bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P3-10-24: Not presented
Authors: Gasparini E , Bisagni A , Di Cicilia R , Kuhn E , Falco G , Ferrari G , Foroni M , Tamagnini I , Bassano C , Ragazzi M , Gardini G , Cecchi F , Hembrough T , Bisagni G 
Published: May 2019

Abstract
This abstract was not presented at the conference.
Citation Format: Gasparini E, Bisagni A, Di Cicilia R, Kuhn E, Falco G, Ferrari G, Foroni M, Tamagnini I, Bassano C, Ragazzi M, Gardini G, Cecchi F, Hembrough T, Bisagni G. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-10-24.
Abstract P3-10-27: Profiling of metastatic carcinomas to the breast for the biomarkers of immuno-oncology therapy
Authors: Gatalica Z , Senarathne W , Vranic S , Pockaj BA 
Published: May 2019

Abstract
Introduction: Breast metastases from non-mammary carcinomas are very rare and the molecular characteristics of these metastases have not been studied. Due to the uniqueness of this type of metastases, we evaluated whether there was any molecular or immunologic similarities among the patients with metastases to the breast.
Patients and Methods: Fifty-one patients with metastatic carcinomas to the breast (49 female and 2 male) were identified in the files of Caris Life Sciences (Phoenix, AZ). Average age at presentation was 57 years (range, 20-90 years). Immunohistochemistry for PD-L1 was performed using SP142 (Ventana) or 22c3 (DAKO) antibodies; 592 genes sequencing (n=47), DNA microsatellite instability (MSI) (n=6) and total mutational burden (TMB) (n=14) were obtained from a next generation sequencing platform (Illumina).
Results: Three most common primary sites were lung (19, 37%), ovary (15, 29%) and fallopian tubes/peritoneum (7, 14%). Ten metastases (20%) demonstrated neuroendocrine differentiation. When 1% cutoff was applied, tumor cells PD-L1 expression was detected in 10 cases (20%), and immune cells expression of PD-L1 in 19 patients (37%). Three cases (6%) had PD-L1 staining in both cancer and infiltrating immune cells. 50% of the cases exhibited mutations in TP53 gene, while other mutated genes followed the pathways typically seen in their primary sites (e.g. VHL in renal carcinomas, BRCA1 in fallopian tube carcinoma). Total mutational burden was high (≥10 mutations/Mb) in five out of 14 successfully analyzed cases (36%) and no case (0%) exhibited high microsatellite instability. Interestingly, estrogen receptor status was positive in 13/49 patients (26.5%) including 12 adenocarcinomas originating from ovary, Fallopian tube or peritoneum and one duodenal neuroendocrine. No tumor was HER2 positive.
Conclusions: Metastases to the breast proved to be heterogeneous but there were molecular, endocrine and immunologic findings that yielded information that could be used to make therapeutic decisions which including the use of new immunotherapeutic strategies.
Citation Format: Gatalica Z, Senarathne W, Vranic S, Pockaj BA. Profiling of metastatic carcinomas to the breast for the biomarkers of immuno-oncology therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-10-27.
Abstract P3-10-28: The impact of HER2-directed targeted therapy on HER2-positive DCIS of the breast
Authors: Lewis GD , Haque W , Farach A , Hatch SS , Butler EB , Schwartz MR , Bonefas E , Teh BS 
Published: May 2019

