bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract ES4-1: Adaptive Resistance to Hormonal Therapy
Authors: Fuqua S 
Published: March 2020

Abstract
While recurrences are delayed by the use of endocrine therapy (ET), resistance can evolve with the development of metastatic breast cancer (MBC) in about one-fourth of ER-positive patients. MBC is incurable with a median 5-year survival rate of less than 25%. We know that ET resistance can result from an adaptive process in which escape survival mechanisms are used to evade treatment. One of the best-characterized ET resistance mechanisms is transcriptional activation of growth factor receptor (GFR) signaling, and subsequent estrogen-independent activation of ER via “cross-talk” with downstream signaling from GFRs. We will discuss distinct mechanisms of ligand-independent activation of ER discovered using transcriptional profiling of metastatic, ET-resistant tumors. It is now estimated that ~20% of therapy-resistant MBCs contain ESR1 mutations. Recent data has also shown that mutations in the MAPK/RAS pathway and transcription factor regulatory programs (for example, MYC) only account for an additional 22% of recurrent breast tumors. Thus, acquired mutations alone do not account for the majority of ET resistance mechanisms in MBC. ER-positive breast cancer cell lines display profound transcriptional variability at the single cell level associated with the acquisition of therapy resistance. Recently, bulk and single cell RNA sequencing was used on sequential samples from patients with ER-positive, ET-resistant patients and identified RNA expression patterns that represented different cellular phenotypes, including an increased epithelial mesenchymal transition state that could provide a selective advantage for selective phenotypic subclones to dominate. We will focus our discussion of transcriptional reprograming as a major mechanism of ET resistance.
Citation Format: S Fuqua. Adaptive Resistance to Hormonal Therapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr ES4-1.
Abstract ES6-3: Breast cancer genetic testing: moving from cancer risk assessment to therapeutic biomarker
Authors: Balmaña J 
Published: March 2020

Abstract
In the last two decades germline genetic testing for breast cancer (BC) susceptibility has evolved from a single-gene analysis to a multigene cancer panel risk assessment tool. In addition, identifying a mutation in the BRCA1/2 genes may nowadays represent an opportunity for cancer targeted therapy. Current challenges in our routine clinical practice and for public health policies are to reconcile the implications derived from the identification of a hereditary cancer susceptibility that may impact beyond the person who is performing the genetic test, with and increasing and faster access to the test. Assessment of cancer risk was the first reason to incorporate germline BC genetic testing. As a consequence, mutation carriers are recommended specific screening and/or risk reduction options. While prophylactic bilateral salpingoophorectomy has shown a decrease in mortality and ovarian cancer-specific mortality, its role as a risk reduction option for breast cancer remains controversial. Radiologic imaging with magnetic resonance and mammogram has demonstrated beneficial in early detection of breast cancer, but risk reducing mastectomy may also be an option. Recent prospective data has shown that cancer risks differ between BRCA1 and BRCA2 mutation carriers, and that this estimation may be influenced by a combination of single-nucleotide polymorphism that constitute the polygenic risk score (PRS). Whether a more precise accuracy in cancer risk estimation in the short term (ie 5-10 years) may help to tailor screening and/or risk reduction options is unknown. As more BC-associated genes have been identified and technology has evolved, single gene testing has evolved to multigene panel testing. Available data suggests that patients can cope with multigene cancer panels although more research is needed to fully understand the psychosocial implications of multigene cancer panels, especially for those who have variants of unknown significance or moderate penetrance variants. Research is also needed to explore and develop communication models that maximize patients’ understanding and empower them to make informed decisions. The impact on reproductive-decision making will also be explored. Finally, a mutation in the BRCA1/2 genes is a predictive biomarker for targeted therapies in breast, ovarian, pancreatic and prostate cancer. Therefore, knowing the genetic status of our BC patients may influence their therapeutic options. The challenges and opportunities derived from new clinical scenarios that accompany these advances will be addressed during the educational session.
Citation Format: J Balmaña. Breast cancer genetic testing: moving from cancer risk assessment to therapeutic biomarker [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr ES6-3.
Abstract ES8-1: Adjuvant endocrine therapy in 2020: It's complicated
Authors: McCartney A , Leo A Di 
Published: March 2020

