bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P4-01-32: BAT8008, a novel Trop-2 ADC with strong bystander effect, for the treatment of Trop-2 positive cancer
Authors: Mei Xingxing , Tang Weijia , Zhou Xin , Qi Xuekang , Mai Siqi , Zhong Zhi , Li Shuoxu , Fan Jianjun , Gan Jirong , Tan Binghua , Qi Yao , Guo Yanling , Yu Jin-Chen , Li Shengfeng 
Published: March 2023

Abstract
Trophoblast cell surface antigen 2 (Trop-2) is overexpressed on many epithelial carcinomas, yet is expressed at much lower level on normal tissue. Elevated expression of TROP-2 is often associated with tumor invasion/aggression, progression, and metastasis. Efficacy of anti-TROP2 ADC have been demonstrated in clinical trials for both TNBC (triple negative breast cancer) and HR+/HER2- breast cancer. We have developed a novel Trop-2 ADC with strong bystander killing effect, BAT8008, which consists of an enzymatically cleavable linker and a topoisomerase I inhibitor as the payload, with DAR of 6. BAT8008 demonstrated potent in vitro cell growth inhibitory activity to Trop2-positive cells with IC50 values of &lt; 1 nM. In an in vitro bystander killing assay, proliferation of Trop-2-negative cells was potently inhibited by addition/transfer of culture medium of BAT8008-treated Trop-2-positive cells, but not that of BAT8008-treated Trop-2-negative cells, indicating the bystander killing effect of the released payload in the culture medium. Less than 0.1% of the payload was released from BAT8008 when incubated with human or monkey plasma for 7 days in 37°C, suggesting the stability of BAT8008 in blood circulation. Single dose of BAT8008 at 1 and 2.5 mg/kg could inhibit 73% and 81% tumor growth in the Trop-2-positive MDA-MB-468 and MX-1 xenograft mice model, respectively. BAT8008 also demonstrated superior tumor inhibition activity than a modified ADC using Daiichi’s ADC technology or Trodelvy in a pancreatic BxPC-3 xenograft mice model. In addition, BAT8008 showed favorable pharmacokinetic and safety profiles in cynomolgus monkeys with the highest non-severely toxic dose (HNSTD) of at least 25 mg/kg when dosed once every two weeks for 3 times. Together these results indicate that BAT8008 could potentially provide a therapeutic benefit to treat TROP2-positive breast cancers in clinical trial.
Citation Format: Xingxing Mei, Weijia Tang, Xin Zhou, Xuekang Qi, Siqi Mai, Zhi Zhong, Shuoxu Li, Jianjun Fan, Jirong Gan, Binghua Tan, Yao Qi, Yanling Guo, Jin-Chen Yu, Shengfeng Li. BAT8008, a novel Trop-2 ADC with strong bystander effect, for the treatment of Trop-2 positive 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 P4-01-32.
Abstract P4-03-16: Association between tamoxifen and the incidence of cataract in ductal carcinoma in situ patients
Authors: Kim Dooreh , Park Woo-Chan , Jeon Soyoung , Lee Hye Sun , Yoon Chang Ik 
Published: March 2023

Abstract
Background Tamoxifen is used to improve oncologic outcomes in a hormone receptor-positive breast cancer. High-dose tamoxifen induced ocular toxicities, and regular dose of tamoxifen is known to increase the risk of cataracts in landmark studies. The current study’s objective is to review the incidence of cataracts in ductal carcinoma in situ (DCIS) patients who received adjuvant tamoxifen treatment, which can exclude the effect of other treatment modalities such as chemotherapy and target therapy. Method Data were obtained from the National Health Insurance claims database of the Health Insurance Review and Assessment Service in South Korea. Patients diagnosed with DCIS were sorted and retrospectively reviewed for the incidence of cataracts. The primary study outcome was the incidence of cataracts according to tamoxifen, and the incidence of cataracts was defined by concomitant diagnostic and behavioral code based on International Code of Disease, 10th revision. Results A total of 12,032 patients diagnosed with DCIS and received breast surgery from 2009 to 2015 were cut down to 4,759 patients, excluding those who already had cataracts, malignancies, or had developed cataracts within a year of breast cancer surgery. There were 3,037 patients who received tamoxifen and 1,722 patients who did not, median age of 49 years old. The incidence of cataracts was similar according to the use of tamoxifen, 7.6% and 7.7% respectively. The risk of developing cataracts did not increase with or without tamoxifen, even in the group who received adjuvant tamoxifen for more than two years (HR 0.978, 95% CI 0.782-1.222, p=0.843). The findings were consistent after propensity score matching (HR 1.072, 95% CI 0.829-1.388, p=0.595). Conclusions In a nationwide cohort study, the risk of cataracts in DCIS patients is similar whether the tamoxifen is used or not.
Citation Format: Dooreh Kim, Woo-Chan Park, Soyoung Jeon, Hye Sun Lee, Chang Ik Yoon. Association between tamoxifen and the incidence of cataract in ductal carcinoma in situ patients [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 P4-03-16.
Abstract P4-06-08: HER2-protein expression is a predictive marker for treatment response in patients with HER2-positive breast cancer who received neoadjuvant chemotherapy with dual HER2-blockade
Authors: Bae Soong June , Jang Ji Soo , Kook Yoonwon , Baek Seung Ho , Kim Jee Hung , Ahn Sung Gwe , Jeong Joon 
Published: March 2023

