Poster Session Abstracts最新文献

{"title":"Abstract P1-18-28: Myocet or carboplatin as part of chemotherapy in HER2-positive operable breast cancer treated with trastuzumab and pertuzumab in the neoadjuvant setting: Efficacy data and cardiotoxicity in 60 patients diagnosed from 2016-2019 at a single institution","authors":"S. Antolín, C. Reboredo, Rocio Lesta, A. Molina, J. Mosquera, P. Cordeiro, E. Pérez, L. Calvo","doi":"10.1158/1538-7445.sabcs19-p1-18-28","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs19-p1-18-28","url":null,"abstract":"Objectives: To evaluate the efficacy and cardiotoxicity profile of liposomal anthracycline or Carboplatin as part of neoadjuvant therapy added to taxanes and dual blockade in HER2-positive operable breast cancer patients. Methods: A total of 60 patients diagnosed from August 2016 to May 2019 were included in the study. The treatment consisted of a sequential regimen of taxanes and non- pegilated liposomal anthracycline (Myocet) plus trastuzumab and pertuzumab, or taxanes in combination with carboplatin plus trastuzumab and pertuzumab. The clinical and pathologic responses were evaluated and correlated with clinical and biological factors. Pathologic complete response was defined as the total absence of invasive tumor in both breast and axillary nodes (ypT0/is ypN0).The cardiotoxicity profile was also analyzed. Results: The median age was 52(26-77) years and 5%, 62% and 33% of patients had stage I, II and III breast cancer, respectively, while 7% had inflammatory breast cancer at diagnosis. Hormone receptor (HR) status was negative in 48%, and 65% and 50% had grade III and ki-67 value up to 35%, respectively breast cancer. 65% of patients received weekly paclitaxelx12-trastuzumab-pertuzumab followed by Myocet-cyclophosphamide with -trastuzumab x 4 cycles or this sequence but beginning with the anthracycline, 23% of patients the same regimen but with pertuzumab concurrently with all chemotherapy treatment. The remaining 12% received docetaxel-carboplatin x6 cycles plus trastuzumab and pertuzumab. All treatment was administered previous surgery. The clinical complete response rate, was 57% and 63%, as assessed using ultrasound and MRI, respectively, and this allowed a high rate of conservative surgery (60%). The pathologic complete response (pCR) rate was 52%, and it was higher in HR-negative (61%) than in HR-positive (39%), in grade 3 (71%) than in grade 2(29%) tumors. There were not statistical significant differences in pCR between different chemotherapy treatments. Five patients showed a 10% decrease in left ventricular ejection fraction (LVEF) to below 50% at the end of neoadjuvant treatment. Asymptomatic drops in 2 patients and with heart failure symptoms in 3 of them. Myocet was part of chemotherapy in all of them. All patients recovered after discontinuation of adjuvant trastuzumab and heart medication. Two of these patients did not complete all preplanned adjuvant trastuzumab doses. Conclusion: A sequential regimen of taxanes and non-pegilated liposomal anthracycline or carboplatin plus trastuzumab and pertuzumab was effective, with high pCR rates and a good cardiotoxicity profile. Citation Format: Silvia Antolin, Cristina Reboredo, Rocio Lesta, Aurea Molina, Joaquin Mosquera, Patricia Cordeiro, Eva Perez, Lourdes Calvo. Myocet or carboplatin as part of chemotherapy in HER2-positive operable breast cancer treated with trastuzumab and pertuzumab in the neoadjuvant setting: Efficacy data and cardiotoxicity in 60 patients diagnosed from 2016-2","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":"81785165","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}

