bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Design and In-Silico Analysis of Trisubstituted Benzimidazole Derivatives as Ftsz Inhibitor
Authors: Thapa Shankar , Nargund Shachindra L. , Biradar Mahalakshmi Suresha
Published: March 2023

Tuberculosis (TB) is the fastest spreading infectious disease and one of the top ten diseases that kill millions of people annually. The rapid spread of a multidrug-resistant strain of Mycobacterium tuberculosis leads to multidrug-resistance tuberculosis (MDR-TB), which is very difficult to treat. Filament temperature-sensitive protein ring-Z (Ftsz) protein could be the best target to inhibit bacterial cytokinesis. This research is conducted to predict the antitubercular activity of trisubstituted benzimidazole derivatives targeting FtsZ protein by an in-silico approach (molecular docking, pharmacokinetic parameter, drug likeliness, toxicity prediction, and biological activity prediction). Amine and aldehyde substitutions are used as primary scaffolds to design 20 trisubstituted benzimidazole derivatives for molecular docking. AutoDock vina v.1.2.0 software was used to predict the binding interaction between ligand and receptor (FtsZ, PDB ID : 1RQ7). The drug-likeliness properties and toxicity of ligands were predicted from SwissADMET and ToxiM web servers, respectively. Compound A15 (2,3,5,6-tetrafluoro-N1-{6-fluoro-5-[4-(1H-imidazole-1-yl) phenoxy]-1H-1,3-benzodiazol-2-yl} benzene-1,4-diamine) showed the best binding energy (ΔG = −10.2 kcal/mol/) along with four hydrogen bond interactions (GLY107, PHE180, ASP 184). Similarly, compounds A19 and A20 have the best binding score of −9.8 kcal/mol, with excellent pharmacokinetic parameters. It is found that the binding energy of all ligands (ΔG = −8.0 to −10.2 kcal/mol) is better than the reference compound Moxifloxacin (ΔG = −7.7 kcal/mol). None of the ligands violate Lipinski’s rule, but all ligands’ toxicity is slightly high (>0.8 score). It is reported that the amine-substituted benzimidazole derivatives have better binding energy than the aldehyde substitution. Therefore, it is concluded that compounds A19 and A20 can be the best candidate as Ftsz protein inhibitors but an in-vitro animal study and toxicity study are necessary to validate these data.
Abstract CC1-2-1: Duration of endocrine therapy
Authors: Mamounas Eleftherios (Terry) , Ruddy Kathryn
Published: March 2023

Patients with hormone-receptor positive, early-stage breast cancer are at considerable risk for late recurrence.

Previous randomized clinical trials have shown that extending adjuvant tamoxifen to ten vs. five years improves disease-free survival (and overall survival in one trial). Adding five years of an aromatase inhibitor (AI) after five years of tamoxifen has also been shown to significantly improve disease-free survival in postmenopausal patients. Benefit from extending adjuvant AI therapy beyond five years in patients who have received five years of an AI or tamoxifenàAI has also been recently demonstrated in several clinical trials but the absolute benefit appears small and the ideal duration of the extended therapy is still a topic of debate.

Over the past decade, efforts have focused on identifying predictors of risk of late recurrence and predictors of benefit from extended endocrine therapy. Clinicopathologic factors and circulating tumor cells can predict risk of late recurrence but not benefit from extended ET. Several commercially available genomic classifiers can further stratify risk of late recurrence, and some have also been found to predict benefit from extended ET. Their clinical utility for tailoring the use of extended endocrine therapy continues to evolve.

Citation Format: Eleftherios (Terry) Mamounas, Kathryn Ruddy. Duration of endocrine therapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr CC1-2-1.
Abstract ED1-3: Where are we going with digital interventions and PROs
Authors: Luis Ines Vaz
Published: March 2023

Rational: Lately, digital health has shown potential to facilitate cancer care delivery. We now have data that demonstrated that systems integrating self-reporting of common symptoms during treatment for both adjuvant and metastatic breast cancer treatment and allowing for patient remote monitoring result not only result in better quality of life and less emergency room visits, but, in some settings, also lead to significant survival benefit. In addition, some studies incorporating self-management strategies that do not need heavy clinician involvement have shown promising results to manage acute and long and late term physical, social, and psychological effects of cancer and its treatment.

Objectives: In this talk, we will 1) review data on the existing digital health solutions that can be used in clinical care. In addition, 2) we will reflect on what is next in digital health innovation, particularly a) how the integration of technology, including digital companions facilitating remote monitoring, education and self-management, may serve as a vehicle to promote continuous care b) innovative emerging digital health tools (including, although not limited to wearables and digital therapeutics).Finally, 3) we will examine how digital health can address the needs of every patient, avoid pitfalls such as contributing to health disparities.

