Sudeep Gupta, R. Chaubal, N. Gardi, Sunil Pachakar, Dimple R. Bhatia, P. Gera, N. Nair, S. Joshi, V. Parmar, P. Thakkar, G. Chitkara, Rasika Kadam, S. Gujarathi, H. Oza, R. Hawaldar, V. Vanmali, K. Buetow, A. Dutt, R. Badwe
{"title":"Abstract P3-05-01: Molecular effects of surgical resection on primary breast tumor","authors":"Sudeep Gupta, R. Chaubal, N. Gardi, Sunil Pachakar, Dimple R. Bhatia, P. Gera, N. Nair, S. Joshi, V. Parmar, P. Thakkar, G. Chitkara, Rasika Kadam, S. Gujarathi, H. Oza, R. Hawaldar, V. Vanmali, K. Buetow, A. Dutt, R. Badwe","doi":"10.1158/1538-7445.SABCS19-P3-05-01","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS19-P3-05-01","url":null,"abstract":"Rationale: Surgery results in rapid and progressively severe exposure of tumor tissue to hypoxia, up to the point of complete removal, but its effect on tumor gene expression is not well characterized. We document the molecular effects of surgery on primary breast cancer tumor with a serial tissue sampling strategy, including an intra-operative sample. Methods: We included treatment naive, non-metastatic breast cancer patients and sampled tumor and tumour adjacent normal tissue during surgery at three time points: beginning of surgery (Sample A), after half the tumor circumference had been devascularized (Sample B) and from completely resected tumor (Sample C). Patients were divided into two groups: discovery and validation. Tumor or adjacent normal samples from the discovery group underwent whole transcriptome paired-end sequencing (RNA-Seq) generating at least 50 million reads using next generation sequencing. Findings from discovery group were evaluated in a validation group using qRT-PCR and Nanostring nCounter gene expression profiling. Results: 81 breast cancer patients were eligible for this study of whom 46 with at least 1 quality passed sample at time-point A, B or C comprised the discovery group whose samples underwent RNA-seq. Validation group comprised two subsets: 35 independent patients (8 patients’ samples qRT-PCR, data included here; 27 patients’ samples nCounter gene expression, data will be presented) and 17 patients from discovery group whose samples also underwent nCounter gene expression profiling (data will be presented). Individual patient based analyses for A vs B vs C in discovery group revealed 249 significantly de-regulated genes in at least 20% of patients, in at least one comparison (AvB or BvC or AvC). Genes involved in stress response (FOSB, FOS, JUN, JUNB, DUSP1, CYR61, EGR1-3, ATF3, RGS1, RGS2), inflammation (IL20, IL8, SOCS3, GABRP, PIGR, NR4A1-2, CCL2- 3, CCL21, CCL14, CCL18-19, CXCL2, CXCL9-10, CXCL14), invasion & migration (PTGS2, MMP9-13), lipid metabolism (CD36, LIPE, TAT, FABP4, PLIN1, PLIN4, LPL, LEP), epithelial markers (KRT5, KRT7, KRT14-17, KRT23, KRT6A-6B) and cellular differentiation(SOX10, LRP2, S100A2, S100A7-A9, S100B, S100P) were significantly deregulated at time-point B versus A and many of these genes were also significantly deregulated in C versus A comparison, suggesting sustained deregulation through surgical resection. Replicative analysis involving comparison of tumors grouped by time points (A vs B vs C) identified 192 genes uniquely de-regulated in any one of the 3 comparisons, of which 42 overlapped with patient-wise analysis. These 42 genes included all the AP-1 transcription factor network signaling genes, epithelial markers (KRT14, KRT6A), inflammation related genes (SOCS3, PIGR, GABRP, NR4A1, NR4A2), lipid metabolism related genes (PLIN1) and cellular differentiation & cell fate related genes (SOX10, LRP2). Pathway analyses will be presented. qRT-PCR on paired samples in 8 independen","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79740910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Steenhoven, A. Kuijer, A. Leeuwen, J. Gorp, P. Diest, T. Dalen
{"title":"Abstract P5-02-11: Assessment of tumor proliferation by mitotic activity index, phosphohistone H3 and Ki67 in early stage ER+/Her2- breast cancer","authors":"J. Steenhoven, A. Kuijer, A. Leeuwen, J. Gorp, P. Diest, T. Dalen","doi":"10.1158/1538-7445.sabcs19-p5-02-11","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs19-p5-02-11","url":null,"abstract":"Introduction: Determining expression of tumor proliferation by mitotic index or Ki67 expression is one of the strongest prognostic factors in breast cancer, but its reproducibility is not optimal. Recently, phosphohistone H3 (PHH3) was proposed as a novel marker specific for mitosis. For the present study, we hypothesized that counting PHH3 positive cells would be more reproducible than mitoses counting in HE 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-02-11.","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85956424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
