bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P3-02-04: The contribution of the national health system to mammographic screening in Brazil
Authors: Freitas-Junior Ruffo , Rodrigues Danielle CN , Correa Rosangela S , Peixoto João-Emilio , Rahal Rosemar MS 
Published: May 2015

Abstract
INTRODUCTION: In Brazil, access to mammography is provided through the National Health System (SUS), the Supplemental Health System, or is paid for directly by the patient. SUS is the official government system and was established to conform to the constitutional requirement that health is a right of all Brazilian citizens and a duty of the state. In recent years SUS breast cancer control policies have advanced and government strategies for early detection have strengthened. However, evaluations are needed to monitor the effectiveness of these actions. OBJECTIVE: To describe the coverage of mammography in breast cancer screening conducted by the National Health System in Brazilian macro-regions and states in 2012. METHODS: An ecological study, where the estimate of coverage was the number of exams performed expressed as a percentage of the number of exams expected in the target population of women 50-69 years old. The exams performed refer to target population mammography production data from the Outpatient Information System (CIS) of DATASUS. To calculate the expected number of exams for this population, the biennial screening recommendations of the National Cancer Institute (NCI) and an estimate of the female population based on the census of the Brazilian Institute of Geography and Statistics (IBGE) were used. RESULTS: The coverage estimate for SUS-performed mammography in Brazil in 2012 was 26.6%. Stratified by macro region, the lowest coverage was in the northern region (12.1%) and highest in the South (34.6%).
National coverage of screening mammography in Brazil, performed by the National Health System (SUS), according to the geographical regions.Macro-regionsCoverageMinimumMaximump*North Region12.10.227.2Northeast Region23.910.337.20.001Southeast Region28.515.532.5South Region34.630.341.0Midwest Region14.810.319.7* Chi-square test
Units of the Federation an estimated coverage ranged from 0.2% to 41%, the lowest in the state of Amapa and the largest in Santa Catarina. 48% of states were in the range of 10.1% to 20% coverage. CONCLUSION: The results imply that the contribution of SUS to mammography screening in Brazil is higher in both macro-regions and states with higher income and better organised health system.
Citation Format: Ruffo Freitas-Junior, Danielle CN Rodrigues, Rosangela S Correa, João-Emilio Peixoto, Rosemar MS Rahal. The contribution of the national health system to mammographic screening in Brazil [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-02-04.
Abstract P3-04-14: Prognostic impact of Her2 and hormone receptor expression in inflammatory breast cancer: A SEER database analysis
Authors: Affan Anna Maria , Mohan Babu P , Iruku Kali Praveena , Ravakhah Keyvan 
Published: May 2015

Abstract
INTRODUCTION: Inflammatory breast cancer (IBC) is known to be one of the most aggressive forms of breast cancer. Patients with IBC generally present with early metastases and are frequently resistant to conventional chemotherapies. By using the SEER database, we explored the clinical relevance of Her2 and hormone receptor (HR) expression in IBC tumors and the possible impact it may have on management.
METHODS: Data for patients with IBC was extracted from the Surveillance, Epidemiology, and End Results (SEER 18) database from 2010 to 2011. A sub-analysis with the available receptor status data for the same period was analyzed using CanSurv survival software. The Actuarial method was used to construct survival curves according to the following receptor variables; Her2+/HR+, Her2+/HR-, Her2-/HR+, and triple negative IBC groups. Demographic data including race and age was also extracted.
RESULTS: Of 354 cases of IBC reported, 5% (n=18) of the tumors were Her2+/HR+, 7.9% (n=28) Her2+/HR-, 15.3% (n=54) Her2-/HR+, and 12.4% (n=44) triple negative. Highest 1 year survival rates were seen in those patients with Her2-/HR+ tumors at &gt;95% while Her2+/HR+ had the lowest 1 yr survival rates at 65%.
Caucasian patients above 30 years represented the highest racial group at approximately 70% (n=105). Analysis of this subgroup showed 38% (n=40) of these patients having HER2-/HR+. Despite more than 75% (n=33) of these patients presenting with advanced disease, the 1 year survival remained highest among all the receptor combinations analyzed. This observation held true across all racial groups even with those population numbers for IBC being less.
