bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P3-07-24: Role of tumor cell-derived lactic acid in the PD-1/PD-L1 blockade resistant tumor
Authors: Oh Wonkyung , Lim Seung-Oe 
Published: March 2023

Abstract
Immune checkpoint blockade therapy targeting the PD-1/PD-L1 axis (PD-1/PD-L1 blockade therapy) has shown remarkable clinical impact in multiple cancer types. Despite the recent success of PD-1/PD-L1 blockade therapy, acquired resistance, emerging as late relapses or recurrences, has been reported in the long-term follow-up of clinical trials. The altered metabolic activity of cancer cells shapes the anti-tumor immune response by affecting the activity of immune cells. In particular, glycolytic metabolites, such as glucose and lactate, regulate T cell proliferation and function. However, it remains mostly unknown how the altered metabolic activity of cancer cells impacts the therapeutic efficacy of, and resistance to, PD-1/PD-L1 blockade therapy. Here, we found that increased lactic acid functionally contributes to an immunosuppressive tumor microenvironment in the PD-1/PD-L1 blockade therapy resistant tumors through decreasing PD-L1 and PD-L1 antibody interaction. Furthermore, combinating PD-L1 targeting with our PD-L1-antibody-drug conjugate (ADC) and reducing lactic acid by an MCT-1 inhibitor, AZD3965, within the tumor microenvironment effectively eradicated the resistant tumor cells. Together, our results suggest a new combination treatment strategy to improve the therapeutic efficacy of immune checkpoint blockade therapies
Citation Format: Wonkyung Oh, Seung-Oe Lim. Role of tumor cell-derived lactic acid in the PD-1/PD-L1 blockade resistant tumor [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 P3-07-24.
Abstract P4-01-13: A retrospective study of anlotinib in patients with HER-2 negative metastatic breast cancer after prior two or more lines treatment
Authors: Sun Jing , Tang Yijun , Liu Xiaohui , Li Jiangli , Xia Jin , xu Liang , Guo Junlan , Wang Jing , Guo Shengnan , Sheng Zhaojie , Zhang Yanfang , Yuan Yuan 
Published: March 2023

Abstract
Background: Anlotinib is a novel small molecule antiangiogenic drug that can inhibit multiple tyrosine kinase receptor activities. It has demonstrated antitumor activity in various cancers. This retrospective study explored the efficacy and safety of anlotinib combined chemotherapy in HER-2 negative metastatic breast cancer patients who have disease progressed after prior two or more lines of therapy. Methods: This retrospective study enrolled twenty-two HER-2 negative metastatic breast cancer patients including TNBC and HR+ subtypes. These patients pretreated with at least two lines of chemotherapy and/or endocrine drugs before receiving anlotinib. These patients received anlotinib combination with investigator-selected chemotherapy agents, including docetaxel, vinorelbine, gemcitabine, etoposide, alibrine and so on. Anlotinib was administered 12mg d1-d14 for a 21-day cycle. The primary end point of this study was progression free survival (PFS). Secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and toxicity. The treatment continued until disease progression or intolerability or the patient withdraw informed consent. Results: The enrolled breast cancer patients received anlotinib with a median age of 52.5 (rang 30 to 73). The patients with multiple metastases were 59.1% (13/22). All patients were evaluated and the ORR was 50% (95% Cl 0.282-0.718), DCR 95.5% (95% Cl 0.772-0.999) and the mPFS was 8 months (95% Cl 5.15-10.85). We also analyzed the efficacy of anlotinib combination with chemotherapy in different subtypes. For HR+HER2- metastatic breast cancer patients, the ORR was 77.8% (95% Cl 0.4-0.972), DCR 100% (95% Cl 0.664-1.0) and the mPFS was 8.5 months (95% Cl 7.217-9.783). And for TNBC patients, the ORR was 30.8% (95% Cl 0.091-0.614), DCR 92.3% (95% Cl 0.640-0.998) and the mPFS was 6 months (95%Cl 4.405-7.595). The most common adverse events were grade 1/2 including fatigue, hand-foot syndrome and thrombocytopenia et.al., and no serious adverse events occurred. Conclusion: Anlotinib is safe and effective in patients with HER-2 negative metastatic breast cancer after prior two or more lines treatments, and it is well tolerated.
Citation Format: Jing Sun, Yijun Tang, Xiaohui Liu, Jiangli Li, Jin Xia, Liang xu, Junlan Guo, Jing Wang, Shengnan Guo, Zhaojie Sheng, Yanfang Zhang, Yuan Yuan. A retrospective study of anlotinib in patients with HER-2 negative metastatic breast cancer after prior two or more lines treatment [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 P4-01-13.
Abstract P4-05-07: Making Choices with Scarce Resources While Battling Breast Cancer In Nigeria
Authors: Okwu Gloria C. , Nwosu-Zita Theodora O. , Haruna Amina E. 
Published: March 2023

