bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P3-04-11: Longitudinal Changes of Contralateral Breast Mammographic Artificial Intelligence Algorithms Score in Ductal Carcinoma In Situ patient with Tamoxifen
Authors: Lim Changjin , Park Eun Kyung , Kim Hong-Kyu , Kang Eunhye , Jung Ji-Jung , Yeoh Hyunsu , Kim Jang-il , Chun Jung Whan , Lee Han-Byoel , Moon Hyeong-Gon , Han Wonshik
Published: March 2023

Background Mammographic Artificial intelligence (AI) algorithms (Lunit insight MMG) draws attention as a diagnostic support tool for breast cancer detection. Lunit insight MMG provides a location suspected of breast cancer with a heatmap and a score reflecting the probability of the presence of suspicious areas. We investigated whether the Lunit insight MMG score is relevant for predicting the response to adjuvant tamoxifen. Methods Patients diagnosed with DCIS and underwent treatment at Seoul National University Hospital in 2010 were retrospectively enrolled. Clinical characteristics, tamoxifen use, survival data, and mammography images were extracted from the electronic medical records, and Lunit insight MMG scores were calculated retrospectively. We classified two groups according to tamoxifen treatment and compared the score change of contralateral breast from baseline to 5 years after surgery for DCIS. Change categories of Lunit insight MMG score included maintaining high risk, maintaining low risk, increasing from low risk to high risk, and decreasing from high risk to low risk. Results Of 100 patients, 50 (50%) had undergone tamoxifen treatment (group 1) and 50 (50%) had not (group 2). The median age of the patients was 48.4 years for group 1 and 51.5 years for group 2 (p=0.172). The median follow-up duration was 8.7 years for the whole cohort. Using Lunit insight MMG score, more patients in group 1 decreased in contralateral breast cancer (CBC) risk compared with group 2 (6.0% vs. 2.0%; P=.008). No patients in group 1 had an increase in CBC risk while 9 patients increased in group 2 (0% vs. 18.0%; P =.008). There was no ipsilateral breast cancer recurrence for the whole cohort, and two patients experienced contralateral invasive breast cancer in group 2. In two patients with CBC, the Lunit insight MMG score increased five years after surgery, one year and three years before the CBC diagnosis. Conclusions Longitudinal Changes of Mammographic AI algorithms Score may be a predictive surrogate marker for response to tamoxifen therapy in hormone receptor-positive DCIS.

Citation Format: Changjin Lim, Eun Kyung Park, Hong-Kyu Kim, Eunhye Kang, Ji-Jung Jung, Hyunsu Yeoh, Jang-il Kim, Jung Whan Chun, Han-Byoel Lee, Hyeong-Gon Moon, Wonshik Han. Longitudinal Changes of Contralateral Breast Mammographic Artificial Intelligence Algorithms Score in Ductal Carcinoma In Situ patient with Tamoxifen [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 P3-04-11.
Abstract P3-05-46: scRNA-seq profiling reveals different tumor immune-microenvironment in triple negative breast cancer and decodes pivotal role of THBS1- SDC1 axis in tumor metastasis
Authors: Zhang Liyi , Zhang Qi , Li Pei , Xiong Min , Zhou Yue , Xue Jingyan , Chen Ming , Chi Wei-Ru , Ren Hengyu , Goh Chih Wan , Liu Douwaner , Wangxu Liren , Chi Yayun , Xiu Bingqiu , Wu Jiong
Published: March 2023