Citation Format: Ines Vaz Luis. Where are we going with digital interventions and PROs [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED1-3.
Abstract ED13-1: Beyond anthracyclines and trastuzumab: Cardiotoxicity of novel agents
Authors: Dent Susan
Published: March 2023

Breast cancer treatment can have a diverse array of delayed and long-term effects, including cardiovascular events such as heart failure, valvular damage, coronary artery disease, arrythmias, and cardiac dysfunction. The adverse cardiovascular effects of anthracyclines and trastuzumab in the treatment of early and advanced breast cancer have been well elucidated withing the literature; however, there is less understanding of the potential cardiovascular impact of more recent novel breast cancer therapies. Dual HER2 targeted therapy (pertuzumab/trastuzumab) is now standard of care for neoadjuvant and adjuvant treatment, particularly in the setting of lymph node involvement, but is there a higher risk of cardiotoxicity? There is a limited understanding of the potential short- and long-term cardiovascular toxicity associated with antibody-drug conjugates, such as T-DM1 and fam-trastuzumab deruxtecan, and well as oral anti-HER2 tyrosine kinase inhibitors such as lapatinib, neratinib, and more recently tucatinib. CDK4/6 inhibitors (eg ribociclib) combined with endocrine therapy have significantly improved clinical outcomes for individuals with hormone receptor positive, HER-2 advanced breast cancer but are associated with an increased risk of QTc prolongation, which can be compounded by electrolyte abnormalities and drug-drug interactions. Immune checkpoint inhibitors (pembrolizumab) are approved in the neoadjuvant (high risk) and advanced setting (PDL-1 positive) for triple negative breast cancer but are associated with several toxicities including endocrinopathies and rarely fatal myocarditis. The goal of this session is to improve the awareness and understanding of the potential cardiovascular toxicities associated with modern anti-cancer therapies used in the treatment of breast cancer.

Citation Format: Susan Dent. Beyond anthracyclines and trastuzumab: Cardiotoxicity of novel agents [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED13-1.
Abstract ED4-2: Metaplastic Breast Cancer
Authors: Thomas Alexandra
Published: March 2023

Metaplastic breast cancer (MPC) is a less common subtype of breast cancer, representing approximately 0.2-0.5% of breast cancer diagnoses, which is often associated with poor outcomes. MPC is an overarching term for breast tumors which demonstrate differentiation toward epithelial or mesenchymal components, or a mixture of these. In the context of challenging subtypes of breast cancer, thiseducational discussion will review epidemiology and clinical course of these tumors. Molecular characteristics of MPC and how this might impact current, as well as possible future, management strategies will be discussed. Finally, opportunities for laboratory investigations and clinical trial approaches to further understand and better treat MPC will also be discussed.

Citation Format: Alexandra Thomas. Metaplastic Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED4-2.
Abstract ED9-2A: Can ctDNA substitute tissue testing
Authors: O’Leary Ben
Published: March 2023

Circulating tumor DNA (ctDNA) is at the forefront of liquid biopsy technology. A key advantage of ctDNA is being able to achieve genomic profiling from a blood test rather than from a more invasive tissue biopsy, reducing risk and discomfort for patients as well as costs and logistical complexity. Increasing evidence supports ctDNA as a useful clinical tool in specific indications, for example in the detection of PIK3CA mutations to identify patients suitable for alpelisib plus fulvestrant.The expectation is that indications for routine ctDNA testing will expand as more data become available and ctDNA is embedded into clinical trials and paired with novel therapies.

Biological and technical factors both contribute to the feasibility of ctDNA expansion into the clinic. Representation of heterogeneity might be a key strength of ctDNA analysis over tumour biopsy analysis, as sampling the circulation compartment can in principle allow representation of a wider array of disease sites than a tumor sample acquired with a single needle.

However, the factors influencing how different metastases might contribute to the circulating compartment are poorly understood, presenting a challenge to clinical interpretation. Moreover, the limit of detection of ctDNA assays, the timing of treatment and stochastic effects can contribute to uncertainty, particularly in the interpretation of negative results. Recent work analyzing tumor mutational burden using ctDNA has highlighted these challenges as applied to biomarker development.

Circulating tumour DNA is likely to complement tissue biopsy in the future, and may substitute tumor biopsy in specific indications supported by the data. Ultimately, clinical utility for different ctDNA indications, as opposed to tissue biopsy, will need ongoing confirmation within clinical trials.

Citation Format: Ben O’Leary. Can ctDNA substitute tissue testing [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED9-2A.
Abstract MS2-2: Extra cellular matrix and dormancy
Authors: Bravo-Cordero Jose Javier
Published: March 2023

Breast cancer metastasis develops from disseminated cancer cells (DCCs) that leave the primary tumor and seed in distant organs. In those organs, DCCs undergo a period of dormancy during which cancer cells remain occult, in a non-proliferative state, before metastases become detectable. In this seminar I will discuss how disseminated cancer cells enter in dormancy at metastatic sites and the importance of the ECM in this process. We have found that dormant cancer cells express a specific set of ECM genes, "the matrisome", that is lost upon break from dormancy. ECM proteomics identify tumor-derived COL3A1 as a key ECM component required for tumor cell dormancy at metastatic organs. Intravital imaging and SHG microscopy reveals that the dormancy-to-reactivation transition is accompanied by changes in collagen three-dimensional architecture. Our data reveal a novel barrier to metastasis through a mechanism by which DCCs depend on the assembly of a pro-quiescence ECM to establish a niche that sustains dormancy.

