General Session Abstracts最新文献

{"title":"Abstract GS1-01: Landscape of the breast tumour microenvironment at single-cell resolution","authors":"A. Swarbrick, Sz Wu, D. Roden, Ghamdan Al-Eryani, S. O'toole, E. Lim","doi":"10.1158/1538-7445.SABCS18-GS1-01","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-GS1-01","url":null,"abstract":"Breast cancers are a complex 9ecosystem9 of diverse cell types, whose heterotypic interactions play central roles in defining the aetiology of disease and its response to therapy. The next generation of therapies will likely be based upon an integrated understanding of the malignant, microenvironmental and immune states that define the tumour and inform treatment response. However, our poor understanding of the tumour microenvironment (TME) of breast cancers has limited the development and implementation of new drugs that target stromal and immune cells. Single cell genomics (SCG) is a remarkable new platform to examine the compositional, gene expression and other parameters of thousands of cells, rapidly and at scale. We have used a multi-dimensional SCG approach to characterise the TME in a unique cohort of early and metastatic breast cancers with rich clinico-pathological annotation. We have conducted single cell RNA-Sequencing on more than 125,000 cells collected from 22 patients. Malignant cells showed remarkable intra-tumoural heterogeneity for canonical breast cancer features, such as intrinsic subtype, hormone receptor expression and activity, drug targets, drug resistance signatures and transcriptional drivers. Cancer Associated Fibroblasts (CAFs), which are classically studied as a single cell type, were heterogeneous across primary and metastatic sites. Interestingly we identified a myofibroblast-like subset and an inflammatory-mediator subset and propose multi-faceted roles in regulating malignancy and tumour immunity. Distinct transcription factor networks regulated these polarised states. We applied a new method known as CITE-Seq to measure cell surface immune markers and checkpoint proteins simultaneous to RNA-Sequencing. We resolve the tumour-immune milieu with high precision and generate new transcriptional signatures of breast tumour-infiltrating leukocytes. To track lymphocyte clonal dynamics through space and time, we developed a novel method known as RAGE-Seq to permit simultaneous full length lymphocyte receptor- and RNA-sequencing at single cell resolution. We observe clonal expansion and trafficking of CD4+ and CD8+ T lymphocytes between the lymph nodes, blood and tumor of patients. In comparison, B cells were polyclonal, suggesting an absence of antigen-dependent clonal expansion. This data provides by far the most extensive insights into the cellular landscape of breast cancer and will reveal new biomarkers and opportunities for stromal- and immune-based therapy. Citation Format: Swarbrick A, Wu SZ, Roden D, Al-Eryani G, O9Toole S, Lim E. Landscape of the breast tumour microenvironment at single-cell resolution [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS1-01.","PeriodicalId":12697,"journal":{"name":"General Session Abstracts","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78757389","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 GS5-07: International pooled analysis of the prognostic impact of disseminated tumor cells from the bone marrow in early breast cancer: Results from the PADDY study","authors":"A. Hartkopf, S. Brucker, F. Taran, N. Harbeck, A. Au, B. Naume, J. Pierga, O. Hoffmann, M. W. Beckmann, L. Rydén, T. Fehm, R. Aft, S. Montserrat, V. Walter, B. Rack, F. Schuetz, E. Borgen, M. Ta, A. Bittner, P. Fasching, M. Fernö, N. Krawczyk, K. Weilbaecher, M. Margelí, M. Hahn, J. Jueckstock, C. Domschke, F. Bidard, S. Kasimir-Bauer, B. Schoenfisch, A. Kurt, M. Wallwiener, G. Gebauer, D. Wallwiener, W. Janni, K. Pantel","doi":"10.1158/1538-7445.SABCS18-GS5-07","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-GS5-07","url":null,"abstract":"","PeriodicalId":12697,"journal":{"name":"General Session Abstracts","volume":"64 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90532489","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 GS6-06: Local therapy and quality of life outcomes in young women with breast