ABSTRACT Background: Breast cancer has become the most common cancer worldwide and triple-negative breast cancer (TNBC) is the most aggressive subtype due to the lacks of hormone receptors and HER2 expression. Increasing rate of breast cancer metastasis also need to be solved. Nearly one in four breast cancer patients developed metastasis after treatment, which attributed to 90% cancer related death. Considering highly aggressive pattern of TNBC, TNBC showed higher metastasis probability rather than other subtypes. Therefore, exploring more biomarkers and therapeutic targets are on urgent. Methods: We profiled the transcriptomes of 59646 cells from 12 primary and 4 metastatic tumor samples from Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/). Results: Comparing with primary site, metastatic site was predominated with immunosuppressive tumor microenvironment. In brief, metastatic samples showed increasing numbers of macrophages, lower anti-tumor microenvironment scores, higher malignant cell properties scores, less effective T cells and macrophages, enhanced immune escape potential tumor cells and a later pseudotime state of malignant cells, compared with primary samples. Remarkably, metastatic samples exhibited a stronger interaction of THBS1-SDC1 axis between macrophage subcluster named angiogenesis-1 and malignant cell subcluster named CDKN2A epithelial cells. We subsequently confirmed that higher THBS1-SDC1 expression indicated with poor overall survival and distant metastatic free survival of TNBC patients in The Cancer Genome Atlas (TCGA) TNBC cohort. Conclusion: Our immune landscape of TNBC ecosystem provide deeper insights into tumor metastasis and offer potential biomarkers and therapeutic target for TNBC. Key words: Breast cancer; immune-microenvironment; THBS1; SDC1; metastasis

Citation Format: Liyi Zhang, Qi Zhang, Pei Li, Min Xiong, Yue Zhou, Jingyan Xue, Ming Chen, Wei-Ru Chi, Hengyu Ren, Chih Wan Goh, Douwaner Liu, Liren Wangxu, Yayun Chi, Bingqiu Xiu, Jiong Wu. scRNA-seq profiling reveals different tumor immune-microenvironment in triple negative breast cancer and decodes pivotal role of THBS1- SDC1 axis in tumor metastasis [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 P3-05-46.
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

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

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

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

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 < 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 < 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

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< 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

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< 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

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

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 >=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.
Abstract P5-09-03: Real World Data on Neoadjuvant Endocrine Treatment and Ki67 Assessment in ER+/HER2- Breast Cancer. Results from a Single-Institution Prospective Cohort Study
Authors: Marti Covadonga , Frias Laura , Loayza Adolfo , Moreno Elisa , Meléndez Marcos , Sanchez-Mendez Jose Ignacio
Published: March 2023

Purpose: Neoadjuvant endocrine treatment (NET) has become a useful tool for the downstaging of luminal-like breast cancers in postmenopausal patients. It enables us to increase breast conserving surgery (BCS) rates and provides an opportunity for assessing in vivo NET effectiveness and studying any biological changes that may act as valid biomarkers. The purpose of this study was to evaluate the effectiveness of NET as well as to assess the role of Ki67 proliferation rate changes as an indicator of endocrine responsiveness.

Methods: From June 2016 to January 2022, a single-institution cohort of patients treated with NET and further surgery was evaluated. In patients with Ki67≥10%, a second core biopsy was performed after four weeks. Information regarding histopathological and clinical changes, as well as surgical management, was gathered.

Results: A total of 168 estrogen receptor positive (ER+)/HER2 negative patients were included. The median age at diagnosis was 69.5 years old (IQR: 16.0). The median treatment duration was 5.0 months (IQR: 4.0). Median maximum size in the surgical sample was 44.0% smaller than pretreatment size measured by ultrasound (p<.0001), showing an inverse linear relationship with treatment duration. Median pretreatment Ki67 expression was 20.0% (IQR: 18.0) and was reduced to 5.0% (IQR: 8.0) after four weeks, and to 2.0% (IQR: 7.25) in the surgical sample (p< 0.0001). Other significant downgrading changes were observed with respect to tumor grade (p< 0.0001) and progesterone receptor (PR) expression (p< 0.0001). BCS was performed on 145 patients (86.3%). One case of pathological complete response was recorded. A larger Ki67 fold-change after four weeks was significantly related to a PEPI score of 0 (p< 0.002). No differences were observed between luminal A- and B-like tumors with regard to fold-change and PEPI score. No treatment abandonment was produced during the study.