Citation Format: Jose Javier Bravo-Cordero. Extra cellular matrix and dormancy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr MS2-2.
Abstract OT1-14-01: Efficiency and safety of palbociclib in patients with locally advanced or metastatic breast cancer: a muti-center real world study
Authors: Yin Yongmei , huang Xiang , Li Wei , Wu Xinyu , Hua Yijia , Sun Chunxiao
Published: March 2023

Endocrine therapy is the main treatment for premenopausal women with HR+/HER2- breast cancer. Palbociclib is an oral CDK4/6 inhibitor which preclinical evidence that ER+ and HER2-amplified breast cancer cell lines are most sensitive to CDK4/6 inhibition of proliferation and is used in vitro in combination with endocrine therapy showed better tumor suppressive effect. To evaluate the efficacy and safety of palbociclib in patients with locally advanced or metastatic breast cancer, we enrolled females with hormone receptor-positive breast cancer who treat with Palbociclib from July 2018 to March 2022. The study has so far included 267 patients in 4 centers. 32.83% patients were treated in first-line, 31.32% and 38.85% patients in second and third lines. 30.34% patients had hepatic metastasis. 35.47% patients were sensitive to previous endocrine therapy; 18.23% patients had primary resistance to endocrine therapy, while 46.31% patients had secondary resistance to endocrine therapy. The median PFS was 12.67 months (95% CI 11.51-13.92), and Median overall survival (OS) was not reached. Among all patients, the overall response rate (ORR) was 25.84%, and the disease control rate (DCR) was 78.62%. The main adverse events related to treatment were neutropenia (91.38%), white blood cell decreased (90.09%), anemia (43.78%), and thrombocytopenia (37.93%). The most common grade 3/4 adverse event was neutropenia (55.61%). 11.99% of patients had dose reductions. More patients still needed for further analyze.

Citation Format: Yongmei Yin, Xiang huang, Wei Li, Xinyu Wu, Yijia Hua, Chunxiao Sun. Efficiency and safety of palbociclib in patients with locally advanced or metastatic breast cancer: a muti-center real world study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-14-01.
Abstract OT2-18-03: Neoadjuvant anlotinib plus nab-paclitaxel based chemotherapy in patients with HER2-negative breast cancer: A prospective, single-arm, single-center, phase II clinical study
Authors: Fan Jing , Wang Ting , Meng Huimin , Li Songpeng , Kong Jing , Wang Yidi
Published: March 2023

BACKGROUND: Antiangiogenic agent plus neoadjuvant chemotherapy confers an improvement in pathological complete response (pCR) rate among patients with HER2-negative breast cancer. Anlotinib is a novel multi-target tyrosine kinase inhibitor that effectively inhibit VEGFR, FGFR, c-KIT, c-MET, and RET. This phase II study aims to evaluate the efficacy and safety of anlotinib combined with chemotherapy as neoadjuvant treatment in HER2-negative breast cancer. PATIENTS AND METHODS: Eligible patients (pts) were women, aged 18-70 years, ECOG status 0-2, previously untreated HER2-negative breast cancer. The HER2-negative, defined as immunohistochemistry of 0, 1+, and 2+/ISH-. Pts were required to have a palpable primary tumor at least 200mm in diameter in the breast, as assessed by physical examination, and to be classified as having tumor stage T1c to T3, nodal stage N0 to N2a, and metastasis stage M0. Thirty pts will be enrolled and received 5 cycles of anlotinib (12 mg qd, d1-14; 21 days per cycle) plus 6 cycles of nab-paclitaxel (200 mg/m2, once every 3 weeks), anthracycline (pirarubicin 50 mg/m2) and cyclophosphamide at 500 mg/m2, followed by surgery. The primary endpoint is pCR rate (ypT0/Tis ypN0) and the secondary endpoints include disease-free survival (DFS), overall survival (OS), and safety. The study was initiated in August 2021.This study is currently open and 10 patients had been enrolled. The estimated primary completion date is October 1, 2023. Results: The trail is in progress. Conclusion: The trail is in progress.

Citation Format: Jing Fan, Ting Wang, Huimin Meng, Songpeng Li, Jing Kong, Yidi Wang. Neoadjuvant anlotinib plus nab-paclitaxel based chemotherapy in patients with HER2-negative breast cancer: A prospective, single-arm, single-center, phase II clinical study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-18-03.
Abstract P1-04-16: A nomogram based on clinicopathologic factors and pretreatment systemic inflammation response index to predict pathological complete response of neoadjuvant systemic therapy in HER2-positive breast cancer: A dual-center study
Authors: Wu Hong Yu , Tzeng Yen-Dun , Yang Jie Ru , Hung Chih Chiang
Published: March 2023

Purpose: Multiple pretreatment systemic inflammatory markers (SIMs) have been reported as predictors of pathological complete response (pCR) after neoadjuvant systemic therapy (NST) in patients with breast cancer (BC). However, the most significant SIM remains to be conclusively identified, and variations among different molecular subtypes remain unknown. The objective of the study was to identify the most significant SIM in patients with human epidermal growth factor receptor 2 (HER2) positive BC, and to construct a pCR-predictive nomogram combining it with other clinicopathological factors.

Methods: We retrospectively reviewed the findings for 240 patients with stage I–III HER2-positive BC who underwent NST and subsequent surgery at Kaohsiung and Taichung Veterans General Hospital from 2011 to 2021. Clinicopathological factors were analyzed by stepwise logistic regression with forward selection. The data were used to construct a nomogram plot for determining the probability of pCR.

