tbuckley/cabot-search huggingface dataset:
Abstract PO2-08-06: Metformin may improve the outcome of patients with breast cancer and type 2 diabetes mellitus through the effect of tumor immune microenvironment
Authors: Satomi Shiba, Michiko Harao, Kasumi Ogihara, Takayo Fukuda, Masako Sakuragi, Kitayama Joji, Naohiro Sata
Journal: Cancer Research (2024)

Abstract Metformin, an anti-diabetic drug, is known to have anti-tumor effects. We examined the outcome of 177 patients with type 2 diabetes mellitus (T2DM) who received surgery for breast cancer. Among them, 49 patients were treated with drugs including metformin. In those patients, recurrence in distant organs was less frequent and postoperative disease-free survival (DFS) tended to be better than those without metformin intake. In patients who received preoperative systemic therapy (PST), rate of pathological complete response (pCR) was significantly more frequent in patients with metformin treatment (p &amp;lt; 0.05). Multiplex immunohistochemical staining of resected tumors revealed that the density of tumor associated macrophages (TAM), especially of CD68(+)CD163(+) M2-type TAM, was significantly lower in tumors with metformin treatment. In contrast, the rate of CD8(+) phenotype in CD3(+) tumor infiltrating lymphocytes (TILs) was significantly higher in metformin group. The results suggest that metformin can change the immune microenvironment from pro-tumorigenic to anti-tumorigenic status, which leads to the favorable outcome of the patients with breast cancer and T2DM. Citation Format: Satomi Shiba, Michiko Harao, Kasumi Ogihara, Takayo Fukuda, Masako Sakuragi, Kitayama Joji, Naohiro Sata. Metformin may improve the outcome of patients with breast cancer and type 2 diabetes mellitus through the effect of tumor immune microenvironment [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 PO2-08-06.
Abstract PO4-07-06: Development of MRI-based Radiomics Nomogram for the Prediction of Recurrence in Patients with Luminal-type Breast Cancer: A Nested Case-Control Study
Authors: Minji Song, Hee Jung Shin
Journal: Cancer Research (2024)

Abstract Purpose: The aim of this study was to develop a radiomics nomogram using breast MRI data and preoperative pathologic information to predict oncotype DX recurrence score (RS) in patients with estrogen receptor-positive early-stage breast cancer (EBC). Materials and methods: In this retrospective study, a total of 493 patients with EBC, diagnosed through core needle biopsy and who underwent preoperative breast MRI at a single institution between 2011 and 2017, were included. The patients were categorized based on RS, age at surgery, and nodal status, as suggested by the TAILORX trial, and out of the included patients, 249 were identified as likely to benefit from chemotherapy, while 244 were deemed safe to forgo chemotherapy. Radiomic features were extracted from three-dimensional segmentations of each tumor, and computer-extracted image phenotypes (CEIP) were generated from early post-contrast T1-weighted images, percent enhancement (PE) maps, and signal enhancement ratio (SER) maps. The patient cohort was divided into a training set (n=329) and a validation set (n=164). Feature selection and radiomics score construction were performed using elastic net, and a prediction model was developed using multivariate logistic regression analysis. The radiomics score, along with independent pathologic risk factors, was incorporated into a radiomics nomogram. Internal validation was conducted using an independent validation set (n=164). Results: The radiomics score, composed of 24 selected CEIPs, demonstrated a significant association with recurrence prediction (C-index, 0.769 for training set and 0.745 for validation set). The independent pathologic predictors included in the nomogram were histology, estrogen receptor status, progesterone receptor status, nuclear grade, histologic grade, HER1, CK56, P53, and Ki67 status, with a C-index of 0.858 for the training set and 0.774 for the validation set. Adding the radiomics score to the pathologic nomogram resulted in incremental values of 0.054 and 0.092, respectively. The radiomics nomogram showed favorable prediction of low-risk RS, with a C-index of 0.912 for the training set and 0.866 for the validation set. Conclusion: This study demonstrated that an MRI-based radiomics nomogram incorporating the radiomics score and preoperatively obtained pathologic data can effectively predict oncotype DX RS and the benefit of adjuvant chemotherapy in EBC patients. The model improves risk assessment availability and timeliness for patients with EBC. Citation Format: Minji Song, Hee Jung Shin. Development of MRI-based Radiomics Nomogram for the Prediction of Recurrence in Patients with Luminal-type Breast Cancer: A Nested Case-Control Study [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 PO4-07-06.
Abstract PO1-14-03: Discovery of proliferation essential gene signature and ACTL6A as potential biomarker for predicting prognosis and neoadjuvant therapy response in triple-positive breast cancer
Authors: Xiaofen Li, Wenfen Fu, Shiping Luo, Jie Zhang, Qingshui Wang, Chuangui Song
Journal: Cancer Research (2024)