cancer","authors":"L. Dominici, Jiani Hu, T. King, K. Ruddy, R. Tamimi, J. Peppercorn, L. Schapira, V. Borges, S. Come, E. Warner, A. Partridge, Shoshana M. Rosenberg","doi":"10.1158/1538-7445.SABCS18-GS6-06","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-GS6-06","url":null,"abstract":"Background: Increasing rates of mastectomy, primarily bilateral mastectomy (BMx), have been most dramatic in young women with breast cancer (BC). Impact on long-term quality of life (QOL) is largely unknown. Methods: Between 10/2016-11/2017, we administered the BREAST-Q, a validated patient-reported outcomes measure, to women dx with BC at age ≤40 in a large prospective cohort study. Demographic and treatment information was obtained by surveys and chart review. Mean BREAST-Q scores for each domain (breast satisfaction, physical, psychosocial, and sexual) were compared by surgery types; higher BREAST-Q scores (range: 0-100) indicate better QOL. Linear regression was used to identify predictors of BREAST-Q domain scores. Results: 581 women with stage 0-3 BC completed the BREAST-Q a median of 5.8 years from dx. Median age at dx was 37 (range: 26-40) years; 86% had stage 0, 1 or 2 disease; 28% had breast-conserving surgery (BCS); 72% had mastectomy (Mx), among whom 72% underwent BMx and 89% had reconstruction. Mean BREAST-Q scores (unadjusted) for breast satisfaction, psychosocial, and sexual well-being were lower for patients having unilateral mastectomy (UMx) or BMx compared to BCS; physical function was similar among groups. In multivariate analysis, lower BREAST-Q psychosocial scores were associated with radiation and Mx (UMx or BMx). Lower sexual well-being scores were also associated with Mx. Lower satisfaction with breast scores following radiation were of a clinically significant magnitude (β -8.1 95% CI -11.9- -4.3, p-value 0.03). Lower scores for physical well-being were seen for patients reporting lymphedema and higher for those who had undergone surgery more than 5 years prior. Lower scores across all 4 domains were associated with reported financial distress. Conclusion: Local therapy in young breast cancer survivors may have a persistent impact on their breast satisfaction, psychosocial, and sexual outcomes, with particular effects from UMx or BMx. Socio-economic stressors also appear to play a role. When counseling young women about their surgical decisions, knowledge of potential long-term QOL impact is of critical importance. Citation Format: Dominici LS, Hu J, King TA, Ruddy KJ, Tamimi RM, Peppercorn J, Schapira L, Borges VF, Come SE, Warner E, Partridge AH, Rosenberg SM. Local therapy and quality of life outcomes in young women with breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS6-06.","PeriodicalId":12697,"journal":{"name":"General Session Abstracts","volume":"75 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86379260","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 GS5-03: Lifestyle Intervention and Effect on Disease-free Survival in Early Breast Cancer Pts: Interim Analysis from the Randomized SUCCESS C Study","authors":"W. Janni, B. Rack, T. Friedl, V. Müller, R. Lorenz, M. Rezai, H. Tesch, G. Heinrich, U. Andergassen, N. Harbeck, F. Schochter, A. D. Gregorio, M. Tzschaschel, J. Huober, P. Hepp, T. Fehm, A. Schneeweiss, W. Lichtenegger, J. Blohmer, Dagmar Hauner, M. Beckmann, L. Häberle, P. Fasching, Hans Hauner","doi":"10.1158/1538-7445.SABCS18-GS5-03","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-GS5-03","url":null,"abstract":"Background: Recent trials have provided evidence that obesity and a low level of physical activity are not only associated with a higher risk of developing breast cancer, but also with an increased risk for recurrence and reduced survival in breast cancer patients (pts). The SUCCESS C study is the first randomized Phase III trial to evaluate the effect of an intensive lifestyle intervention program, focusing on both physical activity and healthy diet following adjuvant chemotherapy on disease-free survival in women with early breast cancer. Methods: SUCCESS C is a German multicenter, 2×2 factorial design, randomized phase III study comparing disease-free survival (DFS) in pts with HER2-negative early breast cancer treated with either 3 cycles of