Abstract
Background In HER2-positive breast cancer, pathologic complete response (pCR) has been known to be a surrogate marker for favorable prognosis after neoadjuvant chemotherapy. We aimed to identify the clinico-pathologic factors related to pCR in patients with HER2-positive breast cancer treated with neoadjuvant dual HER2-targeted therapy. Methods Two-hundred ninty-five patients with HER2-positive breast cancer who received neoadjuvant chemotherapy with docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP) were included in this retrospective analysis. We assessed the association between age, clinical T, N stage, pathologic factors such as histologic grade, hormone receptor (HR), tumor-infiltrating lymphocytes, the membranous expression of HER2 protein evaluated by immunohistochemistry (IHC) and pCR. The fluorescent in situ hybridization (FISH) was performed in a tumor with HER2 score of 2+. Results Of the 295 patients, 195 (66.1%) achieved pCR (ypT0/is and ypN0). Besides, 240 (81.4%) patients were HER2 score of 3+, and 55 (18.6%) patients were HER2 score of 2+. The pCR was frequently observed in patients with HER2 score of 3+ (64 of 176 [73.3%]) than in those with HER2 score of 2+ (19 of 55 [34.5%]), regardless of HR status. After adjusting other clinicopathologic factors, the high HER2 protein expression was only an independent factor for pCR (adjusted OR 3.85, 95% CI, 1.66-8.91, p=0.002). Conclusions Our results suggest that high expression of HER2 protein assessed by IHC is important in predicting neoadjuvant TCHP response in HER2-positive breast cancer.
Citation Format: Soong June Bae, Ji Soo Jang, Yoonwon Kook, Seung Ho Baek, Jee Hung Kim, Sung Gwe Ahn, Joon Jeong. HER2-protein expression is a predictive marker for treatment response in patients with HER2-positive breast cancer who received neoadjuvant chemotherapy with dual HER2-blockade [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 P4-06-08.
Abstract P4-07-44: Association between tissue mobilization with physical exercise and physical exercise alone in patients with axillary web syndrome who underwent breast cancer surgery
Authors: Figueira Patricia V. , Haddad Cinira , de Almeida Rizzi Samantha K. Lopes , Estevao Amanda , Elias Simone , Facina Gil , Nazário Afonso 
Published: March 2023

Abstract
Introduction: Axillary web syndrome (AWS) is a complication in women with breast cancer and occurs immediately after axillary surgery. It is characterized by pain, limited shoulder range of motion (ROM), and presence of cords. Objectives: This study aimed to evaluate the impact of physical therapy interventions, such as physical exercise with tissue mobilization and exercise alone. Methods: A randomized clinical trial was conducted at the Divison of Breast Cancer disease of the Universidade Federal de São Paulo. Seventy-three women with AWS were randomized into the mobilization (ME) group (N=37) and exercise (E) group (N=36) and followed up for 3 months after breast cancer surgery. Both groups were provided with specific guidelines for performing regular shoulder exercise at home, while tissue mobilization was performed in a specific group with a maximum of six sessions, according to the patient’s need. ROM, pain, and presence of cords were evaluated in each postoperative period (PO). Results: In both treatment groups, at the end of 90 days, improvement in flexion was observed as well as less pain and number of cords. In terms of abduction, the E group was better than the ME group. Conclusions: Physical exercise after breast cancer surgery is extremely important for functional recovery, resumption of activities of daily living, improvement of pain, and reduction in the number of cords. Tissue mobilization appears as an adjunct for causing a more immediate improvement in ROM, pain, and presence of cords, but at times not sustaining the gains for the following PO. Keywords: breast neoplasms, axillary web syndrome, physical exercise, articular range of motion, pain
Citation Format: Patricia V. Figueira, Cinira Haddad, Samantha K. Lopes de Almeida Rizzi, Amanda Estevao, Simone Elias, Gil Facina, Afonso Nazário. Association between tissue mobilization with physical exercise and physical exercise alone in patients with axillary web syndrome who underwent breast cancer surgery [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 P4-07-44.
Abstract P4-07-57: Outcomes of Triple-Negative Breast Cancer In Older Versus Younger Women
Authors: Munir Asma , Khawaja Saira , Khan Sohail , Sharaiha Yousuf , Huws Anita M. 
Published: March 2023