V. Panuganty, Denise Keller, W. Teft, J. Lenehan, K. Potvin, J. Younus, T. Vandenberg, D. Logan, K. Hahn, M. Brackstone, P. Blanchette, F. Perera, Yun-Hee Choi, R. Kim
{"title":"Abstract P5-12-05: Clinical outcomes in early breast cancer patients on adjuvant tamoxifen: Impact of CYP2D6 genotype and observed endoxifen concentrations","authors":"V. Panuganty, Denise Keller, W. Teft, J. Lenehan, K. Potvin, J. Younus, T. Vandenberg, D. Logan, K. Hahn, M. Brackstone, P. Blanchette, F. Perera, Yun-Hee Choi, R. Kim","doi":"10.1158/1538-7445.sabcs19-p5-12-05","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs19-p5-12-05","url":null,"abstract":"Background: Tamoxifen is widely used in patients with hormone sensitive breast cancer in the adjuvant setting to decrease risk of recurrence and metastasis. 5-10 years of tamoxifen has demonstrated a near 50% reduction in recurrence risk. Despite marked interpatient variation in the metabolism of tamoxifen to its active metabolite endoxifen, all patients are prescribed 20 mg daily dose of tamoxifen. Current evidence suggests that patients are at risk for suboptimal benefit if measured endoxifen concentration is below 5.9 ng/ml (~15nM). However, there have been conflicting data on the clinical utility of CYP2D6 genotype testing, and measuring endoxifen plasma concentration as a predictor of breast cancer recurrence. The goal of this prospective study was to determine the impact of endoxifen levels and CYP2D6 genetic variations to clinical outcome among patients with early breast cancer. Methods: Since 2010, as part of Personalized Medicine Program in Oncology, our team has been prospectively enrolling patients on tamoxifen therapy. To date 950 patients have been enrolled and preliminary analysis has been completed in 429. After initial CYP2D6 genotype testing, plasma concentration of tamoxifen and its metabolites were quantified using liquid chromatography-tandem mass spectrometry during each clinic visit. Baseline characteristic are outlined in table 1. Primary outcome assessed was invasive disease-free survival (IDFS) defined as time since start of tamoxifen therapy till an event of interest such as loco-regional recurrence, distant metastasis, new contralateral primary breast cancer, death due to breast cancer and other causes. Patients were censored at their last encounter at our institution (London Health Sciences Centre). Results: IDFS data for 426 patients were obtained. Outcome was stratified by CYP2D6 phenotypes (ultra-rapid, extensive, intermediate and poor metabolizers) and endoxifen levels (>5.9ng/ml or vs Conclusion: Preliminary finding suggests endoxifen concentration, but not CYP2D6 phenotype, may be a predictor of risk for suboptimal benefit during tamoxifen therapy. Detailed statistical analysis is planned for the full cohort, including adjustment for covariates including tumor stage, menopausal status, drug interactions, and use of aromatase inhibitors. To our knowledge, this is the first study of its type to prospectively collect multiple plasma samples for tamoxifen and endoxifen level in real-world patients during tamoxifen therapy, with sufficient sample size and follow-up period for primary clinical outcome. Citation Format: Veera Durga Sravanthi Panuganty, Denise Keller, Wendy A Teft, John Gordon Lenehan, Kylea Raijann Potvin, Jawaid Younus, Theodorus Anthony Vandenberg, Diane Mary Logan, Karin Hahn, Muriel Brackstone, Phillip Stanley Blanchette, Francisco Perera, Yun-Hee Choi, Richard Brian Kim. Clinical outcomes in early breast cancer patients on adjuvant tamoxifen: Impact of CYP2D6 genotype and observed endoxifen concent","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75862221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Koumarianou, P. Makrantonakis, F. Zagouri, C. Papadimitriou, A. Christopoulou, E. Samantas, C. Christodoulou, A. Psyrri, D. Bafaloukos, G. Aravantinos, P. Papakotoulas, S. Baka, C. Andreadis, A. Alexopoulos, I. Bombolaki, K. Kampoli, S. Liori, K. Karvounis, A. Ardavanis