CONCLUSION: The Her2-/HR+ receptor combination group showed the greatest 1 year relative survival when compared to the other groups. These results suggest that HR expression in the absence of Her2 is associated with an increased survival. This can play in a role in the management of IBC by incorporating hormonal therapy into the treatment protocols for patients with IBC to possibly improve survival.
Citation Format: Anna Maria Affan, Babu P Mohan, Kali Praveena Iruku, Keyvan Ravakhah. Prognostic impact of Her2 and hormone receptor expression in inflammatory breast cancer: A SEER database analysis [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-04-14.
Abstract P3-05-10: Glucocorticoid and aldosterone mimic progestin-induction of a therapy-resistant cytokeratin-5 positive cell population in estrogen receptor-positive breast cancer through a Bcl6-dependent mechanism
Authors: Rui Hallgeir , Sato Takahiro , Peck Amy , Girondo Melanie A , Liu Chengbao , Kovatich Albert J , Hooke Jeffery A , Shriver Craig D , Mitchell Edith , Hyslop Terry , Goodman Chelain 
Published: May 2015

Abstract
Resistance to anti-estrogen therapy remains a significant problem in patients diagnosed with estrogen receptor-α (ERα) positive breast cancer. Recent progress has defined a "lumino-basal" subclass of ERα-positive breast cancer characterized by mosaic presence of a minor population of ERα-negative cells expressing the basal cytokeratin-5 (CK5). The CK5-positive cells are therapy-resistant and have increased tumorigenic potential. Initial studies have suggested that progestins but not other steroids expand this CK5+ cell population. Unexpectedly, we discovered that at least two 3-ketosteroids other than progestins, glucocorticoids and mineralocorticoids, are capable of inducing the CK5+/ERα- cell population. CK5+ cells induced by glucocorticoid or aldosterone showed increased clonogenicity in soft agar, expressed the stem cell marker CD44, showed loss of ERα and PR expression, and demonstrated therapy-resistance with reduced apoptosis in response to chemotherapy, and were further enriched following adjuvant antiestrogen or chemotherapies. Induction of CK5+ cells by 3-ketosteroids was consistently preceded by induction of Bcl6, a transcriptional repressor implicated in breast cancer progression. Suppression of Bcl6 by shRNA or the Bcl6 suppressor, prolactin, abolished 3-ketosteroid-induction of CK5+ cells. Prolactin also blocked 3-ketosteroid-induced colony formation in vitro and suppressed progestin-induction of the CK5+ cell population in T47D xenograft tumors in vivo. Survival analyses with recursive partitioning revealed that CK5 and Bcl6 transcripts or protein levels in ERα+ breast cancer identify patients at high or low risk for tumor in two independent cohorts. The observations provide a mechanism by which stress-related or pharmacologic elevation of glucocorticoids may adversely affect patients with ERα+/CK5+ breast cancer, and may justify further exploring of inhibitors to 3-ketosteroid receptors or Bcl6 for therapeutic benefit.
Citation Format: Hallgeir Rui, Takahiro Sato, Amy Peck, Melanie A Girondo, Chengbao Liu, Albert J Kovatich, Jeffery A Hooke, Craig D Shriver, Edith Mitchell, Terry Hyslop, Chelain Goodman. Glucocorticoid and aldosterone mimic progestin-induction of a therapy-resistant cytokeratin-5 positive cell population in estrogen receptor-positive breast cancer through a Bcl6-dependent mechanism [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-05-10.
Abstract P3-05-15: Divergent activation of AKT1 and AKT2 isoforms downstream of PI3K mutation impacts response of breast cancer cells to estradiol and PI3K inhibitors
Authors: Nakshatri Harikrishna , Goswami Chirayu , Badve Sunil , Magnani Luca , Lupien Mathieu , Bhat-Nakshatri Poornima 
Published: May 2015

Abstract
Background: PI3K mutations are observed in 30% of breast cancers, which are more common in estrogen receptor (ERα) positive breast cancers compared to ERα-negative breast cancers. AKT, a the major kinase downstream of PI3K, modulates ERα activity. It is unknown whether PI3K mutation leads to preferential activation of specific AKT isoform with ability to modulate ERα function.
