tbuckley/cabot-search huggingface dataset:
Abstract PO2-06-14: Kynurenine induces senescence reprogramming to promote metastasis in young triple-negative breast cancer
Authors: Cui-Cui Liu, Ke-da Yu
Journal: Cancer Research (2024)

Abstract Triple-negative breast cancer (TNBC), which has been associated with a high risk of relapse and poor prognosis, has an increasing incidence among young women and ongoing inferior long-term outcomes. Given TNBC arising at a young age are more likely to present at advanced stages and to have aggressive biology, it is necessary to investigate the underlying mechanism and develop multidisciplinary strategies for optimal therapy of young women with breast cancer. Here, we integrated the multiomics data of our large TNBC cohort (n=456) to investigate different molecular mechanism between younger and older patients in the context of genetic and transcriptional subtypes and immune cell infiltration. We discovered that young TNBC patients exhibited a poorer outcome of both 2-year relapse-free survival and 2-year distant disease-free survival. Multi-omics analysis revealed that kynurenine (KYN) was preferentially enriched in young TNBC and activated tumor cellular senescence pathway which was positively correlated with increased metastasis. Mechanistically, KYN activated the aryl hydrocarbon receptor (AHR) signaling pathway in an ARNT2-dependent manner which was critical for cellular senescence, to mediate senescence reprogramming and promote tumor metastasis in young TNBC. Our findings unveil a novel interplay between cancer cell metabolites and cell senescence, which provides valuable insights that can potentially enhance therapeutic strategies for young TNBC patients. Keywords: young TNBC, metastasis, kynurenine, cellular senescence, AHR pathway Citation Format: Cui-Cui Liu, Ke-da Yu. Kynurenine induces senescence reprogramming to promote metastasis in young triple-negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-06-14.
Abstract PO2-08-10: Effect of 6 months of bazedoxifene + conjugated estrogens on body composition and insulin resistance
Authors: Carol Fabian, Adrian Zelenchuk, Kandy Powers, Amy Kreutzjans, Krystal Pittman, Bill Hendry, Christy Altman, Erin Giles, Katherine L. Cook, Stephen Hursting, Bruce Kimler
Journal: Cancer Research (2024)

Abstract Menopause transition is often marked by an acceleration of visceral fat accumulation. Excess visceral fat is associated with insulin resistance and increased risk for breast cancer as well as heart disease and diabetes. We measured change in body composition (via iDXA), fasting insulin and glucose as part of an ongoing, Phase IIB trial (NCT04821141) of 6 months of bazedoxifene (BZA) + conjugated estrogen (CE) vs control with primary endpoints of change in mammographic density and breast tissue Ki-67. Participants are women ages 45-60 with vasomotor symptoms at increased risk for development of breast cancer. Methods: Visceral and total fat, lean, and total mass, were measured with iDXA (GE CoreScan™). Fasting plasma was assayed same day as drawn for total insulin using a chemiluminescence assay and glucose using a hexokinase method. Values generated were used to calculate HOMA IR (as a measure of insulin resistance) using the formula insulin µl/ml x glucose mg/dl/405. HOMA %S was calculated as 1/HOMA IR X100 as a measure of insulin sensitivity. Optimal HOMA IR is considered as ≤1; HOMA IR &amp;gt;1.5 is considered abnormal with &amp;gt;2.0 as evidence of insulin resistance. Optimal HOMA %S is 100%. Results: 24 women (12 BZA+CE, 12 Control) have completed baseline and 6-month body composition and insulin resistance assessments. Women randomized to BZA+CE were more likely to experience reduction in insulin resistance and improved insulin sensitivity despite a small weight gain over the initial 6 months. 7/12 randomized to BZA+CE had ≥15% reduction in HOMA IR vs only 2/12 controls. Three participants had HOMA IR &amp;gt;2 at baseline. Of these, one was randomized to BZA+CE and had a normal HOMA IR value at 6 months. The remaining two women were in the control group and saw no improvement in HOMA IR at 6 months. In addition, one woman randomized to control with normal HOMA-IR at baseline had HOMA IR &amp;gt; 2 at 6 months. Next Steps: The improvements in insulin resistance parameters with BZA+CE are similar to those observed in our rodent studies, supporting this combination as promising for use in breast cancer risk reduction in women with vasomotor symptoms at high-risk for metabolic disease. Citation Format: Carol Fabian, Adrian Zelenchuk, Kandy Powers, Amy Kreutzjans, Krystal Pittman, Bill Hendry, Christy Altman, Erin Giles, Katherine L. Cook, Stephen Hursting, Bruce Kimler. Effect of 6 months of bazedoxifene + conjugated estrogens on body composition and insulin resistance [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-08-10.