epirubicine, fluorouracil, cyclophosphamide chemotherapy followed by 3 cycles of docetaxel (FEC-D) or 6 cycles of docetaxel-cyclophosphamide (DC). The second randomization compares DFS in pts with a body mass index (BMI) of 24—40 kg/m2 receiving either a telephone-based individualized lifestyle intervention (LI) program aiming at moderate weight loss for 2 years (LI arm) or general recommendations for a healthy lifestyle alone (non-LI arm). DFS according to lifestyle intervention was analyzed using both univariable cox regressions and multivariable cox regressions adjusted for age (years, continuous), BMI (kg/m2, continuous), menopausal status (premenopausal, postmenopausal), tumor size (pT1, pT2, pT3/pT4), nodal stage (pN0, pN1, pN2, pN3), hormone receptor status (positive, negative), grading (G1, G2, G3), histological type (ductal, lobular, other) and chemotherapy randomization (FEC-D, DC). Median follow-up was 64.2 months. Results: Overall, 2292 of the 3643 pts recruited for the SUCCESS C study were randomized for the lifestyle intervention program (1146 pts in both the non-LI arm and the LI arm). The Intention-to-treat analysis revealed no difference in DFS between the two treatment arms (LI vs. non-LI) in univariable analysis (hazard ratio [HR] 0.99, 95% confidence interval [CI] 0.76 — 1.28, p = 0.922) and in adjusted multivariable cox regression (HR 0.91, 95% CI 0.70 — 1.18, p = 0.48). At the 2-year follow up, pts in the LI arm lost on average 1.0 kg weight compared to the start of the LI program, while pts in the non-LI arm gained on average 0.95 kg (p Conclusions: This explorative and non-planned interim analysis indicates that the completion of a systematic telephone life style intervention program may positively impact patient outcome in early breast cancer. Citation Format: Janni W, Rack BK, Friedl TW, Muller V, Lorenz R, Rezai M, Tesch H, Heinrich G, Andergassen U, Harbeck N, Schochter F, De Gregorio A, Tzschaschel M, Huober J, Hepp P, Fehm TN, Schneeweiss A, Lichtenegger W, Blohmer J, Hauner D, Beckmann MW, Haberle L, Fasching PA, Hauner H. Lifestyle Intervention and Effect on Disease-free Survival in Early Breast Cancer Pts: Interim Analysis from the Randomized SUCCESS C Study [abstract]. In","PeriodicalId":12697,"journal":{"name":"General Session Abstracts","volume":"70 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86749422","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 GS6-01: Surgical treatment after neoadjuvant systemic therapy in young women with breast cancer: Results from a prospective cohort study","authors":"Hj. Kim, L. Dominici, Shoshana M. Rosenberg, L. Pak, P. Poorvu, K. Ruddy, R. Tamimi, L. Schapira, S. Come, J. Peppercorn, V. Borges, E. Warner, Hilde G. Vardeh, L. Collins, T. King, A. Partridge","doi":"10.1158/1538-7445.SABCS18-GS6-01","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-GS6-01","url":null,"abstract":"Background Young women are more likely than older women to present with higher stage breast cancer (BC) and may benefit to a greater extent from downstaging with neoadjuvant systemic treatment (NST). Young age is also associated with greater likelihood of pathologic complete response (pCR). Using a large prospective cohort of young women with BC, we investigated response to neoadjuvant therapy, eligibility for breast conserving surgery (BCS) pre- and post-NST, and surgical treatment. Methods The Young Women9s Breast Cancer Study (YWS) is a multi-center cohort of women diagnosed with BC at age ≤40, that enrolled 1302 patients from 2006 to 2016. Disease characteristics and treatment information were obtained through medical record and central pathology review. Surgical recommendation before and after NST, conversion from BCS borderline/ineligible to BCS eligible, surgery, documented reasons for choosing mastectomy (MTX) among BCS eligible women, and final pathologic response were independently reviewed. Results Among 1302 women enrolled in YWS, 801 (62%) presented with unilateral stage I-III breast cancer and 317(40%) received NST. Median age was 36 years old (22-40). Pre-NST, 85/317 (27%) were BCS eligible, 49 (15%) were borderline, and 169 (53%) were not eligible (16 inflammatory breast cancer (IBC), 88 large tumor size /cosmetic, 48 diffuse calcifications, and 83 