Abstract Background: Based on the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), a special subtype of breast cancer which expresses all three receptors can be distinguished, namely triple-positive breast cancer (TPBC). TPBC patients has a higher risk of recurrence and lower survival rate compared to other luminal breast cancers. However, there are few studies on predicting molecules of prognosis and treatment response for TPBC. Methods: Proliferation essential genes (PEGs) were identified using CRISPR-Cas9 dataset of DepMap. The expression profiles and clinical data of TPBC were obtained from the TCGA database, GEO datasets and our center cohort. To develop a TPBC-PEG prognostic signature, cox regression and Lasso (Least absolute shrinkage and selection operator) regression analysis were applied. Functional analysis was performed using Gene Set Enrichment analysis. Finally, the relationship between candidate genes and neoadjuvant therapy (NAT) sensitivity was explored using real-time qPCR (RT-qPCR) and immunohistochemistry (IHC) based on clinical samples. Results: Among 900 TPBC-PEGs, 437 genes showed significant differential expression between TPBC and normal tissues. Subsequently, we identified 3 prognostic PEGs (ACTL6A, CCT2, TARS) and used them to construct a PEG signature. Patients with high PEG signature scores exhibited worse overall survival and lower sensitivity to NAT compared to those with low PEG signature scores. RT-qPCR indicated that in patients who lacked sensitivity to NAT, ACTL6A and CCT2 were significantly upregulated. The IHC results showed that ACTL6A protein was highly expressed in the NAT-insensitive group and non-pathological complete response patients. Conclusion: In this study, we developed an efficient PEG prognostic model that can predict the outcome for TPBC. Furthermore, we found that the expression of ACTL6A is associated with neoadjuvant therapy sensitivity in TPBC patients and can serve as an important factor in predicting patient prognosis and drug sensitivity. Figure 3. Construction and validation of a PEG signature for TPBC patients. Figure 6. The predictive value of ACTL6A on NAT efficacy and its correlation with clinical characteristics. Citation Format: Xiaofen Li, Wenfen Fu, Shiping Luo, Jie Zhang, Qingshui Wang, Chuangui Song. Discovery of proliferation essential gene signature and ACTL6A as potential biomarker for predicting prognosis and neoadjuvant therapy response in triple-positive 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 PO1-14-03.
Abstract PO1-13-01: Safety profiles of Chinese breast cancer patients who received abemaciclib in MONARCH plus and monarchE study
Authors: Zhimin Shao, Qingyuan Zhang, Quchang Ouyang, Qiang Liu, Jifeng Feng, Hui-Ping Li, Xiaojia Wang, Ning Liao, Liu Yang, Qinyi Zhu, Chenxi Qian, Zefei Jiang
Journal: Cancer Research (2024)

