bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P5-15-06: 10-year follow-up of adjuvant ovarian suppression in high risk premenopausal breast cancer
Authors: Recchia F , Candeloro G , Rosselli M , Bratta M , Rea S 
Published: May 2016

Abstract
Background: A large randomized study has shown the value of temporary ovarian suppression during the administration of chemotherapy in the treatment of high risk estrogen receptor positive (ER+) breast cancer (BC) (Pagani et al. N Engl J Med 2014). In another study ovarian suppression added to chemotherapy appeared to protect ovarian function (Moore et al. N Engl J Med 2014) and improve the expected outcome of estrogen receptor negative (ER-) BC. Nevertheless, both these studies have a median follow-up time limited to 68 months and 49 months, respectively. Here we present the data of a large non randomized phase II study of adjuvant ovarian suppression in ER+ and ER- breast cancer with a median follow-up of 120 months (range 90-220 months). The primary end point was the ovarian function preservation rate, secondary end points were disease-free survival (DFS) and overall survival (OS). Methods: Between 06-1997 and 06-2007, 200 premenopausal, high risk early BC patients entered the study. All patients received the LH-RH analogue before starting chemotherapy. Breast conserving and radical surgery were performed in 74% and 26% of patients, respectively. Systemic therapy was tailored to the biological characteristics of each patient, and followed by radiation therapy and hormonal therapy in ER+ tumors. Results: The median patient's age was 43 years (range 26-45). The mean number of positive axillary nodes was 3.2 (range 1-25). Seventy-one % of patients were ER+ and/or progesterone receptor positive (PGR+), 29% were ER - and PGR-. The median KI-67 was 30% (range 15% -100%). Twenty-one % of patients were c-ErbB-2 positive. After a median follow up of 120 months (range 90-220), normal menses returned in 90% of patients younger than 40 years and in 56% of patients older than 40 years. The 10 and 15-year DFS rate were 85.5% and 71%, respectively, while the 10 and 15-year OS rate were 91%, and 71%, respectively. The standard pattern of toxicity of chemotherapy was observed. Hot flashes and G1 osteopenia occurring after LH-RH analogue administration were temporary and subsided after the cessation of therapy. Conclusions: LH-RH administration, concurrent with chemotherapy is tolerable and effective. Five full term pregnancies were documented. A favourable impact on the expected DFS and OS was observed. ER- patients had late new primaries, but no recurrence after 5 years, while ER+ patients had disease recurrence even after 13 years.
Citation Format: Recchia F, Candeloro G, Rosselli M, Bratta M, Rea S. 10-year follow-up of adjuvant ovarian suppression in high risk premenopausal breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-15-06.
Abstract P5-17-04: Breast conserving surgery alone for ductal carcinoma in situ: Factors associated with increased risk of local recurrence
Authors: Recht A , Mele A , Mehta P , Brook A , Slanetz P , Sharma R 
Published: May 2016

Abstract
Background: There is ongoing debate regarding the added benefit of radiation therapy (RT) for patients with ductal carcinoma in situ (DCIS) believed to be at low risk for recurrence after wide local excision (WLE) alone since RT is costly and can cause significant adverse effects. In this retrospective study we aimed to identify clinicopathological characteristics associated with an increased risk for ipsilateral local recurrence (LR) in patients not undergoing RT.
Methods: All patients with DCIS treated with WLE alone at the Beth Israel Deaconess Medical Center, Boston between 2000 and 2010 were identified. We collected data on demographics, parity, personal or family history of breast cancer, exogenous hormone use, tobacco use, comorbidities, genetic mutation carrier status, imaging interval, and tumor-specific characteristics (size, margins, grade, architectural subtype, presence of necrosis, estrogen receptor status). We analyzed their effects on the risk of LR.
