bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P3-19-19: Intraoperative Radiation Therapy (IORT) : A large integrated healthcare system’s approach and outcomes
Authors: Tang Annie , Kelly Jason , Cureton Elizabeth , Svahn Jonathan , Thomas Eva , Lyon Liisa , Shim Veronica 
Published: March 2022

Abstract
Background: With TARGIT-R(Retrospective) showing a higher-than-expected ipsilateral breast tumor recurrence (IBTR) the community setting for intraoperative radiation therapy (IORT), we evaluated IORT outcomes in an integrated health care system.Methods: A retrospective review of early breast cancer patients who received IORT between February 2014-February 2020 was performed. IORT was offered at a single medical center within a large integrated healthcare system. Criteria for IORT included patients ≥50 years with T1, low to intermediate grade, endocrine-responsive HER2- invasive ductal carcinoma. All breast cancer patients were reviewed at weekly multidisciplinary breast conferences, and IORT was offered when patients met the eligibility criteria. Primary outcomes include IBTR, mortality, and complications. Results: Of 5,731 potentially eligible patients, 245 patients (4.3%) underwent IORT. Mean age was 65.4 ± 0.4 years with median follow-up 3.5 years ± 2.2 months. Based on American Society of Radiation Oncology guideline, 51% were suitable, 38.4% cautionary, and 10.6% unsuitable candidates based on the final pathology. The patients were reassigned to the cautionary group because of the margin width and/or extensive DCIS. Unintended boost (primary IORT followed by whole-breast radiation) was given in 6.5% of IORT patients. At median follow-up of 3.5 years, IBRT was 3.7% for all patients. There was one breast-cancer-related mortality (0.4%), and 7 mortality (2.9%) from other causes. Although not statistically significant, there was a trend towards higher recurrence in those not adherent with endocrine treatment than those who were (7.4% vs 1.9%, p=0.07). The overall complication rate was 14.7% with seroma as the most common.Conclusions: At 3.5-year follow-up, our IORT IBTR rate of 3.7%. Our protocol subsequently was modified to require all IORT patients to receive surgical shave margins, WBI for all cautionary patients on the final pathology, and requirement of endocrine treatment.
Citation Format: Annie Tang, Jason Kelly, Elizabeth Cureton, Jonathan Svahn, Eva Thomas, Liisa Lyon, Veronica Shim. Intraoperative Radiation Therapy (IORT) : A large integrated healthcare system’s approach and outcomes [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-19.
Abstract P3-20-05: Trends of axillary treatment in sentinel node-positive breast cancer patients undergoing amputation
Authors: Verreck Eline EF , van Steenhoven Julia , Kuijer Anne , van Maaren Marissa , Siesling Sabine , van Dalen Thijs 
Published: March 2022

Abstract
Objectives: To evaluate patterns of care in axillary treatment of Dutch patients - who were diagnosed with stage I-IV primary invasive breast cancer, underwent amputation and were found positive by sentinel lymph node biopsy (SLNB) - in the years following the publication of the American College for Surgeons Oncology Group (ACOSOG)-Z0011 and After Mapping of the Axilla: Radiotherapy Or Surgery (AMAROS) trials. Methods: Data from females diagnosed between January 1st 2009 and December 31st 2018 were obtained from the Netherlands Cancer Registry (NKR). Trends in completion axillary lymph node dissection (cALND), administration of adjunctive radiotherapy and, inversely, of omission of any kind of axillary treatment, were revealed by descriptive analyses on SNL positive patients. Results: Of 28,070 cT1-4 breast cancer patients undergoing amputation with SLNB from 2009 up until 2018, 10,706 were diagnosed as SLN positive. In the latter, the frequency of subsequent cALND went down significantly from 78% in 2009 to 10% in 2018 (P &lt; 0.001), while adjunctive radiotherapy increased from 4% to 49% (P &lt; 0.001). Omission of any additional local treatment increased from 18% to 41% (P &lt; 0.001). In N1 patients cALND decreased from 57% to 13% (P &lt; 0.001) and was mostly replaced by radiotherapy, increasing from 2% to 70% (P &lt; 0.001). In N1mi and N0i+ patients, cALND decreased to less than 1% of cases in 2018, while radiotherapy increased from 4% to 40% and 8% to 13% (P &lt; 0.001), respectively. Conclusion: In SLN positive breast cancer patients undergoing breast amputation, cALND had become rare 10 years following the AMAROS and Z0011 trial results. While radiotherapy mostly replaced cALND in the vast majority of N1 patients, less than half of N1mi and only a tenth of N0i+ patients received radiotherapy as the only adjunctive axillary treatment by the end of 2018.
