Poster Spotlight Session Abstracts最新文献

{"title":"Abstract PD2-09: The role of CYP2D6 mediated tamoxifen metabolism in the suppression of ovarian function trial (SOFT)","authors":"M. Goetz, G. Fleming, M. Kuffel, J. Hawse, J. Black, R. Weinshilboum, J. Ingle, P. Dell'Orto, O. Biasi, R. Kammler, S. Loi, M. Colleoni, G. Viale, P. Francis, M. Regan","doi":"10.1158/1538-7445.SABCS20-PD2-09","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS20-PD2-09","url":null,"abstract":"Tamoxifen (T) is a pro-drug that undergoes CYP2D6-mediated metabolic activation to metabolites that more potently inhibit estrogen stimulated growth compared to the parent drug. While many studies have examined the role of CYP2D6 genotype in T-treated postmenopausal women, the role of CYP2D6 metabolism in premenopausal women (pre-MW) receiving T, with or without ovarian function suppression (OFS) or exemestane (E) and OFS is unknown. Methods: SOFT randomized 3066 (pre-MW) from 2003-2011 in 27 countries, stratified according to prior receipt or nonreceipt of chemotherapy and nodal status, to receive 5 years of T, T+OFS, or E+OFS. We designed a pharmacogenetics substudy (activated October 2010) to collect blood DNA from North American (NA) patients (pts) or to extract non-tumor DNA from available formalin fixed paraffin embedded (FFPE) tissue blocks. For pts with a blood sample, CYP2D6 was genotyped beginning with the Luminex Tag-It Mutation Detection Kit and when needed, with a copy number variation assay and/or sequencing assays. For pts with FFPE-derived DNA, CYP2D6 genotyping for *3, *4, *6, *9, *10, *17 and *41 was performed using a Taqman Allelic Discrimination Assay. CYP2D6 phenotypes were called by classifying pts on the basis of a combination of poor (PM: *3, *4, *5, *6, *7, *8), slow (SM: *10), intermediate (IM: *9, *17, *29, *41) and extensive metabolizer alleles (EM; all others). Activity scores (AS) from phenotypes assigned for each allele: 0 if PM, 0.25 if SM, 0.5 if IM and 1 if EM allele, and multiplied x2 or x3 if duplicate or triplicate. With concomitant use of potent CYP2D6 inhibitor, AS=0; use of weak inhibitor subtracted 0.5. Metabolizer status was defined by CYP2D6 genotype alone or in combination with CYP2D6 inhibitor use at randomization from the AS: extensive (AS 1.25 to 3), intermediate (AS >0.5 to 0.3 ng/ml in 1053, and successfully derived CYP2D6 genotypes for 765/3047 pts (25%). 182 (15%) pts had DFS events after 8 yrs median follow-up. Metabolizer status from genotype was 57% extensive, 29% intermediate, 15% slow/poor. Metabolizer status was not associated with DFS in pts assigned T alone (P=0.60; Table), nor in pts assigned T+OFS (P=0.41) or E+OFS (P=0.30). 11% of pts used CYP2D6 inhibitors concomitantly at randomization; for 8% it changed the metabolizer status. The results using this definition were consistent. Conclusion: This retrospective-prospective SOFT pharmacogenetics substudy found no relation of CYP2D6 metabolizer status with DFS in premenopausal pts receiving T, T + OFS, or E + OFS. Given that 50% were pretreated with chemotherapy, further study is needed regarding the role of CYP2D6 metabolism in patients treated with T monotherapy. Citation Format: Matthew P. Goetz, Gini F. Fleming, Mary Kuffel, John R. Hawse, John L. Black, Richard Weinshilboum, James N. Ingle, Patrizia dell’Orto, Olivia Biasi, Roswitha Kammler, Sherene Loi, Marco Colleoni, Giuseppe Viale, Prudence A Francis, Meredith M Regan. The role o","PeriodicalId":415047,"journal":{"name":"Poster Spotlight Session Abstracts","volume":"45 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123840040","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 PD4-01: Preservation of axillary lymph nodes compared to complete dissection in T1-T2 breast cancer patients presenting 1-2 metastatic sentinel lymph nodes : A multicenter randomized clinical trial. Sinodar One.","authors":"C. Tinterri, E. Marrazzo, C. Anghelone, E. Barbieri, A. Sagona, A. Bottini, A. Rubino, D. Gentile, W. Gatzemeier, V. Errico, A. Testori, G. Canavese","doi":"10.1158/1538-7445.sabcs20-pd4-01","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs20-pd4-01","url":null,"abstract":"","PeriodicalId":415047,"journal":{"name":"Poster Spotlight Session Abstracts","volume":"131 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121475198","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 PD7-05: Neoadjuvant chemotherapy selectively alters spatially-defined immune landscapes in clinical luminal B HR+/HER2- breast cancers: Analysis of the breast cancer genome guided therapy study (BEAUTY)","authors":"J. Carter, J. Boughey, Jun He, V. Suman, Xue Wang, J. Kachergus, Krishna R. Kalari, Liewei Wang, R. Weinshilboum, A. Moyer, S. Mclaughlin, A. Moreno-Aspitia, D. Northfelt, R. Gray, J. Ingle, E. Thompson, M. Goetz","doi":"10.1158/1538-7445.SABCS20-PD7-05","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS20-PD7-05","url":null,"abstract":"","PeriodicalId":415047,"journal":{"name":"Poster Spotlight Session Abstracts","volume":"11 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116316510","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 PD8-03: A FOXA1/FRA1-centered transcriptional axis regulates interferon signaling in high FOXA1-associated endocrine-resistant and metastatic breast cancer","authors":"Xiaoyong Fu, Resel Pereira, L. Qin, C. Angelis, Sarmistha