Pub Date : 2019-02-15DOI: 10.1158/1538-7445.SABCS18-GS1-01
A. Swarbrick, Sz Wu, D. Roden, Ghamdan Al-Eryani, S. O'toole, E. Lim
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.
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Pub Date : 2019-02-15DOI: 10.1158/1538-7445.SABCS18-GS5-07
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
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Pub Date : 2019-02-15DOI: 10.1158/1538-7445.SABCS18-GS6-06
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
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.
背景:乳房切除术，主要是双侧乳房切除术(BMx)的发生率在年轻乳腺癌(BC)患者中最为显著。对长期生活质量(QOL)的影响很大程度上是未知的。方法:在2016年10月至2017年11月期间，我们在一项大型前瞻性队列研究中对年龄≤40岁的乳腺癌患者进行了BREAST-Q(一种经过验证的患者报告结果测量)。通过调查和图表回顾获得人口统计和治疗信息。每个领域(乳房满意度、生理、社会心理和性)的平均breast - q分数按手术类型进行比较;BREAST-Q评分(范围:0-100)越高，表明生活质量越好。采用线性回归确定BREAST-Q域评分的预测因子。结果:581名0-3期BC患者完成了BREAST-Q检查，中位时间为5.8年。dx的中位年龄为37岁(范围:26-40岁);86%为0期、1期或2期;28%做过保乳手术;72%行乳房切除术(Mx)，其中72%行BMx, 89%行乳房重建。与BCS相比，单侧乳房切除术(UMx)或BMx患者的乳房满意度、社会心理和性健康的平均breast - q评分(未经调整)较低;各组之间的身体功能相似。在多变量分析中，较低的BREAST-Q心理社会评分与放疗和Mx (UMx或BMx)有关。较低的性幸福感得分也与Mx。放疗后乳房评分满意度降低具有临床意义(β -8.1 95% CI -11.9- 4.3, p值0.03)。报告淋巴水肿的患者身体健康得分较低，而接受手术超过5年的患者身体健康得分较高。在所有4个领域得分较低与报告的财务困境有关。结论:年轻乳腺癌幸存者的局部治疗可能对其乳房满意度、心理社会和性结局有持续的影响，特别是UMx或BMx的效果。社会经济压力因素似乎也起到了一定作用。当向年轻女性咨询手术决定时，了解潜在的长期生活质量影响是至关重要的。引用格式:Dominici LS, Hu J, King TA, Ruddy KJ, Tamimi RM, Peppercorn J, Schapira L, Borges VF, Come SE, Warner E, Partridge AH, Rosenberg SM。年轻女性乳腺癌的局部治疗和生活质量结局[摘要]。2018年圣安东尼奥乳腺癌研讨会论文集;2018年12月4-8日;费城(PA): AACR;癌症杂志，2019;79(4增刊):摘要nr GS6-06。
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Pub Date : 2019-02-15DOI: 10.1158/1538-7445.SABCS18-GS5-03
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
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
背景:最近的试验提供的证据表明，肥胖和低水平的体育活动不仅与患乳腺癌的风险增加有关，而且还与乳腺癌患者复发风险增加和生存率降低有关。SUCCESS C研究是第一个评估强化生活方式干预计划效果的随机III期试验，重点关注辅助化疗后的身体活动和健康饮食对早期乳腺癌女性无病生存的影响。方法:SUCCESS C是一项德国多中心，2×2因子设计，随机III期研究，比较her2阴性早期乳腺癌患者的无病生存率(DFS)，分别接受3个周期的表柔比星、氟尿嘧啶、环磷酰胺化疗，随后接受3个周期的多西紫杉醇(FEC-D)或6个周期的多西紫杉醇-环磷酰胺(DC)治疗。第二次随机化比较了体重指数(BMI)为24-40 kg/m2的患者的DFS，这些患者要么接受以电话为基础的个体化生活方式干预(LI)计划，旨在2年内适度减肥(LI组)，要么接受仅健康生活方式的一般建议(非LI组)。