multicentricity). Among the 218 patients who were BCS ineligible/borderline pre-NST, 82 (38%) became eligible for BCS after NST. 4 patients who were BCS eligible pre-NST became ineligible. Of all patients eligible for BCS post-NST (n=163), 80 (49%) attempted BCS, 74 (93%) of whom were successful, and 83 (51%) chose MTX. Reasons for choosing MTX included: patient preference (38/83 (46%)), BRCA or TP53 mutation (31 (37%)), family history (3 (4%)), unknown (11 (13%)). On final pathology, 75 (24%) patients had pCR. Among patients who achieved a pCR, 48 (64%) underwent MTX, fewer than half (21/48 (44%)) were for anatomic indications (IBC, large tumor at diagnosis, diffuse calcifications, multicentric disease). Conclusion While NST doubled the proportion of young women eligible for BCS, nearly half chose MTX regardless of response to NST, mostly for personal preference or high-risk preventative reasons. These data highlight that surgical decision making among young women with breast cancer is often driven by factors beyond extent of disease and clinical response to therapy. Citation Format: Kim HJ, Dominici L, Rosenberg S, Pak LM, Poorvu PD, Ruddy K, Tamimi R, Schapira L, Come S, Peppercorn J, Borges V, Warner E, Vardeh H, Collins L, King T, Partridge A. Surgical treatment after neoadjuvant systemic therapy in young women with breast cancer: Results from a prospective cohort study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS6-01.","PeriodicalId":12697,"journal":{"name":"General Session Abstracts","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89464310","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 GS3-01: A randomized placebo controlled phase III trial of low dose tamoxifen for the prevention of recurrence in women with operated hormone sensitive breast ductal or lobular carcinoma in situ","authors":"A. Decensi, M. Puntoni, A. G. Gonzaga, F. Avino, L. Cortesi, M. Donadio, M. Pacquola, F. Falcini, M. Gulisano, M. Digennaro, A. Tienghi, K. Cagossi, G. Pinotti, C. Varicchio, S. Caviglia, L. Boni, B. Bonanni","doi":"10.1158/1538-7445.SABCS18-GS3-01","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-GS3-01","url":null,"abstract":"Background: Tamoxifen is an effective drug for breast cancer prevention and treatment, but the risk of endometrial cancer and venous thromboembolism has limited its broader use. We have repeatedly shown in biomarker trials that the minimal effective dose of tamoxifen is lower than 20 mg/day, but a definitive answer on efficacy and safety required a phase III trial. The optimal treatment of ductal carcinoma in situ (DCIS) is still controversial. Methods: We conducted a phase III trial of tamoxifen (T), 5 mg/day versus placebo (P) in women with operated hormone sensitive breast intraepithelial neoplasia (DCIS or LCIS). Women with G3, positive margins or comedo/necrosis DCIS received radiotherapy. Women were seen every 6 months with an annual mammography for at last 5 years after randomization. Initial statistical calculations were revised according to the lower than expected accrual, and the Independent Data Safety Monitoring Board recommended the disclosure of results as 80% of the originally expected events were observed. Results: Between November 1, 2008 and March 31, 2015 a total of 500 women were randomized to either T, 5 mg/day or P for 3 years. A total of 10 patients are not assessable becuse of consent withdrawal or drop out. The main subject characteristics were well balanced between arms. As of May 31, 2018, after a median follow-up of 5.1 years (interquartile range, 3.9-6.3), there were 14 recurrences in the T arm and 29 in the P arm (hazard ratio=0.48, 95% CI, 0.25-0.89, p=0.02). The incidence rate of events was 11.8/1000 py in the T arm and 24.9/1000 py in the P arm. Most recurrences were invasive breast cancers: 11/14 (78%) in the T arm and 16/29 (55%) in the P arm. There were 8 serious adverse events in the T arm and 12 in the P arm, including 2 arterial events in each arm, 2 superficial phlebitis in the T arm and 1 endometrial cancer (annual rate 0.85/1000 py) in the T arm. There were 6 versus 4 second primary cancers in the T and P arm, respectively, and 2 deaths in the P arm. Menopausal symptoms were more frequent in the T arm and will be reported in