Abstract
Adjuvant endocrine therapy in 2020: It’s complicated Data regarding the use of adjuvant endocrine therapy in patients with hormone receptor-positive early breast cancer has grown over the past decades, and yet still uncertainty remains in management recommendations. In pre-menopausal women, treatment decisions are often driven by estimation of risk of recurrence, measured in terms of clinical and pathological parameters, algorithm-based prognostic modelling derived from breast cancer registries, molecular profiling and gene signature assays. Despite these significant advances, risk of distant disease recurrence is still over-estimated in a significant proportion of women. The addition of ovarian suppression to tamoxifen in pre-menopausal women has been shown to increase rates of both disease-free survival and overall survival than tamoxifen alone, with the use of the steroidal aromatase inhibitor exemestane producing further higher rates of freedom from recurrence. However, the addition of ovarian suppression in this generally low-risk population comes at the cost of increased adverse events and potential to interpose child-bearing years. Further to this, the SOFT/TEXT studies mandated five years of active treatment; little is known as to whether extended treatment beyond those five years would be comparatively equal, better or worse in terms of outcome endpoints.
In the post-menopausal population, the updated ASCO Clinical Practice Guideline suggests that all women with node-positive disease should be offered extended therapy including an aromatase inhibitor for a total of ten years, as well as women with node-negative disease possessing high-risk prognostic factors. The question of how best to identify those women who may fare equally well with de-escalated, shorter therapy remains open. The issue of adverse events and drug-related side effects, particularly in the setting of extended therapy, is relevant and may impact negatively on overall treatment compliance and quality of life. As such, the choice of endocrine therapy remains an important consideration, as is evidence that intermittent administration of aromatase inhibitors may be feasible in selected patients.
CDK4/6 inhibitors, administered in tandem with endocrine therapy, have radically changed the approach to managing metastatic endocrine receptor-positive disease. There is now much interest in moving these agents forward into the neoadjuvant and adjuvant setting, with a number of phase II and III trials ongoing. If positive data is consistently reported in adjuvant studies, this will undoubtedly create another layer of complexity to the clinical management of endocrine-sensitive disease.
Citation Format: A McCartney, A Di Leo. Adjuvant endocrine therapy in 2020: It's complicated [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr ES8-1.
Abstract OT1-08-05: Phase II trial of GDC-0084 in combination with trastuzumab for patients with HER2-positive breast cancer brain metastases (BCBM)
Authors: Leone Jose P , Trippa Lorenzo , Milisits Lindsey , Andrews Chelsea , Ligibel Jennifer , Parsons Heather , Bi Wenya L , Zhao Jean , Winer Eric P , Lin Nancy U 
Published: March 2020

Abstract
Background: The PI3K/Akt/mTOR is an important pathway in BCBM. Mutations in PIK3CA or PTEN loss are associated with trastuzumab resistance. Inhibition of PI3K and mTOR led to durable responses in 3 of 5 patient-derived xenografts (PDX) models of BCBM. GDC-0084 is a potent, brain-penetrant inhibitor of class I PI3K and mTOR.
Methods: This is a single-center, phase II study to evaluate the efficacy of the combination of GDC-0084 with trastuzumab for the treatment of central nervous system (CNS) metastases in patients with HER2-positive breast cancer. Patients will receive GDC-0084 (45 mg daily) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg every 3 weeks). Two cohorts will be enrolled: Cohort A: a single-arm, two-stage, phase II cohort; and Cohort B: a pre-surgical window cohort. Inclusion criteria include unequivocal evidence of new and/or progressive HER2-positive CNS metastases, at least one measurable (≥10 mm) CNS metastasis (Cohort A), clinical indication for CNS metastasis resection (Cohort B). Primary endpoint for Cohort A is objective response rate (ORR) in the CNS per Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria. For Cohort B, the primary endpoint is the correlation between p4EBP1 levels in the resected CNS tumor tissue from patients and intracranial response to GDC-0084/trastuzumab in the PDX model generated from the same patient. Secondary endpoints include overall survival, safety and patient-reported outcomes. Mandatory blood and cerebrospinal fluid with optional tumor biopsy will be collected at baseline, on-treatment and at progression. In Cohort A, we will enroll 37 patients in a Simon two-stage design. If ≥4 responses are seen, the regimen will be considered successful. This design has 90% power with alpha &lt;10%. Cohort B will enroll 10 patients. The trial opened in February, 2019. NCT03765983.
Citation Format: Jose P Leone, Lorenzo Trippa, Lindsey Milisits, Chelsea Andrews, Jennifer Ligibel, Heather Parsons, Wenya L Bi, Jean Zhao, Eric P Winer, Nancy U Lin. Phase II trial of GDC-0084 in combination with trastuzumab for patients with HER2-positive breast cancer brain metastases (BCBM) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT1-08-05.
Abstract OT3-02-03: Radiomics multi-parametric MRI of before and after neoadjuvant chemotherapy associated with axillary lymph node metastasis and prognostic in patients with breast cancer: A multicenter RBC-002 study
Authors: Yao Herui , Li ChenChen , Yu Yunfang , Xie Chuanmiao , Ouyang Jie , Tan Yujie , Lu Nian , Wang Ying , Zhao Jianli , Chen Kai , Ma Jiafan 
Published: March 2020

