bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P5-05-06: Progesterone receptor (PR) isoform-specific expansion of breast cancer stem-like cells occurs through a phospho-PR/FOXO1 driven signaling axis
Authors: Truong TH , Dwyer AR , Diep CH , Lange CA 
Published: May 2019

Abstract
Luminal breast cancers account for ˜75% of cases and are positive for progesterone receptor (PR) and estrogen receptor (ER) expression. PR is a classical ER-target gene and is used as a biomarker of ER activity; however, a growing body of evidence supports the role of PR as an important modifier of ER actions and a key driver of luminal breast cancer progression. Progesterone signaling is mediated by two PR isoforms: full-length PR-B and truncated PR-A, which lacks the N-terminal 164 amino acids. Little is known about PR isoform-specific actions in PR-expressing breast tumors, given that total PR expression is measured clinically. Herein, we sought to identify phenotypic differences in luminal breast cancer cells (T47D) overexpressing PR-A (T47D-YA) or PR-B (T47D-YB). We demonstrate that PR-B expression is required for anchorage-independent colony formation, while PR-A expressing cells fail to proliferate in soft agar. PR-B driven proliferation has been mapped to PR phosphorylation events, which include MAPK or CDK consensus sites such as Ser294. We demonstrate that in contrast to previous reports, PR-A is well phosphorylated at Ser294 in response to progestins (e.g. R5020) using our custom phospho-PR (Ser294) polyclonal antibody. Interestingly, Ser294 phosphorylation of PR-A occurs more rapidly and robustly following hormone treatment compared to PR-B expressing cells. Our findings indicate that PR-A is a dominant driver of stem-like expansion in breast cancer cells. PR-A tumorspheres exhibited enriched ALDH+ and CD44+/CD24- populations compared to PR-B and promoted heightened gene expression of stem-like genes (e.g. FOXO1). We demonstrate that the PR target gene and co-activator FOXO1 promotes both PR-A and PR-B phosphorylation at Ser294 and augments tumorsphere formation. Direct inhibition of FOXO1 levels abrogates phospho-PR (Ser294) levels and tumorsphere formation in PR expressing cells. Finally, we show that Ser294 is required for PR-A induced expression of stem-like genes (e.g. FOXO1) and stem-like behavior as measured by ALDH+/CD44+ tumorspheres. Taken together, our data reveal unique functions of PR isoforms as modulators of distinct and opposing pathways (i.e. proliferation versus stem-like expansion) in luminal breast cancer models. A clear understanding of PR isoform-specific actions, phosphorylation events, and the role of co-factors such as FOXO1 may lead to novel biomarkers of advanced tumor behavior and reveal new approaches to pharmacologically target PR isoforms in luminal breast cancers.
Citation Format: Truong TH, Dwyer AR, Diep CH, Lange CA. Progesterone receptor (PR) isoform-specific expansion of breast cancer stem-like cells occurs through a phospho-PR/FOXO1 driven signaling axis [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 P5-05-06.
Abstract P5-05-10: Estrogen receptor β suppresses metastasis of inflammatory breast cancer by regulating cell cytoskeleton and cytokine signaling
Authors: Thomas C , Karagounis I , Srivastava RK , Kumar S , Karar J , Chao H-H , Kazimierczak A , Bado I , Nikolos F , Leli N , Koumenis C , Krishnamurthy S , Ueno NT , Chakrabarti R , Maity A 
Published: May 2019