details at the conference. Conclusions: Tamoxifen at the dose of 5 mg/day can halve the incidence of recurrence in women with operated hormone sensitive DCIS or LCIS with a limited toxicity, providing a valid treatment option in women with disease. In addition, this study has important implications for the preventive therapy of high risk unaffected women. ClinicalTrials.gov Identifier: NCT01357772; Supported by the Italian Ministry of Health - RFPS-2006-1-339898 and the Italian Association for Cancer Research (AIRC) - IG 2008 Grant no. 5611. Citation Format: DeCensi A, Puntoni M, Guerrieri Gonzaga A, Avino F, Cortesi L, Donadio M, Pacquola M, Falcini F, Gulisano M, Digennaro M, Tienghi A, Cagossi K, Pinotti G, Varicchio C, Caviglia S, Boni L, Bonanni B. A randomized placebo controlled phase III trial of low dose tamoxifen for the prevention of recurrence in women with operated hormone","PeriodicalId":12697,"journal":{"name":"General Session Abstracts","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84751781","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 GS2-07: PHARE randomized trial final results comparing 6 to 12 months of trastuzumab in adjuvant early breast cancer","authors":"X. Pivot, G. Romieu, M. Debled, J. Pierga, P. Kerbrat, T. Bachelot, M. Espié, A. Lortholary, P. Fumoleau, D. Serin, J. Jacquin, C. Jouannaud, M. Rios, S. Abadie-Lacourtoisie, L. Venat-Bouvet, L. Cany, S. Catala, D. Khayat, L. Gambotti, I. Pauporté, C. Mercier, S. Paget‐Bailly, J. Henriques, J. Grouin","doi":"10.1158/1538-7445.SABCS18-GS2-07","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-GS2-07","url":null,"abstract":"Since 2005, 12 months of trastuzumab added to chemotherapy alone is the standard of care in patients with HER2-positive breast cancer. PHARE (9Protocol for Herceptin® as Adjuvant therapy with Reduced Exposure9) is the first trial comparing a reduction of adjuvant trastuzumab versus the standard 12 months. In 2012, the first analysis failed to prove that 6-months was non-inferior to 12-months of adjuvant trastuzumab (NCT00381901). The current presentation reports the final analysis. Methods: The trial was sponsored by the French National Cancer Institute (INCa) (www.e-cancer.fr), and approved by central Ethical Committee on May 15 th 2006. Patients with HER2-positive early breast cancer were randomly assigned between 12 and 6 months of adjuvant trastuzumab duration. The randomization was stratified by concomitant or sequential trastuzumab administration with chemotherapy, estrogen receptor (ER) status and center. The primary objective was non-inferiority of 6- versus 12-months arms in the intent to treat population, in terms of disease-free survival (DFS) with a pre-specified hazard margin of 1.15. Overall Survival (OS) and metastasis free survival (MFS) were secondary endpoints. Results: A total of 3380 patients were randomized, their median age was 54 years (21-86). Patients and disease characteristics were well balanced between the two arms. No involved axillary node was observed in 54.5% of cases, 41.7% of tumors were ER negative. At a median follow-up of 7.5 years, 704 events counting for DFS were observed. Between the 12- and 6-months arms, the adjusted Hazard Ratio (HR) for DFS rates was 1.08 (95%CI: 0.93-1.25; p=0.39) favoring the longer exposure. The 1.15 margin of non-inferiority was included in the 95%CI. No heterogeneity in terms of treatment effect was observed, no significant difference for trastuzumab duration effects was found in any subgroups.For OS and MFS, the adjusted HR were 1.13 (95%CI 0.92-1.39) and 1.15 (95%CI 0.96-1.37), respectively. Conclusion: The choice of the non-inferiority margin will remain inherently a subject of controversy especially in the context of oncology trials where the primary outcome is survival and the least additional death could be considered unacceptable questioning the very feasibility of such trials. Nevertheless, PHARE failed to show that 6 months of adjuvant trastuzumab was non-inferior to 12 months. The standard of care should remain 12 months of adjuvant trastuzumab. Citation Format: Pivot X, Romieu G, Debled M, Pierga J-Y, Kerbrat P, Bachelot T, Espie M, Lortholary A, Fumoleau P, Serin D, Jacquin J-P, Jouannaud C, Rios M, Abadie-Lacourtoisie