Abstract PO1-12-01: 'Not even my husband knows that I have this [breast cancer]': Survivors’ Experiences in Accessing, Navigating and Coping with Treatment
Authors: Runcie C.W. Chidebe, Tochukwu C. Orjiakor, Gloria C. Okwu, Mary-Gloria A. Orji, THEODORA Nwosu-Zita, Agha A. Agha, Simeon C. Aruah, Chika Okem-Akwiwu, Candidus C. Nwakasi, Akwasi Adjei Gyimah, Zainab Shinkafi-Bagudu, Ifeoma J. Okoye, Darlingtina K. Esiaka
Journal: Cancer Research (2024)

Abstract Purpose: Nigeria has the highest breast cancer (BC) burden in Africa. While the survival rates for BC are over 90% in many high-income countries; low-and middle-income countries like Nigeria have 40% BC survival rates. Prior studies show that the burden and poor BC survival rates are exacerbated by both health system and individual level factors, yet there is a paucity of literature on the experiences of BC survivors in Nigeria. Hence, this study explored BC survivors' divergent and convergent experiences in accessing, navigating, and coping with treatment. Methods: Participants (N=24, aged 35 to 73 years) were recruited and engaged in focus group discussions (Group 1, n = 11; Group 2, n = 13 participants). Transcripts were transcribed verbatim and analyzed with inductive thematic analysis. Results: Four themes were identified: “I am carrying this [breast cancer] alone”, “Living my life”, “‘God’ helped me”, and “A very painful journey”. Participants described how they concealed their BC diagnosis from family and significant others while accessing and navigating BC treatment. Also, they adopted spiritual beliefs as a coping mechanism while sticking to their treatment and acknowledging the burden of BC on their wellbeing. Conclusions: Our findings point to the urgent need for improved BC treatment facilities in Nigeria. Implications for Breast Cancer Survivors: Nigeria BC survivors are navigating both limited treatment facilities and coping with the personal challenges of BC diagnosis. There is a need for the government and clinicians to explore innovative technologies in improving BC treatment experiences in Nigeria. Citation Format: Runcie C.W. Chidebe, Tochukwu C. Orjiakor, Gloria C. Okwu, Mary-Gloria A. Orji, THEODORA Nwosu-Zita, Agha A. Agha, Simeon C. Aruah, Chika Okem-Akwiwu, Candidus C. Nwakasi, Akwasi Adjei Gyimah, Zainab Shinkafi-Bagudu, Ifeoma J. Okoye, Darlingtina K. Esiaka. 'Not even my husband knows that I have this [breast cancer]': Survivors’ Experiences in Accessing, Navigating and Coping with Treatment [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-12-01.