Results: We report elevated AKT1 but not AKT2 mRNA in breast cancers with PI3K mutation. Breast epithelial cells with targeted substitution of PI3K with PI3K-E545K or PI3K-H1047R demonstrated elevated AKT1_pS473 compared to AKT2_pS474, distinct AKT substrate phosphorylation, and enhanced Estrogen Receptor (ERα) activity. AKT1 had a dominant role in ERα:estradiol (E2)-dependent gene expression and proliferation. We have identified an unique gene expression signature in ERα-positive breast cancers that is dependent on ERα, estradiol (E2), AKT1, and the pioneer factor FOXA1. Elevated expression of this signature in ERα-positive tumor was associated with better response to endocrine therapy and outcome. In addition, AKT1 determined the sensitivity to PI3α-specific inhibitor BYL719 and pan-PI3K inhibitor BKM120. In contrast, AKT2 controlled global gene expression and elevated levels of an AKT2-directed protein signature predicted poor outcome in breast cancer patients.
Conclusions: PI3K mutation favors AKT1 activation leading to imbalance in AKT isoform-specific kinome/proteome and an effect on specific signaling pathways, particularly ERα:E2 signaling network. Knowledge gained from this functional dissection of AKT isoform activity downstream of PI3K mutation can be exploited for therapeutic stratification, particularly for anti-estrogen and PI3K inhibitor-based therapies.
Citation Format: Harikrishna Nakshatri, Chirayu Goswami, Sunil Badve, Luca Magnani, Mathieu Lupien, Poornima Bhat-Nakshatri. Divergent activation of AKT1 and AKT2 isoforms downstream of PI3K mutation impacts response of breast cancer cells to estradiol and PI3K inhibitors [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-05-15.
Abstract P3-13-09: Personalized therapy in breast cancer: Brazilian experience
Authors: Moreira Raphael Brandao , Alessandretti Matheus Bongers , Buzaid Antonio Carlos , Cruz Marcelo Rocha 
Published: May 2015

Abstract
INTRODUCTION
Cancer biology is characterised by genomic alterations. There is an ongoing revolution in cancer research due to the emergence of novel technologies based on next generation sequencing (NGS).
OBJECTIVES
To identify abnormalities in individual patients with the aim of providing targeted therapy matched to individuals genomic alterations.
METHODS
From April 2013, to February 2014, we included patients who had metastatic breast cancer with lesion accessible for biopsy. The tumor tissue stored in paraffin was evaluated by the method of next-generation sequencing (NGS) where 236 cancer-related genes were sequenced.
ResultsPatientsTarget TherapyObjective ResponseMutations1EverolimusNOERBB2, PIK3CA2EverolimusYesPI3KCA, FGFR, AKT3EverolimusYesPI3KCA, FGFR4EverolimusYesAKT1, PI3KCA5EverolimusYesAKT16EverolimusYesAKT1, FGFR7EverolimusYesAKT1. FGFR8EverolimusNoERBB2, PI3KTable1
Mutations PrevalenceMutationPrevalenceTP5383,30%PIK3CA60,60%FGFR33%CCND125%PTEN25%BRCA216%AKT50%Table2
RESULTS
Fourteen patients were included and NGS was feasible. An actionable genomic alteration was identified in 12 (85,7%) patients, most frequently in TP53 (10 [83,3%], PIK3CA (8 [66,6%]), AKT (5 [50%]), FGFR1 (4 [33%]), CCND1 (3 [25%]), PTEN (3[25%]) and BRCA2 (2[16%]). Therapy could be personalized in 12 of 14 patients. Of the 8 patients who received targeted therapy, 5 presented objective response.
CONCLUSION
. NGS was able to find genomic alterations in the majority of breast cancer tissues;
. Most patients did not have "actionable" mutations for which a specific therapy could be offered;
. We are just at the dawn of exploring this strategy and NGS can effectively contribute for increasing the understanding of the disease.