Abstract
Inflammatory breast cancer (IBC) is the most lethal form of breast cancer that accounts for about 10% of breast cancer mortality annually in US. Poor prognosis is largely due to the high propensity of IBC tumors to develop distant metastasis that occurs directly from the gland epithelium and through lymphatic invasion in which dermal lymphatics are filled with tumor emboli. Owing to the complex metastatic process, the molecular basis of IBC aggressiveness is poorly understood, and no specific therapeutic target has been identified. Despite the lack of estrogen receptor α (ERα) in the majority of IBC tumors, estrogen may still play a role in these cancers through pathways that involve ERβ. Our tissue staining reveals expression of ERβ in more than 50% of IBCs that is reproduced in IBC cell lines. Furthermore, analysis of IBC datasets indicates correlation of receptor expression with good prognosis. We studied this association in preclinical models of IBC by knocking out ERβ in IBC cells. This promotes migration and invasion through cytoskeleton remodeling whereas re-expression of the receptor in knockout cells restores the cytoskeletal structure and migration to the levels of control cells. Consistent with increased migration, deletion of ERβ activates large gene networks of cell de-differentiation and cytokine synthesis that trigger tumor microenvironment responses to promote the motile phenotype of IBC cells. In contrast, ligands that activate the receptor inhibit signaling that contributes to metastasis in IBC. Analysis of an orthotopic xenograft model shows that IBC tumors lacking ERβ have higher propensity for metastasis compared with the ERβ-proficient tumors supporting the anti-metastatic activity of the receptor. Our findings point towards a role of ERβ in preventing distant metastases by inhibiting dissemination of IBC cells and maintaining the integrity of emboli. This function combined with distinct expression indicates the potential of ERβ to represent a unique prognostic marker and therapeutic target that can be utilized to repress IBC metastasis and eliminate its associated mortality.
Citation Format: Thomas C, Karagounis I, Srivastava RK, Kumar S, Karar J, Chao H-H, Kazimierczak A, Bado I, Nikolos F, Leli N, Koumenis C, Krishnamurthy S, Ueno NT, Chakrabarti R, Maity A. Estrogen receptor β suppresses metastasis of inflammatory breast cancer by regulating cell cytoskeleton and cytokine signaling [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 P5-05-10.
Abstract P5-07-10: The prognostic significance of estrogen formation as a consequence of aromatase expression in tumor microenvironment
Authors: Kim TH , Lee A , Han JW , Jung SJ , Byun K-D 
Published: May 2019

Abstract
Estrogen synthesis via aromatase in adipose tissue has an important role in progression of postmenopausal breast cancer. The increased local concentrations of estrogen in breast cancer via aromatase overexpression within the tumor tissue have been demonstrated by some investigators. Although aromatase inhibitor is the standard endocrine therapy for postmenopausal breast cancer patients, it is not uncommon for patients to have poor compliance to the drugs due to their side effects. This research is based on the hypothesis that if aromatase expression is related to prognosis and if therapeutic effect varies depending on the degree of aromatase expression, then this study may be able to suggest a new guideline in terms of choosing between aromatase inhibitors and tamoxifen.
Methods: 154 postmenopausal breast cancer patients who underwent surgery and aromatase inhibitor therapy in Busan Paik Hospital, Inje University from January 2005 to December 2010 were enrolled. Patients with DCIS or stage IV breast cancer were excluded. Patients' clinicopathological data were collected and TMA blocks were created for immunohistochemistry studies to examine aromatase expression.
Results: The recurrence has occured in 7 patients (6.9%). Stage, tumor size and number of lymph node metastasis were related to increased risk of recurrence (p=0.051, 0.043, 0.001). The aromatase expression in cancer cells had significant correlation with clinical stage (p=0.041). There was also a positive correlation between Ki67 and aromatase expression in cancer tissue (p=0.006). However, aromatase expression in cancer, stromal, and adipose tissue had no relationship with recurrence (p=0.410, 0.627, 0.552).
Correlation between clinicopathologic factors and aromatase expression (Linear by linear association and Spearman's correlation coefficient test)Site of aromatase expressionERPRKi67P53BMIStageIn Cancer0.6060.5920.0060.4510.9560.041In Stroma0.2200.4710.5840.3290.3670.229In Adipose0.9880.2650.1590.1170.7701.000
Conclusions: Aromatase expression in cancer cells was correlated with clinical stage. This implies that aromatase expression might have a role of prognostic marker in addition to role of treatment indicator. There was no direct correlation between aromatase expression and recurrence.
Citation Format: Kim TH, Lee A, Han JW, Jung SJ, Byun K-D. The prognostic significance of estrogen formation as a consequence of aromatase expression in tumor microenvironment [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 P5-07-10.
Abstract P5-09-09: CHEK2: the third susceptibility BReast CAncer (BC) gene?
Authors: Gomes VL , Machado P , Fragoso S , Santos S , Coelho I , Parreira J , Rodrigues P , Rodrigues F , Clara A , Bento S , Luís A , Opinião A , Vaz F 
Published: May 2019

