bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P4-17-05: Survival and clinicopathologic characteristics of male breast cancer patients using Korea national cancer incidence database
Authors: Lee Eungyeong , Jo Heein , Han Jai Hong , Jung So-Youn , Lee Seeyoun , Kang Han-Sung , Lim Myong Cheol , Won Young-Joo , Lee Eun Sook , Lee Eun Sook 
Published: March 2020

Abstract
Background: Male breast cancer (MBC) is a very rare disease. There are ambiguous opinions about treatment outcomes and survival outcome. This study aimed to investigate the incidence and survival outcome of male breast cancer in Korea. Additionally, we evaluated the differences between male and female breast cancer (FBC).
Method: We identified 226,612 breast cancer cases diagnosed between 1999 and 2016 in the Korea Central Cancer Registry (KCCR). We retrospectively analyzed the data that patient demographics and clinical information between MBC and FBC. Overall survival (OS) was estimated according to sex, age, histologic type, stage.
Results: Of the 226,612 patients, 1,052 had male breast cancer patient and 225,560 had female breast cancer patients. The ratio of male to female was 0.0047. MBC patients were diagnosed the most frequently in those aged 60-69 years. In contrast, FBC was diagnosed the most frequently in those aged 40-49 years (p&lt;.0001). Male patient received less adjuvant therapy than female patients (radiotherapy, MBC vs. FBC = 8% vs. 22%, chemotherapy, 41.9% vs. 55.7%, p&lt;.0001). The 5-years OS rates after the diagnosis of breast cancer were 88.8% for all patients. MBC has a lower 5-years OS rate than FBC (76.2% for men, and 88.9% for women, p&lt;.0001). Both groups showed lower survival in patients aged ≥60 years. The 5-years OS rates of invasive type were 75.8% for men and 89% for women. The OS rate was lower in both groups as the stage increased.
Conclusion: We found that there is a difference between MBC and FBC. The survival outcomes in MBC were worse than that of FBC. This study showed the different OS patterns according to the age, histology, and stage. Based on these results, clinicians need to recognize the difference from FBC when treating MBC.
Citation Format: Eungyeong Lee, Heein Jo, Jai Hong Han, So-Youn Jung, Seeyoun Lee, Han-Sung Kang, Myong Cheol Lim, Young-Joo Won, Eun Sook Lee, Eun Sook Lee. Survival and clinicopathologic characteristics of male breast cancer patients using Korea national cancer incidence database [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 P4-17-05.
Abstract P4-17-07: Demographics and survival in male breast cancer: An updated analysis of SEER database
Authors: Khoury John , Anusim Nwabundo , Macari David , Jaiyesimi Ishmael 
Published: March 2020

Abstract
Background: Male breast cancer is rare accounting for less than 0.5% of all cancer diagnoses in men. Previous epidemiological studies reported conflicting results regarding the prognosis of male breast cancer in comparison to female breast cancer. As treatment for breast cancer has improved significantly, we conducted this study to evaluate male breast cancer characteristics and mortality.
Methods: All patients diagnosed with breast cancer between 2010 and 2015 from the population-based cancer registries of the Surveillance Epidemiology and End Results program (SEER) were analyzed. Descriptive statistics, Kaplan-Meier analysis and COX regression model were used to examine the data.
Results: A total of 380,116 cases of breast cancer were found including 2,978 cases of male breast cancer. The age-adjusted incidence rate for male breast cancer during the study period was 1.2 per 100,000 individuals per year which is slightly higher than the rate during the 10 years period preceding our study date (1.1 per 100,000 per year). Out of all male breast cancer patients, 80.7% of them were white, 14.6% black and 4.7% from other races. The median age of diagnosis was 68. 34% of male breast cancer patients were diagnosed with stage I, 41.6% with stage II, 16.2% with stage III and 8.2% with stage IV. 97% of male breast cancer cases were ER/PR positive and 11.9% were HER2 positive. 5-year survival rate for male breast cancer patients was 90% for stage I, 86% for stage II, 78% for stage III and 28% for stage IV. Cox proportional-hazards model revealed a slight increase in mortality associated with male breast cancer in comparison to female breast cancer (adjusted hazard ratio, 1.15; 95% confidence interval, 1.06 to 1.24; P&lt;0.01).