Abstract
Background: Triple-negative breast cancer (TNBC) is an aggressive disease characterized by lack of targeted therapy; main-stay of treatment being limited to surgery and chemotherapy. Older patients with TNBC are often underrepresented in the clinical trials, due to competing mortality risks. This study aims to assess the treatment and outcomes of triple negative breast cancer (TNBC) in older women relative to younger women. Methods: This was a retrospective cohort study of patients who presented with primary TNBC, age 34-94 years; stage I-III from Jan 1, 2013 to Dec 31, 2015. Patients’ demographics, clinical characteristics, treatment and outcomes were retrieved from the CANISC Register and individual patient (N=88). Breast cancer-specific survival (BCSS) was estimated by using Kaplan–Meier method, and adjusted for age, tumor size, tumor grade, nodal status and chemotherapy, using SPSS-19. Results: Fifty-one patients were less than 70 years old (57.9%) and 37 were 70 years and older (42.1%). There was no difference in the stage at presentation (stage I: 43% vs. 35%; stage 2: 49% vs. 49%; stage 3: 8% vs. 11%; P=.061). Older patients were less often treated with adjuvant chemotherapy (75% vs. 24%; P&lt; 0.001). Mean follow-up was 48 months. Five-year BCSS was significantly poor for older patients (54% vs. 75%, P=.032). 5-year overall survival was also significantly worse for patients who did not receive adjuvant chemotherapy (50% vs. 88% P =0&lt; 021). Conclusions: Overall survival in triple negative breast cancer is much worse in older women as compared to younger women and there is a significant benefit with adjuvant chemotherapy.
Citation Format: Asma Munir, Saira Khawaja, Sohail Khan, Yousuf Sharaiha, Anita M. Huws. Outcomes of Triple-Negative Breast Cancer In Older Versus Younger Women [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 P4-07-57.
Abstract P4-08-25: Unravelling the role of human endogenous retrovirus K (HERV-K) in inducible nitric oxide synthase (iNOS) mediated triple negative breast cancer progression
Authors: Bhattacharyya Dibyangana , Dervan Eoin , Glynn Sharon , Callagy Grace 
Published: March 2023

Abstract
Human endogenous retrovirus K (HERV-K) belongs to a family of endogenous retroviruses that are present in our genome with similarities to present day exogenous retroviruses. This virus can express several proteins but our knowledge of HERV-K expression in human cancers is mainly limited to the envelope (Env) protein. Elevated HERV-K env protein expression has been shown in breast cancer both in in vitro and in vivo studies. This project aimed to decipher mechanisms of HERV-K induction in triple negative breast cancer (TNBC), and the impact of HERV-K targeting shRNA mediated knockdown on TNBC characteristics including cell migration, invasion and proliferative capacity in 2D and 3D cell culture models. Our results show that a role for inducible nitric oxide synthase (iNOS) in the induction of HERV-K in TNBC cell lines. RNA seq and bioinformatics analysis was performed to identify key molecular processes regulated by HERV-K and nitric oxide (NO) in MDA-MB-231 TNBC cells. Reduced rates of migration, invasion and proliferation in HERV-K knockdowns points towards the essential role of HERV-K in tumorigenesis and metastasis. HERV-K knockdown also modulated key gene expression signatures traditionally associated with the basal and mesenchymal phenotypes in breast cancer, cellular senescence and MHC class gene regulation. The co-expression of iNOS and HERV-K was assessed in over 150 TNBC cases and the association with patient outcomes assessed. Taken together, our findings indicate that NO and HERV-K may be a useful molecular target for the treatment of TNBC.
Citation Format: Dibyangana Bhattacharyya, Eoin Dervan, Sharon Glynn, Grace Callagy. Unravelling the role of human endogenous retrovirus K (HERV-K) in inducible nitric oxide synthase (iNOS) mediated triple negative breast cancer progression [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 P4-08-25.
Abstract P5-02-52: Predictive and prognosis value of PIK3CA mutations in HER2-positive breast cancer treated with tyrosine kinase inhibitors (TKIs): a systemic review and meta-analysis
Authors: Shi Qiyun , Xuhong Juncheng , Tian Hao , Zhang Yi , Jiang Jun , Qi Xiaowei 
Published: March 2023