Abstract
Background Breast cancer diagnosis in Nigeria is perceived by most as a death sentence and women who have been diagnosed have to battle with different choices at any given time, whether to fight so as to survive, what if they fight and lose, or maybe it is better not to fight at all judging from different cases discussed during our monthly cancer patient support group meetings. Making informed choices with limited resources is the bane of many breast cancer patients who feel guilty spending so much on their medical care while their family suffers financial neglect. This is because health insurance covers barely 10% of the country’s population and most families pays out of pocket. Some women on the other hand completely ignore their treatment and channel these resources towards education and general welfare of other members of their families. Aim To determine the extent to which financial choices made by women who are diagnosed and are undergoing treatment of breast cancer in Nigeria affects their treatment journey. Method A qualitative research approach was used and structural interview was used to collect data. Female breast cancer patient who are undergoing treatment and those who are through with their treatment {chemotherapy, surgery, and radiotherapy} and are currently on periodic check up with their oncologists participated in the study. Grounded theory was used in data analyses. Results Most of the patients interviewed had at one time or the other suspended their treatments in order to take care of pressing family issues and these had caused delays in proceeding with their treatment with its attendant consequences. Presentation Oral Presentation
Citation Format: Gloria C. Okwu, Theodora O. Nwosu-Zita, Amina E. Haruna. Making Choices with Scarce Resources While Battling Breast Cancer In Nigeria [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 P4-05-07.
Abstract P4-06-12: Decision of Neoadjuvant Therapy in Younger vs. Older Breast Cancer Patients: A Real-World Data Analysis
Authors: Alanya Enrique , Falcon-Lizaraso Silvia , Aldecoa-Falcon Sebastian , Aldecoa-Bedoya Franklin 
Published: March 2023

Abstract
Background: The incidence of breast cancer among younger patients (age ≤ 40) is higher in Latin America than in other regions. The multidisciplinary approach of breast cancer cases has been related with better survival, and the knowledge about specific clinicopathological features of this population is needed to optimize the therapeutic approach. The aim of our study was to describe the clinicopathological characteristics of breast cancer in younger (Y) compared with older patients (O), and to determine which characteristics were associated with the use of primary systemic therapy.
Methods: A retrospective cohort study was designed. Clinicopathological data of consecutive invasive non-metastatic breast cancer patients diagnosed between Jan 2015 to Dec 2019 in two private oncological centers in Lima, Perú were collected. Logistic regression analysis was performed to obtain models to predict primary systemic therapy as first treatment.
Results: We included 503 cases (mean age 49.8 years [SD 11.8]), 30.6% younger (n = 109) and 69.4% O (n = 394). No significant differences were found for ductal histology (89% Y vs. 87.7% O, p = 0.49) and HER2-overexpression (28.4% Y vs. 23.9% O, p = 0.39). Significant differences were found for stage III (37.6% Y vs. 20% O, p &lt; 0.01), grade 3 (44.4% Y vs 33% O, p = 0.04) and HR-positive (64.2% Y vs. 75.1% O, p = 0.03). Univariate analysis showed significant OR = 2.1 to receive primary systemic therapy for Y (95%CI 1.37 – 3.24; p &lt; 0.01), however, multivariate analysis adjusted for age, hormone receptors (HR), HER2, grade and stage showed non-significant OR = 1.5 to receive primary systemic therapy for Y (95%CI 0.90 – 2.50; p = 0.12) as detailed in the table below:
Conclusions: In our series we found a greater proportion of young breast cancer patients than previously reported. Clinical-pathological characteristics of breast cancer were different between younger and older patients, showing more aggressive phenotypes for younger patients with greater proportion of stage III, grade 3 and non-expression of hormone receptors. Decision of using primary systemic therapy in our series was based on anatomic and biologic characteristics and not on age.