S, Venat-Bouvet L, Cany L, Catala S, Khayat D, Gambotti L, Pauporte I, Faure Mercier C, Paget-Bailly S, Henriques J, Grouin J-M. PHARE randomized trial final results comparing 6 to 12 months of trastuzumab in adjuvant early breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphi","PeriodicalId":12697,"journal":{"name":"General Session Abstracts","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73876736","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 GS6-03: Symptoms and health-related quality of life on endocrine therapy alone (E) versus chemoendocrine therapy (C+E): TAILORx patient-reported outcomes results","authors":"L. Wagner, R. Gray, S. Garcia, T. Whelan, A. Tevarweerk, B. Yanez, R. Carlos, I. Gareen, W. McCaskill-Stevens, D. Cella, J. Sparano, G. Sledge","doi":"10.1158/1538-7445.SABCS18-GS6-03","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-GS6-03","url":null,"abstract":"Background: TAILORx patient-reported outcomes (PRO) quantify symptoms and health-related quality of life (HRQL) from C+E beyond E alone from the patient9s perspective, thus can inform decision-making for women in the intermediate risk group for whom chemotherapy may still be considered. Methods: TAILORx participants with OncoType DX Recurrence Scores 11-25 were randomly assigned to E or C+E. All TAILORx participants enrolled 1/2010-10/2010 (N=612) completed PROs measuring fatigue, endocrine symptoms, cognitive impairments (PCI), and fear of recurrence at baseline, 3, 6, 12, 24 and 36 months. HRQL was assessed at baseline, 12, and 36 months. Linear regression (LR) examined PRO scores among the per-protocol sample. Results: Overall, participants reported significantly more fatigue, endocrine symptoms and PCI at 3, 6, 12, 24 and 36 months compared to baseline and those randomized to C+E reported a greater magnitude of change baseline-3 months compared to those randomized to E alone (Table 1). Overall, by 12 months symptoms were comparable between groups. Pre-menopausal women had comparable symptoms at 24 and 36 months. Post-menopausal women randomized to C+E had greater endocrine symptoms at 24 and 36 months and greater fatigue at 6 and 24 months. Fear of recurrence was comparable between arms during treatment and follow-up. Multiple linear regression identified increased fatigue (LR slope β=0.67), endocrine symptoms (β =0.14), and PCI (β=0.11) as significant predictors of decreased HRQL across arms (p Conclusions: TAILORx is the first trial to examine patient-reported fatigue, endocrine symptoms, PCI and HRQL among breast cancer patients randomized to endocrine therapy alone vs chemoendocrine therapy, thus allowing us to quantify acute and long-term symptoms uniquely attributable to chemotherapy. As expected, chemotherapy is associated with greater fatigue, endocrine symptoms and PCI acutely during treatment, and for post-menopausal women with greater long-term endocrine symptoms. Increased symptoms were associated with poorer HRQL. Long-term HRQL was comparable between groups. Citation Format: Wagner LI, Gray RJ, Garcia S, Whelan TJ, Tevarweerk A, Yanez B, Carlos R, Gareen I, McCaskill-Stevens W, Cella D, Sparano JA, Sledge, Jr. GW, On behalf of the TAILORx Study Team. Symptoms and health-related quality of life on endocrine therapy alone (E) versus chemoendocrine therapy (C+E): TAILORx patient-reported outcomes results [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS6-03.","PeriodicalId":12697,"journal":{"name":"General Session Abstracts","volume":"50 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79790417","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 GS1-02: Towards a human breast cell atlas","authors":"Tk Seth, S. Bai, M. Hu, Emi Sei, Al Wood, J. Wiley, Huiqin Chen, A. Contreras, M. Teshome, B. Lim, N. Navin","doi":"10.1158/1538-7445.SABCS18-GS1-02","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-GS1-02","url":null,"abstract":"The human breast tissue consists of lobules connected to a complex network of ducts that are evolutionarily designed to produce and transport milk to nourish offspring. Histopathology has identified 10 major cell types based on morphological features but have provided limited information on cell states - the transcriptional programs of cell types that reflect different