Nanda, M. Shea, A. Nardone, R. Jeselsohn, Ofir Cohen, N. Wagle, M. Rimawi, C. Osborne, R. Schiff","doi":"10.1158/1538-7445.SABCS20-PD8-03","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS20-PD8-03","url":null,"abstract":"","PeriodicalId":415047,"journal":{"name":"Poster Spotlight Session Abstracts","volume":"144 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127488333","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 PD11-09: Vadis trial: Phase II trial of nelipepimut-s peptide vaccine in women with DCIS of the breast","authors":"A. O'Shea, G. Clifton, N. Qiao, B. Heckman-Stoddard, M. Wojtowicz, E. Dimond, I. Bedrosian, D. Weber, Alexander Husband, R. Pastorello, L. Vornik, G. Peoples, E. Mittendorf","doi":"10.1158/1538-7445.sabcs20-pd11-09","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs20-pd11-09","url":null,"abstract":"","PeriodicalId":415047,"journal":{"name":"Poster Spotlight Session Abstracts","volume":"467 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115285649","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 PD12-12: Floor and ceiling effects in the EORTC QLQ-C30 physical functioning subscale among patients with breast cancer enrolled in commercial clinical trials vs. a community trial","authors":"M. Murugappan, B. King-Kallimanis, Christina Mangir, Lyn Howie, V. Bhatnagar, J. Beaver, E. Basch, P. Kluetz","doi":"10.1158/1538-7445.SABCS20-PD12-12","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS20-PD12-12","url":null,"abstract":"","PeriodicalId":415047,"journal":{"name":"Poster Spotlight Session Abstracts","volume":"14 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132317405","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 PD3-09: Sulindac reduces breast density and alters collagen alignment in patients on aromatase inhibitors","authors":"P. Thompson, Chuan Huang, B. Wertheim, C. Preece, Jie Yang, Jessica A. Martinez, D. Roe, P. Chalasani, A. Stopeck","doi":"10.1158/1538-7445.sabcs19-pd3-09","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs19-pd3-09","url":null,"abstract":"Background. Preclinical and observational evidence supports cancer prevention activity of non-steroidal anti-inflammatory drugs (NSAIDs) in the breast via suppression of prostaglandin E2 (PGE2) synthesis by cyclooxygenase-2 (COX2). Evidence includes linking of PGE2 to aromatase activity and estrogen synthesis in breast adipose tissue, as well as effects on collagen and breast density (BD). Methods. In an open-label trial, we evaluated the effect of the non-selective NSAID sulindac at 150 mg bid for 12 months on BD in 52 postmenopausal women taking adjuvant aromatase inhibitors (AIs) for breast cancer. BD was measured using a fat-water decomposition MRI based BD measure (MRD) previously shown to be more quantitative than mammographic density. A non-randomized observation cohort of 46 postmenopausal women on AI without NSAID use was conducted in parallel to assess the effect of AI on MRD over 12 months. Eligible participants were recruited at two study sites and included women with an intact, unaffected contralateral breast and BI-RADS ≥ 2. Each subject’s MRI_BD measures at baseline and at 6 and 12 months were included in linear mixed models for longitudinal data. Log-transformation was applied to the outcome of BD. Covariates included log-transformed baseline BD, time on AI, and baseline body mass index (BMI) and change in BMI. Breast tissue collagen fiber alignment for 30 women with paired breast biopsies, before and after 6 months on sulindac, was examined using Second-Harmonic Generation (SHG) microscopy and analysis of the distribution (histogram) of ‘straight’ fibers in three randomly selected areas of breast tissue. Straightness of individual fibers was calculated as the linear length of a fiber divided by the distance along the fiber. Results. Participants on sulindac intervention had a significant change in BD relative to baseline BD at 6 (p=0.05) and 12 months (p Citation Format: Patricia Thompson, Chuan Huang, Betsy Wertheim, Christina Preece, Jie Yang, Jessica Martinez, Denise Roe, Pavani Chalasani, Alison Stopeck. Sulindac reduces breast density and alters collagen alignment in patients on aromatase inhibitors [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 PD3-09.","PeriodicalId":415047,"journal":{"name":"Poster Spotlight Session Abstracts","volume":"37 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130443600","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 PD7-05: A first-in-human phase I study to evaluate the oral selective estrogen receptor degrader (SERD), GDC-9545, in postmenopausal women with estrogen receptor-positive (ER+) HER2-negative (HER2-) metastatic breast cancer","authors":"K. Jhaveri, E. Winer, E. Lim, Jose AlejandroPerez Fidalgo, M. Bellet, I. Mayer, V. Boni, J. Patel, A. Bardia, Jose M Garcia, P. Kabos, Mary Gates, Ya-Chi Chen, J. Fredrickson, Xiaojing Wang, L. Friedman, J. Spoerke, S. Gendreau, Ciara Metcalfe, Lichuan Liu, Ching-Wei Chang, S. Monemi, Monica Gonzalez, U. McCurry, S. Milan, E. Humke, S. Loi","doi":"10.1158/1538-7445.sabcs19-pd7-05","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs19-pd7-05","url":null,"abstract":"","PeriodicalId":415047,"journal":{"name":"Poster Spotlight Session Abstracts","volume":"26 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124979599","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}