Abstract
INTRODUTION:
Considered a medium penetrance gene, CHEK2 codes for a kinase that is a key component of the DNA damage-signaling pathway. CHEK2 pathogenic variants were previously associated with breast and colorectal families and also with Li-Fraumeni phenotypes. Next generation sequencing (NGS) allowed for systematic inclusion of CHEK2 into gene panels. In here, we characterize the growing subgroup of CHECK2 BC families identified through our multidisciplinary program.
METHODS: Identification and review of CHEK2 families identified between 01/2000-06/2018 (until 2014 only the c.1100delC was tested (MLPA, MRC Holland); since 2014 NGS methods used were either,Trusight Cancer sequencing panel (Illumina, San Diego, CA, USA) or BRCA MASTR Dx (Multiplicom, Niel, Belgium). Carriers were included in a prospective follow up program.
RESULTS: 3646 index pts consented on gene testing. Most hereditary families (HF) were BRCA1/2 (374) (92%) but among non-BRCA HF bigger subgroups were 16 CHEK2, 10 Tp53 and 5 PALB2 HF. All CHEK2 index pts were diagnosed with only 3 different pathogenic variants: c.1100delC (9) c.319+2T&gt;A (6) and c.593-1G&gt;T (1 case of the only male BC pt in all CHEK2 pedigrees).
Index pts: mostly (93,8%) to females, with a mean age at first cancer diagnosis of 39 years (yrs) (30-52), 62,5% between 30-39yrs. With the exception of a Non Hodgking's Lymphoma index case, all index pts had BC(93,8%), 68,8% of which were ductal carcinomas and 12,5% of intraductal, all strongly positive for the estrogen receptor. With a mean follow up of 8,26yrs (3-15), secondary cancer cases occurred in 37,5% of index pts (mostly, 12,5%, BC at a mean of 53yrs (41-59).
Family phenotypes: data form 98 relatives (53,5% females) revealed diagnoses of BC (31,6%), prostate (8,1%), colorectal (7,1%) cancers. Only 22,2% of family cancers were diagnosed before 50yrs.
VUS: Among several complex variants of unknown significance, c.1036C&gt;T;p.Arg346Cys co-segregates in a predominantly male family with 3 prostate, 1 male and 1 female BC.
DISCUSSION AND CONCLUSIONS:
In the Portuguese population, emerging recurrent pathogenic variants in the CHEK2 gene, make it the most important non-BRCA BC gene so far. Carriers are included in prospective follow up but non-CHEK2 relatives are a challenge to genetic testing, as well as pedigree review, that questions its classification as a medium penetrance gene (or suggest the role of modifier factors).
Citation Format: Gomes VL, Machado P, Fragoso S, Santos S, Coelho I, Parreira J, Rodrigues P, Rodrigues F, Clara A, Bento S, Luís A, Opinião A, Vaz F. CHEK2: the third susceptibility BReast CAncer (BC) gene? [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 P5-09-09.
Abstract P5-09-10: Uptake of genetic testing and prevalence of mutations among minority populations: A retrospective cohort study
Authors: Nagireddy P , Ganschow P 
Published: May 2019