{"title":"Abstract P1-10-18: Serum protein expression predicts neoadjuvant chemotherapy response in patients with locally advanced breast cancer","authors":"Ji-yeon Kim, Kyunghee Park, Hae Hyun Jung, Se Kyung Lee, Jonghan Yu, J. Lee, S. Kim, S. Nam, Yeon-Hee Park","doi":"10.1158/1538-7445.sabcs19-p1-10-18","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs19-p1-10-18","url":null,"abstract":"Introduction: Neoadjuvant chemotherapy (NAC) enables curative surgery and deprives micrometastasis in locally advanced breast cancer (LABC). Indeed, response of NAC, representatives of pathologic complete response (pCR) as well as residual cancer burden (RCB) class, is the most powerful indicator to predict BC prognosis. Therefore, NAC has been commonly used to treat LABC especially for HER2+ and TNBC subtype. While BC was treated with NAC, BC pathologic characteristics could be switched as a consequence of NAC. However, serial tumor biopsies are not feasible in clinical practiceeven though NAC has been used “in vitro vehicle” for translational research. Therefore, plasma biomarker is unmet need for treatment response prediction. In this study, we aimed to identify potential plasma biomarkers using multiplex immunoassay in BC patients with NAC. In total, we evaluated 45 plasma biomarkers and analyzed the association between the level of biomarkers and clinical outcomes. Methods: This study was prospectively conducted for LABC patients with NAC. Patients were treated with a standard NAC protocol for 6 months, consisting of four cycles of adriamycin/cyclophosphamide (AC) (60/600 mg/m2) combination chemotherapies followed by four cycles of docetaxel(D) (80mg/ m2) chemotherapy. HER2+ BC patients were treated with docetaxel plus trastuzumab (DH) combination therapies after AC. Surgical response was evaluated according to pathologic complete remission (pCR) defined as no residual invasive carcinoma in primary tumor bed and axillary lymph node. We also calculated residual cancer burden (RCB) score based on surgical pathology report. For each patient, blood sampling were prospectively taken 3times; before treatment (T1), three weeks after the first cycle of AC (T2) and at surgery following six months of treatment (T3). Plasma samples were assayed by multiplex immunoassays for 45 biomarkers, including growth factor, cytokines and chemokines using 45-Plex Human ProcartaPlexTM Panel (Thermo Fisher Scientific, Inc. Carlsbad, CA, USA). Results: In total, 167 patients diagnosed with LABC were participated in serial plasma sampling. Fifty eight patients were diagnosed with HER2+ BCs (34.7%) and 63 of TNBCs (37.7%). Clinical stage at BC diagnosis was variate; 59 of stage II (35.3%), 108 of stage III (64.7%). After BC surgery, pCR (RCB class 0) was observed in 53 BCs (6 hormone receptor positive and HER2- BCs (13.0%), 27 HER2+ BCs (46.6%) and 20 TNBCs (31.7%)). In terms of RCB class, 20 BCs were class I, 63 of class II and 28 of class III. Two patients diagnosed with LABC had undergone disease progression during NAC. Among clinical variables, RCB class after NAC in LABC patients has the highest predictive value for relapse free survival (RFS) (c-index: 0.787, 95% confidence interval [CI]:0.690, 0.884, p-value Conclusion: Seven plasma protein expressions predict RCB class in LABC patients with NAC and predicted RCB class also has a similar predictive value for RFS","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":"78888230","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}

{"title":"Abstract P5-04-19: Sulindac sulfide as a non-immune suppressive gamma secretase modifier to target triple negative breast cancer","authors":"Fokhrul M. Hossain, Deniz A. Ucar, Samarpan Majumder, M. Matossian, G. Monticone, Keli Xu, Yong Ran, L. Minter, Y. Xi, M. Burow, T. Golde, B. Osborne, L. Miele","doi":"10.1158/1538-7445.sabcs19-p5-04-19","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs19-p5-04-19","url":null,"abstract":"Triple negative breast cancer (TNBC) is defined as pathologically negative for estrogen receptor (ER-), progesterone receptor (PR-), and human epidermal growth factor receptor 2 amplification (HER2-). TNBCs are a heterogeneous group of clinically aggressive cancers with high risk of recurrence and metastasis, and current treatment options remain limited. Immunotherapy with checkpoint inhibitors shows promise. However, recent data show that crosstalk between cancer stem cells (CSC) and the immune microenvironment leads to immunotherapy resistance, while myeloid-derived suppressor cells (MDSC) promote CSC survival via Notch signaling. Strong evidence supports the involvement of Notch, a prominent CSC pathway, in TNBC progression. Expression of Notch1 and its ligand Jagged1 correlate