Abstract Aim: Abemaciclib demonstrated efficacy with tolerable safety profile in Chinese patients (CN pts) with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (ABC) and high-risk early breast cancer (EBC). The overall safety profile of abemaciclib in Chinese ABC and EBC pts was consistent with overall population in the MONARCH plus and monarchE studies. To better understand the safety of abemaciclib in CN pts, beyond the previously reported most frequent adverse events (AEs), we report a comprehensive summary of other selected AEs in CN pts in the two trials. Methods: Study designs of MONARCH plus (NCT02763566) and monarchE (NCT03155997) studies were reported previously. To report detailed characteristics of a selected AE profile, including alanine aminotransferase increased, aspartate aminotransferase increased, blood creatinine increased, fatigue, nausea, and vomiting, data were pooled across all CN pts from these two phase 3 studies. The safety population was defined as all randomized patients receiving at least 1 dose of Abemaciclib or endocrine therapy. Data cutoff time is May 18, 2020 and July 1, 2022, respectively. Results: Among 6052 participants in the overall safety population, 875 CN pts (14.5%) were included (512/3100 abemaciclib, 363/2952 placebo). CN pts treated with abemaciclib indicated consistent AE profiles in combination with different endocrine therapies (aromatase inhibitors or Fulvestrant). Detailed characteristics of selected AEs are summarized in table. No deaths due to the selected AEs were reported in CN pts. Conclusion: The selected AEs of abemaciclib group were in low severity with limited grade 3-4 events. Those AEs were tolerable and generally manageable in CN pts in the MONARCH plus and monarchE trials. Citation Format: Zhimin Shao, Qingyuan Zhang, Quchang Ouyang, Qiang Liu, Jifeng Feng, Hui-Ping Li, Xiaojia Wang, Ning Liao, Liu Yang, Qinyi Zhu, Chenxi Qian, Zefei Jiang. Safety profiles of Chinese breast cancer patients who received abemaciclib in MONARCH plus and monarchE study [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 PO1-13-01.
Abstract SoA3-01: SERMs versus SERDs for targeting ESR1 mutations
Authors: G. Greene
Journal: Cancer Research (2024)

Abstract Estrogen receptor positive (ER+) breast cancers are effectively treated with adjuvant endocrine therapies, with or without the addition of CDK4/6 inhibitors. However, many patients develop resistance and progress to ER+ metastatic disease (MBC). Acquired mutations in ESR1, which encodes estrogen receptor alpha (ERa), contribute to 20-40% of endocrine therapy resistant MBC. An emerging, unanswered and controversial question is the best choice of ER-targeted therapy for ET-resistant mutant ER+ MBC, recognizing that for most patients, a balance between compliance, effectiveness and quality of life are competing issues. To partially address some of these issues, we have tested and compared a relatively nontoxic SERM, lasofoxifene, to a complete estrogen receptor antagonist (CERAN), OP1250, in a mutant ERa (MCF-7 Y537S ERa) MBC endocrine therapy resistant xenograft tumor model (MIND = Mammary intraductal) to examine the efficacy of both drugs in a metastatic context in which a frequently observed, aggressive mutant ERa is expressed. As single agents, both Lasofoxifene and OP1250 inhibited primary tumor growth as well as metastasis to the lung, liver, brain and bone, with greater effect at higher doses of each drug, and both were substantially more effective than fulvestrant, the current gold standard for treating progressive disease. When combined with palbociclib, an additional decrease in metastasis was observed, compared to lasofoxifene, OP1250 or palbociclib as single agents. In total, these results demonstrate that lasofoxifene, a SERM, is as effective as OP-1250, a complete ER antagonist and SERD in a xenograft MIND model of mutant ER+ metastatic breast cancer. The potential use of lasofoxifene or OP1250, both alone and in combination with CDK4/6 inhibitors, to reduce tumor growth and metastasis in patients with ET-resistant metastatic breast cancer, is being tested in clinical trials to determine whether either drug is a preferred therapy versus current standard of care for mutant ER+ MCB. Citation Format: G. Greene. SERMs versus SERDs for targeting ESR1 mutations [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 SoA3-01.
Abstract SS03-06: Screening for Health Related Social Needs, and now what?
Authors: B. Segarra-Vazquez
Journal: Cancer Research (2024)