REFERENCES
1. Jeffrey. Ross, Massimo Cristofanilli et al, JClin Oncol 3, 2013 (suppl; abster 1009).
Citation Format: Raphael Brandao Moreira, Matheus Bongers Alessandretti, Antonio Carlos Buzaid, Marcelo Rocha Cruz. Personalized therapy in breast cancer: Brazilian experience [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-13-09.
Abstract P4-06-03: Targeting the insulin receptor with a small peptide (S961) in cancer
Authors: LaPara Kelly , Yee Douglas 
Published: May 2015

Abstract
The insulin-like growth factor (IGF)/insulin receptors are members of the superfamily of growth factor receptor tyrosine kinases. The insulin and type I IGF-I receptors (IGF-1R) have very similar structure and share high homology (∼84%) in the kinase domain. Their dimeric structure allows for the formation of either holo or hybrid receptors. Thus, targeting of any individual receptor has been a challenge. We have previously shown that the insulin receptor is expressed in tamoxifen resistant breast cancer cell lines. Therefore, specific targeting might be a useful strategy to block this pathway. The antagonist S961 is a single chain peptide that binds insulin receptor and has been reported to have partial antagonist activity. The affinity of S961 for the insulin receptor is comparable to that of insulin and the selectivity of the insulin receptor versus IGF1 is higher than that of insulin itself (Sturis et al). To determine if S961 has activity in breast cancer cells, we tested its ability to disrupt insulin and IGF-I signaling and growth in a panel of cancer cell lines (MCF-7L, MCF-7L TamR, MDA-231, and HepG2 cells). MCF-7L cells express high levels of IGF1, while HepG2 express mostly insulin receptor. Pre-incubation with S961 significantly suppressed p-Akt and p-MAPK after insulin stimulation in the HepG2, but not in MCF-7L. In contrast, insulin receptor stimulation in MCF-7L TamR cells, which do not express IGF1R, was inhibited by S961. Even a 1000-fold increase in S961 was unable to suppress insulin receptor activation in cells expressing both insulin receptor and IGF1R. S961 inhibits insulin-stimulate cell cycle progression in MCF7L TamR cells. In these TamR cells, S961 also suppresses colony formation in anchorage independent growth assays. These data suggest S961 is an effective inhibitor of insulin receptor activation but only when little IGF1R is expressed. Thus, insulin receptor targeting might be useful in the management of endocrine resistant breast cancer.
Citation Format: Kelly LaPara, Douglas Yee. Targeting the insulin receptor with a small peptide (S961) in cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-06-03.
Abstract P4-11-32: Routine histopathological variables predict oncotype DX risk categories
Authors: Kawabata Hidetaka , Kinowaki Keiichi , Tamura Nobuko , Kobayashi Yoko , Kadowaki Masami , Miura Daishu , Takano Toshimi , Shimomura Akihiko , Iwatani Tsuguo , Kitawaki Yuko , Fujii Takeshi 
Published: May 2015

Abstract
Background: Oncotype DX(ODX) is a clinically validated, commercially available multi-gene assay that provides prognostic and predictive information in estrogen receptor(ER)-positive, Her2-negative breast cancer. Because health care system does not cover this expensive assay in many countries, physicians and researchers try to use routine histopathological variables predict ODX Recurrence Score (RS). Hyunseok Kim et.al presented at ASCO that Estimated Recurrence Score (ERS) model could identify those patients most likely to benefit from including ODX RS results in therapeutic decision-making (J Clin Oncol 32:5s, 2014 suppl; abstr 559).
Methods: We retrospectively reviewed histopathological slides between July 2007 and April 2014 from Toranomon Hospital patients (n=149) with early stage ER-positive, Her2-negative breast cancer, for whom ODX was ordered. We developed an original linear regression model using routine histopathological markers (Allred Score for progesterone receptor (PR), nuclear grade(NG), and Ki67) to calculate an Estimated Recurrence Score (ERS), and correlated it with the observed ODX RS assay result. ERS=20.46+0.298xKi67–1.48xPR+1.41xNG predicts the ODX RS with an R2 of 0.48. In order to internally validate this model in the Toranomon Hospital cohort in Japan, we adapted Hyunseok’s algorithm.