Abstract PO1-07-03: An Accurate Breast Cancer Diagnosis Method Using a Multi-Feature Fusion Neural Network on Contrast-Enhanced Spectral Mammography
Authors: Yipeng Song, Wei Jiang
Journal: Cancer Research (2024)

Abstract Objectives: Our study aims to develop an accurate and comprehensive deep neural network capable of classifying CESM images to aid in the early detection and diagnosis of breast cancer in clinical settings. Methods: We enrolled diagnostic CESM examinations conducted between January 1, 2019 and January 17, 2021. We developed and tested the performance of a multi-feature fusion network for breast lesion classification by combining low-energy (LE) and dual-energy subtracted (DES) images, dual-view, and bilateral information using a large and diverse CESM dataset. We have evaluated the ability of the proposed network to generalize on external datasets and the results were reported using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. Results: In the study period 1973CESMs were included. Mean age was 53 years ± 12 (standard deviation). In the internal test dataset, the model with CESM (LE +DES) inputs combined not only bilateral information (left and right breasts) but also dualview information (CC and MLO), achieved best diagnosis performance with AUC of 0.96 [95% confidence interval (CI): 0.95–0.97], accuracy of 0.9 [95% confidence interval (CI): 0.88–0.92], sensitivity of 0.84 [95% confidence interval (CI): 0.80–0.88] and specificity of 0.93 [95% confidence interval (CI): 0.91–0.95], while the model with LE inputs only got an AUC of 0.94 [95% (CI): 0.93–0.95], accuracy of 0.88 [95% confidence interval (CI): 0.86–0.90], sensitivity of 0.79 [95% confidence interval (CI): 0.74–0.83] and specificity of 0.93 [95% confidence interval (CI): 0.91–0.95] (external dataset: an AUC of 0.90 [95% (CI): 0.85–0.94], accuracy of 0.84 [95% confidence interval (CI): 0.78–0.89], sensitivity of 0.77 [95% confidence interval (CI): 0.61–0.88] and specificity of 0.87 [95% confidence interval (CI):0.80–0.92]). Conclusion: CESM is a promising technique in breast cancer diagnosis due to its high feasibility and potential. The results demonstrate that left-right breast fusion and dual-view fusion are helpful for accurate diagnosis on CESM images. Specifically, dual-energy subtracted (DES) images generated by CESM improve diagnostic accuracy when compared to low-energy (LE) images alone. Keywords: Contrast-enhanced spectral mammography; Deep neural network; Breast cancer diagnosis; Multi-feature fusion Citation Format: Yipeng Song, Wei Jiang. An Accurate Breast Cancer Diagnosis Method Using a Multi-Feature Fusion Neural Network on Contrast-Enhanced Spectral Mammography [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-07-03.
Abstract PO2-05-06: Palbociclib in advanced hormone receptor positive breast cancer: A real world study in South America
Authors: Cesar SÁNCHEZ, Suraj Samtani, Henry Gómez, Silvia Falcon-Lizaraso, René Muñoz, Tannia Soria
Journal: Cancer Research (2024)

Abstract BACKGROUND: First-line combined endocrine therapy is the standard of care for hormone receptor-positive (HR+) human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC). Palbociclib, in combination with aromatase inhibitors or fulvestrant, is a treatment option for HR+/HER2-negative ABC patients. We aimed to analyze the real-world experience of palbociclib in this setting in South America. METHODS: Real-world study collecting sociodemographic and clinical data from women with ABC treated with palbociclib in centers from Chile (n = 40), Perú (n = 61), and Ecuador (n = 10). Treatment efficacy and safety were analyzed. RESULTS: The median age was 54 years (range: 28 – 83), and 81.1% of women had received previous treatment: adjuvant therapy (20.0%), ABC treatment (31.1%), or both (48.9%). The median duration of palbociclib treatment was 14 months (range: 1 – 57), with differences among countries (longer in Perú; p = 0.009). The dose was reduced in 28.2% of women and only 6.5% returned to the previous one. Most women (97.3%) received combined endocrine therapy, letrozole (48.1%) or fulvestrant (44.4%), with differences between countries (p &amp;lt; 0.001). Palbociclib was usually the first-line therapy in Ecuador (60.0%) and Perú (80.3%), and the third line in Chile (37.5%). Considering all women, it was the first- or second-line therapy for 52.3% and 20.7% of them, respectively. The overall response rate was 34.2% and progressive disease was significantly lower in patients receiving first-line palbociclib (25.9 vs. 66.0%, p &amp;lt; 0.001). The disease-free survival was longer than 12 months in 67.2% of patients treated with first-line palbociclib. Regarding safety, 38.7% of women had any relevant adverse event (AE) during the treatment, most frequently neutropenia (39.5%), diarrhea (9.3%), and elevated transaminase levels (4.7%). The number of patients who developed any relevant AE was lower among the first-line treated patients (19.0% vs. 60.4%, p&amp;lt; 0.001). CONCLUSION: The study reflects differences among countries in routine palbociclib use. But considering all data, palbociclib has confirmed its efficacy and safety, supporting its use in HR+/HER2-negative patients, especially as a first-line therapy. Citation Format: Cesar SÁNCHEZ, Suraj Samtani, Henry Gómez, Silvia Falcon-Lizaraso, René Muñoz, Tannia Soria. Palbociclib in advanced hormone receptor positive breast cancer: A real world study in South America [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-05-06.