biological functions. In this study, we have generated an unbiased 9cell atlas9 of the normal human breast to define the cell types and cell states using single cell RNA sequencing methods. We performed 39 microdroplet based single cell RNA sequencing of 31,442 stromal cells from 11 women with pathologically normal breast tissues that were collected from mastectomies. Unbiased expression analysis identified three major cell types: epithelial cells (luminal and basal), fibroblasts and endothelial cells, in addition to several minor cell types: macrophages, T-cells, natural killer cells, pericytes and smooth muscle cells. Analysis of cell states of these cell types revealed different transcriptional programs in luminal epithelial cells (hormone receptor positive and secretory), basal epithelial cells (myoepithelial or basement-like), endothelial cells (lymphatic or vascular), macrophages (M1 or M2) and fibroblasts (three subgroups) and provided insight into progenitors of each cell types. These data provide a valuable reference for the research community and will provide new insights into how normal cell types are transformed in the tumor microenvironment to promote or inhibit the progression of breast cancer. Citation Format: Seth TK, Bai S, Hu M, Sei E, Wood A, Wiley J, Chen H, Contreras A, Teshome M, Lim B, Navin NE. Towards a human breast cell atlas [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS1-02.","PeriodicalId":12697,"journal":{"name":"General Session Abstracts","volume":"118 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88040471","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 GS4-03: RAPID: A randomized trial of accelerated partial breast irradiation using 3-dimensional conformal radiotherapy (3D-CRT)","authors":"T. Whelan, J. Julian, M. Levine, T. Berrang, D. Kim, C. Gu, I. Germain, A. Nichol, M. Akra, S. Lavertu, F. Germain, A. Fyles, T. Trotter, F. Perera, S. Balkwill, S. Chafe, T. McGowan, T. Muanza, W. Beckham, B. Chua, I. Olivotto","doi":"10.1158/1538-7445.SABCS18-GS4-03","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-GS4-03","url":null,"abstract":"Background Whole breast irradiation (WBI) after lumpectomy reduces the risk of local recurrence, thereby avoiding subsequent mastectomy. It is a key component of breast conserving therapy. WBI is usually given in daily fractions over 3-6 weeks. With accelerated partial breast irradiation (APBI), radiation is delivered over a week or less to the surgical cavity with a margin of normal tissue. It was introduced to provide treatment in a shorter more convenient form. 3D-CRT is an attractive approach as it is non-invasive and uses standard techniques for external beam RT that are widely available. The objective of the RAPID trial was to determine if APBI using 3D-CRT was not inferior to WBI following breast conserving surgery (BCS). Methods Women ≥40 years of age with axillary node-negative invasive ductal carcinoma, or ductal carcinoma in situ (DCIS) ≤3cm treated by BCS with clear margins of excision were eligible. Randomization was stratified for age ( Results From February 2006 to July 2011, 2135 patients from sites in Canada, Australia, and New Zealand were randomly assigned: 1070 to APBI and 1065 to WBI. The median follow-up was 8.6 years. The mean age of the study population was 61 years; 82% of patients had invasive breast cancer and 18% had DCIS only. For invasive cancers: 60% were Conclusions The APBI regimen used in our trial was non-inferior to WBI in preventing local recurrence. Although it was associated with less acute toxicity, an increase in late normal tissue toxicity and adverse cosmesis was observed with APBI. Citation Format: Whelan T, Julian J, Levine M, Berrang T, Kim D-H, Gu CS, Germain I, Nichol A, Akra M, Lavertu S, Germain F, Fyles A, Trotter T, Perera F, Balkwill S, Chafe S, McGowan T, Muanza T, Beckham W, Chua B, Olivotto I. RAPID: A randomized trial of accelerated partial breast irradiation using 3-dimensional conformal radiotherapy (3D-CRT) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS4-03.","PeriodicalId":12697,"journal":{"name":"General Session Abstracts","volume":"18 72 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84252578","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}