Conclusions: Male breast cancer represents less than 1% of breast cancer cases. Its age-adjusted incidence rate has slightly increased. It is mostly diagnosed as early stage with positive hormone receptors status. After controlling for other risk factors, male breast cancer patients have a worse survival outcome than female patients.
Citation Format: John Khoury, Nwabundo Anusim, David Macari, Ishmael Jaiyesimi. Demographics and survival in male breast cancer: An updated analysis of SEER database [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 P4-17-07.
Abstract P5-02-06: Improved histologic grading of breast cancer by a novel deep learning-based model
Authors: Rantalainen Mattias , Wang Yinxi , Ácz Balázs , Robertson Stephanie , Hartman Johan 
Published: March 2020

Abstract
Breast cancer histologic grade is a well-established prognostic factor utilized in clinical decision making. In current clinical practice grading is conducted manually by pathologists and this procedure is associated with a substantial inter-observer variability. Furthermore, patients classified as histologic grade 2 has been reported to exhibit an intermediate recurrence risk, resulting in less prognostic value. With the aim of improving patient stratification, we have developed a model-based approach for histological grading using deep convolutional neural networks (CNNs). In this study, we developed a CNN model for improved histologic grading, with a focus on further stratification of grade 2 patients into high and low risk groups.
Histopathology images from the Clinseq breast cancer study and the Cancer Genome Atlas (TCGA) containing 730 patients were scanned at 40X magnification and tiled into patches at 20X. In total, we obtained 5.3 million patches of size 299 × 299 pixels. Using image annotations of invasive cancer regions in Clinseq study, we trained a deep CNN model to segment cancer regions in TCGA data. Subsequently, the cancer regions from both Clinseq and TCGA were used to optimize a second deep CNN model for classification of grade 1 and 3, this model was applied to re-classify 291 patients with histologic grade 2 into low and high risk.
The CNN model classified cancer and non-cancer with area under the receiver operating characteristic curve (AUC) of 0.941. The second CNN model achieved an AUC of 0.910 in terms of classification of grade 1 and 3 tumors (cross-validation). For grade 2 tumors (independent test data), 184 were re-classified into the lower risk group whereas 107 were classified as high risk. The risk of recurrence for the grade 2 higher risk group is significantly higher than that in lower risk group, with an estimated hazard ratio of 2.86 (95% confidence interval: 1.21-6.69) after adjusting for age, tumor size, estrogen receptor status and lymph node status.
In conclusion, we found that the deep CNN model demonstrated a high capability to distinguish between breast cancer with histologic grade 1 and 3. We also found that re-stratification of Grade 2 patients into high and low risk groups was significantly associated with risk of recurrence. Improved histological grading, and further risk stratification of grade 2 patients, by deep CNN models could contribute towards a reduction of both over- and under-treatment of breast cancer patients.
Citation Format: Mattias Rantalainen, Yinxi Wang, Balázs Ácz, Stephanie Robertson, Johan Hartman. Improved histologic grading of breast cancer by a novel deep learning-based model [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 P5-02-06.
Abstract P5-02-13: A novel detection technique for collagen (and other macromolecules) on H&E slides without special stains for improved cancer prognostics
Authors: Fereidouni Farzad , Borowsky Alexander D. , Levenson Richard M. 