Conclusions: In our cohort, NET has proven effective for tumor size and Ki67 downstaging. This results in a higher rate of conservative surgery, aids in therapeutic decision-making, provides prognostic information, and constitutes a safe and well-tolerated approach

Biological changes after NET

Patient and tumor characteristics

Citation Format: Covadonga Marti, Laura Frias, Adolfo Loayza, Elisa Moreno, Marcos Meléndez, Jose Ignacio Sanchez-Mendez. Real World Data on Neoadjuvant Endocrine Treatment and Ki67 Assessment in ER+/HER2- Breast Cancer. Results from a Single-Institution Prospective Cohort 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 P5-09-03.
Abstract P6-01-13: Identification of Protein Biomarkers for Early Detection and Stratification of Triple Negative Breast Cancer
Authors: metwali Essraa , Pennington Stephen
Published: March 2023

Breast cancer (BC) is the most frequent malignancy in women worldwide. Breast cancer affects roughly 3,000,000 people worldwide, with triple negative breast cancer (TNBC) accounting for 10-15% of all cases. In comparison to other types of breast cancer, TNBC stands out for its heterogenies disease, poor prognosis and aggressive behaviour. In the early stages of TNBC, neoadjuvant chemotherapy (NAC), which is given to the patient before surgery, has been considered a viable treatment strategy. Pathological complete response (pCR), which has been shown to increase estimates of disease-free (the amount of time following treatment during which there are no signs of malignancy), distant recurrence-free (the cancer has spread to far-off regions of the body) and overall survival, has been linked to NAC in 30% of patients. The objective of this study was to apply mass-spectrometry-based proteomics to serum samples from TNBC patients who have received NAC to identify i) biomarkers that might predict response to NAC, ii) biomarkers that might correlate with the extent of residual disease. These biomarkers will potentially inform treatment decisions such as the escalation/de-escalation of chemotherapy dosage for early TNBC patients. In this study, two proteomic approaches have been used to identify and measure protein candidate biomarkers: un-biased LC-MS/MS and targeted proteomics respectively. The discovery approach led to the identification of 17 unique proteins and 118 unique peptides that were differently expressed. The developing of a multiple reaction monitoring (MRM) assay for biomarker evaluation will be based on the prioritization of the potential signature proteins and other proteins obtained from public resources. Subject to successful evaluation and subsequent validation the candidate biomarkers may be beneficial for identifying TNBC patients who will achieve residual disease after NAC.

Citation Format: Essraa metwali, Stephen Pennington. Identification of Protein Biomarkers for Early Detection and Stratification of 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 P6-01-13.
Abstract P6-05-30: Effects of a 12-Week Exercise Program on Breast Cancer Survivors’ Quality of Life
Authors: Imai Lauren , Baron Kirsten , Toyama Matthew , Pagano Ian , Yamada Paulette , Teranishi-Hashimoto Cheri , Fukui Jami
Published: March 2023

Background: Previous studies have demonstrated that breast cancer survivors commonly experience a decrease in quality of life including an increased risk of depression, insomnia, cancer-related fatigue, and negative body image. Several studies have shown that exercise interventions, such as yoga, Pilates, water aerobics, and strengthening exercises, can improve survivors’ quality of life. We implemented a 12-week exercise program in breast cancer survivors and evaluated body composition and quality of life changes. Here we discuss our findings evaluating 5 quality of life questionnaires.

Methods: We evaluated 22 participants who completed a baseline and post 12-week questionnaire assessments. All participants underwent a 12-week exercise program 3 times/week for 90 minutes/session. We calculated differences in baseline and post 12-week quality of life through 5 questionnaires: Functional Assessment of Cancer Therapy - General (FACT-G), Social Support, Insomnia Severity Index, Brief Fatigue Inventory, and Body Image after Breast Cancer (BIBCQ) and assessed the intervention’s efficacy by comparing the baseline and post 12-week scores using paired t-tests.

Results: The difference between baseline and post 12-week quality of life are presented in Table 1. 7/13 questionnaires showed statistical significance: FACT-G Emotional, FACT-G Functional, Insomnia Severity Index, BIBCQ Vulnerability Scale (VS), BIBCQ Body Stigma Scale (BSS), BIBCQ Limitation Scale (LS), and BIBCQ Body Concern Scale (BCS). Interestingly, 4/6 of the BIBCQ questionnaires showed statistical significance: BIBCQ VS, BIBCQ BSS, BIBCQ LS, and BIBCQ BCS.

Summary: Our study showed improvement in all metrics evaluated in breast cancer survivors who underwent the personalized exercise program. Specifically, multiple questionnaires including body image were improved with exercise which further exemplifies the impact of lifestyle changes on quality of life measures and is an important adjunct to future cancer survivorship studies.