Citation Format: Eline EF Verreck, Julia van Steenhoven, Anne Kuijer, Marissa van Maaren, Sabine Siesling, Thijs van Dalen. Trends of axillary treatment in sentinel node-positive breast cancer patients undergoing amputation [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-20-05.
Abstract P3-20-10: Local recurrences after mammary adenectomy with clear retroareolar margin for the treatment of early infiltrating breast carcinomas
Authors: Heinzen Rebeca Neves , de Barros Alfredo CarlosSimõesDornellas , Jacomo Alfredo , Cinquini Marcella 
Published: March 2022

Abstract
Introduction. Mammary adenectomy (MA) is an evolving surgical procedure for patients with breast cancer (BC). It entails the resection of all gross visible glandular tissue, while preserving the overlying breast skin envelope and the nipple-areolar complex (NAC). For achieving the best oncologic outcomes it is recommended the obtainance of clear surgical margins, mainly the retroareolar, and careful selection of the patients to be treated accordingly. Here, we performed a study aiming to assess the local recurrences rate in patients who underwent MA for BC therapy. Methods. A retrospective cross-sectional study was carried out at a private Service (Clínica Prof. Alfredo Barros). Patients with invasive BC measuring up to 3.0 cm and at least 2.0 cm far from the NAC by resonance magnetic imaging, were elegible, while others with more than 3 foci of neoplasia, nipple discharge or neoadjuvant chemotherapy were excluded. All of them were submitted to MA and selective axillary dissection and reconstruction by immediate prothesis implants, with clear retroareolar margin by intraoperative cytology and frozen section exams, and intra-nipple ducts excision. External radiotherapy was delivered when more than 3 affected axillary lymph nodes were involved. Results. A total of 18 cases were analysed. Patient’s mean age was 51.5 years. The histopathologic subtypes were: invasive carcinoma (NOS) 146 (80.7%), infiltrative lobular 26 (14.4%), micropapilar 3 (1.7%) and others 6 (3.3%). Mean tumor size was observed 1.8 cm (0.4-5.0). Multicentricity/multifocality was observed in 62 cases (34.2%) a total of 144 cases presented positivity for estrogen receptor (86.7%), 144 (79.6%) for progesterone receptor, and 29 were HER2 positive (16.0%). In 98 cases (54.1%) a small padge of skin covering the tumor area was removed. Irradiation was ministered to 50 patients (27.6%). After a mean follow up period of 39.9 months (6-178), ten cases of local recurrences were detected (5.5%). No one case of local relapse was detected in the sub-NAC area Conclusion. Our data indicated that the local recurrences rate after therapeutic MA for well selected BC patients is low and acceptable. 2
Citation Format: Rebeca Neves Heinzen, Alfredo CarlosSimõesDornellas de Barros, Alfredo Jacomo, Marcella Cinquini. Local recurrences after mammary adenectomy with clear retroareolar margin for the treatment of early infiltrating breast carcinomas [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-20-10.