Published: March 2020

Abstract
Background: Stromal density including the characterization of the type, abundance and alignment of collagen and other extracellular matrix (ECM) protein fibers in proximity to breast precancers and cancers has emerged as an important and evolving tool for understanding tumor progression and stratifying/classifying mortality risk. Standard methods for this evaluation including second harmonic generation (SHG) microscopy requires access to fresh or FFPE tissue samples of limited availability. In contrast, standard diagnostic H&E slides are more readily available for large retrospective and prospective studies. Methods: We developed a method for dual emission and transmission (DUET) microscopy that employs combined brightfield and fluorescence modalities, plus quantitative image analysis. The prototype instrument has whole-slide scanning capabilities for collagen detection and pixel-accurate alignment with conventional H&E-stained images. We have analyzed a retrospective cohort of 700 breast cancers with available outcome follow-up of greater than 5 years using this DUET method Results: DUET microscopy provides clear discrimination of collagen and ECM directly from standard H&E specimens, requiring only a few minutes to scan whole slides. Using the method, contrast enhancement similar to special staining techniques (e.g. trichrome, periodic acid Schiff’s, and picrosirius red stains). Image analysis from DUET directly corresponds to SHG data. DUET imaging discriminates between stroma surrounding invasive cancer and benign epithelium. DUET imaging of 700 breast cancers shows outcome correlation. Ongoing multivariate analysis comparing standard measures (grade, tumor infiltrating lymphocytes, tumor phenotype, etc.) to the DUET stromal score will be reported. Conclusions: DUET provides a straightforward, rapid and inexpensive approach for highlighting collagen distribution patterns on existing histology slides. This method should enable current research using improved quantitative tools, including AI-based, for correlation with patient outcomes, by enabling the use of standard and available H&E slides.
Citation Format: Farzad Fereidouni, Alexander D. Borowsky, Richard M. Levenson. A novel detection technique for collagen (and other macromolecules) on H&E slides without special stains for improved cancer prognostics [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 P5-02-13.
Abstract P5-02-14: The MAPK pathway is variably active across breast cancer subtypes, and increased activity may be associated with hormonal therapy resistance
Authors: Stolpe Anja van de , Holtzer Laurent , Wesseling-Rozendaal Yvonne , Verhaegh Wim 
Published: March 2020

Abstract
Background: Based on preclinical research, the MAPK growth factor pathway is thought to be an oncogenic pathway driving breast cancer, potentially in association with the ER pathway. In patients it is unclear how functional activity of the MAPK pathway activity relates to activity of the ER pathway to drive cancer growth. We have reported before on the development of assays, e.g. for the ER pathway, that enable quantitative measurement of activity of signal transduction pathways based on Bayesian computational model inference of pathway activity from measurements of mRNA levels of target genes of the ER transcription factor (Cancer Res., 2014, vol. 74, no. 11, pp. 2936-2945). We now present (1) development of the MAPK-AP1 pathway model, (2) MAPK-AP1 pathway activity and its relation to ER pathway activity in breast cancer; (3) emergence of MAPK pathway activity associated with hormonal therapy resistance. Methods: The MAPK-AP1 pathway model was developed and biologically validated on Affymetrix mRNA data from samples (different cell types) with a known MAPK pathway activity. MAPK-AP1 and ER pathway activity scores were measured on Affymetrix expression data of primary untreated breast cancer samples (GSE45827, n=141) and of fulvestrant sensitive and resistant MCF7 cell line clones (GSE74391). Results: In clinical breast cancer samples, average MAPK pathway activity was increased in all subtypes compared to normal breast tissue, with a large dynamic range indicating that in each subtype there are samples with high and with low pathway activity; ER pathway activity in Luminal A and B subtypes ranged from high to low, and was low in all other subtypes. MAPK-AP1 pathway activity did not correlate with ER pathway activity. Fulvestrant-sensitive MCF7 cells had high ER and low MAPK pathway activity scores, while resistant MCF7 clones exhibited increased MAPK pathway activity and complete loss of ER pathway activity, explaining therapy resistance. Discussion: The MAPK-AP1 pathway is frequently activated in all breast cancer subtypes, independent of ER pathway activity. We hypothesize that in case of resistance to hormonal therapy measurement of both pathway activities may be informative as to the underlying resistance mechanism, i.e. loss of ER pathway activity and/or gain of MAPK pathway activity. Future clinical studies are needed to confirm the role of these signaling pathways in hormonal resistance.
Citation Format: Anja van de Stolpe, Laurent Holtzer, Yvonne Wesseling-Rozendaal, Wim Verhaegh. The MAPK pathway is variably active across breast cancer subtypes, and increased activity may be associated with hormonal therapy resistance [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 P5-02-14.