Results: The study cohort included 281 eligible patients (mean age at diagnosis 59 years, range 33-90). Median follow-up time was 8 years (range 0.11-16.59 years); 59 patients were excluded because they were not followed in our institution after undergoing WLE. LR occurred in 19 of 222 patients (9%), with a recurrence rate of 11.3 per 1000 person-years. The median time from excision to LR was 4.2 years (range, 0.8-11.7). The risk of recurrence was lower for the 64 patients with nuclear grade (NG) I tumors than for the 110 patients with a NG II or 20 patients NG III tumors (3%, 9%, and 20%, respectively, p for trend = 0.01). The mean margin width was 1.8 mm in patients experiencing LR, versus 2.5 mm in patients without LR (p=0.4). Patients who had used hormone replacement therapy or oral contraceptives (n=61) or patients with a history of tobacco use (n=41) had higher rates of LR than those who did not, although these did not reach statistical significance (15% versus 6%, p=0.06; and 17% versus 7%, p=0.07 respectively). There was no significant correlation between the use of tamoxifen or aromatase inhibitors and the risk of LR.
Conclusions: Our data indicate that higher nuclear grade, narrower margin width, use of exogenous hormones, and smoking history may be associated with an increased risk of LR. The evaluation of these factors may be helpful when considering whether to use adjuvant RT or not for patients with DCIS.
Citation Format: Recht A, Mele A, Mehta P, Brook A, Slanetz P, Sharma R. Breast conserving surgery alone for ductal carcinoma in situ: Factors associated with increased risk of local recurrence. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-17-04.
Abstract P6-02-04: Screen detected and interval cancers; genomic analysis points to different molecular etiology?
Authors: Gorringe KL , Hunter SM , Byrne D , Devereux L , Rowley SM , Elder K , Huynh R , Pridmore V , Hopper J , Kavanagh A , Mitchell G , Mann BG , Fox SB , Campbell IG 
Published: May 2016

Abstract
Breast cancers diagnosed after a negative mammogram but prior to the next screening episode are termed "interval cancers" and comprise as many as 25% of all cancers detected in women attending population-based screening programs. The high interval cancer rate is a major problem affecting the effectiveness of mammographic screening. It is unclear whether interval cancers represent a distinct biological entity compared to screen-detected cancers or whether their designation is simply an arbitrary outcome of screening timing. Using an Australian prospective population-based cohort of over 53,000 women (lifepool), 537 cases of breast carcinoma (in situ and invasive breast cancer) were identified, of which 293 had known screening status at time of diagnosis. Pathology reports, mammographic density data, germline DNA and tumor tissue were available for analysis.
Screen and interval cases showed no significant differences in mammographic density or PR status but there were trends towards higher proportions of ER negative and HER2 positive cases in interval cancers (p&lt;0.1). Interval cancers also had a younger age at diagnosis (p&lt;0.01), increased tumor size (p&lt;0.01) and higher grade (p&lt;0.01). Copy number analysis was performed on a subset of invasive breast cancer cases using OncoScan MIP arrays. No difference in the overall number of copy number aberrations or fraction of the genome altered were observed, however specific differences were noted between interval and screen detected cases. These included copy number changes on chromosomes 8 and 11. Analysis of germline DNA was performed using a panel sequencing approach of known breast cancer genes as well as lower-penetrance SNPs. Pathogenic mutations in BRCA1, BRCA2, TP53 and PALB2 were identified in 1/13 interval cases (in BRCA2), 1/66 screen-detected cases and 8/74 cases with currently unknown screen/interval status. Screen detected cancers may thus have a reduced contribution from high-penetrance predisposing variants.
Citation Format: Gorringe KL, Hunter SM, Byrne D, Devereux L, Rowley SM, Elder K, Huynh R, Pridmore V, Hopper J, Kavanagh A, Mitchell G, Mann BG, Fox SB, Campbell IG. Screen detected and interval cancers; genomic analysis points to different molecular etiology?. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-02-04.