Abstract
Background: Axillary lymph node metastasis is a vital factor of prognosis in patients with invasive breast cancer. However, sensitivity and noninvasive for prediction of lymph node metastasis and survival after neoadjuvant chemotherapy is limited. This study aims to develop radiomics combining multi-parametric MRI before and after neoadjuvant chemotherapy to predict axillary lymph node metastasis and prognosis, as well as investigate the relationship between the radiomics and tumor microenvironment in invasive breast- cancer.
Methods: RBC-02 is a multicenter, ambispective cohort study proposes to build a clinical predictive model to predict axillary lymph node metastasis and prognosis in invasive-breast- cancer patients who received neoadjuvant chemotherapy. Patients are recruited from Sun Yat-sen Memorial Hospital of Sun Yat-sen University (training cohort), Sun Yat-sen University Cancer Center (validation cohort), and Tungwah hospital of Sun Yat-sen University (validation cohort) in China. Invasive breast cancer patients undergo multi-parametric MRI at baseline, then undergo multi-parametric MRI after received neoadjuvant chemotherapy for at least 4 cycles as planned. After the surgery, responses to neoadjuvant chemotherapy are determined according to the histopathologically examination of the surgically resected specimens. The model is built based on breast MRI signatures extracted and analyzed via deep machine- learning algorithm methods. The correlation between radiomics features and tumor microenvironment is also planned to investigate. Decision curve analysis was performed with the combined training and validation set to estimate the clinical usefulness of the radiomics nomogram, which is built with a multivariate logistic regression model. The primary endpoint is disease-free survival. Secondary endpoints include pathological complete response, pathological axillary lymph node status, and overall survival. The trial is registered with ClinicalTrials.gov, number NCT04004559, and Chinese Clinical Trail Registry, number ChiCTR1900024113.
Citation Format: Herui Yao, ChenChen Li, Yunfang Yu, Chuanmiao Xie, Jie Ouyang, Yujie Tan, Nian Lu, Ying Wang, Jianli Zhao, Kai Chen, Jiafan Ma. Radiomics multi-parametric MRI of before and after neoadjuvant chemotherapy associated with axillary lymph node metastasis and prognostic in patients with breast cancer: A multicenter RBC-002 study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT3-02-03.
Abstract P1-09-06: Metabolic coupling in phyllodes tumor of the breast and its correlation to tumor progression
Authors: Leee Ji Shin , Kim Nah Ihm , Park Min Ho 
Published: March 2020

Abstract
Background: Markers of metabolic coupling have been associated with clinical outcomes in numerous human cancers, including breast cancer. Loss of caveolin-1(CAV1) in stromal cells and upregulation of monocarboxylate transporters (MCTs), especially MCT1 and MCT4, in both stromal and cancer cells have been identified as playing an important role in the metabolic coupling necessary for release and uptake of metabolites. However, this phenomenon has been rarely described in phyllodes tumors (PTs) of the breast. Materials and methods: One hundred-one PTs (60 benign, 26 borderline, and 15 malignant) and 9 breast tissues with no pathological lesions were analyzed. Automated immunohistochemical staining for CAV-1, MCT1, and MCT4 was performed using tissue microarray blocks, and their expressions were assessed in both stromal and epithelial components. Results: Compared with normal breast, CAV-1 expression in PTs showed a significant decrease in stromal component (P &lt; 0.001). MCT1 expression was significantly increased in both epithelial and stromal components of PTs compared to normal breast (P &lt; 0.001 and P &lt; 0.001, respectively). Stromal MCT1 and MCT4 expression was different according to the tumor grade of PTs and stromal MCT1 expression tended to increase with increasing tumor grade (P &lt; 0.001). Although not statistically significant, stromal CAV-1 expression tended to decrease with increasing PTs grade. The recurrence rate was higher in the stromal MCT1-positive groups (19.2%, 14/73) than in the stromal MCT1-negative groups (3.9%, 1/28) (P &lt; 0.05). Conclusions: This result suggested that changes of CAV-1, MCT1, and MCT4 may be associated with tumorigenesis and progression of PTs of the breast. Keywords Phyllodes tumor, CAV-1, MCT 1, MCT4, Metabolic coupling.
Citation Format: Ji Shin Leee, Nah Ihm Kim, Min Ho Park. Metabolic coupling in phyllodes tumor of the breast and its correlation to tumor progression [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-09-06.
Abstract P1-09-08: Development and characterization of PTEN IHC assay for testing breast cancer patients specimens
Authors: Gong Hua , Pacia Emmanuel , Manjeshwar Sharmila , Chen Beiru , Li Xun , Dabbas Bashar , Lameh Jelveh , Babbar Naveen , Tangri Shabnam 
Published: March 2020