Abstract P5-02-16: Is surgical excision of intraductal papillomas justified by the rate of upstaging to breast cancer?
Authors: Cotzia Paolo , Ozerdem Ugur , Lee Jiyon , Chun Jennifer , Kaplowitz Elianna , Schnabel Freya , Darvishian Farbod 
Published: March 2020

Abstract
Introduction: The management of intraductal papilloma (IDP) diagnosed on core needle biopsy (CNB) is controversial. Some investigators advocate surgical excision based on an upgrade risk of as high as 24%. Others contend that after adjusting for confounders, including size, clinical presentation, presence of other accompanying high-risk lesions and radiologic correlation, the upgrade risk may be as low as 2.3%. The implications for patient care would be the avoidance of invasive surgical procedures. The purpose of our study was to investigate the upgrade rate of IDP diagnosed on CNB to ductal carcinoma in situ (DCIS) and invasive carcinoma on subsequent surgical excision and the impact of associated high-risk borderline lesions and other clinicopathologic and radiologic variables.
Methods: Our institutional pathology database was queried for all women who had a CNB with a diagnosis of intraductal papilloma between 2005-2018. Two independent pathologists reviewed all the core biopsy slides and excisional biopsy slides. Variables of interest included clinical, imaging and pathologic characteristics. Statistical analyses included Pearson’s chi-square, Wilcoxon rank-sum and logistic regression.
Results: Out of 216 women, 19 (8.8%) upgraded to breast cancer (BC), including 14 (74%) DCIS and 5 (26%) invasive carcinoma. Out of 161 pure IDP without any atypia, 5 (3.1%) upgraded to BC and out of 45 IDP with atypical ductal hyperplasia (ADH), 13 (28.9%) upgraded to BC. Only one patient who upgraded to BC from IDP with ADH had a discordant finding on imaging. When we evaluated the clinicopathologic and radiologic variables associated with upgrading from pure IDP to BC on final pathology, we found that older age (&gt;53 years) at time of biopsy (OR=1.05, 95%CI 1.01-1.09, p=0.027) and concomitant ipsilateral atypical ductal hyperplasia (ADH) (OR=9.69, 95%CI 3.37-27.81, p&lt;0.0001) were associated with a BC upgrade. There was no significant association of upgrading to BC after having a concomitant ipsilateral or contralateral breast cancer.
Conclusions: Our results support surgical excision of IDP on CNB when associated with ADH or diagnosed in women older than 53 years of age. The upgrade rate of 3.1% for IDP without atypia on CNB in younger women does not justify a universal recommendation for routine surgical excision.
Citation Format: Paolo Cotzia, Ugur Ozerdem, Jiyon Lee, Jennifer Chun, Elianna Kaplowitz, Freya Schnabel, Farbod Darvishian. Is surgical excision of intraductal papillomas justified by the rate of upstaging to breast cancer? [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 P5-02-16.
Abstract P5-03-09: Multigene panel analysis in breast and ovarian cancer
Authors: Trapp Elisabeth Katharina , Speicher Michael , Geigl Jochen B , Kolovetsiou-Kreiner Vassiliki , Reisinger Julia , Haas Josef , Petru Edgar , Tamussino Karl , Pristauz Gunda 
Published: March 2020

Abstract
Background: Genetic testing is of prognostic and predictive importance in patients with ovarian cancer and breast cancer. The best explored mutations are those of the BRCA 1 and BRCA2 genes, and the result of BRCA testing impacts treatment and prophylactic options. Data on other breast-cancer-associated genes are accumulating. Methods: All patients who underwent genetic counseling and testing for BRCA 1 and BRCA 2 between 2007 and 2019 at the Medical University of Graz were reviewed. If BRCA testing was negative patients were offered panel testing for other breast and ovarian cancer associated genes including ATM, PETEN, RAD50, RAD51D, RAD51C, TP53, STK11, ATM, NBN, CDH, MSH6, MSH2, MLH1, CHEK2, PALB2, BRIP1, SMO, PETEN, SMO. Results: In total 1905 patients were counseled for genetic testing between 2007 to 2019. In 292 patients (mean age 53yrs) panel gene testing was performed. 114 (39%) of these 292 BRCA-negative patients (55 with breast cancer, 24 with ovarian cancer) had a pathogenic variant (n=32) or a mutation of unknown significance (n=82). The most common pathogenic variant occurred in the CHEK2 gene (n=15). Interpretation: In this series approximately one third of high-risk patients who tested negative for a BRCA mutation had a mutation of unknown significance and/or pathogenic mutation in gene panel testing. This indicates that genetic panel testing should be considered more frequently.