Abstract P6-03-03: The Q-CROC-3 project reveals novel genomic alterations in triple negative breast cancers in residual tumors after neoadjuvant chemotherapy
Authors: Basik M , Aguilar-Mahecha A , Lafleur J , Bareke E , Przybytkowski E , Alirezaie N , Discepola F , Légaré S , Kovacina B , Lan C , Mihalcioiu CL , Robidoux A , Marcus E , Roy J-A , Pelmus M , Aleynikova O , Nabavi S , Tonellato P , Majewski J 
Published: May 2016

Abstract
The prognosis of triple negative breast cancer that shows resistance and/or incomplete response to cytotoxic chemotherapy is poor. In order to understand the mechanisms of resistance to chemotherapy and the genomic evolution of TNBCs treated with chemotherapy, an international multi-center biopsy-driven clinical trial was created for the collection and study of drug-resistant primary and metastatic freshly frozen tumors (Q-CROC-03: NCT01276899). We consented 60 patients with operable TNBC undergoing neoadjuvant Anthracycline/Taxane-based chemotherapy for pre and post-treatment biopsies as well as collection of residual tumor at the time of surgery and serial blood sampling. In 12-15 patients, adequate residual tumor material was available for genomic studies, which included whole exome sequencing, array CGH, gene expression microarray profiling and RNAseq of paired tumors. Whole exome sequencing revealed clonal shifts as well as the relatively infrequent appearance of novel mutations in individual tumors, without any recurrently detected variants. Array CGH revealed a remarkable stability in the number of DNA copy number alterations with a few functional alterations enriched for in the residual tumor, including an amplicon involving the NFIB gene. Finally, gene expression profiling showed shifts towards the immune-modulatory and basal TNBC subtypes after chemotherapy as well as an increase in the expression of several targetable genes, including DUSP1, a dual specificity phosphatase. In the 4 cases of primary and matching metastatic tumors, the post-NAC residual tumor had acquired changes many of which persisted in the metastatic sites, indicating that the analysis of the residual tumors can provide a partial picture of genomic changes present in metastases but not in the primary tumor. In summary, the genomic characterization of residual post-NAC tumor tissue provides important information for the development of novel therapeutic strategies for drug-resistant TNBCs as well as a portrait of genomic evolution of TNBCs subjected to chemotherapy.
Citation Format: Basik M, Aguilar-Mahecha A, Lafleur J, Bareke E, Przybytkowski E, Alirezaie N, Discepola F, Légaré S, Kovacina B, Lan C, Mihalcioiu CL, Robidoux A, Marcus E, Roy J-A, Pelmus M, Aleynikova O, Nabavi S, Tonellato P, Majewski J. The Q-CROC-3 project reveals novel genomic alterations in triple negative breast cancers in residual tumors after neoadjuvant chemotherapy. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-03-03.
Abstract P6-03-04: Amplification of the WHSC1L1 oncogene regulates expression and estrogen-independent activation of ERα in SUM-44 breast cancer cells and is associated with ERα over expression in breast cancer
Authors: Ethier SP , Irish J , Mills J , Ivey B , Hardiam G , Wilson R , Domkowski A , Guest S 
Published: May 2016

Abstract
The 8p11-p12 amplicon occurs in approximately 15% of breast cancers and occurs almost exclusively in aggressive luminal B type tumors. Our lab and other labs have identified the WHSC1L1 oncogene as a driving oncogene from this region with potent transforming activity. In the present studies, we found that over expression of WHSC1L1 is linked to over expression of the ESR1 and ERα protein in the SUM-44 breast cancer cell line, and also in primary human breast cancer specimens. Knockdown of WHSC1L1, and particularly the short isoform of WHSC1L1, had a dramatic effect on ESR1 mRNA and ERα protein levels. SUM-44 cells do not require exogenous estrogen for continuous growth in vitro; however these cells are dependent on ERα expression as determined from ESR1 knockdown experiments, and potent growth inhibition and ERα degradation following exposure to the selective estrogen receptor degrader (SERD) fulvestrant. ChIP-Seq experiments utilizing ERα antibodies demonstrated potent ERα binding to chromatin in SUM-44 cells under estrogen-free conditions. ERα bound to ERE and FOXA1 binding motifs under estrogen-free conditions and regulated expression of number of well-known estrogen responsive genes. Short term treatment with estradiol enhanced binding of ERα to chromatin and influenced expression of many of the same genes expressed and to which ERα was bound under estrogen-free conditions. Finally, knockdown of WHSC1L1 in SUM-44 cells resulted in loss of ERα binding to chromatin under estrogen-free conditions; however treatment estradiol restored ERα binding to chromatin at key estrogen-response elements and genes. These results indicate the SUM-44 cells are a good model for a subset of luminal B breast cancers that have the 8p11-p12 amplicon, over express the WHSC1L1 oncogene, and over express ERα that is independent of estrogen for binding to chromatin and regulation of gene expression. Dependence on ERα activity for growth and survival of breast cancer cells but independence of estradiol is a major cause of breast cancer mortality as such cells become non-responsive to current hormonally based therapies.