Abstract
Background: Hereditary cancer syndromes account for 5-10% of cancers. Limited data exists on the uptake of genetic testing and the prevalence of mutations in minority populations.
Objective: To estimate genetic testing uptake and prevalence of mutations in a minority population seeking care in a safety net healthcare system.
Methods: We conducted a retrospective cohort study of patients who were assessed at John H Stroger Jr., Hospital of Cook County cancer genetics risk clinic between October 2015 and March 2018 to determine the uptake of genetic testing and the prevalence of genetic mutations. Patients who met National Comprehensive Cancer Network (NCCN) guidelines for genetic testing for hereditary breast and ovarian cancer syndrome (HBOC), Lynch syndrome and familial adenomatous polyposis were included. Data was abstracted through chart review to obtain age, socio-demographics, personal cancer history, primary language, personal and family history of cancer including type of cancer and age at diagnosis, insurance status, genetic testing status and test results. Uptake of testing was calculated as the percentage of patients who underwent testing among those patients who met NCCN criteria for testing. Prevalence of mutations among those patients who underwent testing was determined and compared between different ethnicities using Chi-square test.
Results: Of 510 patients offered genetic counseling & testing, 478 (94%) underwent genetic testing. Among those who tested, 34% (n=165) were African American and 45% (n=212) were of Hispanic origin. Prevalence of any mutation was 48%(n=232), Pathogenic mutations were identified in 11% (n=54) of testers and variants of uncertain significance (VUS) were identified in 37% (n=178). Deleterious mutations and VUS rates in patients affected with hereditary cancer syndromes were 13% (n=42) and 39 % (n=132) respectively. Deleterious mutations and VUS rates in women unaffected with cancer were 9% (n=12) and 33 % (n=46) respectively. Overall mutation prevalence did not differ between affected and unaffected patients (p=0.12) or between Black and Hispanic patients (p=0.96). Deleterious mutation rate in Hispanic patients was 15.6% (CI 20.5%-10.7%) and in Black patients was 3.6% (CI 3%-4%). There was a significant difference in the percentage of deleterious mutations between Hispanic and Black patients (p=0.0009) .
Conclusion: Genetic testing uptake was high in minority populations. In the Population who were tested prevalence of pathogenic mutations was higher among Hispanics than African Americans.
Citation Format: Nagireddy P, Ganschow P. Uptake of genetic testing and prevalence of mutations among minority populations: A retrospective cohort study [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 P5-09-10.
Abstract P5-11-09: Feasibility of tracking plasma DNA mutation kinetics in estrogen receptor positive metastatic breast cancer using a novel digital PCR amplicon sequencing assay
Authors: Kumar S , Lindsay D , Chen B , Garrett AL , Tan XM , Anders CK , Carey LA , Gupta GP 
Published: May 2019

Abstract
Estrogen Receptor 1 (ESR1) gene mutations in estrogen receptor positive (ER+) metastatic breast cancer (MBC) are associated with clinical resistance to endocrine therapy. A highly sensitive digital PCR (dPCR) assay was developed to evaluate the baseline abundance and kinetics of hotspot ESR1 mutations in plasma circulating tumor DNA (ctDNA) from 58 ER+ MBC patients who had progressed on at least one line of prior endocrine therapy. Consistent with prior reports, we demonstrate that detection of hotspot ESR1 mutations in plasma ctDNA is associated with shorter progression-free survival. However, after patients initiated a new course of systemic therapy, changes in plasma ESR1 mutation abundance did not correlate with the duration of disease control. To investigate whether mutational heterogeneity may account for this lack of correlation, we developed a customized dPCR multiplexed amplicon next-generation sequencing (NGS) assay to detect plasma ctDNA mutations in the complete coding sequence of ESR1 and TP53, as well as hotspot regions in PIK3CA. Assay validation revealed a 79% sensitivity and 100% specificity for detecting plasma ctDNA mutations with a lower limit of detecting a 1.6% mutant allele fraction. The NGS assay revealed non-hotspot ESR1 mutations in plasma DNA from 14 of 31 (45%) patients. We also observed dynamic changes in plasma ctDNA mutant allele fraction of PIK3CA and TP53 during systemic therapy. Changes in the cumulative mutant allele fraction of ESR1, PIK3CA, and TP53 in plasma ctDNA correlated with duration of clinical treatment response in a limited subset of patients (n=8) for whom NGS was performed at two or more time points. Thus, mutational heterogeneity limits the clinical utility of monitoring individual hotspot mutations in ESR1 over time in ER+ MBC patients. However, a plasma ctDNA NGS assay targeting ESR1, PIK3CA, and TP53 may be useful as an early predictor of response to systemic therapy.
Citation Format: Kumar S, Lindsay D, Chen B, Garrett AL, Tan XM, Anders CK, Carey LA, Gupta GP. Feasibility of tracking plasma DNA mutation kinetics in estrogen receptor positive metastatic breast cancer using a novel digital PCR amplicon sequencing assay [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 P5-11-09.
Abstract P5-12-08: Not presented
Authors: Botticelli A , Cerbelli B , Pisano A , Naso G , Monti M , Ascierto PA , Costarelli L , Magri V , Mauri M , Pignataro MG , Campagna D , Pernazza A , Nuti M , Fortunato L , Della Rocca C , D'Amati G , Marchetti P 
Published: May 2019