Citation Format: Enrique Alanya, Silvia Falcon-Lizaraso, Sebastian Aldecoa-Falcon, Franklin Aldecoa-Bedoya. Decision of Neoadjuvant Therapy in Younger vs. Older Breast Cancer Patients: A Real-World Data 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 P4-06-12.
Abstract P4-07-01: Overall survival with locoregional surgery in de novo metastatic breast cancer
Authors: Chongxi Ren , Jianna Sun , Lingjun Kong 
Published: March 2023

Abstract
Background: Breast cancer remains the most frequent type of cancer in women, with de novo metastatic breast cancer (dnMBC) accounting for approximately 6-10% of patients. Advances in treatment of dnMBC have led to an increase in overall survival (OS), but the role of locoregional surgery remains unclear. Aim: To determine the value of locoregional surgery compared with no surgery on OS of women with dnMBC Settings and design: This study was designed as a randomized clinical study and was approved by the Ethics Committee of the Ethics Committee of Cangzhou Clinical College of Integrated Traditional Chinese and Western Medicine of Hebei Medical University (NO.20200212). Methods: Patient characteristics were previously reported in ASCO2022. Eighty-six patients with dnMBC were randomised to surgery of the primary tumor followed by systemic therapy (surgery group) or to primary systemic therapy without surgery (non-surgery group), by a computer generated block randomisation sequence. Randomisation was stratified by site of distant metastases, number of metastatic lesions, and molecular subtypes. Follow-up visits were conducted during treatment, monthly in first year, every 3 months thereafter. The primary endpoint was overall survival analysed by intention to treat. The stratified log-rank test and Cox proportional hazards model were used to compare OS between groups. The level for significance was set at p&lt; 0.05. All analyses were performed with STATA 17. Results: Between Jan 3, 2019, and Mar 29, 2021, of the 103 women presenting with dnMBC, we randomly assigned 86 patients: 44 to surgery of the primary tumor followed by systemic therapy and 42 to primary systemic therapy without surgery. At data cut-off of Dec 1, 2021, median follow-up was 27 months with 44 deaths (surgery group n=21, non-surgery group n=23). The 2-year OS was 45.2% without and 52.3% with locoregional surgery (hazard ratio=0.59; 95% CI, 0.32 to 1.12; p = 0.11). The median OS was 25.5 months (95% CI, 23.52 to 29.38) in non-surgery group and 33 months (95% CI, 27.43 to 34.53) in surgery group. Conclusions: Our prospective randomized trial showed that compared with non-surgery counterparts, locoregional surgery does not improve OS of patients with dnMBC. Large, well-designed studies involving a large number of cases, multi-institution trials and longer follow-up are needed to verify the finding.
Citation Format: Ren Chongxi, Sun Jianna, Kong Lingjun. Overall survival with locoregional surgery in de novo metastatic 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 P4-07-01.
Abstract P4-07-42: Intervention to Distant Metastatic Lesions in Patients with Breast Cancer
Authors: Abidi Hira , Ozbas Serdar , Ozcinar Beyza , Dogan Lutfi , Isik Arda , Diego Emilia , McAuliffe Priscilla F. , Johnson Ronald , Steiman Jennifer , Sezgin Efe , Soran Atilla 
Published: March 2023