Citation Format: Ethier SP, Irish J, Mills J, Ivey B, Hardiam G, Wilson R, Domkowski A, Guest S. Amplification of the WHSC1L1 oncogene regulates expression and estrogen-independent activation of ERα in SUM-44 breast cancer cells and is associated with ERα over expression in breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-03-04.
Abstract P6-04-05: Genotype-phenotype classification of triple negative breast cancers (TNBC) in women of African descent using the PAM50 NanoString platform and genomic data
Authors: Olayiwola OA , Ogundiran TO , Hardeman A , Yoshimatsu TF , Clayton W , Adeoye A , Ademola A , Ajani MA , Khramtsova G , Grushko TA , Huo D , Zheng Y , Parker J , Perou C , Olopade OI 
Published: May 2016

Abstract
Introduction: TNBC has the highest mortality rate amongst all other breast cancer types due to its complex tumor heterogeneity and lack of well-defined molecular targets. It is known that women of African descent are two to three times more likely to develop TNBC compared to women of European ancestry, yet wide-scale genomic studies of African and African American breast tumors are limited. To elucidate genotypes and molecular subtypes associated with the most aggressive forms of breast cancer, we used the PAM50 NanoString platform to reclassify Nigerian (NG), African American (AA) and Caucasian (CA) tumors previously annotated by Immunohistochemistry (IHC), and correlated our findings to their germline genotype data obtained using high-throughput technologies.
Methods: RNAs were isolated from formalin-fixed, paraffin embedded (FFPE) tumor tissues using the High Pure Paraffin Kit (Roche) following manufacturer's protocol, and assayed on NanoString nCounter Analysis System using a custom Nano110 (PAM50 + claudin-low & VEGF signatures) probe set. Intrinsic subtyping and gene-expression data were evaluated using R statistical software. All study samples were previously annotated and subtyped by the ER/PR/HER2 IHC classifier. Genotypes were obtained from next generation sequencing or Illumina Human2.5M BeadChip platform using germline DNA from more than 2000 breast cancer cases and 2000 controls were studied.
Results: To date, Intrinsic molecular subtyping by Nano110 has been completed on 69 NG, 81 AA and 74 CA tumors. Concordance between IHC and PAM50 was 59%, which is adequate and comparable to previous studies. Basal-like subtype was overrepresented and accounted for nearly 30% of NG and AA cases, compared to 17% in CA cases. HER2-enriched subtype was overrepresented only in NG cases (9%). The proportion with Luminal A tumors were 44% NG, 56% AA and 68% CA, respectively.
Conclusions: PAM50 NanoString assay is reliable and high-throughput for molecular subtyping breast cancer using RNA extracted from FFPE tumors. Ongoing work will correlate PAM50 intrinsic subtypes to genotype data.
Citation Format: Olayiwola OA, Ogundiran TO, Hardeman A, Yoshimatsu TF, Clayton W, Adeoye A, Ademola A, Ajani MA, Khramtsova G, Grushko TA, Huo D, Zheng Y, Parker J, Perou C, Olopade OI. Genotype-phenotype classification of triple negative breast cancers (TNBC) in women of African descent using the PAM50 NanoString platform and genomic data. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-04-05.