Results: Among the pretreatment SIMs, only SIRI was significantly related to pCR, with an optimal cutoff value of 1.27 × 10^9/L. Stepwise logistic analyses indicated that clinical N stage, HER2 immunohistochemistry (IHC) score, hormone receptor status, targeted therapy regimen, and SIRI were independent predictors of pCR, with an area under the curve (AUC) of 0.722. The Hosmer–Lemeshow test and calibration curve revealed that the predictive ability was a good fit to actual observations. A nomogram was constructed based on the logistic model.

Conclusions: Pretreatment SIRI < 1.27 is predictive of pCR in HER2-positive BC. Our nomogram could efficiently predict pCR and facilitate clinical decision-making before neoadjuvant treatment.

Univariable and multivariable analyses for predictive factors of pathological complete response of neoadjuvant systemic therapy in HER2-positive breast cancer

Citation Format: Hong Yu Wu, Yen-Dun Tzeng, Jie Ru Yang, Chih Chiang Hung. A nomogram based on clinicopathologic factors and pretreatment systemic inflammation response index to predict pathological complete response of neoadjuvant systemic therapy in HER2-positive breast cancer: A dual-center study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-04-16.
Abstract P1-06-07: Interrogating the Molecular Profile of Breast Cancer Tumors in Hispanics Living in Puerto Rico (PRH)
Authors: Martinez-Viota Norianne , Bittman-Soto Xavier , Montes-Rodriguez Ingrid M. , Carrasquillo Kelvin , Centeno-Girona Hilmaris , Cruz-Correa Marcia
Published: March 2023

Breast cancer (BC) has the highest incidence and mortality rates among Puerto Rican women. However, the representation of Hispanics living in Puerto Rico (PRH) in breast cancer clinical trials may be limited due to the lack of a defined genetic profile from BC tumors in Puerto Rican patients. Mutations in genes associated with tumor suppressors, tumor progression, and genome stability are shared among all BCs. Nonetheless, differences in the frequency of these mutations have been observed among racial/ethnic groups. This study aims to characterize the genomic landscape of BC tumors in PRH and identify the most common genetic mutations. We conducted secondary data analysis to evaluate the mutational profile of 189 BC tumors from PRH who underwent NGS testing from 2015 to 2020 and compared the prevalence of breast tumor somatic mutations and gene amplifications with profiles reported for other races/ethnicities available through The Cancer Genome Atlas (TCGA) and the AACR Genomics Evidence Neoplasia Information Exchange (GENIE). The most mutated genes among PRH breast tumors were TP53, PIK3CA, ARID1A, NF1, and RB1, while the most frequent gene amplifications were FGF19, H3F3B, ZN703, MCL1, and ADGRA2. H1047R and E545K were the most frequent specific mutations in PRH for PIK3CA; R248Q and R273C for TP53 and Q1212*, S634* and Q557fs for ARID1A. Statistically significant differences were found between populations. This study reports a unique mutational profile of BC tumors in PRH and makes comparisons with non-Hispanic and USH populations, providing novel knowledge to increase Hispanic representation in future BC studies and treatments.

Citation Format: Norianne Martinez-Viota, Xavier Bittman-Soto, Ingrid M. Montes-Rodriguez, Kelvin Carrasquillo, Hilmaris Centeno-Girona, Marcia Cruz-Correa. Interrogating the Molecular Profile of Breast Cancer Tumors in Hispanics Living in Puerto Rico (PRH) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-06-07.
Abstract P1-08-02: Implementation of Integrative Medicine Program for Breast Medical Oncology Professionals in an Academic Cancer Center
Authors: Zhi W. Iris , Wanq Rui , Bao Ting
Published: March 2023

BACKGROUND: Integrative medicine such as acupuncture, meditation, yoga and massage are highly desired by breast cancer survivors. Breast medical oncology professionals including physicians, advanced nurse practitioners and physician assistants are often the first clinicians that patients would expect to discuss the use of integrative medicine. Many distressing symptoms, such as hot flashes, insomnia, anxiety, and pain, are common and remain challenging to manage with limited pharmacological intervention available and potential toxicities. Evidence-based integrative medicine approaches, including acupuncture, meditation, yoga, and massage, may help reduce this symptom burden and improve quality of life. However, many breast medical oncology professions are not familiar with current evidence and knowledge in integrative medicine. Therefore, there is an urgent need to educate them on the fundamentals of evidence-based integrative medicine interventions that could improve quality of life for breast cancer survivors. METHODS: We designed the Integrative Oncology training Program for breast medicine professionals at our institution. The program faculty are composed of five breast medical oncologists, five integrative medicine faculty, and one education coordinator. RESULTS: We developed an online, interdisciplinary five-hour course on evidence-based integrative oncology with essential knowledge on integrative medicine approaches for breast cancer survivors. We determined the topic of interest based on feedback from the program faculty. The integrative medicine approaches in management of hot flashes, arthralgia, insomnia, are cannabis uses are some examples that were highly in-demand. The program summarizes high-quality evidence in herbal supplements, acupuncture, meditation, and yoga, pertinent to the audience, as well as the referral flow to our Integrative Medicine Service. CONCLUSIONS: Integrative medicine education programs for oncological professionals are needed to disseminate integrative medicine knowledge and to prepare them to guide our patients on integrative and complementary approaches during and after anticancer treatments.