Abstract
Purpose/Objectives: In invasive breast cancer, HER2 is a well-established negative prognostic factor. However, its significance on the prognosis of ductal carcinoma in situ (DCIS) of the breast is unclear. As a result, the impact of adding HER2-directed therapy to HER2-positive DCIS is unknown and is currently the subject of ongoing clinical trials. In this study, we aim to determine the impact of HER2 status on DCIS patient outcomes as well as the possible impact of HER2-directed targeted therapy on survival outcomes for HER2-positive DCIS patients.
Materials/Methods: The National Cancer Data Base (NCDB) was used to retrieve patients with biopsy-proven DCIS diagnosed from 2004-2015. Only patients with known estrogen receptor (ER) status, progesterone receptor (PR) status, and HER2 status were included in the analysis. Patients were divided into two groups based on the adjuvant therapy they received: systemic therapy (assumed to be HER2-directed targeted therapy) or no systemic therapy. Statistics included multivariable logistic regression to determine factors predictive of receiving systemic therapy, Kaplan-Meier analysis to evaluate overall survival (OS), and Cox proportional hazards modeling to determine variables associated with OS.
Results: Altogether, 1927 patients met inclusion criteria; 430 (22.3%) received HER2-directed targeted therapy, while 1497 (77.7%) did not. Patients who received HER2-directed targeted therapy were likely more likely to be ER-negative. Patients who received HER2-directed targeted therapy had a higher 5-year OS compared to patients that did not (97.7% vs. 95.8%, p = 0.043). This survival benefit remained on multivariate analysis. Factors associated with worse OS on multivariate analysis included Charlson-Deyo Comorbidity Score ≥ 2 and no receipt of hormonal therapy.
Conclusions: In the largest study to date evaluating HER2-positive DCIS patients, the receipt of HER2-directed targeted therapy was associated with an improvement in OS. The results of currently ongoing clinical trials are needed to confirm this finding.
Citation Format: Lewis GD, Haque W, Farach A, Hatch SS, Butler EB, Schwartz MR, Bonefas E, Teh BS. The impact of HER2-directed targeted therapy on HER2-positive DCIS of the breast [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-10-28.
Abstract P3-11-03: Validation of CIN4 in the DBCG 89D clinical cohort
Authors: Spears M , Jensen M-B , Lyttle N , Liao L , Laenkholm A-V , Ejitlertsen B , Bartlett JM 
Published: May 2019

Abstract
Background: Chromosome instability (CIN) in solid tumours is associated with poor prognosis and results in numerical and structural chromosomal aberrations. Our group previously have developed the CIN signatures and have demonstrated the CIN signatures as prognostic biomarkers in breast cancer cohorts. Furthermore, our work in the BR9601 and MA.5 clinical cohorts CIN4 provided level IIB evidence that CIN4 was predictive of anthracycline sensitivity. An analysis of the DBCG 89D clinical trial was now performed to validate the role of CIN gene expression signatures as a marker of anthracycline sensitivity.
Methods: RNA was extracted from patients in DBCG 89D clinical trial analysed through NanoString technology. The prognostic and predictive values of the signatures on distant relapse-free survival (DRFS) were explored using Cox proportional hazard models. Multivariate models included menopausal status, tumour size, nodal status, ER and Her2 status, histological type and grade, and treatment regimen.
Results: All of the 594 samples available from the DBCG 89D we successfully analysed. CIN25 and CIN70 gene expression signatures did not associate with any of the clinicopathological characteristics tested. In addition, CIN25 and CIN70 were not prognostic or predictive of distant relapse free or breast cancer specific survival in this clinical cohort. Low CIN4 score was associated with ER negativity (p=0.02), HER2 normal expression (p&lt;0.05).
Conclusion: In this study we demonstrated that CIN4 was associated with aggressive disease. We were however in DBCG 89D unable to validate the predictive value of CIN4 concerning anthracycline sensitivity.
Citation Format: Spears M, Jensen M-B, Lyttle N, Liao L, Laenkholm A-V, Ejitlertsen B, Bartlett JM. Validation of CIN4 in the DBCG 89D clinical cohort [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-11-03.
Abstract P3-11-06: HRD (homologous recombination deficiency) score and its clinicopathological features in neoadjuvant chemotherapy treated sporadic breast cancers
Authors: Imanishi S , Naoi Y , Shimazu K , Shimoda M , Kagara N , Tanei T , Miyake T , Kim SJ , Noguchi S 
Published: May 2019