Abstract P6-08-05: Protein tyrosine kinase activity and miRNA expression profiling reveals differences according to progesterone-receptor-status in HER-2 negative breast cancer
Authors: Tahiri A , Satheesh SV , de Wijn R , Lders T , Aure MR , Quigley DA , Bukholm IR , Hurtado A , Kristensen VN , Geisler J 
Published: May 2016

Abstract
Background: Kinases are considered as promising source of biomarkers for diagnostic, prognostic and therapeutic purposes in cancer patients. We assessed tyrosine kinase activity in 39 primary breast cancer samples that were all hormone receptor positive (ER+ and/or PR+) with differential HER-2 status, using microarray technology. Methods: Pamchip® peptide microarrays were used to measure the activity of protein tyrosine kinases in 32 breast cancer samples. The breast cancer cell lines MCF-7, BT474 and ZR75-1, was studied for kinase activity, both untreated and treated with estradiol. Results: Results showed differences in phosphorylation amongst breast cancer samples. A total of 37 peptide kinases were highly phosphorylated in a group of breast cancer samples representing 33 protein tyrosine kinases involved in cancer pathways and immunological responses. In vitro studies with breast cancer cell lines exhibited the same phosphorylation profiles, but increased phosphorylation was only observed in one cell line, ZR75-1. Eliminating HER-2 positive samples, we obtained differences in phosphorylation profiles based on PR-status only. Samples lacking PR-expression exhibited higher kinase activity of downstream kinases compared to PR-positive samples. Similar results were obtained with miRNA expression profiles of 31 breast cancer samples. Five miRNAs were identified to be significantly differentially expressed (p &lt; 0.05) between PR-negative and PR-positive samples. This effect was even stronger when eliminating HER-2 positive samples, with 13 miRNAs exhibiting significant differential expression based on PR-status. Conclusion: Although our data are based on a small dataset, the lack of PR expression seems to have a profound effect on tyrosine kinase activity and miRNA expression in HER-2 negative breast cancers without any effect on gene expression. This indicates that regulatory and functional molecules might exhibit phenotypical features of cancer that cannot be explained by gene expression alone.
Citation Format: Tahiri A, Satheesh SV, de Wijn R, Lders T, Aure MR, Quigley DA, Bukholm IR, Hurtado A, Kristensen VN, Geisler J. Protein tyrosine kinase activity and miRNA expression profiling reveals differences according to progesterone-receptor-status in HER-2 negative breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-08-05.
Abstract P6-09-03: Time-dependent nomogram for risk of locoregional recurrence in early breast cancer patients: 10 year extension
Authors: Witteveen A , Vliegen IMH , Sonke GS , Klaase JM , IJzerman MJ , Siesling S 
Published: May 2016

Abstract
Background
The objective of this study was to extent the recently developed and validated time-dependent logistic regression model and web-based nomogram. This nomogram is suitable for the annual long term risk prediction of locoregional recurrence (LRR) in individual breast cancer patients and clinical decision support with regard to the follow-up.
Methods
Women first diagnosed with early breast cancer between 2003-2006 in all Dutch hospitals were selected from the Netherlands Cancer Registry with five year of recurrence follow-up (n=37,230). Of the year 2003 follow-up was retrieved for ten years. In the first five years following primary breast cancer treatment 3.7% of the selected patients developed a LRR as a first event, in ten years 6.2%. Risk factors were determined using logistic regression and the risks were calculated per year, conditional on not being diagnosed with recurrence in the previous year. Discrimination and calibration were assessed. Bootstrapping was used for internal validation. Data on primary tumors diagnosed between 2007-2008 in 43 Dutch hospitals was used for external validation of the performance of the nomogram (n=12,308).
Results
The final model included the variables grade, size, multifocality, and nodal involvement of the primary tumor, and whether patients were treated with radio-, chemo- or hormone therapy. Model predictions were well calibrated. Estimates in the validation cohort did not differ significantly from the index cohort. The results were incorporated in a web-based nomogram. In 0.7% of the patients, the risk of LRR between year 5-10 was higher than the average risk of all patients in the first five years. All of these patients were aged below 50, had a tumour size larger than 2 cm, non-negative hormone status, received radiotherapy, but no hormone therapy and 19% developed a recurrence during ten years.
Conclusion/discussion
This validated and time-dependent nomogram for the prediction of annual LRR risks over ten years is simple to use and shows a good predictive ability in the Dutch population. It can be used as an instrument to identify patients with a low or high risk of LRR who might benefit from a less or more intensive and longer follow-up after breast cancer and to aid clinical decision-making for personalized follow-up.
Citation Format: Witteveen A, Vliegen IMH, Sonke GS, Klaase JM, IJzerman MJ, Siesling S. Time-dependent nomogram for risk of locoregional recurrence in early breast cancer patients: 10 year extension. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-09-03.