Citation Format: W. Iris Zhi, Rui Wanq, Ting Bao. Implementation of Integrative Medicine Program for Breast Medical Oncology Professionals in an Academic Cancer Center [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-08-02.
Abstract P1-09-10: Factors associate with borderline or invaded margins in breast cancer surgery at the Val d’Aurelle Montpellier CRLC
Authors: Batoum veronique M. Mboua , Bell esther D. Dina
Published: March 2023

Factors associate with borderline or invaded margins in breast cancer surgery at the Val d’Aurelle Montpellier CRLC Véronique Mboua Batoum*, Esther Dina Bell, Christianne Nsahlai, Junie Annick Metogo Ntsama, Esther Juliette Meka, Marian Gutowski, Simon Thezenas, William Jacot *Corresponding autor : vbatoum@gmail.com Introduction: The inadequate status of the resection margins after breast cancer surgery is an important predictor of local tumor recurrence. The objective of our study was to determine the factors associated with positive or invaded resection margins. Methodology: Our retrospective study included a cohort of 652 patients with early invasive breast cancer who underwent breast cancer conserving surgery at the Val d’Aurelle Regional Cancer Center. We defined positive margins as those with a distance of less than or equal to 2 mm from the tumour. The data were analysed using STATA® 10.0 software. Results: In our study, The median distance from the tumour to the surgical resection site was 5mm [0.0 - 35.0mm]. Resection margins were positive in 208 patients (31.9%). The rate of positive resection margins was significantly higher in non-menopausal patientss (P =0,0050), in those with tumours less than 2 cm in size (P = 0,0004), with ductal carcinoma in situ (DCIS) component and without lymph node involvement (P =0,0082). Re-excision surgery was performed in 229 patients (35.1%). Conclusion: Consideration of each of these factors associated with positive resection margins shoud help the surgeons to perform a wider excision, in other to obtain clear resection margin during the initial breast cancer surgery. Key words: breast cancer, conservative surgery, resection margins, risk factors for positive margins

Citation Format: veronique M. Mboua Batoum, esther D. Dina Bell. Factors associate with borderline or invaded margins in breast cancer surgery at the Val d’Aurelle Montpellier CRLC [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-09-10.
Abstract P1-10-18: Impact of Adjuvant Chemoradiation on cardiopulmonary function and Quality of Life in Breast Cancer
Authors: ANUP AKANKSHA , Wadasadawala Tabassum , JOHNNY CARLTON , SARIN RAJIV , PATHAK RIMA , KRISHNAMURTHY REVATHY , Gupta Sudeep , PARMAR VANI , Ghosh Jaya , BAJPAI JYOTI , GULIA SEEMA
Published: March 2023

Aims and Objectives – To evaluate the safety of adjuvant chemo-radiation (CTRT) for breast cancer. We report the cardio-pulmonary safety and quality of life outcome of this regimen.

Methods – Stage II-III invasive breast cancer patients planned for adjuvant taxane-based chemotherapy and adjuvant radiotherapy (RT) between April 2019 to December 2020 were eligible irrespective of prior neo-adjuvant therapy. Patients received standard 3D conformal radiotherapy (40 Gy in 15 fractions over 3 weeks ± boost for breast conservation) along with the third cycle of adjuvant taxanes in a 3- weekly schedule or the eighth cycle in a weekly schedule. Troponin T, echo cardiography and pulmonary function test were done pre-RT and repeated at 6 months from RT conclusion while quality of life was evaluated pre-RT, at RT conclusion and after 6 months using EORTC QLQ C30 and BR23.

Results – Sixty patients were analysed. The median ejection fraction pre and post CTRT was 60% (p=0.177). The median value of Troponin T at baseline was 37 which decreased to 20 post CTRT (p=0.009). Of the 54 patients who underwent the PFT, the functional vital capacity (FCV) was 2.29 litres at baseline which was 2.2 litres post CTRT (p=0.375). No significant difference was seen for forced expiratory volume (FEV) at 1 second (1.86 vs. 1.82: p=0.365), FEV1/FVC (81.5 vs. 81.43; p=0.9) and diffusing capacity for carbon monoxide (DLCO) (88.3 vs. 87.6; p=0.62) at baseline and post CTRT respectively. There was a significant improvement in QOL scores for nausea, vomiting, pain, constipation, loss of appetite and hair loss post RT 6 months.

Conclusion- Patients treated with taxane-based adjuvant CTRT had stable cardio-pulmonary profile at 6 months compared to pre-RT. Quality of life scores improved after treatment for most of the domains compared to the pre-RT scores.

Table 1. Calculated scores of EORTC QLQ-C30 and BR23 scales for breast cancer patients at baseline, post CTRT and at first follow up of six months.

