bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PO2-05-06: Palbociclib in advanced hormone receptor positive breast cancer: A real world study in South America
Authors: SÁNCHEZ Cesar , Samtani Suraj , Gómez Henry , Falcon-Lizaraso Silvia , Muñoz René , Soria Tannia 
Published: May 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 &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 &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&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 PO2-06-05: Neutrophil-to-lymphocyte ratio (NLR) Predict the Outcome Significance for Primary Tumor Surgery in Patients with De novo stage Ⅳ Breast Cancer
Authors: Sugihara Rie , Toh Uhi , Watanabe Hidetaka , Katagiri Yuriko , Matsushima Shuntaro , Mina Okabe , Takao Yuko , Iwakuma Nobutaka , Fujita Fumihiko 
Published: May 2024

Abstract
[Background] Although several prospective randomized trials have not shown a statistically significant difference in overall survival(OS),and quality-of-life(QOL) for the primary tumor surgery(PTS) of De novo stageⅣ breast cancer(BC), but more recent studies showed that could prolong OS in selected cases. This study respectively evaluated the value of neutrophil-to-lymphocyte ratio(NLR) as a biomarker for predicting the benefit of PTS in patients(pts) with stageⅣ BC.
[Method] The clinical outcome and associated prognostic factors of pts with De novo stageⅣ BC were investigated. The decision of surgery option for primary tumor was shared with pts and determined by treating physicians according to the clinical symptoms. Laboratory blood examinations were performed before and after surgery or each treatment courses. The kinetics of peripheral blood lymph cell counts, NLR etc. were analyzed simultaneously.
[Result] A total of 141 pts with stageⅣ BC were treated and enrolled from January 2004 to December 2022. 61 pts (Surgery group: SG) received and 80 pts (Non surgery group: NSG) not received PTS. The biological subtypes of primary BC included that 76 HR+(Luminal), 13 HR+Her2+(Luminal Her2), 29 Her2+ and 21 triple negative, respectively. The median PFS of SG and NSG were 88 ms and 30.3 ms, the median OS were 100.1 ms and 31.8 ms, respectively. Pts of SG who had high NLR ( &gt;3) before the surgery showed a significant worse OS (p= &lt; 0.0001)( Fig.1). And pts who responded to the systemic therapies prior to PTS for longer than 8.1 months showed a better OS(p=0.044). In contrast, pts of NSG who had a low ALC(≦1500/μL) at 6 months(p=0.026) and 1 year(p=0.007) after systemic therapies, and high NLR( &gt;3) at 1 year(p=0001) had worse prognosis.
[Summary] Our results suggested that pts with De novo stageⅣ BC who responded to the systemic therapies prior to PTS longer than 8.1 months, and who had a preoperative low NLR(≦3) might be benefit to PTS after the systemic therapies. And peripheral blood NLR before surgery may be a predictive marker for the indication of PTS in those pts. Further larger scale prospective studies are warranted.

Citation Format: Rie Sugihara, Uhi Toh, Hidetaka Watanabe, Yuriko Katagiri, Shuntaro Matsushima, Okabe Mina, Yuko Takao, Nobutaka Iwakuma, Fumihiko Fujita. Neutrophil-to-lymphocyte ratio (NLR) Predict the Outcome Significance for Primary Tumor Surgery in Patients with De novo stage Ⅳ 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 PO2-06-05.
Abstract PO2-08-10: Effect of 6 months of bazedoxifene + conjugated estrogens on body composition and insulin resistance
Authors: Fabian Carol , Zelenchuk Adrian , Powers Kandy , Kreutzjans Amy , Pittman Krystal , Hendry Bill , Altman Christy , Giles Erin , Cook Katherine L. , Hursting Stephen , Kimler Bruce 
Published: May 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 &gt;1.5 is considered abnormal with &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 &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 &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 PO2-10-06: The Rising Burden of Contraception Requirements in Breast Cancer Clinical Trials: Time for Change?
Authors: Chiodi Camila , Hamid Munzir , Weadick Catherine , Hennessy Maeve , Martin-Quesada Ana , Kenny Louise , Lambertini Matteo , Luis Ines Vaz , O'Reilly Seamus 
Published: May 2024

Abstract
Background: Breast cancer clinical trials often involve therapies with potentially deleterious effects on the fetus and the baby in the event of pregnancy or breastfeeding. Consequently, eligibility criteria include contraceptive requirements for both the patient and their partner. Patient feedback on the burden of requirements in clinical trials prompted an evaluation of changes in contraceptive requirements in breast cancer clinical trials over the past two decades.
Methods: Breast cancer ClinicalTrials.gov trials protocols over three periods of enrollment were reviewed: 01/01/2001 - 01/01/2002, 01/01/2011 - 01/01/2012, and 01/01/2021 - 01/01/2022. Inclusion criteria: 1. Interventional studies including (neo)adjuvant or palliative systemic therapy, 2. Premenopausal female patients. Data, including the required number, types, and duration of contraceptive strategies, treatment regimen, and study design, were collated. A descriptive analysis by time period was performed.
Results: 305 studies were included from the three periods: 63 (2001), 127 (2011), and 115 (2021). Of these, contraception requirements were specified in ClinicalTrial.gov protocol information in 4, 61, and 71 CT for 2001, 2011, and 2021, respectively, limiting our analyses in the two later periods. Complete data is available in Table 1.
Conclusions: Our data demonstrates a time trend towards more stringent contraception requirements in breast cancer clinical trials inclusion criteria. The impact of contraception burden on enrollment, patient compliance, and investigator insight warrants further assessment.