Abstract
[Purpose]Homologous Recombination Deficiency (HRD) score has been developed to evaluate the DNA double-strand break repair function. BRCA1/2 germline mutation-associated breast cancers are known to show a high HRD score and a high sensitivity to platinum-based chemotherapy as well as PARP inhibitor. HRD can be theoretically induced by not only the dysfunction of BRA1/2 but also the dysfunction of the other molecules involved in homologous recombination, and, actually, high HRD score is reported to be seen in a significant proportion of sporadic breast tumors without BRCA1/2 mutation. The aim of the present study was to elucidate the clinicopathological characteristics of sporadic breast tumors with high HRD score as well as their sensitivity to sequential paclitaxel and FEC chemotherapy (P-FEC).
[Methods]Tumor tissues obtained by Mammotome from 132 sporadic breast cancer patients (stage II-III) before neoadjuvant chemotherapy with P-FEC were subjected to assay for HRD score using Oncoscan CNV kit®. HRD score was a simple sum of NtAI, LOH, and LST (cutoff, 42), and were also subjected to the gene expression analysis using the Affymetrix microarray (U133 plus 2.0). BRCA1 promoter methylation was assayed by methylation specific real-time PCR.
[Result]Of the 132 breast tumors, 32% showed a high HRD score which were significantly associated with high histological grade (P=0.001), negative progesterone receptor (P=0.023) and high Ki67 index (P=0.004). Triple negative breast cancer (TNBC)(n=19) showed a significantly (P&lt;0.001) higher HRD score than the other subtypes (HR+/HER2-(n=73), HR+/HER2+(n=12), HR-/HER2+(n=18)). BRCA1 promoter methylation was significantly associated with a high HRD score. There was no significant correlation between HRD score and pCR to P-FEC when all tumors were considered but tumors with a high HRD score showed a significantly (P=0.020) lower pCR rate when only TNBC were considered. In TNBC, majority of tumors showed a high HRD score in five subtypes (BL1, BL2, IM, M, MSL) but no tumor showed a high HRD score in LAR (luminal androgen receptor) subtype.
[Conclusion]Approximately one third of sporadic breast tumors show a high HRD score, indicating the presence of homologous recombination dysfunction, and they are most often seen in TNBC with BRCA1 promoter methylation and never in LAR subtype. Interestingly, breast tumors with a high HRD score were less sensitive to P-FEC.
Citation Format: Imanishi S, Naoi Y, Shimazu K, Shimoda M, Kagara N, Tanei T, Miyake T, Kim SJ, Noguchi S. HRD (homologous recombination deficiency) score and its clinicopathological features in neoadjuvant chemotherapy treated sporadic breast cancers [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-11-06.
Abstract P3-11-11: Prediction of treatment response to neoadjuvant chemotherapy in breast cancer by subtype using tumor-infiltrating lymphocytes: Study of a large Mexican cohort
Authors: Campos Gomez S , Cabañas Chávez N , Hernández Alvarez J , Campos Gómez K 
Published: May 2019

Abstract
Background/aim:
Tumor-infiltrating lymphocytes (TILs) are emerging as biomarkers mediating tumor response to treatments. Studies have provided evidence that the level of TILs has prognostic value in breast cancer. The level of TILs has been associated with treatment outcome and pathologic response in patients undergoing neoadjuvant chemotherapy. In this study, we analyzed TILs before neoadjuvant therapy and if they correlate with pathological response to treatment
Patients and methods
We retrospectively analyzed the specimen slides of patients with Breast Cancer from the Centro Oncologico Estatal ISSEMyM treated with Neoadjuvant Chemotherapy (NAC) during 2007–2014. We identified 410 patients fulfilling the inclusion criteria of this study. The histological sections had already been evaluated by hematoxylin and eosin slides. They were reassessed by our pathologist for the percentage of intratumoral and stromal TILs. The correlation with pathological response of the tumor after neoadjuvant therapy was also studied in these patients. The proportions of TILs were categorized into high and low groups using a cut-off value of 10%
Resultados
The mean age was 51.4 years. The most frequent type of breast cancer histology was invasive ductal breast carcinoma in 369 (90%) patients, 34 (8.3%) lobular and 1.7% other. The BC subtypes among the 410 patients who received NAC were TNBC in 82 (20%), HER2BC in 70 (17.1%), and HRBC in 258 (62.9%) patients. Treatment response was pCR in 164 (40%) and non-pCR in 245 (60%) patients. Based on subtype, pCR was achieved in 43 (52 %) patients with TNBC, 35 (50.0%) with HER2BC, and 87 (33%) with HRBC. There were 191 (46.5%) patients in the high-TIL group and 219 (53.5%) patients in the low-TIL group. Patients were divided into high-TIL and low-TIL groups, and the clinicopathological characteristics of each group were examined. High TILs that had a pathologically complete response were found in 56 % of patients, and low TILs were found in 44 %. There was a significant correlation between TILs and pathological response in patients with neoadjuvant chemotherapy (p = 0.04).
Conclusion
TILs may be a biomarker for predicting treatment response to NAC in patients with Breast Cancer. Studies assessing outcomes and therapeutic efficacies should consider.
Citation Format: Campos Gomez S, Cabañas Chávez N, Hernández Alvarez J, Campos Gómez K. Prediction of treatment response to neoadjuvant chemotherapy in breast cancer by subtype using tumor-infiltrating lymphocytes: Study of a large Mexican cohort [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-11-11.
Abstract P3-11-13: On-treatment biomarkers can improve prediction of response to neoadjuvant chemotherapy in breast cancer
Authors: Bownes RJ , Turnbull AK , Cameron D , Sims AH , Oikonomidou O 
Published: May 2019