Citation Format: Elisabeth Katharina Trapp, Michael Speicher, Jochen B Geigl, Vassiliki Kolovetsiou-Kreiner, Julia Reisinger, Josef Haas, Edgar Petru, Karl Tamussino, Gunda Pristauz. Multigene panel analysis in breast and ovarian cancer [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 P5-03-09.
Abstract P5-03-11: Germline and somatic variants in patients with inflammatory breast cancer (IBC) detected using cell-free DNA
Authors: Winn Jennifer S. , Hasse Zachary , Pei Jianming , Slifker Michael , Arisi-Fernandez Sebastian M. , Talarchek Jacqueline N. , Obeid Elias , Devarajan Karthik , Wu Hong , Gong Yulan , Cristofanilli Massimo , Alpaugh R.Katherine , Fernandez Sandra Viviana 
Published: March 2020

Abstract
In order to better understand the etiology of inflammatory breast cancer (IBC), we performed a retrospective study to evaluate genomic alterations in 32 IBC patients using circulating DNA from blood. In 20 patients, mutation analyses were also conducted on tumor tissue or tumor cells from pleural effusions; in 15 of these patients, blood and tissue or pleural effusions were collected at the same time. Next generation sequencing (NGS) and a panel of 93 breast cancer related genes (Qiagen) were used for these studies. We found that of the 32 total patients, 11 (34.4%) carried at least one putative pathogenic germline variant, and another 8 patients (25%) carried at least one likely pathogenic germline variant. Ten patients (31.3%) carried only germline variants of uncertain significance and in 3 patients (9.4%) germline variants were not detected. Putative germline pathogenic variants were observed in the BRCA2 (2/32), TP53 (2/32), BRCA1 (1/32), PALB2 (1/32), CHEK2 (1/32), ATM (1/32), PMS1 (1/32), MUTYH (1/32), and MSH2 (1/32) genes. In addition, putative germline likely pathogenic variants were observed in the BARD1 (10/32), RB1 (2/32), APC (1/32), FANCC (1/32), AR (1/32), RAD51C (1/32), RAD51D (1/32) and CASP8 (1/32) genes. Most of the patients in our study had a family history of cancer and seventeen of the patients (53.1%) had family history of breast cancer in particular. Of those patients, 7 had a family history of breast cancer at a young age (&lt;45 years old). Other cancer in their families included prostate (28.1%), colon (28.1%) and skin cancer (12.5%). Somatic variants, pathogenic or likely pathogenic, were detected in: TP53, PTEN, MRE11, PMS2, RB1, AR, KMT2C, PIK3CA and BRCA1. These results suggest a high incidence of germline variants in patients with IBC that could be associated with an increased risk of developing the disease. This data, if validated in a larger cohort, would demonstrate the power that genomic analysis has to identify women at high-risk of developing IBC and who would benefit from early screening.
Citation Format: Jennifer S. Winn, Zachary Hasse, Jianming Pei, Michael Slifker, Sebastian M. Arisi-Fernandez, Jacqueline N. Talarchek, Elias Obeid, Karthik Devarajan, Hong Wu, Yulan Gong, Massimo Cristofanilli, R.Katherine Alpaugh, Sandra Viviana Fernandez. Germline and somatic variants in patients with inflammatory breast cancer (IBC) detected using cell-free DNA [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 P5-03-11.