Citation Format: Camila Chiodi, Munzir Hamid, Catherine Weadick, Maeve Hennessy, Ana Martin-Quesada, Louise Kenny, Matteo Lambertini, Ines Vaz Luis, Seamus O'Reilly. The Rising Burden of Contraception Requirements in Breast Cancer Clinical Trials: Time for Change? [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 PO2-10-06.
Abstract PO2-12-11: Ocular Toxicity of Tamoxifen in Patients with Breast Cancer
Authors: Alhouz Husain , Azmeh Arwa , Saifo Maher 
Published: May 2024

Abstract
Background: The latest recommendations in breast cancer treatment protocols with tamoxifen indicate that it should be used from five to 10 years. It depends mainly on the cumulative dose of the drug in the body. Despite its multiplicity, the various studies conducted on this subject did not reach conclusive results. Objectives: This research aims to study retinopathy associated with hormonal treatment of breast cancer using tamoxifen. Methods: A cross-sectional study was conducted at Al-Mouwasat University Hospital on a sample of 130 eyes according to (G-Power) with a statistical power of 95%. The participants were briefed on the research and consented on the ethical considerations. Then, the patients who entered the study were interrogated, clinically examined, and were asked about their medical history, the time of breast cancer diagnosis along with the details about the treatment protocols they underwent or currently undergoing. The refractive errors were measured with an automatic refractive device, then they were examined on the slit lamp to investigate the refractory media, then the corrected and uncorrected visual acuity were taken. Finally, after ensuring that the inclusion criteria were met and excluding those who fulfil one or more of the exclusion criteria, optical coherence tomography was performed using SD-OCT technique to measure and review the retinal thickness map in circles of 1-3-6 mm, respectively, to notice possible changes on it. Results: We found that the use of tamoxifen irrespective to cumulative dose leads to increase in the macula thickness values in the upper and lower sectors within the 3 mm circle, and to significant decrease in the macula thickness values in the upper and lower sectors within the 6 mm circle, in addition to decrease in nasal sector thickness within the circles of 3 and 6 mm. Conclusion: We conclude that the difference between people treated with tamoxifen and those not treated with it is not limited to the occurrence of crystals deposition in the macular area or the presence of a cavity in the central macula (with or without typical cystic macular edema), but rather to existence of macula thickness differences unrelated to the cumulative dose of the drug, whether by increase or decrease in thickness of the upper, lower and nasal segments.
Citation Format: Husain Alhouz, Arwa Azmeh, Maher Saifo. Ocular Toxicity of Tamoxifen in Patients with 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 PO2-12-11.
Abstract PO2-25-01: Tumor Derived Chitinase-3 like 1 Induces Neutrophil Extracellular Traps that Promote T cell Exclusion and Resistance to Immunotherapies in Breast Cancer
Authors: Taifour Tarek , Attalla Sherif Samer , Zuo Dongmei , Gu Yu , Sanguin-Gendreau Virginie , Dall-Proud Hailey , Solymoss Emilie , Bui Tung , Kuasne Hellen , Papavasiliou Vasilios , Lee Chun Geun , Kamle Suchitra , Siegel Peter , Elias Jack , Park Morag , Muller William 
Published: May 2024

Abstract
Breast cancer remains the most prevalent cancer and a major cause of mortality affecting women worldwide. Chemotherapy along with radiation and surgery have long been the standard of care for breast cancer patients. However, devastating side effects, resistance to treatments and relapse are major concerns for patients and physicians. With the rise of immunotherapies as a treatment option for various cancers, there is a critical need to understand the mechanisms through which cancers evade the immune system. Targeting such mechanisms holds the key to improve patient response to immunotherapy, especially in breast cancer where efficacy rates remain low.
In a subset of poor outcome Triple Negative Breast Cancers, cytotoxic T cells are excluded from the tumor nest and restricted to the surrounding stroma, a phenomenon known as stromal restriction. Our data from genetically engineered mouse models and human tumors identified that the secreted cytokine Chitinase-3 like 1 (Chi3l1) promotes stromal restriction of T cells in several tumor types including breast, lung and colon. Chi3l1 ablation in pre-clinical models of breast cancer results in increased T cell infiltration into the tumor nest which delayed mammary tumorigenesis and improved response to immunotherapy. We further demonstrate that Chi3l1 promotes T cell exclusion through the direct induction and deposition of neutrophil extracellular traps (NETs) which form a barrier that restricts T cell entry. Neutrophil depletion or pharmacological disruption of NET formation abrogates Chi3l1-induced T cell exclusion and histologically phenocopies Chi3l1 ablation.
Thus, our results indicate that Chi3l1 is a major immunosuppressive cytokine that promotes breast cancer progression by inducing NET formation and inhibiting T cell infiltration. Given the importance of T cell infiltration in immune elimination of nascent tumors, the future targeting of Chi3l1 should improve immunotherapy efficacy and outcomes in patients with tumors characterized by a T cell excluded microenvironment.
Citation Format: Tarek Taifour, Sherif Samer Attalla, Dongmei Zuo, Yu Gu, Virginie Sanguin-Gendreau, Hailey Dall-Proud, Emilie Solymoss, Tung Bui, Hellen Kuasne, Vasilios Papavasiliou, Chun Geun Lee, Suchitra Kamle, Peter Siegel, Jack Elias, Morag Park, William Muller. Tumor Derived Chitinase-3 like 1 Induces Neutrophil Extracellular Traps that Promote T cell Exclusion and Resistance to Immunotherapies 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 PO2-25-01.
Abstract PO2-27-02: Re-sensitizing the Refractory Breast Cancer Bone Metastasis to Endocrine Therapies
Authors: Das Anindita , Ernst Cheyenne 
Published: May 2024