Citation Format: AKANKSHA ANUP, Tabassum Wadasadawala, CARLTON JOHNNY, RAJIV SARIN, RIMA PATHAK, REVATHY KRISHNAMURTHY, Sudeep Gupta, VANI PARMAR, Jaya Ghosh, JYOTI BAJPAI, SEEMA GULIA. Impact of Adjuvant Chemoradiation on cardiopulmonary function and Quality of Life in Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-10-18.
Abstract P2-11-25: A 10-gene signature to predict the prognosis of early-stage triple-negative breast cancer
Authors: Kim Chang Min , Park Kyong Hwa , Yu Yun Suk , Kim Ju Won , Park Jin Young , Lee Jeong Eon , Sim Sung Hoon , Seo Bo Kyoung , Kim Jin Kyeoung , Lee Eun Sook , Park Yeon Hee , Kong Sun-Young
Published: March 2023

Background: Triple-negative breast cancer (TNBC) is highly heterogeneous cancer and the most challenging subtype of breast cancer. And its prognosis is poor compared to the other subtypes. Unlike luminal type cancers, there is no valid biomarker to predict the prognosis of patients with early TNBC. To establish an elaborate therapeutic strategy for TNBC, biomarkers that accurately predict the prognosis and response to treatment are needed. Method: 184 patients with early stage TNBC (training cohort, n = 76; validation cohort, n = 108) were enrolled. Median Follow-up period was 51.5 months (range: 4.6-230.8) for training cohort and 58.3 months (range: 6.6-99.8) for validation cohort. Of the patients in training cohort, 13 patients had recurrence or metastasis. Of the patients in validation cohort, 23 patients had recurrence or metastasis. Using a HiSeq sequencer, RNA sequencing was conducted to analyze the gene expression profiles of tumor samples from TNBC patients. Gene signature was analyzed by combination of DEGs which found in gene expression profiles. Cross validation and meta-analysis were conducted as pre-validation. Meta-analysis was conducted using CBS probePINGS. To compare gene signature and other methods, PAM 50 call and TCR diversity analysis were investigated. Statistical analyses were conducted using R language (v.3.4.3). Result: To predict prognosis of recurrence or metastasis for TNBC patients, we identified the 10-gene signature (DGKH, GADD45B, KLF7, LYST, NR6A1, PYCARD, ROBO1, SLC22A20P, SLC24A3 and SLC45A4) that stratified patients with TNBC by risk score (sensitivity = 92.31%; specificity = 92.06%; accuracy = 92.11%) and validated in a cohort of separate institutions. Meta-analysis supported the biological relevance of the 10-gene signature to well-known driving pathways in TNBC. When compared with other potential biomarkers like PAM 50 call and T-cell receptor β diversity, the 10-gene signature was the only independent factor that can predict prognosis for invasive disease-free survival in multivariate analysis. Conclusion: Our novel findings can contribute to solving the diagnostic challenges in TNBC and the 10-gene signature may serve as a novel biomarker for risk-based patient care.

Citation Format: Chang Min Kim, Kyong Hwa Park, Yun Suk Yu, Ju Won Kim, Jin Young Park, Jeong Eon Lee, Sung Hoon Sim, Bo Kyoung Seo, Jin Kyeoung Kim, Eun Sook Lee, Yeon Hee Park, Sun-Young Kong. A 10-gene signature to predict the prognosis of early-stage triple-negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-25.
Abstract P2-11-30: Performance of tumor vascularity as a biomarker is correlated with the change of tumor vascularity after preoperative systemic treatment in patients with breast cancer
Authors: Choi Hyang Suk , Son Eun Ju , Noh Hany Hany , Cho In-Jeong Cho In-Jeong , Lim Seung Taek , Lee Jong-In , Han Airi
Published: March 2023

Background) Breast cancer is a leading cause of death worldwide. Tumor vascularity is a hallmark of cancer including breast cancer. However, targeting tumor vascularity did not show consistent benefit when applied in clinic. This study aimed to investigate in which group of patients can tumor vascularity be a prognostic factor and how does change of tumor vascularity play in this situation. Materials and methods) Female patients with breast cancer who received preoperative chemotherapy due to breast cancer between 2003 and 2018 at Wonju Severance Hospital, Korea, were included. Clinocopathological characteristics were collected. Hounsfield units(HU) on contrast-enhanced computed tomography(CT) was used as a marker indicating tumor vascularity. Tumor to aortic arch ratio(TAR) of HU on contrast enhanced CT was applied to enhance objectivity of measurement. Patients were categorized according to the cut-off values retrieved from the receiver operating characteristic curve. Kaplan-Meier curves were generated to compare recurrence-free interval (RFI) and overall survival (OS). Results) The final cohort included 162 patients with a mean age of 48.63±7.9 (30-69) years. Initial TAR was 0.38±0.103 (range, 0.184-0.946) and TAR after completion of preoperative systemic treatment was 0.29 0.094(0.677-0.298). Difference between TAR of immediate before surgery and first clinical presentation was -0.0860.094(-0.386 – 0.176). TAR was decreased in 122 (75.3%) patients. Initial TAR was significantly correlated with recurrence free survival(RFS)(p=0.002). However, TAR after preoperative systemic treatment (p=0.221) or delta TAR (area under receiver operating characteristics = 0.498) were not significant. Interestingly, initial TAR was significant only in patients with decreased TAR after preoperative systemic treatment(p=0.005). Conclusion) Tumor vascularity represented with HU was significantly related with patients’ survival only when tumor vascularity was decreased in response to systemic treatment. Considering no antiangiogenic agents were applied as preoperative systemic treatment and still capacity of tumor vascularity as a biomarker was influenced by the change of itself, antiangiogenic agents could be used as a complimentary agent for the other agents which also impact tumor vascularity.