Abstract PO1-15-08: Genomic characterization of triple-negative breast cancer metastases reveals PKD1 as a novel biomarker for immunotherapy
Authors: Xiu-Zhi Zhu, Yi-Fan Zhou, Yun-Yi Wang, Xiao-Hong Ding, Xi Jin, Zhi-Ming Shao, Yi-Zhou Jiang, Zhong-Hua Wang
Journal: Cancer Research (2024)

Abstract Background: While primary triple-negative breast cancer (TNBC) garners significant research attention, the genomic alterations that occur in metastasis remain insufficiently understood, especially within Asian populations. Furthermore, the genomic information obtained from the primary tumor inadequately guides metastatic cancer treatment, highlighting the critical need for in-depth investigations into metastatic TNBC. Methods: We constructed the largest cohort of TNBC metastases (n = 296) among advanced TNBC patients treated at Fudan University Shanghai Cancer Center (FUSCC) between October 2018 and December 2020. Comprehensive DNA sequencing was conducted on the collected metastatic samples to analyze genomic alterations associated with treatment response. The underlying mechanisms of specific biomarkers were also explored. Results: We presented the genomic landscape of 296 TNBC metastases, encompassing mutant genes, mutation sites and copy number variations. Through multidimensional analysis, significant disparities in TNBC were observed between Western and Asian populations, primary and metastatic tumors, as well as different metastatic sites. Notably, our findings underscore the importance of sequencing TNBC metastases to guide precision therapy, which was associated with longer progression-free survival compared to physician-chosen treatments, shedding light on the pivotal clinical value of genomic studies in metastatic settings. Furthermore, efficacy analysis suggested that PKD1 mutations enriched in metastases mediated resistance to immunotherapy. These findings were further validated through three clinical trials (NCT03805399, NCT04129996, and NCT04395989). Mechanistic studies unveiled the involvement of PKD1 in TNBC immune evasion by upregulating CCL2, thereby facilitating the recruitment of M2-type tumor-associated macrophages. Conclusion: Our study emphasizes the critical significance and necessity of genomic profiling of metastases in guiding precision therapy for TNBC. Moreover, our findings reveal PKD1 as a novel and promising biomarker for immunotherapy. Citation Format: Xiu-Zhi Zhu, Yi-Fan Zhou, Yun-Yi Wang, Xiao-Hong Ding, Xi Jin, Zhi-Ming Shao, Yi-Zhou Jiang, Zhong-Hua Wang. Genomic characterization of triple-negative breast cancer metastases reveals PKD1 as a novel biomarker for immunotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-15-08.