Abstract
Purpose: Neo-Adjuvant chemotherapy treatment is increasingly being used in breast cancer to preoperatively shrink tumour volumes and facilitate surgical plans. These datasets however, are still scarce, making it difficult to assess the relative value of multiple time point biopsies compared to diagnostic only sampling. This study aims to identify sequential samplings intrinsic value.
Method: A total of 97 samples from a cohort of 50 neoadjuvant chemotherapy treated primary breast cancer patients (aged 29-76 at diagnosis, Allred status 47:53% +/-, Her2 status 80:20% +/-, mixed grade and menopausal status) taken pre- treatment, at 2 weeks on-treatment, mid chemotherapy and at resection were sequenced with Ion Ampliseq transcriptome yielding expression values for 12,635 genes. Differential expression analysis was performed across response groups (16 Responders, 34 Non-Responders) as defined by Pathological Complete Response and over treatment time to identify significantly differentially expressed genes, pathways and markers indicative of response status.
Results: An on-treatment marker for response was identified (AAGAB), which resulted in a testing accuracy of 100% and a validation accuracy of 78% in the I-SPY 1 Trial. AAGAB was predictive of long term survival (p = 0.048 testing, p = 0.031 validation) in both chemotherapy cohorts at the same expression level as defined for treatment response. The single gene on-treatment biomarker, AAGAB proves more performant than established prognostic tests, Mammaprint (Edinburgh NEO trial, pre-treatment 61%, on-treatment 63%. I-SPY 1 trial, pre-treatment 60%, on-treatment 66%) and Pam50 RORS (neo trial pre-treatment 50%, on treatment 58%, Magbanua trial pre-treatment 56%, on-treatment 64%)
Conclusion: Changes in gene expression of on-treatment chemotherapy breast cancer resulted in the identification of a novel gene marker that was as effective in predicting prognostic status as established prognostic tests. These results support the use of on-treatment testing in breast cancer to improve the accuracy of tumour response prediction.
Citation Format: Bownes RJ, Turnbull AK, Cameron D, Sims AH, Oikonomidou O. On-treatment biomarkers can improve prediction of response to neoadjuvant chemotherapy in breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-11-13.
Abstract P4-01-03: Withdrawn
Authors: Di Cosimo S , Appierto V , Pizzamiglio S , Baselga J , Piccart M , Huober J , Izquierdo M , de la Pena L , Hilbers F , de Azambuja E , Untch M , Pusztai L , Pritchard KI , Nuciforo P , Salomon AV , Symmans FW , Apolone G , de Braud F , Verderio P , Daidone MG 
Published: May 2019

Abstract
This abstract was withdrawn by the authors.
Citation Format: Di Cosimo S, Appierto V, Pizzamiglio S, Baselga J, Piccart M, Huober J, Izquierdo M, de la Pena L, Hilbers F, de Azambuja E, Untch M, Pusztai L, Pritchard KI, Nuciforo P, Salomon AV, Symmans FW, Apolone G, de Braud F, Verderio P, Daidone MG. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-01-03.
Abstract P4-01-07: A comprehensive liquid biopsy in patients undergoing neoadjuvant therapy
Authors: Sandoval Leon AC , Medina Saenz K , Miller P , Benson A , Calfa C , Mahtani R , Slingerland J , Perez A , Vogel C , Valdes-Albini F , El-Ashry D , Lippman M 
Published: May 2019