Table 1. Summary of questionnaires with overall significant improvements.

Citation Format: Lauren Imai, Kirsten Baron, Matthew Toyama, Ian Pagano, Paulette Yamada, Cheri Teranishi-Hashimoto, Jami Fukui. Effects of a 12-Week Exercise Program on Breast Cancer Survivors’ Quality of Life [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 P6-05-30.
Abstract P6-05-35: Cost-effectiveness of CDK4/6 inhibitors in the first-line treatment of HR+/HER2- metastatic breast cancer in postmenopausal women in Panama
Authors: Castillo-Fernandez Omar O. , Lim Maria , Montano Lilian
Published: March 2023

Background: 4/6 kinase-dependent cyclin inhibitors have been approved for use in combination with first-line aromatase inhibitors in patients with hormone-sensitive, Her 2neu negative metastatic breast cancer. These agents have significantly improved progression-free survival compared to monotherapy aromatase inhibitors. The purpose of this study was to evaluate the cost-evaluation of each of these new agents (palbociclib, ribociclib, and abemaciclib) in the first line in Panama with the perspective of the National Oncological Institute. Methods: A partition survival analysis was carried out that includes three states (free of progression, progression, and death) with cycles of one month and a time horizon of 7.5 years. The efficacy data were taken from pivotal clinical trials, and the costs were estimated locally. A deterministic and probabilistic sensitivity analysis of the Monte Carlo was performed. Results; According to the base case, the update of each of these strategies involved an increase of USD 355,184 per additional QALY for ribociclib with Letrozole compared to Letrozole; USD 944,148/additional QALY for Palbociclib plus Letrozole; and USD 223,956 for Abemaciclib plus Letrozole, when compared with Letrozole, all above the availability threshold to pay 50,000/QALY. Conclusion: Despite the improvement in progression-free survival, none of the strategies have proved cost-effectiveness in our setting. Price negotiations, cost reduction, and risk-sharing agreements between pharmaceutical companies and payers might improve access to new drugs in countries with limited resources.

Citation Format: Omar O. Castillo-Fernandez, Maria Lim, Lilian Montano. Cost-effectiveness of CDK4/6 inhibitors in the first-line treatment of HR+/HER2- metastatic breast cancer in postmenopausal women in Panama. [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 P6-05-35.
Abstract P6-11-02: Mitochondria-Nuclear Crosstalk Regulates the WNT Pathway in Triple-Negative Breast Cancer
Authors: Yang Sukjin , Park Jun Hyoung , Kim Suna , Ghidey Meron , Kaipparettu Benny
Published: March 2023

Compared to hormone receptor (HR) positive breast cancer (BC), basal or triple-negative BC (TNBC) suffers a poor prognosis caused by a limited understanding of its driver signaling pathways. We used the transmitochondrial cybrid approach to understand the metabolic reprogramming and mitochondria-nuclear crosstalk in metastatic TNBC. In cybrids, mitochondria from cancer and benign cells are compared under a commonly defined nuclear background. Using cybrid-based discovery and its validation in cell lines, patient-derived xenografts, and clinical data, we have previously reported the activation of fatty acid oxidation (FAO) in metastatic TNBC. Recently, we developed a unique gene (DEG) signature by integrating gene expression data from cybrids with different omnibus databases such as TCGA and METABRIC. Our DEG could effectively distinguish the PAM50 subtypes of BC. Further analyses nominated negative regulation of the canonical WNT signaling pathway as one of the major pathways altered by mitochondrial character. The WNT pathway is known to regulate cell signaling, metabolism, epithelial-mesenchymal transition (EMT), and cancer stemness. Cybrids with benign mitochondria showed transcriptional activation of negative WNT regulators, including DKK1, SOST, DAB2, and CAV1. Citrate is a key metabolite from the tricarboxylic acid cycle (TCA cycle) and is an intermediate of many other metabolic pathways. Analysis of TNBC cybrids, cell lines, and BC tissues suggest that in TNBC, citrate levels are increased with the activation of CPT1A, the rate-limiting enzyme of FAO. We confirmed the reduction of the beta-catenin protein in TNBC cells after pharmacological and genetic inhibition of CPT1A and mitochondrial citrate transporter (SLC25A1). We further analyzed the gene set enrichment analysis (GSEA) using gene expression data developed from short and long-term CPT1A inhibited TNBC cells and observed that the FAO alters polycomb repressive complex 2 (PRC2) activity. PRC2 is a critical modulator of the H3K27 methylation pattern as well as pathways related to cancer stemness, including WNT/beta-catenin and Hedgehog (SHH) pathways. These results suggest that the mitochondrial FAO transcriptionally inhibits WNT antagonist genes through repressive histone modification and consequently activates the canonical WNT pathway and cancer stemness. Overall, our current observations provide new insights into the regulation WNT pathway by mitochondria-nuclear crosstalk in TNBC.