{"title":"Abstract P2-15-07: Real-world multicenter, prospective study of the effects ofnab-paclitaxel on clinical outcomes and quality of life of patients with metastatic breast cancer in Greece. The ‘ABReast’ study","authors":"A. Koumarianou, P. Makrantonakis, F. Zagouri, C. Papadimitriou, A. Christopoulou, E. Samantas, C. Christodoulou, A. Psyrri, D. Bafaloukos, G. Aravantinos, P. Papakotoulas, S. Baka, C. Andreadis, A. Alexopoulos, I. Bombolaki, K. Kampoli, S. Liori, K. Karvounis, A. Ardavanis","doi":"10.1158/1538-7445.sabcs19-p2-15-07","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs19-p2-15-07","url":null,"abstract":"Introduction: Nanoparticle albumin-bound (nab)-paclitaxel (nab-P) is approved for the treatment of patients with metastatic breast cancer (MBC) who have failed first-line treatment for metastatic disease and for whom standard, anthracycline containing therapy is not indicated. Real-world evidence on the effectiveness of nab-P is sparse. From this perspective, this non-interventional study was designed to assess the impact of nab-P on the clinical outcomes and the quality of life of patients with MBC in the routine care of Greece. Materials and methods: This multicenter prospective study enrolled consented females with MBC initiated (≤7 days prior to enrollment) on nab-P according to physicians decision. Clinicopathologic parameters and patient-reported outcomes [Functional Assessment of Cancer Therapy-Breast (FACT-B)] were collected at approximately 9-week intervals during the first 12 months of study participation and approximately every 18 weeks thereafter, until the end of the study observation period (maximum 30 months). Results: Between April 2016 and October 2017, 150 eligible patients (99.3% Caucasian) were enrolled in the study in 16 oncology centers. The patients’ median age was 64.5 years (range: 30.7-84.0) and ECOG performance status was 0 in 66.4% and 1 in 26.2%. 45.3% of patients had ≥1 comorbidity (21.3% cardiovascular diseases). The median time elapsed since MBC diagnosis was 22.4 months, while 36.0% of patients were de novo metastatic. The distribution of hormone receptor (HR)/human epidermal growth factor receptor 2 (HER2) status was 74.6% HR+/HER2-, 11.9% HR-/HER2-, 11.2% HR+/HER2+, and 2.2% HR-/HER2+. Most commonly occurring metastatic sites were the bones (55.3%), lung (50.0%), and liver (40.0%). Prior taxane-based therapy was annotated in 40.0% of patients. Of the patients, 11.3% received nab-P as first, 36.0% as second, 23.3% as third, and 29.3% as fourth or further treatment line. A median of 6 cycles (range: 1-33) was administered; 42.7% of the patients completed >6 and 22.0% >8 cycles. Dose reductions were required for 26.0% of the patients, mainly due to toxicity. The objective response rate was 26.7% and the clinical benefit rate was 44.0%. After a median follow-up of 19.3 months, 92 patients had progressed and 57 had died (14 without progression). The median progression-free survival (PFS) was 6.2 months [95% confidence interval (CI): 5.2-7.3]. The 6- and 12-month PFS rates were 50.6% and 30.5%, respectively. The median overall survival was 21.1 months (95% CI: 17.2-not estimable). Liver [hazard ratio (HR): 1.81; 95% CI: 1.24-2.66] and lung (HR: 1.53; 95% CI: 1.04-2.25) metastases were associated with a higher risk of progression or death. No statistically significant change in the patients’ baseline FACT-B total score (median: 93.0) was observed. The serious and non-serious adverse event (AE) incidence rates were 12.7% and 48.0%, respectively with a total of 37 grade ≥3 AEs (not including disease progression) reported","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77937951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H. McArthur, S. Shiao, S. Karlan, F. Amersi, B. Arnold, R. Basho, M. Burnison, A. Chung, C. Chung, C. Dang, A. Giuliano, Negin Habibi Khameneh, S. Knott, Cynthia Martin, P. McAndrew, M. Mita, D. Park, C. Abaya, A. Ho