Abstract
INTRODUCTION Approximately one-fourth of patients presenting with early-stage breast cancer develop distant metastatic disease, a prominent cause of mortality. The role of metastasis-directed intervention is still uncertain in this cohort. The aim of this study is to evaluate whether intervention to metastatic lesions impacts overall survival (OS) and post-distant recurrence survival (PDRS), defined as survival after first occurrence of metastatic disease.
METHODS Our prospectively maintained international multi-center database of patients diagnosed with distant recurrence was retrospectively reviewed. Patients initially presenting with stage I-III breast cancer and diagnosed with metastatic disease to the bone, liver or lung from 2014-2020 were divided into cohorts receiving intervention to their metastases (IM, n=180) versus no interventions to their metastases (NI, n=120). The characteristics of the patients were compared with X2 test. OS curves were calculated by Kaplan-Meier method and multivariable analysis by Cox regression. Statistical significance was set at p&lt; 0.05.
RESULTS No significant differences in OS and PDRS were noted between the two groups when comparing age at diagnosis, menopausal status, tumor histopathology, pathological stage, axillary lymph node involvement, and hormone receptor and HER2 status. However, median OS and PDRS were significantly longer for patients who received IM compared to those who did not. The hazard of death was 59% lower with IM than with NI for both OS (HR 0.59: 95% CI 0.42 – 0.83; p=0.002) and for PDRS (HR 0.59: 95% CI 0.42 – 0.84). On multivariable analysis, OS was improved among patients with IM, and among those with lung metastases, compared to liver and bone metastases.
CONCLUSIONS Metastatic site intervention had both an OS and PDRS benefit in this cohort. In order to explore the potential for interventions to their metastases, patients who develop limited metastatic disease following initial breast surgery should be discussed at a multidisciplinary tumor board.
Post-Distant Recurrence Survival in Patients with Breast Cancer Receiving Intervention to Metastatic Lesions (IM) Versus No Intervention (NI)
Citation Format: Hira Abidi, Serdar Ozbas, Beyza Ozcinar, Lutfi Dogan, Arda Isik, Emilia Diego, Priscilla F. McAuliffe, Ronald Johnson, Jennifer Steiman, Efe Sezgin, Atilla Soran. Intervention to Distant Metastatic Lesions 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 P4-07-42.
Abstract P4-08-23: ZHX2 promotes HIF1α oncogenic signaling in triple-negative breast cancer
Authors: Liao Chengheng , Fang Wentong , Shi Rachel , Simon Jeremy , Ptacek Travis , Zurlo Giada , Ye Youqiong , Han Leng , Fan Cheng , Bao Lei , Ortiz Christopher Llynard , Lin Hong-Rui , Manocha Ujjawal , Luo Weibo , Peng Yan , Kim William Y , Yang Lee-Wei , Zhang Qing 
Published: March 2023