Abstract
Background: Precision medicine is revolutionizing breast cancer (BC) care. Comprehensive liquid biopsies are a tool for personalized care in patients with locally advanced breast cancer (LABC). Identifying robust biomarkers as part of a comprehensive liquid biopsy to predict response to treatment is of immense clinical interest.
Methods: After obtaining IRB approval, serial blood samples were collected from patients with LABC undergoing neoadjuvant therapy. Paired biopsies were collected prior to treatment and were sent to Foundation Medicine for next-generation sequencing (NGS). We used a sized-base microfilter technology to capture circulating tumor cells (CTCs) and circulating cancer associated fibroblasts (cCAFs). Patients with one or more CTCs or cCAFs were deemed positive for these tests. Additionally, in collaboration with Foundation Medicine, we extracted circulating tumor DNA (ctDNA) and we analyzed it using the FoundationACT platform. Patients with a detectable genomic alteration in their plasma were considered as having a positive ctDNA test. Our primary objective is to determine if a comprehensive liquid biopsy can serve as a prognostic marker of pathologic complete response (pCR).
Results: For this analysis we describe our findings in the initial blood draw of the first 18 patients enrolled. The mean age is 54 years (38-70). All patients who had their tumors sequenced had a detectable mutation. Consistent with the findings of others, we found TP53 mutations to be the most prevalent at 83.3%. We found that 44% of patients had ctDNA, 68.4% had cCAFs and 78.9% had CTCs. Many patients also had clusters of cells, consisting of one cell type, or co-clusters, consisting of both. 38.9% had CTC clusters, 16.7% had cCAF clusters and 16.7% had co-clusters (CTCs and cCAFs together). Some patients with CTCs did not have cCAFs and vice versa. The number of CTCs and cCAFS did not correlate with stage of disease or receptor status.
Conclusions: We describe a comprehensive liquid biopsy combining a sized-based microfilter technology for CTC and cCAFs identification and the FoundationACT platform for ctDNA analysis is feasible and these biomarkers can be detected in patients with LABC prior to the initiation of neoadjuvant therapy. Our study is accruing rapidly, and we will update our results with the longitudinal collection and the prognostic value of a comprehensive liquid biopsy at the time of the meeting.
Citation Format: Sandoval Leon AC, Medina Saenz K, Miller P, Benson A, Calfa C, Mahtani R, Slingerland J, Perez A, Vogel C, Valdes-Albini F, El-Ashry D, Lippman M. A comprehensive liquid biopsy in patients undergoing neoadjuvant therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-01-07.
Abstract P4-01-12: Low peripheral blood CD4/CD8 ratio at the time of surgery is a negative long-term prognostic factor in women with early stage breast cancer
Authors: Magbanua MJM , Yau C , Scott JH , van't Veer L , Park JW , Esserman L , Campbell M 
Published: May 2019

Abstract
It is hypothesized that cancer prognosis may be related to the functional status of the immune system. We examined the correlation between peripheral blood CD4/CD8 ratio measured at the time of surgery and clinical outcome in patients diagnosed with early stage breast cancer.
Patient and Methods
Peripheral blood from 57 treatment-naïve early breast cancer patients, not eligible for neoadjuvant chemotherapy, was collected on the day of definitive surgery. CD4+ and CD8+ T cells were enumerated using flow cytometry and the ratio between the two immune cell populations was calculated. Cox regression analyses were performed to determine the relationship between CD4/CD8 ratio vs. distant disease-free survival (DRFS), breast cancer-specific survival (BCSS) and overall survival (OS). The median follow-up times were 10.1 years (range: 0.4-17.5) and 15.0 (range: 1.0-18.5) for DRFS and BCSS/OS, respectively.
Results
The patients' mean age at diagnosis was 54 years old (range: 31-78). 82% were hormone receptor-positive, 21% HER2-positive, and 61% node-negative. The median CD4/CD8 ratio was 2; and a ratio ≤ 2 was considered low. CD4/CD8 ratio was not associated with any of the clinicopathologic variable examined. Multivariate analysis using a survival model that adjusted for potential confounding factors (age, tumor size, grade, stage, hormone receptor, HER2, lymph-node status) revealed that patients with low CD4/CD8 ratio have statistically significant increased risk of distant recurrence (DRFS HR 5.3, Wald p=0.0381) and death (OS HR 3.8 Wald p=0.0271).
Conclusions
Immune dysfunction at the time surgery is correlated with long-term increased risk for metastatic recurrence and death. Larger clinical studies are warranted to confirm the results of this study.
Citation Format: Magbanua MJM, Yau C, Scott JH, van't Veer L, Park JW, Esserman L, Campbell M. Low peripheral blood CD4/CD8 ratio at the time of surgery is a negative long-term prognostic factor in women with early stage breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-01-12.