Abstract Screening cancer patients for health related social needs (HRSN) presents benefits and challenges for the patients as well as for the health care facilities. Who gets screened? How often? What are the results used for? What services can be provided? These are some of the issues that institutions face. At the same time patients can feel singled out, afraid to be honest thinking they would receive sub-optimal treatment, and have wrong expectations, among others. In this session we will address the importance of screening for HRSN such as transportation, housing, food security, and financial strain. Strategies to approach the patient and possible ways to address the needs will also be discussed. Citation Format: B. Segarra-Vazquez. Screening for Health Related Social Needs, and now what? [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 SS03-06.
Abstract PO4-09-02: Making a Case for Access to Genetic Testing in a Low Resource Country: A review of 313 Cases of MBC
Authors: Adewumi Alabi, AbdulRazzak Lawal, Tolulope Falowo, Olamijulo Fatiregun
Journal: Cancer Research (2024)

Abstract Background Breast Cancer is the most common malignancy in Nigerian Women. It is responsible for the highest mortality amongst all malignant conditions. Breast cancer in Nigerian women typically presents at an earlier age and with a more aggressive tumour with triple negative molecular pattern in Nigerian women. These are usually some of the criteria for Genetic testing in the NCCN Guidelines. Due to resource challenges, Genetic testing is not readily available to Nigerian women We believe that if we can demonstrate that a high proportion of Nigerian women with breast cancer meet the criteria for Genetic Testing for Hereditary Breast and Ovarian Cancers, a case can be made for deploying resources towards Genetic Testing in this population of Women. Materials and Methods We collected prospective data about Nigerian Patients with Metastatic Breast Cancer as part of a UICC MBC Grant. We evaluated these patients for criteria for testing for breast cancer and present the result of our evaluation. Results Three hundred and Thirteen patients were recruited for this study. There were 2 male and 311 female. Twelve participants did not know their age, but 146 (40.3%) were younger than 45 years while 175 (55.9%) were older than 45 years. Twenty four (7.7%) had bilateral breast cancer while the 289 (92.3%) had unilateral breast cancer. One hundred and sixty two (54.8%) participants were triple negative, 124 of whom were 60 years or younger. In total, out of 313 participants, 202 (64.5%) patients were candidates for Genetic testing in a cohort of Metastatic Breast Cancer patients in Nigeria. Conclusion Various Indications for Genetic Testing in a cohort of Nigerian patients with breast cancer exists in more than 60% of patients. Considering the importance of PARP inhibitors in the management of breast cancer and implications for family members of these patients. It is important that cost appropriate genetic testing is made available to this group of breast cancer patients. Table. Risk Factors for Genetic Testing in Nigerian Patients Citation Format: Adewumi Alabi, AbdulRazzak Lawal, Tolulope Falowo, Olamijulo Fatiregun. Making a Case for Access to Genetic Testing in a Low Resource Country: A review of 313 Cases of MBC [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 PO4-09-02.
Abstract PO1-13-12: Mechanistic Analysis and Potential Therapeutic Implications in Breast Cancer with Fibrotic Focus
Authors: Canbin Fang, Julia Y. S. Tsang, Gary M.K. Tse
Journal: Cancer Research (2024)