Citation Format: Sukjin Yang, Jun Hyoung Park, Suna Kim, Meron Ghidey, Benny Kaipparettu. Mitochondria-Nuclear Crosstalk Regulates the WNT Pathway 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 P6-11-02.
Abstract P6-11-04: Novel roles of Inosine Monophosphate Dehydrogenase 2 (IMPDH2) in TNBC doxorubicin resistance
Authors: Fernandes Tatiane da Silva , Bianchi-Smiraglia Anna
Published: March 2023

Triple negative breast cancer (TNBC) is one of the major subtypes of breast cancer, being associated with the lowest survival rate after metastasis occurs. TNBC patients face limited therapeutic options, relying mostly on a combination of chemotherapies (anthracycline, taxanes and cyclophosphamide). However, around 40% of patients treated with chemotherapy relapse due to onset of chemoresistance, contributing to the dismal survival of this aggressive subtype. Therefore, understanding the molecular mechanisms underlying chemoresistance is critical to identify better therapeutic target options. Guanosine triphosphate (GTP) is important for several biological processes, including cell proliferation. We and others have shown that inosine 5’-monophosphate dehydrogenase 2 (IMPDH2), the rate limiting enzyme in the de novo synthesis of GTP, is important in migration and invasion of cancer, including TNBC, however the role it plays in chemoresistance remains to be elucidated. Our preliminary data revealed that IMPDH2 expression levels modulate doxorubicin sensitivity in different TNBC cell lines. Moreover, we have generated MDA-MB-231 cells that are resistant to doxorubicin (referred to as DoxoR), and revealed IMPDH2 to be upregulated in DoxoR cells, at both protein and mRNA levels as well as having higher activity. Consistently, DoxoR cells have ~50% more GTP than their naïve counterpart and, interestingly, are twice more sensitive to treatment with Ribavirin, a well-tolerated FDA approved IMPDH inhibitor, suggesting that Ribavirin could be repurposed for the treatment of chemoresistant TNBC. As expected, RNA sequencing of DoxoR cells revealed increased stemness properties when compared to naïve cells, which we confirmed experimentally in tumor sphere formation assays. Importantly, knockdown of IMPDH2 reverted the ability of DoxoR cells to form bigger tumor spheres, as well as reduced the IC50 of doxorubicin to that of naïve cells. Therefore, our data suggests that increased IMPDH2 and GTP levels in resistant setting could be a potential new vulnerability to be leveraged therapeutically to suppress and/or prevent the growth of chemoresistant lesions.

Citation Format: Tatiane da Silva Fernandes, Anna Bianchi-Smiraglia. Novel roles of Inosine Monophosphate Dehydrogenase 2 (IMPDH2) in TNBC doxorubicin resistance [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 P6-11-04.
Abstract PD6-03: PD6-03 Serum methylmalonic acid concentrations at breast cancer diagnosis strongly correlate with frailty: a retrospective cross-sectional study
Authors: Wu Qi , Hatse Sigrid , Kenis Cindy , Lambrechts Yentl , Punie Kevin , Neven Patrick , Smeets Ann , Laenen Annouschka , Gomes Ana , Fendt Sarah-Maria , Wildiers Hans
Published: March 2023