Abstract P4-01-18: Acquired sensitivity strategies in ER+ breast cancer progressing on CDK4/6 and mTOR inhibitors
Authors: Farmaki Eleni , Emond Rena , Cosgrove Patrick , Bild Andrea 
Published: March 2022

Abstract
Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors and mammalian target of rapamycin (mTOR) inhibitors have become important components of the clinical management of metastatic ER+ breast cancer. Despite the benefit of these treatments, progression and resistance will still develop in the majority of patients. Therefore, it is important to research strategies that can increase response durability and effectiveness of these therapies. The aim of our study is to use the identified acquired resistance targets in progressing patients for treatment approaches. Our previous studies on the evolution of resistance using transcriptomic analysis in earlier stage patients as they progress on therapy identified resistance pathways that include the MAPK, AKT, and survival signaling pathways. We used isogenic breast cancer cell lineages sensitive and resistant to CDK4/6 inhibitors, ribociclib and abemaciclib, and the mTOR inhibitor, everolimus, to determine the efficacy of drug combinations targeting the acquired resistance JNK, MAPK and AKT pathways. The effect of the pathways’ inhibition in the resistant cells was examined in vitro, in 2D drug response assays, and in 3D spheroid assays. Our results indicate increased potency in the resistant cells to the combination therapies with JNK and TIC10/ONC201 inhibitors which are currently seeing promise in clinical trials. These findings were validated in 2D and 3D in vitro studies with patient derived breast cancer cells under the same combination treatments, recapitulating the increased response to combination therapy and further supporting clinical relevance. In conclusion, our study leveraged our patient data cohorts as well as pre-clinical models to identify acquired sensitivity to JNK, MAPK and AKT inhibition. With the linking of both patient derived data with isogenic cell line driven experiments, our study provides validated findings in various settings strengthening the potential of clinical applications of these targetable pathways.
Citation Format: Eleni Farmaki, Rena Emond, Patrick Cosgrove, Andrea Bild. Acquired sensitivity strategies in ER+ breast cancer progressing on CDK4/6 and mTOR inhibitors [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-01-18.
Abstract P4-02-10: Pfkfb3 inhibition significantly decreases endocrine-resistant breast cancer growth and induces necroptotic cell death
Authors: Jones Brandon C , Sengupta Surojeet , Sevigny Catherine M , Jin Lu , Pohlmann Paula R , Shajahan-Haq Ayesha , Clarke Robert 
Published: March 2022

Abstract
Estrogen receptor-positive breast cancers constitute the majority of newly diagnosed breast cancers in patients. While commonly treated with various approved endocrine therapy strategies, these cancers can unfortunately also develop resistance to such therapies, indicating a need to explore other avenues of treatment in endocrine-resistant breast cancer. Rapidly dividing cancer cells are known to have an increased energy demand and altered reprogramming of glucose metabolism, leading to a subsequent heavy reliance on glycolysis. A critical rate-limiting step in the glycolysis pathway, the conversion of fructose-6-phosphate to fructose-1,6-bisphosphate, is greatly influenced by an allosteric activator produced by the enzyme PFKFB3 (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3), thus making PFKFB3 an essential regulator of glycolytic flux. Furthermore, PFKFB3 has been shown to be overexpressed in many human cancers, including breast cancer, as well as be upregulated by estrogen. Through the following work, we show that endocrine-resistant BC cell growth is strongly reduced by PFKFB3 targeting using different commercial PFKFB3 inhibitors, which can be further exacerbated by combination treatment with well-established endocrine therapies like fulvestrant in some cell lines. Moreover, we relatedly show that PFKFB3 inhibition reduced tumor size in mouse xenografts of endocrine-resistant BC cells. Endocrine-resistant cells also presented higher basal glucose uptake and greater reduction of glucose uptake in response to PFKFB3 inhibition than endocrine-sensitive cells, indicating that endocrine-resistant breast cancer cells may have a more significant reliance on glycolysis and PFKFB3 activity for their metabolic needs than sensitive cells. Additionally, PFKFB3 inhibition produced an increase in phosphorylation of the necroptotic markers RIPK1 (receptor-interacting kinase 1), and MLKL (Mixed Lineage Kinase Domain Like Pseudokinase), and pre-treatment with the necroptosis inhibitor necrostatin-1 was able to partially rescue cell death caused by PFKFB3 targeting, suggesting that necroptosis is a primary method of cell death induced by PFKFB3 inhibition. In summation, this study showcases the glycolytic enzyme PFKFB3 as an encouraging therapeutic target in endocrine-resistant breast cancer, and warrants further review as a monotherapy or in combination with current endocrine therapies.