Abstract
Background: Phosphatase and tensin homolog (PTEN) is a tumor suppressor gene that is a major negative regulator of the Phosphatidylinositol 3-kinase (PI3K) pathway. Loss of PTEN protein expression has been mechanistically linked to tumor progression. Blocking the PI3K pathway might inhibit the growth and proliferation of cells that have deletions in PTEN. Thus characterization of PTEN expression in patient tumor samples may assist prediction of potential response to PI3K inhibitor therapies.
Methods: We developed and validated an immunohistochemical assay on Ventana BenchMark XT to detect PTEN in formalin fixed and paraffin-embedded (FFPE) tissue by utilizing a rabbit monoclonal antibody (clone 138G6) from Cell Signaling Technologies that recognizes the carboxy-terminal domain of PTEN. PTEN immunohistochemical staining was performed on 1577 breast tumor specimens to determine PTEN protein loss. A subset of these cases (n=663) was also assessed for PTEN mutation.
Results: Cellular localization of PTEN expression was observed in both the cytoplasm and the nucleus. Both cellular compartments were scored and used in the staining intensity determination. We observed that PTEN staining is sensitive to variation in tissue handling, fixation and antigen retrieval. PTEN staining was affected significantly by antigen retrieval method. Optimal staining conditions were determined to be 1:60 antibody dilution using Citrate pH 6.0 as antigen retrieval buffer. In a cohort of 1577 hormone receptor positive HER2-negative locally advanced or metastatic breast cancer patients, loss of PTEN protein was observed in 8.6% (135/1577) of patients. There was a positive correlation between PTEN mutation rate (17 out of 66 PTEN IHC positive cases vs 14 out of 587 negative cases) and loss of PTEN protein expression. PTEN loss was observed to correlate with better clinical response to PI3K inhibitor.
Conclusions: Pre-analytical handling of samples is important for PTEN IHC staining. PTEN mutations and insertions/deletions contribute to PTEN protein loss. This study validates a simple method to interrogate PTEN status in clinical specimens and supports the utility of this test in selecting patients who are likely to respond to PI3K inhibitor treatment.
Citation Format: Hua Gong, Emmanuel Pacia, Sharmila Manjeshwar, Beiru Chen, Xun Li, Bashar Dabbas, Jelveh Lameh, Naveen Babbar, Shabnam Tangri. Development and characterization of PTEN IHC assay for testing breast cancer patients specimens [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-09-08.
Abstract P1-10-25: The prognostic and predictive roles of the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio in HER2-negative metastatic breast cancer patients treated with paclitaxel-bevacizumab
Authors: Hayashi Tomomi , Watanabe Junichiro , Nakamoto Shyogo 
Published: March 2020

Abstract
Purpose: Many reports have provided real-world evidence that inflammatory response biomarker (IRB) scores may be useful for predicting the therapeutic effect of chemotherapy and the prognosis for various neoplasms. The aim of this retrospective study was to evaluate the clinical roles of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR) as predictive factors of Paclitaxel + Bevacizumab (PB) therapy for patients with HER2-negative metastatic breast cancer (HER2-MBC).
Methods: We reviewed the medical records of 123 HER2-MBC patients who underwent PB therapy in our institute. The NLR, PLR, and LMR were calculated from blood cell counts prior to the initiation of PB therapy. The optimal cut-off point of each ratio was determined according to receiver operating characteristic (ROC) curves. The Kaplan-Meier test and Wilcoxon test were used to analyze the progression- free survival (PFS) and overall survival (OS). The differences were considered significant for p &lt; 0.05.
Results: The median age at the start of treatment was 53 years old. Of the 123 patients, 98 (80%) were hormone- receptor- positive, and 82 (67%) had multiple (&gt;2) metastatic sites. The median PFS was 7.0 months (95% confidence interval, 5.8-8.4), and the median treatment line before PB therapy was 0 (range: 0-10). The cut-off points of the NLR, PLR, and LMR for the PFS and OS were 2.7, 178, and 3.0, respectively. We found that a high NLR and low LMR were associated with a poor PFS (NLR, median 6.5 vs. 8.4 months, p=0.04: LMR, median 5.6 vs. 8.1 months, p=0.02), and a high LMR was associated with a superior OS (median, not reached vs. 187 months, p=0.02) and 10- year survival rate (76.4% vs. 52.9%, p=0.02). The PLR showed no relationship with the PFS or OS.
Conclusion: The NLR and LMR might be independent biomarkers, i.e. predictive factors, for patients with HER2-MBC receiving PB therapy in the real world. A prospective study to confirm the utility of those biomarkers is warranted.
Citation Format: Tomomi Hayashi, Junichiro Watanabe, Shyogo Nakamoto. The prognostic and predictive roles of the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio in HER2-negative metastatic breast cancer patients treated with paclitaxel-bevacizumab [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-10-25.