Abstract
Background: PIK3CA mutations is one of the most frequent gene alterations in breast cancers, which was reported to be related to the treatment response of anti-HER2 regimens. However, the relationship between PIK3CA mutations and treatment response of a tyrosine kinase inhibitors (TKIs) is still unclear. We thus conducted a systemic review and meta-analysis to investigate the predictive and prognosis value of PIK3CA mutations in HER2-positive breast cancer treated with TKIs. Methods: The following databases were searched from inception to July 2022: Medline, Embase and the Cochrane Library. Abstracts from conferences were also reviewed for inclusion. The critical information was extracted from eligible studies. Results: A total of 16 reports including 17 studies were assessed for eligibility, enrolling 1706 patients. Ten studies including 902 patients were in the neoadjuvant setting, the pCR rate is significantly higher in PIK3CA wild-type (WT) patients than in mutated-type (MT) patients (OR = 0.45; 95% CI: 0.31-0.65; P&lt; 0.001). Seven studies including 804 patients were in the metastatic setting, the pooled objective response rate (ORR) is significantly higher in PIK3CA WT patients than in MT patients (OR = 0.40; 95% CI: 0.23-0.70; P = 0.001), and similarly, the clinical benefit rate (CBR) in WT patients is also higher (OR = 0.43; 95% CI: 0.19-0.98; P=0.045). A total of 4 metastasis studies reported progression free survival (PFS), and 2 of them reported overall survival (OS), revealing a marginally significant relationship between PIK3CA mutation and worse PFS (HR = 0.82; 95% CI: 0.67-1.00; P=0.052) and OS (HR=0.63, 95%CI:0.39-1.02; P=0.062). No evidence of publication bias was found in both the neoadjuvant setting and metastatic setting. Conclusion: Our findings indicate that PIK3CA mutations is significantly associated with a lower rate of pCR when treated with TKI-containing regimens in neoadjuvant chemotherapy of early-stage HER2-positive breast cancer, and is significantly associated with lower ORR and CBR in metastatic HER2-positive breast cancer.
Citation Format: Qiyun Shi, Juncheng Xuhong, Hao Tian, Yi Zhang, Jun Jiang, Xiaowei Qi. Predictive and prognosis value of PIK3CA mutations in HER2-positive breast cancer treated with tyrosine kinase inhibitors (TKIs): a systemic review and meta-analysis [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 P5-02-52.
Abstract P5-05-09: Multianalyte liquid biopsy to aid the diagnostic workup of breast cancer
Authors: Shishido Stephanie , Kuhn Peter , Mason Jeremy , Hicks James , Nevarez Rafael , Matsumoto Nicholas , Kolatkar Anand , Velasco Carmen Ruiz , Anderson Amanda , Kidd Michael , Wilkinson Kathy , Hwang E Shelley , Lu Janice , Nieva Jorge , Higa Nikki , Naghdloo Amin , Hart Olivia , Setayesh Sonia Maryam 
Published: March 2023