{"title":"Abstract P3-09-09: Pre-operative pembrolizumab (pembro) with radiation therapy (RT) in patients with operable triple-negative breast cancer (TNBC)","authors":"H. McArthur, S. Shiao, S. Karlan, F. Amersi, B. Arnold, R. Basho, M. Burnison, A. Chung, C. Chung, C. Dang, A. Giuliano, Negin Habibi Khameneh, S. Knott, Cynthia Martin, P. McAndrew, M. Mita, D. Park, C. Abaya, A. Ho","doi":"10.1158/1538-7445.sabcs19-p3-09-09","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs19-p3-09-09","url":null,"abstract":"","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86899830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Peréz-García, A. Llombart-Cussac, E. Holgado, G. Curigliano, E. Miranda, J. L. Alonso-Romero, B. Bermejo, L. Calvo, V. Carañana, Susana de la Cruz Sánchez, M. Cortés, R. M. Vázquez, A. Prat, M. R. Borrego, M. Sampayo, M. Seguí, J. Soberino, A. Malfettone, P. Schmid, J. Cortés
{"title":"Abstract P3-09-03: A phase II study of pembrolizumab and eribulin in patients with HR-positive/HER2-negative metastatic breast cancer previously treated with anthracyclines and taxanes (KELLY study)","authors":"J. Peréz-García, A. Llombart-Cussac, E. Holgado, G. Curigliano, E. Miranda, J. L. Alonso-Romero, B. Bermejo, L. Calvo, V. Carañana, Susana de la Cruz Sánchez, M. Cortés, R. M. Vázquez, A. Prat, M. R. Borrego, M. Sampayo, M. Seguí, J. Soberino, A. Malfettone, P. Schmid, J. Cortés","doi":"10.1158/1538-7445.sabcs19-p3-09-03","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs19-p3-09-03","url":null,"abstract":"","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87527179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Brezden-Masley, K. Fathers, M. Coombes, Cloris Xue, B. Pourmirza, K. Jerzak
{"title":"Abstract P2-08-08: A population-based study examining the epidemiology, treatment patterns and resource utilization by stage in Ontario patients with triple negative breast cancer","authors":"C. Brezden-Masley, K. Fathers, M. Coombes, Cloris Xue, B. Pourmirza, K. Jerzak","doi":"10.1158/1538-7445.sabcs19-p2-08-08","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs19-p2-08-08","url":null,"abstract":"","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89118644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lorraine Waechter, K. Cao, M. Carton, Y. Kirova, A. Fourquet
{"title":"Abstract P4-12-12: Outcomes of exclusive radiation therapy for breast cancer in older women according to age and comorbidity status: An observational retrospective study","authors":"Lorraine Waechter, K. Cao, M. Carton, Y. Kirova, A. Fourquet","doi":"10.1158/1538-7445.SABCS19-P4-12-12","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS19-P4-12-12","url":null,"abstract":"Introduction: This study aimed to assess the efficacy, tolerance and impact of comorbidities on outcomes in older women treated by exclusive radiation therapy (RT) for non-metastatic breast cancer (BC). Material and methods: We studied retrospectively female patients older 70 years at diagnosis, treated by exclusive RT for their BC between 2003 and 2013 in our Department. We analysed overall survival (OS), progression free survival (PFS), and specific survival (SS). Comorbidities were evaluated with the Charlson Comorbidity Index (CCI), and toxicities with the CCTCAE v3.0. Results: Between 2003 and 2013, there were 978 patients older than 70 treated for BC in our Hospital, and 817 received RT. Hypofractionated RT was delivered in 90.2% of patients. Of them, 66 patients underwent exclusive RT after refusal of surgery. The median age was 84.8 [71.3-91.7]. The median follow-up was 51.9 months [0.5- 99]. OS, SS and PFS at 5 years were 65.5% CI 95% [54.1-79.3], 86.3% CI 95% [77.2-96.4]), and 58.4% CI 95% [46.9-72.7], respectively. Five-year OS was statistically different according to age younger or older than 85 years: 72.9% CI 95% [58.4-91.1] and 57.1%, IC 95% [40.8-79.8], (p = 0.0026). Similar results were found for 5-year PFS: 64.5% CI 95% [49.5-84.1] and 51.6% CI 95% [35.8-74.5] (p = 0.014). The 5-year OS was also statistically different according to CCI score, respectively 70.8% CI 95% [57.0-87.9] and 59.8% CI 95 % [42.4-84.3] (p = 0.039) for a score of 0 or ≥ 1. Median CCI score was 1. There were 10.6% of the patients who experienced no toxicities; there were 59% who presented grade 1 and 2 radiodermatitis. Late toxicities were mainly fibrosis, observed in 39.4% of the patients, mostly of grade 1 and 2.Conclusion: Exclusive radiation therapy for non-metastatic BC in older women is feasible and well tolerated when adapted techniques