Citation Format: Hyang Suk Choi, Eun Ju Son, Hany Hany Noh, In-Jeong Cho In-Jeong Cho, Seung Taek Lim, Jong-In Lee, Airi Han. Performance of tumor vascularity as a biomarker is correlated with the change of tumor vascularity after preoperative systemic treatment in patients with breast cancer. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-30.
Abstract P2-21-11: A high content imaging and analysis approach to screen compounds for novel drug targets in 3D breast cancer co-culture model
Authors: Ali Rizwan , Huwaizi Sarah , Alsubait Arwa , Boudjelal Mohamed
Published: March 2023

The desired effect of cancer therapeutics can only be conceived when applied to complex multicellular structures with different cell types and extracellular matrix (ECM) in three-dimensional (3D) space. Therefore, 3D cell culture systems have become very popular in drug screening and discovery. There is an immense demand for highly efficient and easy methods to produce 3D spheroids in any cell format. However, heterogeneity in size, extended cultivation times, and reproducibility for high throughput assays are limiting factors in the generation of spheroids. Recently we have established a naturally transformed breast cancer cell line, KAIMRC1 (1), from ductal breast carcinoma. We have developed a novel and easy method to produce spheroids (2) from KAIMRC1 cells in vitro, which can be used as a 3D model to study proliferation, differentiation, metabolism, cell death, and drug response of cells in the tumor microenvironment. We developed an in-vitro high content imaging (HCI) based cellular assay using commercially available compound panels to perform initial drug screening in the KAIMRC1 spheroids model. Our approach allows rapid screening of a panel of drugs to assess inhibitory effects on the growth of tumor cells in 3D cultures. To mimic the actual in-vivo tumor microenvironment, we are now developing an HCI-based assay utilizing 3D KAIMRC1 spheroids co-cultured with patient-derived fibroblast cells. 1. Ali, Rizwan, et al. “Isolation and Characterization of a New Naturally Immortalized Human Breast Carcinoma Cell Line, KAIMRC1.” BMC Cancer 17 (2017) 2. Rizwan Ali et al., (2021) New Born Calf Serum (NBCS) can induce spheroid formation in breast cancer KAIMRC1 cell line. Front. Mol. Biosci. DOI: 10.3389/fmolb.2021.769030

Citation Format: Rizwan Ali, Sarah Huwaizi, Arwa Alsubait, Mohamed Boudjelal. A high content imaging and analysis approach to screen compounds for novel drug targets in 3D breast cancer co-culture model [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-21-11.
Abstract P2-23-05: Trastuzumab-Induced Tumor Microenvironment Changes in Early HER2+ Breast Cancer
Authors: Kennedy Laura C. , Alvarez Rebeca , Dintzis Suzanne , Gadi Vijayakrishna K.
Published: March 2023

Background Trastuzumab (H) is a critical component of therapy (tx) for HER2+ breast cancers (BCs) and can induce anti-tumor immune responses that as part of its mechanism of action. Pre-clinical studies have suggested that antibody-dependent cell-mediated cytotoxicity (ADCC) through NK cells is a major driver of the immune response. However, there is also evidence that macrophages and dendritic cells (DCs) can play an important role in H immune response through antibody-dependent cellular phagocytosis (ADCP). Here, we present pre- and post-tx gene expression and immunohistochemistry (IHC) data to characterize the tumor microenvironment (TME) changes in response to a single dose of H in patients (pts) with early HER2+ BC. Methods Pts with Stage I-III HER2+ BC with minimum 1 cm tumors were eligible. Pts received 8 mg/kg IV H followed by tissue collection. There was a minimum of 14 days between (btw) H and post-tx tissue collection. Pre- and post-tx tissues were assessed for tumor-infiltrating lymphocytes (TILs), immune-related gene expression, and AE1/3, CD31, CD4, CD8, CD11b, CD68, and CD56 expression through IHC. Results Thirteen pts were enrolled and evaluable. 5/13 were estrogen-receptor positive (ER+). TILs were assessed independently by two pathologists and the results averaged. Tx with H resulted in an increase in TILs in the post-tx tissue (p < 0.01). Pre-tx TILs ranged from 2-80% (median 6%) and post-tx TILs ranged from 2-80% (median 20%). 6/13 pts had immune infiltration (Inf), defined as a TIL increase of greater than 1 decile btw pre- and post-tx samples. 2/6 pts with Inf were ER+. Pts with Inf had a significantly higher DC immune signature (ISS) compared to pts without Inf (p < 0.01, univariate analysis). No other ISS reached significance. 6 pts had paired pre- and post-tx samples evaluated by IHC. 4/6 pts had Inf per prior definition. Pts with Inf had an increase in CD11b+ (includes macrophages and some DCs) and CD56+ cells (includes NK cells) after H tx within the tumor compartment (p < 0.05). Pts with Inf had an increase in CD11b+, CD56+, and CD44+ cells in the stromal compartment (p < 0.05). Conclusions Innate immune cells such as macrophages and DCs are key players in H-induced immune response in the early HER2+ BC TME. This data is consistent with prior pre-clinical findings.