Abstract
Approximately 90% of Breast Cancer (BrCa) related deaths are caused by metastasis and bone is the first and most frequent site of breast cancer metastatic expansion, which can lead to severe pain, immobility, fractures, and nerve damage, as well as the development of metastases in other organs, hence; a poor quality of life in patients. Currently, treatment options for these bone metastases (BoM) are limited because most patients with BoM shows reduced ER dependency which leads to resistance to standard endocrine or hormonal therapies for estrogen receptor-positive (ER+) BrCa. The long-term goal of the proposed research is to develop a strategy where metastatic cancer cells in bone can be dependent on ER signaling again thereby restoring their sensitivity to endocrine therapies. We observed a transient loss of ER expression in concert with enhanced activity of the transcriptional coactivators YAP/TAZ - the downstream effectors of the Hippo pathway (responsible for regulating cell proliferation and death) during bone colonization by BrCa cells. We hypothesize that the interaction between cancer cells and osteoblasts in the bone microenvironment leads to the activation of calcium signaling in cancer cells, resulting in the de-phosphorylation and nuclear localization of YAP/TAZ which subsequently suppresses the transcription of the estrogen receptor gene (ESR). Our research strategy is as presented below. First, we will employ a combination of 2D/3D co-culture models of BoM along with a mechanical loading system and determine the molecular mechanism driving the dynamical activation of YAP/TAZ in BrCa BoM. Using a unique ex vivo BM model called Bone In Culture Array (BICA) which replicates the in-vivo conditions, we will determine if verteporfin, a YAP/TAZ antagonist, can synergize and possibly enhance the effects of Fulvestrant, an ER antagonist in current use for certain types of BrCa in preventing BoM outgrowths and treating established BoM in mice. This research could ultimately lead to a favorable combination strategy to treat endocrine-resistant BoM in BrCa patients and prolong their survival.
Citation Format: Anindita Das, Cheyenne Ernst. Re-sensitizing the Refractory Breast Cancer Bone Metastasis to Endocrine Therapies [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 PO2-27-02.
Abstract PO3-18-03: Preoperative single-dose camrelizumab and/or microwave ablation in women with early-stage breast cancer: A randomized window-of-opportunity trial
Authors: Zhou Wenbin , Xie Hui , Ding Qiang , Wang Shui 
Published: May 2024

Abstract
Immune checkpoint blockade (ICB) has shown low response rates for advanced breast cancer, and combinatorial strategies are needed to improve the effect of ICB. As an effective local therapy, microwave ablation (MWA) may be a trigger of antitumor immunity. This window-of-opportunity trial was conducted to determine the safety and feasibility of camrelizumab (anti-PD-1 antibody) combined with MWA in the treatment of early-stage breast cancer preoperatively. The peripheral immune response was also investigated. 60 participants were randomized to receive single-dose camrelizumab alone (n=20), microwave ablation (n=20), or both camrelizumab and microwave ablation (n=20), preoperatively. Camrelizumab and MWA were well tolerated alone and in combination. Different from that in single-dose camrelizumab or MWA group, participants showed stable quantity of blood cells after the combination therapy. After the combination therapy, peripheral CD8+T cells showed enhanced cytotoxic and effect-memory functions. Clonal expansional CD8+T cells showed different functions from emergent clones after the combination therapy, suggesting that the expansional clones may play a vital role in the enhanced biological functions of CD8+T cells. Enhanced interactions between clonal expansional CD8+T cells and monocytes was observed, suggesting monocytes contributed to enhanced functions of clonal expansional CD8+T cells. MHC I related pathways and interferon signaling pathways were activated in monocytes by the combination therapy. In conclusion, camrelizumab combined with MWA was feasible for the treatment of early-stage breast cancer. The peripheral CD8+T cells were activated after the combination therapy, dependent on monocytes with activated MHC I pathways.
Citation Format: Wenbin Zhou, Hui Xie, Qiang Ding, Shui Wang. Preoperative single-dose camrelizumab and/or microwave ablation in women with early-stage breast cancer: A randomized window-of-opportunity trial [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 PO3-18-03.