Introduction: Frailty commonly occurs in older persons, including those with breast cancer diagnoses. Methylmalonic acid (MMA), a metabolite and by-product of propionate metabolism, is known to increase significantly with aging. The relation between MMA concentrations and frailty is currently unknown. Objectives: A cross-sectional study was performed to study the association between baseline serum MMA concentrations and clinical frailty (estimated by G8 screening) in older patients with newly diagnosed breast cancer. Methods: 163 patients ≥70 years old with early-stage breast cancer were included (median age 76y). G8 screening and serum sample collection were performed at breast cancer diagnosis before any therapy was administered. MMA concentrations were measured via liquid chromatography with tandem mass spectrometry (LC-MS-MS). Results: MMA concentrations significantly increased with age (rs=0.3, p<.0001) and serum creatinine levels (rs=0.5, p<.0001) in this older population. The group with an abnormal G8 (≤14/17 = ‘frail’, 48% of patients) had significantly higher MMA levels than the group with normal G8 (>14/17 = ‘fit’, 52%): 250nM vs. 189 nM, respectively (p=.0002). Higher MMA concentrations were independently associated with abnormal G8 (Odds ratio, 1.003, 95%CI 1.0 to 1.006, p=.04) after adjusting for age and serum creatinine levels. Among the different components of G8, MMA concentrations correlated most with weight loss (rs= -0.18, p=.02), mobility (rs= -0.23, p=.002), and polypharmacy (rs= -0.22, p=.005). Conclusion: Elevated serum MMA concentrations at breast cancer diagnosis are significantly associated, not only with age but also independently with clinical frailty in older patients with early-stage breast cancer. MMA may be further evaluated as a biomarker of frailty in older persons with breast cancer.

Citation Format: Qi Wu, Sigrid Hatse, Cindy Kenis, Yentl Lambrechts, Kevin Punie, Patrick Neven, Ann Smeets, Annouschka Laenen, Ana Gomes, Sarah-Maria Fendt, Hans Wildiers. PD6-03 Serum methylmalonic acid concentrations at breast cancer diagnosis strongly correlate with frailty: a retrospective cross-sectional 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 PD6-03.
Abstract PL2: Plenary Lecture 2: Premenopausal ER+ Breast Cancer: Past, Present, and Future
Authors: Arteaga Carlos , Francis Prudence
Published: March 2023

Adjuvant endocrine therapy for premenopausal ER+breast cancer had a relatively challenging initial pathway. The earliest trials testing adjuvant ovarian ablation in premenopausal breast cancer were hampered by the lack of ability to test for the relevant target, namely the estrogen receptor (ER). Therefore, trials testing adjuvant ovarian ablation and subsequently ovarian suppression with gonadotropin releasing hormone agonists (GnRHa) were diluted by the inclusion of women with estrogen receptor negative tumors. The subsequent demonstration of the effectiveness of adjuvant chemotherapy, initially with the CMF regimen, diverted some attention away from adjuvant endocrine therapy in premenopausal women, notwithstanding the fact that CMF, initially given for 12 months, resulted in permanent ovarian function suppression in many premenopausal women. Use of adjuvant CMF made it even more challenging to discern the added value of ovarian ablation or suppression. Oral adjuvant endocrine therapy with the selective estrogen receptor modulator tamoxifen became recommended for postmenopausal women, subsequently refined to only those with ER+ breast cancer, but the value of tamoxifen in premenopausal women was initially considered uncertain. Eventually, 5 years of adjuvant tamoxifen became a standard recommendation for premenopausal ER+ early breast cancer, although it took some time for evidence to emerge on the value of adding tamoxifen in women who received chemotherapy. The value of extending adjuvant endocrine therapy beyond 5 years was subsequently studied. More recent randomized premenopausal adjuvant endocrine therapy trials have focused of delineating the value of ovarian function suppression (OFS) added to tamoxifen or to an aromatase inhibitor. There are now a range of options for adjuvant endocrine therapy for premenopausal ER+ breast cancer, and identifying the clinical-pathologic features most appropriate for intensification of adjuvant endocrine therapy can assist with optimizing recommendations for an individual patient.

Citation Format: Carlos Arteaga, Prudence Francis. Plenary Lecture 2: Premenopausal ER+ Breast Cancer: Past, Present, and Future [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 PL2.