Citation Format: Laura C. Kennedy, Rebeca Alvarez, Suzanne Dintzis, Vijayakrishna K. Gadi. Trastuzumab-Induced Tumor Microenvironment Changes in Early HER2+ Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-23-05.
Abstract P2-26-08: Influence of genetic ancestry on breast stromal cells provides biologic basis for increased incidence of metaplastic breast cancer in women of African descent
Authors: Kumar Brijesh , Batic Katie , Bhat-Nakshatri Poornima , Granatir Maggie , Addison Rebekah , Szymanski Megan , Baldridge Lee Ann , Temm Constance , Sandusky George , Althouse Sandra , Storniolo Anna Maria , Nakshatri Harikrishna
Published: March 2023

The biologic basis of genetic ancestry-dependent variability in disease incidence and outcome is just beginning to be explored. We recently reported enrichment of a population of ZEB1-expressing cells located adjacent to the ductal epithelial cells in the normal breast of women of African Ancestry (AA) compared to European Ancestry (EA). By establishing and characterizing cell lines corresponding to these cells and validating in vitro findings with tissue microarrays of healthy breast tissue from AA, EA and Latina Ancestry (LA) women, we demonstrate that these cells have the properties of fibroadipogenic/mesenchymal stromal cells that express PROCR and PDGFR. PROCR+/ZEB1+/PDGFR+ cells, hence renamed as PZP cells, are enriched in the normal breast tissues of AA compared to EA or LA women. In vitro, PZP cells trans-differentiated into adipocytes or osteocytes. In co-culture conditions, PZP:epithelial cell communication resulted in luminal epithelial cells acquiring basal/stem cell characteristics and increased expression of IL-6 suggesting the impact of this communication on the microenvironment and breast epithelial hierarchy. Consistent with this possibility, the level of phospho-STAT3, which is a downstream target of IL-6, was higher in the normal and cancerous breast tissues of AA compared to EA women. PZP cells transformed with HRasG12V ± SV40-T/t antigens generated metaplastic carcinoma in NSG mice suggesting that these cells could be the cell-of-origin of metaplastic breast cancers. Collectively, these results identify a stromal cell component that could influence the biology of breast cancer in AA women.

Citation Format: Brijesh Kumar, Katie Batic, Poornima Bhat-Nakshatri, Maggie Granatir, Rebekah Addison, Megan Szymanski, Lee Ann Baldridge, Constance Temm, George Sandusky, Sandra Althouse, Anna Maria Storniolo, Harikrishna Nakshatri. Influence of genetic ancestry on breast stromal cells provides biologic basis for increased incidence of metaplastic breast cancer in women of African descent [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-26-08.
Abstract P3-04-07: Safety and artifact testing of a nitinol breast biopsy clip in an ultra-high resolution magnetic resonance imaging (MRI) environment
Authors: Dong William , Ramchandran Kanchna , Galloy Adam , Nino Marco A. , Kleingartner Marla , Raghavan Madhavan L. , Phadke Sneha , Magnotta Vincent A.
Published: March 2023

Background: The lack of safety clearance of several metallic breast implants in 7T(Tesla) poses a significant hurdle to standard clinical breast cancer care and research from reaping the benefits of ultra-high resolution MR imaging. A breast biopsy clip (Ultracor Twirl, Becton, Dickinson and Company, Vernon Hills, IL) composed of nitinol, was tested for safety and artifact susceptibility clearance in a 7T MRI scanner, using standardized procedures. This clearance is significant in henceforth allowing patients with this implant to be scanned in now FDA approved ultra-high-field MRI scanners of 7T or less for clinical and research purposes. Methods: Tests for magnetic susceptibility (torque and translational attraction), MRI-related heating, and artifacts were conducted as per standardized protocols. The torque and translational attraction tests evaluated the effects of magnetic force by the MRI to cause the clip to move and twist respectively. The heating test was conducted with customized MR parameters of short TR (repetition time) and maximum echo-train length, designed to induce temperature change. The artifact test using T1 weighted spin and gradient echo imaging sequences, evaluated potential localized signal loss that may result in misrepresentation of the imaged area. This may occur due to the presence of the metallic clip in the MR environment. Results: The torque and translational attraction tests respectively indicated that the MR environment did not induce any movement in the clip in eight orientations, with a deflection angle of 0 degrees. Results of the heating test indicated no significant temperature change of the clip. A temperature change of less than 0.45C° was observed in the phantom gel in both the absence and presence of the clip, which is well within the safety threshold (< 1°C). Results of the artifact test indicated a very small artifact, with the largest artifact cross-sectional area appearing on gradient echo images. Conclusion: These cumulative results indicate that the Ultracor Twirl breast biopsy clip is safe for imaging patients at 7T.

Citation Format: William Dong, Kanchna Ramchandran, Adam Galloy, Marco A. Nino, Marla Kleingartner, Madhavan L. Raghavan, Sneha Phadke, Vincent A. Magnotta. Safety and artifact testing of a nitinol breast biopsy clip in an ultra-high resolution magnetic resonance imaging (MRI) environment [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-04-07.