with poor prognosis. Notch inhibitors, Including Gamma Secretase Inhibitors (GSIs) are quite effective in preclinical models of TNBC. However the success of GSIs in clinical trials has been limited by their intestinal toxicity and potential for adverse immunological effects. Our overarching goal is to replace GSIs with agents that lack their systemic toxicity and adverse immunological effects. We identified Sulindac Sulfide (SS), the active metabolite of FDA-approved NSAID Sulindac, as a potential candidate to replace GSIs. We confirmed that SS has Gamma Secretase Modifier (GSM) activity, in addition to cyclo-oxygenase (COX) inhibition. SS inhibits Notch1 cleavage in TNBC cells, but not in murine T-cells. SS significantly inhibited mammospheres growth in all human and murine TNBC models we tested: 1) human MDA-MB-231 cells; 2) murine TNBC model C0321, from targeted conditional knockout of Lunatic Fringe (LFng-/-); and 3) Two TNBC patient-derived xenograft models, 2K1 and 4IC. In C0321 tumors in mice, we found that SS had remarkable single-agent anti-tumor activity and virtually eliminated Notch1 expression in tumors without intestinal toxicity. SS caused an increase in intra-tumoral CD11c+ dendritic cells and CD8 cells. SS did not affect the numbers of tumor infiltrating macrophages or myeloid-derived suppressor cells (MDSC). However, SS blocked the immunosuppressive function of bone marrow-derived MDSC. RNA-Sequencing of SS-treated tumors revealed significant reduction of CXCL14, EGR1, HOXC6, MAGI2, NCAM1, APOE, CLU (a Wnt target), DTX4 (an E3-ligase positive regulator of Notch activation), and TGFB3 genes and upregulation of CCL17, EPCAM, FABP4, C4A, LTF, ZBTB16, INADL, and FGFR2 genes. Importantly, SS enhanced the antitumor effect of a-PDL1 immunotherapy in our 0321 TNBC mouse model. Our data support further investigation of SS for the treatment of TNBC, with standard of care or with immunotherapy. Repurposing an FDA-approved, safe agent for the treatment of TNBC may be significantly easier and more cost-effective than developing unproven investigational agents. Citation Format: Fokhrul Hossain, Deniz A Ucar, Samarpan Majumder, Margarite Matossian, Giulia Monticone, ","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":"76426678","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}

{"title":"Abstract P5-03-04: Co-segregation of rare possibly-damaging variants in cancer-related genes correlates with phenotypic homogeneity in familial breast cancer","authors":"C. V. Marcke, R. Helaers, C. Schoonjans, J. Ambroise, M. Berlière, J. Canon, P. Vuylsteke, J. Machiels, M. Vikkula, F. Duhoux","doi":"10.1158/1538-7445.sabcs19-p5-03-04","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs19-p5-03-04","url":null,"abstract":"BACKGROUND Breast cancer (BC) is a complex disease. While Mendelian mutations in high-penetrance genes predispose to some familial forms, others are due to multiple common low-penetrance polymorphisms. However, it is unclear if the combination of some rare coding variants has an effect. As some Mendelian forms demonstrate genotype-phenotype correlations, we hypothesized co-segregation of rare variants in cancer-related genes would be more frequent in high-risk families with a uniform BC phenotype among relatives. METHODS Whole-exome sequencing was performed on germline DNA from unrelated BC patients referred for genetic testing but without a causative mutation and for which DNA was available from at least one second relative with BC. We retained rare ( Citation Format: Cedric Van Marcke, Raphael Helaers, Celine A Schoonjans, Jerome Ambroise, Martine Berliere, Jean-Luc Canon, Peter Vuylsteke, Jean-Pascal Machiels, Miikka Vikkula, Francois P Duhoux. Co-segregation of rare possibly-damaging variants in cancer-related genes correlates with phenotypic homogeneity in familial breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-03-04.","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":"72883139","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}