Abstract PO2-05-09: Beyond endocrine resistance: estrogen receptor (ESR1) activating mutations mediate chemotherapy resistance through the JNK/c-Jun MDR1 pathway in breast cancer
Authors: Marwa Taya, Keren Merenbakh-Lamin, Asia Zubkov, Zohar Honig, Ori Mayer, Noam Shomron, Wolf Ido, Tami Rubinek
Journal: Cancer Research (2024)

Abstract Purpose: All patients with metastatic breast cancer (MBC) expressing estrogen receptor-α (ESR1) will eventually develop resistance to endocrine therapies. In up to 40% of patients, this resistance is caused by activating mutations in the ligand-binding domain (LBD) of ESR1. Accumulating clinical evidence indicate adverse outcomes for these patients, beyond that expected by resistance to endocrine therapy. We hypothesized that ESR1 mutations may also confer resistance to chemotherapy. Experimental Design: MCF-7 cells harboring Y537S and D538G ESR1 mutations (mut-ER) were employed to study response to chemotherapy using viability and apoptotic assay in vitro, and tumor growth in vivo. JNK/c-Jun/MDR1 pathway was studied using qRT-PCR, western-blot, gene-reporter and ChIP assays. MDR1 expression was analyzed in clinical samples using IHC. Results: Cell harboring ESR1 mutations displayed relative chemoresistance, evidenced by higher viability and reduced apoptosis as well as resistance to paclitaxel in vivo. To elucidate the underlying mechanism, MDR1 expression was examined and elevated levels were observed in mut-ER cells, and in clinical BC samples. MDR1 is regulated by the JNK/cJun pathway, and indeed, we detected higher JNK/cJun expression and activity in mut-ER cells, as well as increased occupancy of c-Jun in MDR1 promoter. Importantly, JNK inhibition decreased MDR1 expression, particularly of D538G-cells, and reduced viability in response to chemotherapy. Conclusions: Taken together, these data indicate that ESR1 mutations confer chemoresistance in BC through activation of the JNK/MDR1 axis. Targeting this pathway may restore sensitivity to chemotherapy and serve as a novel treatment strategy for MBC patients carrying ESR1 mutations. Citation Format: Marwa Taya, Keren Merenbakh-Lamin, Asia Zubkov, Zohar Honig, Ori Mayer, Noam Shomron, Wolf Ido, Tami Rubinek. Beyond endocrine resistance: estrogen receptor (ESR1) activating mutations mediate chemotherapy resistance through the JNK/c-Jun MDR1 pathway in breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-05-09.
Abstract PO1-20-10: Wernicke Encephalopathy Syndrome in Metastatic Breast Cancer – A Diagnostic Dilemma or An Underdiagnosed Entity
Authors: Archit Patel, Arya Mariam Roy, Ronald Alberico, Shipra Gandhi
Journal: Cancer Research (2024)

Abstract Wernicke encephalopathy (WE) is an acute medical syndrome that manifests as a clinical triad of encephalopathy, gait ataxia, and oculomotor dysfunction, requiring urgent treatment. Early recognition and treatment can prevent severe neurological morbidity and the chronic neurological consequence of WE, known as Korsakoff syndrome. Thiamine (vitamin B1) deficiency is the root cause of WE, which can occur due to several underlying conditions, including chronic alcoholism, hyperemesis of pregnancy, malnutrition, prolonged fasting, and malignancy. In cases of malignancy, WE is often undiagnosed or misdiagnosed because the presenting symptoms can be confused with several other complications of malignancy. We present the case of a 47-year-old woman with no significant medical history who was diagnosed with triple negative metastatic breast cancer and admitted to the hospital with confusion, memory loss, and progressive lower extremity weakness. During her breast cancer treatments, she experienced significant nausea and vomiting, leading to a prolonged state of nutritional imbalance. Patient underwent extensive infectious and neurological workup for encephalopathy including lumbar puncture which was negative for leptomeningeal disease or infection. MRI brain did not show any new metastatic lesions however revealed enhancement of mammillary bodies bilaterally. Mammillary body enhancement can be seen in WE but not always present on imaging. She was treated for WE with high dose of thiamine infusion for five days, resulting in an improvement of her neurological symptoms. Diagnosing WE in cancer patients is challenging, as there are various factors to consider, such as cerebral metastasis, infection, chemotherapy treatment, and electrolyte imbalances, that can cause neurological symptoms. Cancer patients are at high risk for development of WE due to chemotherapy or whole brain radiation induced nausea and vomiting that can lead to chronic malnutrition. The typical triad of symptoms is not present in many cases and presenting symptoms can be nonspecific which makes the diagnosis challenging. As a result, WE is often underdiagnosed in such patients, making it essential to educate the physician community about this acute neurological manifestation that can be easily treated. A high index of suspicion is necessary for early recognition, and prompt treatment can prevent Korsakoff syndrome, thereby enhancing the overall quality of life of patients with malignancy. Citation Format: Archit Patel, Arya Mariam Roy, Ronald Alberico, Shipra Gandhi. Wernicke Encephalopathy Syndrome in Metastatic Breast Cancer – A Diagnostic Dilemma or An Underdiagnosed Entity [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-20-10.