Citation Format: Brandon C Jones, Surojeet Sengupta, Catherine M Sevigny, Lu Jin, Paula R Pohlmann, Ayesha Shajahan-Haq, Robert Clarke. Pfkfb3 inhibition significantly decreases endocrine-resistant breast cancer growth and induces necroptotic cell death [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-02-10.
Abstract P4-05-08: 18F-FDG uptake of visceral adipose tissue on preoperative PET/CT as a predictive marker for breast cancer recurrence
Authors: Paik Pill Sun , Yoon Chang Ik , Kim Hyun Jeong , Cha Yoon Jin , Kim Dooreh , Bae Soong June , Ahn Sung Gwe , Jeong Joon , Park Woo-Chan , Ryu Young Hoon , Jeon Tae Joo , Kim Chai Won 
Published: March 2022

Abstract
Background: Glucose utilisation of visceral adipose tissue (VAT) reflects inflammatory activities, which promote tumour cell growth and carcinogenesis. The impact of the VAT-inflammatory response on survival outcomes in breast cancer is not known. We investigated survival outcomes in breast cancer patients based on the standardised uptake value (SUV) in VAT using 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET/CT). Methods: We retrospectively enrolled breast cancer patients (stages I-III) treated at the Gangnam Severance Hospital between 2007 and 2010. Metabolic activities of VAT and tumour were calculated based on FDG uptake, and the clinical characteristics and survival outcomes were comparatively analysed in the high-SUV and low-SUV groups. Results: The SUV of VAT (SUV-VAT) was obtained for 148 patients. With no significant intergroup differences in clinical characteristics, high SUV-VAT was associated with poor recurrence-free survival (RFS; hazard ratio [HR] 2.754, 95% confidence interval [CI] 1.090-6.958, P=0.032) and distant metastasis-free survival (DMFS; HR 3.500, 95% CI 1.224-10.01, P=0.019). Multivariate analysis showed that high SUV-VAT was a significant clinical factor for both poor RFS and DMFS (P=0.023 and P=0.039, respectively). SUV-tumour was significantly associated with RFS (P=0.0388), but not DMFS (P=0.0718). Conclusion: The glucose metabolism of VAT, assessed by 18F-FDG PET/CT, is a prognostic biomarker of adverse outcomes and of primary tumour metabolism in breast cancer. The glucose utilisation of VAT may reflect the degree of inflammation associated with breast cancer recurrence and metastasis. Keywords: breast cancer, visceral adipose tissue, inflammation, 18F-FDG, PET/CT, glycolysis, metastasis, recurrence
Citation Format: Pill Sun Paik, Chang Ik Yoon, Hyun Jeong Kim, Yoon Jin Cha, Dooreh Kim, Soong June Bae, Sung Gwe Ahn, Joon Jeong, Woo-Chan Park, Young Hoon Ryu, Tae Joo Jeon, Chai Won Kim. 18F-FDG uptake of visceral adipose tissue on preoperative PET/CT as a predictive marker for breast cancer recurrence [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-05-08.