Abstract A fibrotic focus (FF) is a scar-like region that forms in the center of carcinoma due to excessive tumor stroma formation. In our earlier studies, we found FF as an independent poor prognostic factor for breast cancers. However, the underlying mechanisms of how the presence of FF contributed to a poor prognosis are still unknown. To improve our understanding of FF in breast cancer, we have investigated genes associated with FF and their impacts on breast cancer prognosis. Analysis of data from The Cancer Genome Atlas Program (TCGA) indicated that Bone Morphogenetic Protein 8A (BMP8A) was significantly upregulated in breast cancers with FF. To further validate this finding, immunohistochemistry (IHC) on BMP8A was performed on a local cohort of breast cancers (N= 900). Of these samples, 147 (16.3%) were found to be BMP8A positive, and there was a significant association between the presence of FF and high expression of BMP8A (p-value=0.026). We also found that high expression of BMP8A was positively correlated with apocrine phenotype, necrosis, increased Ki67 expression, and triple-negative breast cancer subtype; and most of these are poor prognostic factors for breast cancer. Kaplan-Meier survival estimate analysis revealed that high expression of BMP8A was significantly associated with poor overall survival (p-value=0.035). Gene ontology (GO) analysis showed that "Extracellular matrix organization" was the prominent biological process associated with BMP8A. KEGG pathway analysis suggested that BMP8A was significantly related to "Protein digestion and absorption", "ECM-receptor interaction", and "Focal adhesion" pathways, further validating its correlation with stromal FF. In cellular studies using MCF7 and MDA-MB-231 cell lines, overexpression of BMP8A was found to enhance breast cancer cell proliferation, invasion, and migration. Similar tumor-promoting phenotypes were exhibited when stimulating the cell lines with recombinant human BMP8A. In conclusion, our findings suggested that BMP8A was associated with FF in breast cancer, contributing at least partly to the aggressive features of these cancers. Our findings also provided new insights into the precision treatment and diagnosis of breast cancer. Further exploration of BMP8A as a therapeutic target and prognostic factor may contribute to improved management of breast cancer patients. Citation Format: Canbin Fang, Julia Y. S. Tsang, Gary M.K. Tse. Mechanistic Analysis and Potential Therapeutic Implications in Breast Cancer with Fibrotic Focus [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 PO1-13-12.
Abstract PO1-22-11: Use of magnetic tracer and magnetic resonance imaging for sentinel lymph node detection after breast cancer recurrence and previous axillary surgery: The SentiRecur feasibility study
Authors: Eva VikhePatil, Kian Chin, Amalia SegerbardPlanoudis, Carlos Dussan, Henrik Leonhardt, Pontus Zaar, Pantelis Gialis, Fredrik Wärnberg
Journal: Cancer Research (2024)

Abstract Background: Preoperative imaging increases the chance of finding the sentinel lymph node (SLN) in patients with previous axillary surgery. Current clinical routine for preoperative localization is Technetium (Tc99) and lymphoscintigraphy. An alternative method has been proposed using superparamagnetic iron oxide nanoparticles (SPIO) and non-contrast enhanced magnetic resonance imaging (MRI) of the axillae. In this feasibility study, SPIO+MRI was used in parallel with Tc99+scintigraphy for SLN localization. Methods: Twenty patients with recurrent breast cancer and previous axillary surgery at Sahlgrenska and Linkoping University Hospitals scheduled for SLN-biopsy will be included. All patients received Tc99+scintigraphy as per standard practice. In addition, a SPIO injection and bilateral axillary MRI was performed up to four weeks before surgery. Both preoperative and perioperative SLN-detection rates were studied. Rates and number of concordant SLNs were presented as percentages. Results: So far, ten patients received both SPIO+MRI and Tc99+scintigraphy. The SLN-detection rates per patient were 70% (7/10) for SPIO+MRI and 50% (5/10) for Tc99+scintigraphy, respectively. The perioperative SLN-detection rates per patient were 60% (6/10) for SPIO using the magnetic probe (SentiMagTM) and 30% (3/10) for Tc99 using a gamma-probe. In total, eleven SLNs were detected with SentiMag and four with gamma-probe. Of all SLNs, only four (36%) contained both SPIO and Tc99. Conclusion(s): Although preliminary, the results suggest that Tc99+scintigraphy may be replaced by the magnetic technique for detecting SLNs after earlier axillary surgery. The magnetic technique enables logistic advantages as tracer injection and SLN identification during a wider time frame. Table 1. Sentinel lymph node detection in patients with recurrent breast cancer Table 1. Sentinel lymph node detection in patients with recurrent breast cancer Citation Format: Eva VikhePatil, Kian Chin, Amalia SegerbardPlanoudis, Carlos Dussan, Henrik Leonhardt, Pontus Zaar, Pantelis Gialis, Fredrik Wärnberg. Use of magnetic tracer and magnetic resonance imaging for sentinel lymph node detection after breast cancer recurrence and previous axillary surgery: The SentiRecur feasibility study [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 PO1-22-11.