{"title":"Abstract P1-19-12: Patterns of treatment with everolimus and exemestane in hormone receptor positive HER2 negative metastatic breast cancer in the era of targeted therapy","authors":"Mariya Rozenblit, L. Pusztai, K. Adelson, S. Mougalian","doi":"10.1158/1538-7445.sabcs19-p1-19-12","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs19-p1-19-12","url":null,"abstract":"Background: In 2012 the FDA approved everolimus and exemestane (EE) as second line therapy for patients who have progressed on letrozole or anastrozole, based on the BOLERO-2 trial which showed improvement in PFS with EE compared to exemestane alone (6.9 vs 2.8 months). Currently, aromatase inhibitors (AI), or fulvestrant (F), alone or in combination with a CDK4/6 inhibitor (CDK4/6i) are the most commonly used first line endocrine therapies for hormone receptor (HR) positive HER2 negative metastatic breast cancer (mBC). There is currently no clinical trial data regarding the efficacy of EE in patients previously treated with CDK4/6i. The goal of this project was to explore the treatment patterns of EE in this contemporary patient population, with particular interest in those who had received prior CDK4/6i plus AI/F, as first, second, or third-line treatment. Methods: The Flatiron Health electronic health record-derived nationwide database selected de-identified patients with HR positive HER2 negative mBC and the first (1L), second (2L), and third line (3L) treatments they received. Duration of treatment (DOT) is defined as time from the date of initiation of a line of treatment to the day prior to initiation of subsequent line of treatment; prolonged DOT is defined as duration ≥ 6 months. Medical non-cancer co-morbidities listed as defined by the Charlson Comorbidity Index were included. Median DOT was compared using t-test, unadjusted for patient and disease characteristics. Statistical analysis was performed using Python v3.7. Results: A total of 8457 HR positive HER2 negative patients diagnosed with mBC between 1/2011 and 1/2019 were identified. Of these, 726 patients received EE in 1L (N=127), 2L (N=326), or 3L (N=273). In this cohort, 72.3% of patients were diagnosed between 2011-2014, and 27.7% were diagnosed after 1/2015, and most (94.6%) were treated in the community setting. The majority were female (98.4%), Caucasian (75.1%), and had no co-morbidities (79%); the mean age was 64. A quarter of patients (25%) had de novo mBC. The median DOT for 1L EE was 7.6 months (95% CI 5.6, 9.6); 56.7% received 1L EE for ≥6 months. The median DOT for 2L EE was 9.1 months (95% CI 7.6,10.6) following 1L AI/F and 10.7 months (95% CI 8.5,12.9) following 1L AI/F plus CDK4/6i (p Conclusion: In a cohort of patients with HR positive HER2 negative mBC who received EE in the 2L or 3L, a significant percentage of patients derived clinical benefit (DOT>6 months) from EE, even after CDK4/6i therapy. Patients who received CDK4/6i 1L had longer unadjusted DOT of 2L EE compared to those who received 1L AI/F alone. Citation Format: Mariya Rozenblit, Lajos Pusztai, Kerin Adelson, Sarah Mougalian. Patterns of treatment with everolimus and exemestane in hormone receptor positive HER2 negative metastatic breast cancer in the era of targeted therapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA","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":"77799380","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}

{"title":"Abstract P5-07-10: Progression-free survival (PFS) and overall survival (OS) in HER2-ve advanced breast cancer (ABC) patients (pts) according to the molecular subtype in the era of modern agents. Results from the GIM-13 AMBRA study","authors":"M. Cazzaniga, S. Placido, A. D’Alonzo, M. Piezzo, C. Natoli, A. Milani, A. Bologna, M. Alú, A. Turletti, P. Pugliese, L. Biganzoli, C. D. Angelis, O. Garrone, P. Marchetti, F. Riccardi, A. Bernardo, L. Livi, A. Fabi, C. Taverniti, E. Romagnoli, P. Pronzato, G. Mustacchi","doi":"10.1158/1538-7445.sabcs19-p5-07-10","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs19-p5-07-10","url":null,"abstract":"BACKGROUND Pts with ABC have a diverse clinical course and OS rates vary significantly among pts. New strategies had potentially changed the natural history of these pts, however data from clinical studies are still lacking and Real-World Studies (RWS) are crucial in clinical outcome