Abstract P4-05-11: The clinical importance of the new category, ER low-positive in the ER expression HER2 negative early breast cancer
Authors: Wakako Tajiri 
Published: March 2022

Abstract
&lt;Background&gt;In the latest updated ASCO/CAP guideline, a new category, ER low-positive was introduced, which are determined by the 1% to10 % of positive staining of the tumor nuclei for ER. However clinical meaning of ER-low positive was unclear compared with ER- positive or ER-negative in HER2 negative breast cancer. &lt;Purpose&gt; In order to clarify the clinicopathological features of ER-low positive breast cancer, we compared the clinicopathological factors and prognosis among three groups, ER negative, ER-low positive, and ER-positive groups in the patients with HER2 negative breast cancer. &lt;Patients and Method&gt; A total of 1,882 patients with HER2 negative breast cancer who underwent surgery between 2001 and 2018 were included in this study. We divided them into three groups, ER negative (&lt;1%), ER-low positive (1-10%), and ER positive (10%≦). The relationships between ER status and clinicopathological characteristics and prognosis were evaluated. &lt;Result&gt;According to ER status, 553(29.4%), 183(9.7%), 1146(60.9%) patients were divided into ER negative, low-positive and positive groups. Compared with ER-positive group, patients in the ER negative and low-positive groups were of higher age (p&lt;.0001), and those tumors were significantly associated with the larger tumor size (p&lt;.0001), higher histological grade (p&lt;.0001) and more administration of adjuvant chemotherapy (p&lt;0.0001). Most of the patients with ER low-positive and ER-positive tumors had received the adjuvant endocrine therapy. The prognosis of the patients with ER low-positive tumors were poorer than that of those with ER positive tumors in terms of relapse-free survival (RFS p&lt;.0001), distant metastasis-free survival (DMFS p&lt;.0001) and overall survival (OS p&lt;.0001).In the node negative patients, the prognosis of the ER-negative and ER low-positive groups were equivalent, and poorer than that of the ER-positive group (RFS; p=0.0068, DMFS; p=0.0013, OS: p=0.0032). In addition, in pStage III patients, prognosis of the ER-negative and ER low-positive groups were also equivalent, and poorer than that of the ER-positive group (RFS; p=0.008, DMFS; p=0.0021, OS: p=0.0010). &lt;Conclusion&gt; This study showed that the prognosis of the patients with ER negative and ER low-positive were similar, and poorer than that of those with ER positive tumors. Therefore, the new category of ER-low positive is clinically especially important in order to determine the appropriate adjuvant therapy.
Citation Format: Tajiri Wakako. The clinical importance of the new category, ER low-positive in the ER expression HER2 negative early breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-05-11.
Abstract P4-07-20: Survival analysis using the entire transcriptome to pinpoint biomarkers with the highest prognostic power
Authors: Gyorffy Balazs 
Published: March 2022

Abstract
Introduction. Extensive research is directed to uncover new biomarkers capable to stratify breast cancer patients into clinically relevant cohorts. However, the overall performance ranking of such marker candidates compared to other genes is virtually absent. Here, we present the ranking of all survival related genes in chemotherapy treated basal and estrogen positive/HER2 negative breast cancer. Methods. We searched the GEO repository to uncover transcriptomic datasets with available follow-up and clinical data. After quality control and normalization, samples entered an integrated database. Molecular subtypes were designated using gene expression data. Survival analysis was performed using Cox proportional hazards regression. False discovery rate was computed to combat multiple hypothesis testing. Kaplan-Meier plots were drawn to visualize the best performing genes. Results. The entire database includes 7,830 unique samples from 55 independent datasets. Of those with available relapse-free survival time, 3,382 samples were estrogen receptor-positive and 696 were basal. In chemotherapy treated ER positive/ERBB2 negative patients the significant prognostic biomarker genes achieved hazard rates between 1.76 and 3.33 with a p value below 5.8E-04. The significant prognostic genes in adjuvant chemotherapy treated basal breast cancer samples reached hazard rates between 1.88 and 3.61 with a p value below 7.2E-04. Finally, an online accessible platform utilizing the entire database was set up enabling the validation of future biomarker candidates. Conclusions. A reference ranking for all genes in two chemotherapy treated breast cancer cohorts is presented. The results help to neglect those with unlikely clinical significance and to focus future research on the most promising candidates.
Citation Format: Balazs Gyorffy. Survival analysis using the entire transcriptome to pinpoint biomarkers with the highest prognostic power [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-07-20.