Results: 132 patients had an observed RS ≤ 25 (89%) and 17 patients had an observed RS above 25 (11%). When the ERS was &lt; 21 (n=124), we accurately classified 97% of them (120) who were found to have a low risk (observed RS ≤ 25). Similarly, 83% of those (5/6) with an ERS &gt; 30 fell into a high risk category with observed RS &gt; 25.
Table1 (TAILORx risk categories)Toranomon cohortODX ≤25ODX RS&gt;25TotalERS &lt; 211204124ERS(21-30)11819ERS(&gt; 30)156Total13217149
We also presented the comparison of ERS and observed RS based on original risk categories.
Table2 (Original risk categories )Toranomon cohortODX RS&lt;18ODX RS 18-30ODX RS&gt;30TotalERS(&lt;18)6633099ERS(18-30)1725244ERS(&gt;30)0156Total83597149
Conclusions: We developed an ERS model to find those patients most likely to benefit from ODX RS results in clinical practice setting. Although further external and prospective validation is mandatory, preliminary result supports the usefulness of this ERS model.
Citation Format: Hidetaka Kawabata, Keiichi Kinowaki, Nobuko Tamura, Yoko Kobayashi, Masami Kadowaki, Daishu Miura, Toshimi Takano, Akihiko Shimomura, Tsuguo Iwatani, Yuko Kitawaki, Takeshi Fujii. Routine histopathological variables predict oncotype DX risk categories [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-11-32.
Abstract P4-11-39: Epithelial-mesenchymal transition phenotype in triple negative breast cancer: ZEB1 as a potential biomarker for poor clinical outcome
Authors: Jang Min Hye , Kim Hyun Jeong , Kim Eun Joo , Lee Hee Jin , Park So Yeon 
Published: May 2015

Abstract
Background: Triple negative breast cancer (TNBC) is a heterogeneous group of disease. TNBC is closely related to epithelial-mesenchymal transition (EMT) and breast cancer stem cell (BCSC) phenotype. Recent studies have shown that TNBC can be classified into six subtypes including basal-like, mesenchymal–like and mesenchymal stem-like. However, clinical significance of EMT phenotype in TNBC is not clear.
Methods: We performed immunohistochemical analyses of EMT markers (expression of vimentin, smooth muscle actin, osteonectin and N-cadherin; loss of E-cadherin), BCSC markers (CD44+/CD24- and ALDH1) and EMT inducers (CD146 and ZEB1) in 173 TNBCs using tissue microarrays, and correlated their expressions with clinicopathologic features of the tumor.
Results: Expression of vimentin, CD44+/CD24- and CD146 was significantly higher in basal-like TNBCs (TNBC with expression of CK5/6 and/or EGFR) than in non-basal-like TNBCs. Expression of EMT markers was commonly correlated with high histologic grade, CD44+/CD24- phenotype and metaplastic carcinoma. CD146 expression was related to the expression of EMT markers and CD44+/CD24- phenotype. ZEB1 expression showed an association with the expression of smooth muscle actin, but not with BCSC markers. And it was closely correlated with high histologic grade and metaplastic carcinoma. In survival analyses, although expression of EMT and BCSC makers was not associated with the survival of the patients, ZEB1 expression was found to be an independent prognostic factor for poor disease-free survival of the patients.
Conclusion: EMT phenotype can be a signature of certain subgroup of TNBC. Especially, ZEB1 expression can be used as a potential biomarker to define a subgroup of TNBC associated with poor clinical outcome.
Citation Format: Min Hye Jang, Hyun Jeong Kim, Eun Joo Kim, Hee Jin Lee, So Yeon Park. Epithelial-mesenchymal transition phenotype in triple negative breast cancer: ZEB1 as a potential biomarker for poor clinical outcome [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-11-39.