evaluation. PATIENTS AND METHODS AMBRA is a longitudinal cohort study, aiming to describe the choice of first and subsequent lines of treatment in HER2-ve ABC pts receiving at least one CHT (SABCS 2016, P5-15-07 & P5-14-09) in the years 2012-2015. The present analysis is focused on the description of Progression-Free Survival (PFS) and OS according to the biologic subtype in the deceased population. So far, 791/1500 pts have been registered into the study and 255 (32.2%) are evaluable. Time to event analysis between subtypes was evaluated by Cox-Mantel Hazard Ratio and Logrank Test. DFS by Wilcoxon Rank-Sum Test RESULTS Pts distribution according to molecular subtype was: Luminal A (86, 33.7%), Luminal B (107 (42.1%), TNBC (62, 24.3%). Median ages at diagnosis were 55.8, 52.9 and 55.1 years for the 3 subgroups, respectively. Mean DFS was significantly different according to the molecular subtypes: 87.28, 61.37 and 23.9 months. The difference between Luminal B and TNBC is statistically significant as well. Mean PFS of 1st-line therapy was 17.9 11.7 and 7.8 months respectively. Mean OS from 1stprogression was 32.9 24.2 and 15.8 months respectively. CONCLUSIONS Our data confirm in a RWS the different biological behaviour between Lum A and B. Metastatic life span is quite good for Luminals and disappointing for TNBC. Median time from last CHT and Death is quite short and similar. Citation Format: Marina Elena Cazzaniga, Sabino De Placido, Alessia D9Alonzo, Michela Piezzo, Clara Natoli, Andrea Milani, Alessandra Bologna, Massimiliano Alu, Anna Turletti, Palma Pugliese, Laura Biganzoli, Claudia De Angelis, Ornella Garrone, Paolo Marchetti, Ferdinando Riccardi, Antonio Bernardo, Lorenzo Livi, Alessandra Fabi, Cristiana Taverniti, Emanuela Romagnoli, Paolo Pronzato, Giorgio Mustacchi, on behalf of GIM-13 AMBRA Study Group. Progression-free survival (PFS) and overall survival (OS) in HER2-ve advanced breast cancer (ABC) patients (pts) according to the molecular subtype in the era of modern agents. Results from the GIM-13 AMBRA 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 P5-07-10.","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":"89307736","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}

{"title":"Abstract P2-12-09: Randomized study to determine the efficacy of Olanzapine for the prevention of chemotherapy-induced nausea and vomiting (CINV) in Chinese breast cancer patients (PTS)","authors":"W. Yeo, T. Lau, V. Chan, L. Leung, Dong-Min Lai, E. Pang, M. Cheung, A. Wong, W. Soo, V. T. Yeung, T. Tse, E. W. Yeung, D. Lam, K. Wong, David Johnson, K. P. Ng, H. Loong, Joyce Ng, F. Mok, Mimi Lee, D. Poon, Yvonne Yau, M. Tong, J. Suen, F. Mo","doi":"10.1158/1538-7445.sabcs19-p2-12-09","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs19-p2-12-09","url":null,"abstract":"Background: Adjuvant chemotherapy improves outcomes of pts with early breast cancer, but CINV have been regarded as two of the most disturbing side effects, affecting their quality of life (QoL). In this study, the primary objective was to compare the efficacy of olanzapine in addition to the standard aprepitant-based antiemetic regimen for CINV in pts receiving the 1st cycle of adjuvant AC chemotherapy (adriamycin 60mg/m2 and cyclophosphamide 600mg/m2). The secondary objective was to compare the tolerability and efficacy of such regimen in the 4 cycles of AC. Methods: This is a prospective single center, randomized study. Eligible pts had early stage breast cancer of Chinese ethnicity; they were chemotherapy- naive and treated with adjuvant AC chemotherapy. Antiemetic regimen for all studied population included aprepitant, ondansetron and dexamethasone; patients were randomly allocated to Olanzapine (with olanzapine) or Standard (without olanzapine) arms. Individual patient filled in self-reported diary and visual analogue scale for nausea from which information on nausea, vomiting and use of rescue medication were collected; outcomes were compared during acute phase (0-24 hrs), delay (24-120 hrs) and overall time-frame (0-120 hrs) from initiation of AC. QoL was assessed by Functional Living Index-Emesis (FLIE). Results: 120 pts were randomized. For CINV in Cycle 1 AC, outcomes