are used, but the prognostic is strongly impacted by age and comorbidities. Citation Format: Lorraine Waechter, Kim Cao, Matthieu Carton, Youlia Kirova, Alain Fourquet. Outcomes of exclusive radiation therapy for breast cancer in older women according to age and comorbidity status: An observational retrospective study [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 P4-12-12.","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82338186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N. Keegan, S. Furney, J. Walshe, G. Gullo, J. Kennedy, K. Bulger, J. McCaffrey, C. Kelly, K. Egan, P. O'Donovan, A. Hernando, A. Teiserskiene, I. Parker, A. Farrelly, A. Carr, G. Calzaferri, R. McDermott, M. Keane, L. Grogan, O. Breathnach, P. Morris, S. Toomey, B. Hennessy
{"title":"Abstract P1-19-24: A phase Ib trial of copanlisib in combination with trastuzumab in pretreated recurrent or metastatic HER2-positive breast cancer “PantHER”","authors":"N. Keegan, S. Furney, J. Walshe, G. Gullo, J. Kennedy, K. Bulger, J. McCaffrey, C. Kelly, K. Egan, P. O'Donovan, A. Hernando, A. Teiserskiene, I. Parker, A. Farrelly, A. Carr, G. Calzaferri, R. McDermott, M. Keane, L. Grogan, O. Breathnach, P. Morris, S. Toomey, B. Hennessy","doi":"10.1158/1538-7445.sabcs19-p1-19-24","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs19-p1-19-24","url":null,"abstract":"","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79383333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
B. Katzenellenbogen, Y. Ziegler, M. Laws, V. S. Guillen, Sung-Hoon Kim, Parama Dey, B. Smith, P. Gong, Noah A. Bindman, Yuechao Zhao, K. Carlson, Mayuri A. Yasuda, Divya Singh, Zhong Li, D. El-Ashry, Zeynep Madak-Erdogan, J. Katzenellenbogen
{"title":"Abstract P5-05-05: Suppression of FOXM1 activities and breast cancer growth in vitro and in vivo by a new class of compounds","authors":"B. Katzenellenbogen, Y. Ziegler, M. Laws, V. S. Guillen, Sung-Hoon Kim, Parama Dey, B. Smith, P. Gong, Noah A. Bindman, Yuechao Zhao, K. Carlson, Mayuri A. Yasuda, Divya Singh, Zhong Li, D. El-Ashry, Zeynep Madak-Erdogan, J. Katzenellenbogen","doi":"10.1158/1538-7445.sabcs19-p5-05-05","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs19-p5-05-05","url":null,"abstract":"The transcription factor FOXM1 is up-regulated and overexpressed in aggressive, therapy-resistant forms of hormone receptor-positive and triple negative breast cancers, and is associated with less good patient survival. FOXM1 signaling is also a key driver in many other cancers. Here, we identify a new class of compounds effective in suppressing FOXM1 activity in breast cancers, and displaying good potency for antitumor efficacy. The compounds bind directly to FOXM1 and alter its proteolytic sensitivity, reduce the cellular level of FOXM1 protein by a proteasome-dependent process, and suppress breast cancer cell proliferation and cell cycle progression and increase apoptosis. RNA-seq and gene set enrichment analyses indicate that the compounds decrease expression of FOXM1-regulated genes and suppress gene ontologies under FOXM1 regulation. Several compounds have favorable pharmacokinetic properties and show good tumor suppression in preclinical breast tumor models. These compounds may be suitable for further clinical evaluation in targeting aggressive breast cancers driven by FOXM1. (Supported by Breast Cancer Research Foundation grant (BCRF-083 to BSK), The Julius and Mary Landfield Cancer Research Fund (to BSK), NIH grant R01 DK015556 (to JAK), NIH T32 GM070421 Fellowship (to VSG), Bankhead-Coley Foundation grant 09BW04 (to DEA), USDA award ILLU-698-909 and National Center for Supercomputing Applications Faculty Fellowship (to ZME), and UIUC Environmental Toxicology Scholarship (to BPS)). Citation Format: Benita S. Katzenellenbogen, Yvonne Ziegler, Mary J Laws, Valeria S. Guillen, SungHoon Kim, Parama Dey, Brandi P. Smith, Ping Gong, Noah Bindman, Yuechao Zhao, Kathryn Carlson, Mayuri A. Yasuda, Divya Singh, Zhong Li, Dorraya El-Ashry, Zeynep Madak-Erdogan, John A. Katzenellenbogen. Suppression of FOXM1 activities and breast cancer growth in vitro and in vivo by a new class of compounds [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 P5-05-05.","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75135165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}