Abstract
This abstract was not presented at the conference.
Citation Format: Botticelli A, Cerbelli B, Pisano A, Naso G, Monti M, Ascierto PA, Costarelli L, Magri V, Mauri M, Pignataro MG, Campagna D, Pernazza A, Nuti M, Fortunato L, Della Rocca C, D'Amati G, Marchetti P. 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 P5-12-08.
Abstract P5-13-01: Not presented
Authors: Foerster M , Zietsman A , Galakunde M , Anele A , Adisa C , Schuz J , Dos Santos Silva I , McCormack V 
Published: May 2019

Abstract
This abstract was not presented at the conference.
Citation Format: Foerster M, Zietsman A, Galakunde M, Anele A, Adisa C, Schuz J, Dos Santos Silva I, McCormack V. 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 P5-13-01.
Abstract P5-13-11: Impact of public health insurance “Seguro Popular” on breast cancer recurrence at Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), Mexico City
Authors: Mejía-Fernández L , Medina-Franco H , Armengol-Alonso A 
Published: May 2019

Abstract
Introduction. Public health insurance called Seguro Popular (SP) for breast cancer treatment (BCT) was instituted in Mexico in 2007. Our third level center was enrolled until 2011. SP covers systemic BCT (WHO 20th model list essential medicines). The aims were: 1) Describe frequency and type of breast cancer recurrence (BCR), 2) compare which factors were contributing to recurrence of breast cancer patients (pts) before and after the implementation of SP. Methods. Pts with diagnosis of breast cancer (BC) from 2004 to 2018 were analyzed and pts with BCR whom primary tumor (PBC) was treated and followed at INCMNSZ were recruited. They were divided into two groups according to access to SP: pts without Seguro Popular (non-SP) and, pts with SP. Xi-square, non-parametric tests and Kaplan-Meier curves (log-rank test) were used. Logistic regression was done for multivariate analysis. A p-value &lt;0.05 was considered significant. Results. Between 2004 and 2018, 929 pts with BC were diagnosed; 438 non-SP and 473 SP. Ninety-one (9.7%) had a BCR (loco-regional or distant) during this period. Median follow-up was 125 months. The BCR proportion was higher within non-SP than in SP (74 (16.8%) vs 17 (3.5%) pts) (p=&lt;0.05). Median age at diagnosis was higher in non-SP (p=0.028). Distant relapses were higher in non-SP than in SP (44 (59.4%) vs 8 (47%) pts). St Gallen 2017 Luminal A/B subtypes were most common in non-SP compared to SP where Basal-like subtype was higher (p=0.048). Luminal-A subtype had the best survival among non-SP compared to SP in which HER2 non-luminal had the higher survival (p&lt;0.001). Conclusions. Experience with SP at our center shows promising results in the improvement of BCR. Access to adequate systemic management (hormone-blocking and HER2 targeted therapy) has a positive impact on recurrence, disease-free survival, and cancer-specific global survival. A longer follow-up time is required in the SP group (prospective cohort) to confirm these findings, especially in luminal tumors with late recurrence risk. Efforts should be made in the Mexican public health system to secure basic and continuous access to BCT.
Citation Format: Mejía-Fernández L, Medina-Franco H, Armengol-Alonso A. Impact of public health insurance “Seguro Popular” on breast cancer recurrence at Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), Mexico City [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 P5-13-11.