of Olanzapine vs Standard arms were: complete response (acute phase 70.0 vs 51.7%, p=0.0397; delay phase 75.0 vs 45.0%, p=0.0008; overall time-frame 65.0 vs 38.3%, p=0.0035), complete protection (acute phase 70.0 vs 50.0%, p=0.0253; delay phase 71.7 vs 40.0%, p=0.0005; overall 61.7 vs 36.7%, p=0.0062), total control (acute phase 65.0 vs 41.7%, p=0.0104; delay phase 60.0 vs 31.7%, p=0.0018; overall 51.7 vs 26.7%, p=0.0050), ‘no vomiting’ (acute phase 73.3 vs 51.7%, p=0.0142; delay phase 76.7 vs 48.3%, p=0.0013; overall 68.3 vs 40.0%, p=0.0018), ‘no significant nausea’ (acute phase 95.0 vs 75.0%, p=0.0017; delay phase 91.7 vs 65.0%, p=0.0004; overall 91.7 vs 63.3%, p=0.0002),‘no nausea’ (acute phase 76.7 vs 53.3%, p=0.0074; delay phase 65.0 vs 35.0%, p=0.0010; overall 58.3 vs 33.3%, p=0.0060), and need of rescue medication (acute phase 3.3 vs 11.7%, p=0.0654; delay phase 6.7 vs 21.7%, p=0.0133; overall 8.3 vs 23.3%, p=0.0244). Assessment of FLIE on Day 6 after Cycle 1 AC between the Olanzapine vs Standard arms revealed better QOL mean scores for nausea domain (p Conclusions: In this prospective study of Chinese women with breast cancer, the addition of olanzapine to standard antiemetic regimen increases the control of CINV and improves the QoL of pts during AC chemotherapy. Funding: Madam Diana Hon Fun Kong Donation for Cancer Research. Citation Format: Winnie Yeo, Thomas KH Lau, Vicky TC Chan, Li Leung, Dong Lai, Elizabeth Pang, Maggie Cheung, Ashley Wong, Winnie MT Soo, Vanessa TY Yeung, Teresa Tse, Eva WM Yeung, Daisy CM Lam, Kenneth CW Wong, David R Johnson, Kim PK Ng, ","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":"77616867","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}

{"title":"Abstract P6-04-01: A pre-surgical, window of opportunity study comparing the novel oral SERD AZD9496 with fulvestrant in patients with newly diagnosed ER+ HER2- primary breast cancer","authors":"J. Robertson, A. Evans, S. Henschen, C. Kirwan, A. Jahan, L. Kenny, J. Dixon, P. Schmid, A. Kothari, Omar Mohamed, P. Fasching, K. Cheung, R. Wuerstlein, Danielle Carroll, T. Klinowska, J. Lindemann, Alexander MacDonald, R. Mather, R. Maudsley, M. Moschetta, M. Nikolaou, M. Roudier, T. Sarvotham, G. Schiavon, Diansong Zhou, Li Zhou, N. Harbeck","doi":"10.1158/1538-7445.sabcs19-p6-04-01","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs19-p6-04-01","url":null,"abstract":"Background: Estrogen receptor positive (ER+) breast cancer is routinely treated with endocrine therapies targeting the ER axis. However, primary and secondary resistance ultimately limits the use of these agents. Fulvestrant (FULV) is the first-in-class selective ER degrader (SERD) clinically effective in patients with ER+ breast cancer, both naive and resistant to tamoxifen and aromatase inhibitors. FULV has low oral bioavailability, and its dose-dependent pharmacodynamic (PD) activity and clinical efficacy is limited by the currently approved maximal feasible dose (MFD) of 500 mg, which is administered monthly as two intramuscular injections. AZD9496 is an orally bioavailable, nonsteroidal, selective and potent degrader and antagonist of ER in preclinical models. This pre-surgical, window of opportunity study (NCT03236974) compared PD changes and the PD/pharmacokinetic (PK) relationships of AZD9496 with FULV in patients with newly diagnosed ER+ HER2- breast cancer awaiting curative intent surgery.Methods: In this open-label, multicenter study, patients were randomized 1:1 to receive oral AZD9496 250 mg BID from Day 1 for 5-14 days or FULV 500 mg administered intramuscularly on Day 1 only. On-treatment image-guided core tumor biopsies were taken between Days 5 and 14. The primary objective was to compare the effects of AZD9496 and FULV on ER expression in tumor tissue using pre-dose biopsies as baseline. Secondary objectives were changes in progesterone receptor (PR) and Ki-67 biomarkers, AZD9496 and FULV plasma concentrations during treatment, and safety. Immunohistochemistry was used to determine ER and PR H-scores, and Ki-67 index, and treatment effects were compared using an analysis of covariance model. Blood samples for PK analysis were taken at on-treatment biopsy and 