Abstract
Breast cancer (BC) affects 1 in every 8 women in the United States and is currently the most prevalent cancer worldwide. Precise staging at diagnosis and prognosis are essential components for the clinical management of BC patients. The liquid biopsy (LBx) has promising applications in cancer screening and early diagnosis ultimately leading to better survival results and less disease burden. In this study, we evaluated the feasibility of the high-definition single cell assay (HDSCA) LBx platform to stratify disease states (early- and late-stage BC) and normal donors using peripheral blood samples. In the HDSCA3.0 workflow, both common white blood cells (WBCs) and rare cells, including circulating tumor cells (CTCs), EMT and platelet-coated cells, plus acellular structures are identified and classified computationally from scanned immunofluorescent images. This comprehensive LBx approach provides a quantitative landscape view of each individual case. In a striking example of the insight provided by HDSCA, we compared LBx results for early-stage and late-stage BC patients with two independent cohorts of normal donors to show the utility of a blood draw as a source of biomarkers for early-stage cancer detection. As expected, CTCs were detected at a higher level in late-stage patients, compared to either the early-stage or normal donors. Surprisingly, however, we observed a significantly higher incidence of tumor-associated large extracellular vesicles (LEVs) in the early-stage patients, compared to the other two groups. A patient-level classification model was able to correctly classifying LBx profiles as normal, early, or late with LEV enumeration as the strongest predictor, followed by epi.CTC enumeration. We will present a reproducible LBx profile of rare cells and LEVs of early-stage disease compared to late-stage BC and normal donors with high accuracy, allowing for robust stratification. Our findings illustrate the feasibility of the LBx to assess early disease states prior to clinically defined metastasis, stratified from normal donors, highlighting the general consideration of the liquid biopsy for the diagnostic work-up and potentially screening.
Citation Format: Stephanie Shishido, Peter Kuhn, Jeremy Mason, James Hicks, Rafael Nevarez, Nicholas Matsumoto, Anand Kolatkar, Carmen Ruiz Velasco, Amanda Anderson, Michael Kidd, Kathy Wilkinson, E Shelley Hwang, Janice Lu, Jorge Nieva, Nikki Higa, Amin Naghdloo, Olivia Hart, Sonia Maryam Setayesh. Multianalyte liquid biopsy to aid the diagnostic workup of 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 P5-05-09.
Abstract P5-09-05: A phase II, single-arm study of histone deacetylases inhibitor Tucidinostat and Exemestane as neoadjuvant therapy in patients with hormone receptor positive HER2 negative breast cancer (NeoTEE trial)
Authors: shan zhen , shao nan , zhang xiaoling , shi huijuan , zheng yanling , luo jia , zhen tiantian , chen ruping , Lin Ying 
Published: March 2023

Abstract
Background: Tucidinostat (formerly known as chidamide) plus exemestane is approved for postmenopausal patients with advanced, hormone receptor-positive breast cancer. We evaluated the efficacy and safety of tucidinostat plus exemestane as the neoadjuvant strategy in hormone receptor-positive early breast cancer patients. Methods: NeoTEE is an open-label, single-center, phase II study. Patients with HR-positive, HER2-negative and stage II/III breast cancer were enrolled at the First Affiliated Hospital of Sun Yat-sen University. Eligible patients received 25 mg oral exemestane once daily for 2 weeks followed by 30 mg oral tucidinostat twice weekly in combination with 25mg oral exemestane once daily for 24 weeks. GnRHa was used for premenopausal patients. Endpoints assessed here included objective response rate (ORR), complete cell cycle arrest (CCCA, Ki-67≤2.7%) at surgery, disease control rate (DCR), pathological complete remission (pCR) and safety. Results: Between July 2020 and July 2022, 26 patients were enrolled, of whom 24 were evaluable for response per RECIST 1.1 criteria. Partial response (PR) was observed in 18 patients, with an ORR of 75% (18/24). The DCR was 100%. Of the 14 patients with surgery, one patient achieved pCR and 8 patients were exempt from postoperative adjuvant chemotherapy. CCCA at surgery was 64.3% (9/14). The follow-up remains ongoing and updated results will be presented thereafter. Most adverse events (AEs) were grade 1 or 2. Grade 3 AEs occurred in 8 of 26 patients, the most common were neutropenia 19.2%, leukopenia 7.7%, anemia 3.8%, ALT increased 3.8%, pneumonitis 3.8%. Only 1 patient experienced grade 4 neutropenia. Grade 3/4 neutropenia recovered after dose reduction or discontinuation of tucidinostat. No patient received G-CSF. Conclusions: Tucidinostat combined with exemestane was well tolerated and demonstrated meaningful responses in neoadjuvant setting for women with early HR+/HER2- breast cancer. Further investigation is warranted. Clinical trial information: NCT04465097.
Citation Format: zhen shan, nan shao, xiaoling zhang, huijuan shi, yanling zheng, jia luo, tiantian zhen, ruping chen, Ying Lin. A phase II, single-arm study of histone deacetylases inhibitor Tucidinostat and Exemestane as neoadjuvant therapy in patients with hormone receptor positive HER2 negative breast cancer (NeoTEE trial) [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 P5-09-05.