Abstract
Background: Triple-negative breast cancer (TNBC) is an aggressive and highly lethal disease in women, while the oncogenic mechanisms which contribute to TNBC development, progression, and metastasis are poorly investigated and therefore warrant the critical need to identify novel oncogenic signalings and develop new therapeutic targets. Results: We show that Zinc Fingers and Homeoboxes 2 (ZHX2) is amplified or overexpressed in TNBC cell lines and patients. Functionally, depletion of ZHX2 inhibited TNBC cell growth and invasion in vitro, orthotopic tumor growth, and spontaneous lung metastasis in vivo. Mechanistically, ZHX2 bound with hypoxia-inducible factor (HIF) family members and positively regulated HIF1α protein level and activity in TNBC. Integrated ChIP-seq and gene expression profiling demonstrated that ZHX2 co-occupied with HIF1α on transcriptionally active promoters marked by H3K4me3 and H3K27ac, thereby promoting gene expression. Among the identified ZHX2 and HIF1α coregulated genes, overexpression of AP2B1, COX20, KDM3A, or PTGES3L could partially rescue TNBC cell growth defect by ZHX2 depletion, suggesting that these downstream targets contribute to the oncogenic role of ZHX2 in an accumulative fashion. Furthermore, multiple residues (R491, R581, and R674) on ZHX2 are important in regulating its phenotype, which correspond with their roles in controlling ZHX2 transcriptional activity in TNBC cells. These studies establish that ZHX2 activates oncogenic HIF1α signaling, therefore serving as a potential therapeutic target for TNBC. Conclusion: ZHX2 has been highlighted as one critical hypoxia-related factors regulator contributing to triple-negative breast cancer in this work, which has enriched the upstream regulatory network of HIF-1α signaling. Moreover, identification of key residuals determining biological function of ZHX2 provides novel approaches for treating TNBC via targeting the hypoxia pathway.
Citation Format: Chengheng Liao, Wentong Fang, Rachel Shi, Jeremy Simon, Travis Ptacek, Giada Zurlo, Youqiong Ye, Leng Han, Cheng Fan, Lei Bao, Christopher Llynard Ortiz, Hong-Rui Lin, Ujjawal Manocha, Weibo Luo, Yan Peng, William Y Kim, Lee-Wei Yang, Qing Zhang. ZHX2 promotes HIF1α oncogenic signaling in 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 P4-08-23.
Abstract P5-07-04: Evaluation of Treatment Choices at Baseline Among Breast Cancer Patients Based on the Frailty Status of the Patients
Authors: Kaur Jasmeen , Galaznik Aaron 
Published: March 2023

Abstract
Background: Previous studies have shown that the frailty scores aid in better patient assessment and in advising treatment strategies. The objective of this study is to evaluate the impact of frailty status on the treatment choices among breast cancer patients.
Methods: Patient Reported Outcomes Mobile Platform (PROmpt®), an application for remote patient reporting, was used by breast cancer patients for completing surveys between September 2020 and April 2021. Out of 317 breast cancer patients, there were 84 women for whom frailty assessment was done at baseline based on age, Activities of Daily living (ADLS), Instrumental Activities of Daily living (IADLS) and comorbidities. Frailty status was stratified based on frailty score into fit (score=0), intermediate fit (score = 1) and frail (score &gt;=2). Treatment choices at baseline were stratified into targeted and cytotoxic monotherapy, hormone therapy, and systemic combined therapy. Role of chemotherapy treatment as adjuvant or neoadjuvant therapy was also assessed. Descriptive analysis was performed to assess the association of frailty status on the treatment choices at baseline.
Results: Around 24% of breast cancer patients were below 50 years of age and 76% patients were at least 50 years of age or older. The majority of the study population was White (84.15%) and non-Hispanic and Latino’s (63.09%). Around 61% of patients had early-stage breast cancer and around 36% of the patients had late-stage breast cancer. The majority of fit patients (70.59%) and intermediate fit patients (81.82%) receive systemic combined therapy at baseline. Out of fit patients, 67.80 % patients received adjuvant or neoadjuvant therapy, while 44.44 % of the intermediate fit patients received adjuvant or neoadjuvant therapy.
Discussion/Conclusion: Results demonstrate the feasibility of gathering fitness and frailty data as part of routine breast cancer care. Overall, the treatment choices among fit, intermediate fit and frail groups of patients appear consistent, although adjuvant/neoadjuvant therapy is directionally higher in fit patients. This similarity in regimen choice may be due to sample size, as the number of frail and intermediate fit patients is relatively small when compared to the fit patients. Further exploration related to treatment choices is recommended in a study population with higher levels of patients assessed as frail for comparative evaluation.
Frailty Assessment and Treatment Choice
Citation Format: Jasmeen Kaur, Aaron Galaznik. Evaluation of Treatment Choices at Baseline Among Breast Cancer Patients Based on the Frailty Status of the 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 P5-07-04.