1-2 hours afterwards. Adverse events (AEs) were monitored from screening through to a follow-up visit 28 days after the last study dose.Results: Of the 49 women enrolled, 46 received treatment (AZD9496 n=22; FULV n=24) and of these, 35 paired biopsies were evaluable (AZD9496 n=15; FULV n=20). The least square mean estimate for the reduction in ER H-score after AZD9496 treatment was 24% (80% CI: 34.4, 14.3), and after FULV treatment was 36% (44.9, 27.7), with a least square mean difference between AZD9496 and FULV of 12% (p=0.86). AZD9496 was not superior to FULV in terms of ER modulation at the tested dose. AZD9496 also reduced PR H-scores and Ki-67 levels from baseline (by 33.3% and 39.9%, respectively). These effects were not statistically superior to FULV at the tested dose (PR: -68.7%, p=0.97; Ki 67: 75.4%, p=0.98).Plasma exposure of AZD9496 (AUC -40%, Cmax -25%) was lower than predicted based on PK data from the previous phase 1 study, whereas FULV exposure was consistent with historical data. No clear exposure-response relationship for plasma concentration at biopsy and PD markers for AZD9496 or FULV were observed.The median treatment duration of AZD9496 was 9.5 days (","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":"83517691","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}

{"title":"Abstract P1-05-10: lncRNA UBA6-AS1 participates in the integrated stress response of breast cancer","authors":"Yi-Zhen Wu, Yi-Hsuan Chen, Chun-Ting Cheng, Kevin K. Chi, Tse-Chun Kuo, H. Kung, D. Ann, Ching-Ying Kuo","doi":"10.1158/1538-7445.sabcs19-p1-05-10","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs19-p1-05-10","url":null,"abstract":"Breast cancer is the most prevalent malignant neoplasm among women worldwide and in Taiwan, and the incidence of breast cancer has been increasing over the past years. Accumulating studies has shown that multiple stress responses are activated in breast cancer. Oncogene activation, massive proliferation and increased nutrient demands often result in nutrient and oxygen deprivation, which triggers integrated stress response (ISR) in tumor cells. ISR dictates the cellular adaptive signaling in response to the intrinsic and extrinsic stresses, which lead to endoplasmic reticulum (ER) stress and cytosolic stress. Delineating the regulatory mechanisms of ISR may help us understand how cancer cells adapt and survive under stressed condition. To elucidate the role of long non-coding RNAs (lncRNAs) in the ISR of breast cancer, we have performed a two-step human lncRNA RNA interference (RNAi) screening coupled with cell viability assays in a breast cancer cell line MDA-MB-231 under glucose deprivation to induce extrinsic metabolic stress. A novel lncRNA, UBA6-AS1, was identified to be upregulated to promote breast cancer cell death upon glucose deprivation. Besides of glucose deprivation, UBA6-AS1 was also induced by the deprivation of amino acids including glutamine and arginine in several breast cancer cell lines, suggesting that the upregulation of UBA6-AS1 was a universal metabolic stress event. We also found that UBA6-AS1 expression was increased upon the administration of ER stress inducers, tunicamycin (Tm) and thapsigargin (Tg) in breast cancer cells, implicating a potential role of UBA6-AS1 in harmonizing the nutrient and ER stresses. Moreover, after analyzing the genomic position and sequence of UBA6-AS1, activating transcription factor 4 (ATF4), a critical regulator in the ISR coordinating nutrient and ER stress signaling for controlling cell survival and stress adaption, has been predicted to be the regulator of UBA6-AS1 upon the induction of nutrient stress, further supporting the role of UBA6-AS1 participating in the ISR of breast cancer cells. Depletion of UBA6-AS1 rendered breast cancer cells more resistant to nutrient deprivation, and the opposite results were observed when UBA6-AS1 was overexpressed, indicating that UBA6-AS1 may participate in the regulation of breast cancer cell survival under metabolic stress. To investigate the function of UBA6-AS1, RNA-sequencing (RNA-seq) was performed to profile gene expression in breast cancer cells overexpressing UBA6-AS1. The RNA-seq analysis revealed that the top 10 enriched biological processes were mostly related to apoptosis or programmed cell death in the UBA6-AS1 overexpressing cells, suggesting that the up-regulation of UBA6-AS1 may induce apoptosis in response to metabolic stress. In the future, we will focus on the molecular mechanism of the regulation and function of UBA6-AS1 as well as its biological role and association with breast cancer progression. Citation Format: Yi-Zhen Wu, Yi-","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":"88688797","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}

