more diagnosed with breast cancer between 2004 and 2016 following mastectomy were enrolled. Propensity score matching (PSM) was performed to reduce covariable imbalance. The univariable and multivariable analyses calculated the prognostic factors. Kaplan-Meier survival curves and multivariable Cox regression model were applied to compare breast cancer-specific survival (BCSS) and overall survival (OS) between two arms and among subgroups stratified by various clinicopathological factors. Results: Of the 27,636 female were eligible, 17.2%(n=4,747) received PMRT while 82,8%(n=22,889) not. By multivariable Cox analysis, radiotherapy was still founded to be independent prognostic factors for BCSS and OS. After 1:1 matching, PMRT were associated with significant improvement in BCSS and OS(p <0.001). By contrast, the BCSS and OS benefit from PMRT were not statistically significant in patients with T1 tumor and 1-3 positive lymph nodes(BCSS:HR = 0.716,95%CI 0.406-1.263,p = 0.249;OS:HR = 0.908,95%CI 0.648-1.270,p = 0.572), and the results were consistent in patients with T2 tumor and 1-3 positive lymph nodes(BCSS:HR = 0.866,95%CI 0.664-1.130,p = 0.289;OS:HR = 0.879,95%CI 0.732-1.055,p = 0.166). Stratified by grade, number of positive lymph nodes, and HR status, there were still not survival advantage of PMRT observed for patients with T1-2N1 breast cancer(all p>0.05).Conclusions: This study demonstrates that post-mastectomy radiotherapy has a definite role in improving the survival of females with elderly breast cancer. After a comprehensive assessment of the side effects and the quality of life, the omission of PMRT could be considered in patients with T1-2N1 breast cancer.

Citation Format: Jingyi Lin, Shiping Luo, Jie Zhang, Chuangui Song. The impact of post-mastectomy radiotherapy on the survival of breast cancer patients aged 70 years or older: A study based on SEER database [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 P3-19-26.
Abstract P4-04-10: Pharmacological targeting of cholinergic receptors as a novel breast cancer immunotherapy
Authors: Eliceiri Brian P. , Qian Jin , Blair Sarah
Published: March 2022

There is a general consensus that the devastating effect of malignant breast cancers (MBCs) is due in part to the ability of breast tumors to exploit host immune functions by subverting normal mechanisms of immunosurveillance. For example, while immunotherapies based on immune checkpoint inhibition in lymphocytes have been associated with better prognosis in other cancers, the efficacy in breast cancer has been limited. We focus here on activating biochemical pathways in antigen-presenting dendritic cells (DCs) that are otherwise immunosuppressive to stimulate the activity of tumor-infiltrating lymphocytes through a novel mechanism. To this end, we recently discovered using an immune-competent mouse model of MBC that breast cancer cells exploit adaptive immune cells such as DCs that express CHRNA7, the α7 nicotinic acetylcholine receptor. Based on the importance of the CHRNA7 signaling pathway in the control of normal inflammation in macrophages in general, we show here that CHRNA7 stimulation in DCs leads to an activation of lymphocytes associated with a reduction in MBC. Specifically, mice lacking the CHRNA7 gene have (a) decreased survival, (b) increased tumor growth kinetics, (c) immunophenotyping revealed a reduction in the “cancer-permissive” phenotype in CHRNA7 KO mice, and (d), a commensurate reduction in T cell proliferation. Based on these mechanistic proof of principle studies, we demonstrate that in contrast to the loss of CHRNA7 in KO, pharmacological activation of CHRNA7 with AR-R17779 has the opposite effect by stimulating DCs to activate the adaptive immune response which leads to tumor progression and increased survival. These findings demonstrate the preclinical potential of AR-R17779 as a clinically relevant approach to stimulate the adaptive immune system through a novel pathway that has not been examined to date, and with a small molecule drug that is stable, specific and well-tolerated.

Citation Format: Brian P. Eliceiri, Jin Qian, Sarah Blair. Pharmacological targeting of cholinergic receptors as a novel breast cancer immunotherapy [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 P4-04-10.
Abstract P4-11-12: Integrating the patient and partner distress and perceptions about prognosis in women with metastatic breast cancer guides the medical oncology consultation
Authors: Mortimer Joanne , Waisman James , Yuan  , Lavasani Sayeh , Stewart Daphne , Sedrak Mina , Patel Niki , Bitz Courtney , Clark Karen , Razavi Marianne , Loscalzo Matthew J
Published: March 2022

Methods: Women with metastatic breast cancer and their partners completed couples’ tailored biopsychosocial screening and alignment in perception of prognosis immediately before consultation with a Medical Oncologist. In addition, couples were offered a standardized couples’ session before the medical consultation, individual couples’ counseling, and a strengths-based group intervention. As a component of biopsychosocial screening, each patient and her partner were asked individually their understanding of prognosis. They were asked their perception of likelihood of cure with supporting text and percentages provided: 76-100%; 51-75%; 26-50%, or 0-25%. Results: To date 254 women were considered eligible for this program. Complete data for both partners is available on 205. All the patients had metastatic breast cancer prior to their Medical Oncology appointment. The average age of the patient was 54 years (Range 25-84) and 55 years (Range 26-84) for the partner. In the perception of prognosis, 48.7% of patients and their partner were aligned and 51.3% were misaligned. The patient was more likely to have considered their prognosis worse in 59% and the partner 41%. The most commonly endorsed distress items for the patient were: Worry about the future 61%; Side effects of treatment 60%; Fatigue 59%; How my family will cope 58%; and Sleeping 49%. Distress for the partner included: Feeling anxious or fearful 49%; Wanting to best help my partner 37% and Sleeping 37%. Both the patient and partner sought assistance with Understanding treatment options 73.6%; Feeling anxious or fearful 62.5%, Worry about the future 57.3% Fatigue 56.3%, and Pain 56.3%- Partner practical distress was significantly higher for those couples who were not in alignment, p<.05. Conclusions: It is possible to openly ask patients and their partners about prognosis. In women with metastatic breast cancer, lack of alignment with understanding prognosis was common with the patient being more likely to have realistic expectations than their partner. A better understanding of the patient/partner’s expectations about treatment outcome has the potential to guide the Medical Oncologist to individualize communications including discussion about goals of care.

Citation Format: Joanne Mortimer, James Waisman, Yuan, Sayeh Lavasani, Daphne Stewart, Mina Sedrak, Niki Patel, Courtney Bitz, Karen Clark, Marianne Razavi, Matthew J Loscalzo. Integrating the patient and partner distress and perceptions about prognosis in women with metastatic breast cancer guides the medical oncology consultation [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 P4-11-12.