{"title":"Abstract P2-17-05: Evaluation of safety, pharmacokinetics and pharmacodynamics of proxalutamide (GT0918), a potent androgen receptor (AR) blocker, in patients with metastatic breast cancer (mBC): Phase I dose escalation trial","authors":"Huiping Li, R. Ran, G. Song, Hanfang Jiang, Ruyan Zhang, Yaxin Liu, Luping Meng, Phoebe Zhang, Ke-qi Chen, Qiaoxia Zhou, K. Zhou, Y. Tong","doi":"10.1158/1538-7445.sabcs19-p2-17-05","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs19-p2-17-05","url":null,"abstract":"Background: Androgen receptor (AR) blocker has become an increased interest in the treatment of BC, in which about 60-80% patients showed AR positive. However, currently no AR blocker has been approved in mBC. GT0918 is a new chemical entity of AR blocker with possible AR down-regulation. This study is an open-label, single-center, dose escalation phase I trial to assess GT0918 in mBC female patients who have progressed after systemic treatments in China. The primary objectives are to identify the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs). The secondary objectives are to assess pharmacokinetics and pharmacodynamics of GT0918 with single and multiple dosage applications. (CTR20170757) Methods: Patients (pts) with historically confirmed mBC who had progressed after either chemotherapy, hormonal or targeted therapy, or could not tolerate currently standard therapies were eligible. With the starting dose at 100 mg of GT0918, the decision of dose escalation in the 3+3 design was based on the safety and tolerability assessments. GT0918 was administered orally once, followed by a 7-day off-treatment period for single dose PK analysis of drug elimination. Then GT0918 oral administration was resumed once daily for 28 consecutive days and multiple dose PK analysis was assessed at the end of first cycle (28 days). The first 28-days on treatment (cycle 1) was defined as DLT period. Pts manifesting an objective response or stable disease and likely to have clinical benefit from continued treatment were continued on GT0918 thereafter until they experienced one of following events of intolerable toxicities, disease progression or withdrew consent. Results: 18 pts were enrolled and treated with GT0918 since 9/6/2017 as defined in protocol at five dose levels: 100 mg (n = 3), 200 mg (n = 4), 300 mg (n = 4), 400 mg (n = 4) and 500 mg (n = 3) (as to 7/2/2019). All pts progressed more than two lines of therapies with 83.3% (15/18) pts were treated ≥3rd lines. Out of 6 confirmed AR positive pts, two (33.3%) at 300 mg cohort had finished 17 and 19 cycles individually and continue treatment (as 7/2/19). No DLT was observed and MTD has not been reached. GT0918 related adverse events (AEs) were grade 1 or 2 as per CTCAE v4.03, including fatigue, hypertriglyceridemia, anemia, hypercholesterolemia, increased LDL, nausea, loss of appetite, increased ALT, increase of weight loss, constipation and thrombocytopenia. PK profile analysis showed that in the single-dose study, GT0918 showed a fast absorption profile. In the multiple-dose study, the steady-state serum concentration level of GT0918 and its main metabolite were attained at 21 days. Conclusions: Proxalutamide (GT0918) administrated orally once a day is well tolerated in late-stage pts. No DLT has occurred at maximum dose 500 mg. Pts with AR positive biomarker could have better clinical outcomes with GT0918 treatment. GT0918 and its main metabolite exhibited a nonlinear pharmacokinetic profile ov","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":"74013937","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}