采用单变量cox回归和多变量cox回归分析生活方式干预后的DFS，调整年龄(年龄，连续)、BMI (kg/m2，连续)、绝经前、绝经后、肿瘤大小(pT1、pT2、pT3/pT4)、淋巴结分期(pN0、pN1、pN2、pN3)、激素受体状态(阳性、阴性)、分级(G1、G2、G3)、组织学类型(导管、小叶、其他)和化疗随机化(FEC-D、DC)。中位随访时间为64.2个月。结果:总体而言，成功C研究招募的3643名患者中有2292名被随机分配到生活方式干预计划中(非LI组和LI组均有1146名患者)。意向治疗分析显示，在单变量分析(风险比[HR] 0.99, 95%可信区间[CI] 0.76 - 1.28, p = 0.922)和校正多变量cox回归(HR 0.91, 95% CI 0.70 - 1.18, p = 0.48)中，两个治疗组(LI组与非LI组)的DFS无差异。在2年的随访中，与LI计划开始相比，LI组的患者平均体重减轻了1.0 kg，而非LI组的患者平均体重增加了0.95 kg (p)。结论:这项探索性和非计划性的中期分析表明，完成系统的电话生活方式干预计划可能会对早期乳腺癌患者的预后产生积极影响。引用格式: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.生活方式干预对早期乳腺癌患者无病生存的影响:随机成功研究的中期分析[摘要]。2018年圣安东尼奥乳腺癌研讨会论文集;2018年12月4-8日;费城(PA): AACR;癌症杂志，2019;79(4增刊):摘要nr GS5-03。
{"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}
Pub Date : 2019-02-15DOI: 10.1158/1538-7445.SABCS18-GS6-01
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
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.
背景年轻女性比老年女性更有可能出现高分期乳腺癌(BC)，并且可能更大程度上受益于新辅助全身治疗(NST)的降低分期。年轻也与更大的病理完全反应(pCR)的可能性相关。我们对年轻女性乳腺癌患者进行了一项大型前瞻性队列研究，研究了新辅助治疗的反应、保乳手术(BCS)术前和术后的适格性以及手术治疗。方法年轻女性乳腺癌研究(YWS)是一项多中心队列研究，研究对象为年龄≤40岁诊断为BC的女性，从2006年到2016年共纳入1302例患者。通过病历和中心病理检查获得疾病特征和治疗信息。我们独立回顾了NST前后的手术建议、BCS边缘性/不合格到BCS合格的转变、手术、BCS合格妇女选择乳房切除术(MTX)的记录原因以及最终的病理反应。在参加YWS的1302名女性中，801名(62%)表现为单侧I-III期乳腺癌，317名(40%)接受了NST治疗。年龄中位数为36岁(22-40岁)。在nst前，85/317例(27%)符合BCS标准，49例(15%)为边缘性，169例(53%)不符合BCS标准(炎症性乳腺癌(IBC) 16例，大肿瘤/美容癌88例，弥漫性钙化48例，多中心性83例)。在218例NST前BCS不合格/边缘性患者中，82例(38%)在NST后符合BCS。4例在nst前符合BCS条件的患者变得不符合条件。在所有符合nst后BCS治疗条件的患者中(n=163)， 80例(49%)患者尝试BCS, 74例(93%)患者成功，83例(51%)患者选择MTX。选择MTX的原因包括:患者偏好(38/83(46%))、BRCA或TP53突变(31(37%))、家族史(3(4%))、未知(11(13%))。在最终病理中，75例(24%)患者有pCR。在实现pCR的患者中，48例(64%)接受了MTX治疗，不到一半(21/48例(44%))的患者是解剖指征(IBC，诊断时的大肿瘤，弥漫性钙化，多中心疾病)。结论:虽然NST使符合BCS条件的年轻女性比例增加了一倍，但近一半的女性选择MTX，而不考虑NST的反应，主要是出于个人偏好或高风险的预防原因。这些数据强调，年轻乳腺癌女性的手术决策往往是由疾病程度和临床治疗反应以外的因素驱动的。引用格式: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 .年轻女性乳腺癌新辅助全身治疗后的手术治疗:来自前瞻性队列研究的结果[摘要]。2018年圣安东尼奥乳腺癌研讨会论文集;2018年12月4-8日;费城(PA): AACR;癌症杂志，2019;79(4增刊):GS6-01。
{"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}
Pub Date : 2019-02-15DOI: 10.1158/1538-7445.SABCS18-GS3-01
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
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
背景:他莫昔芬是预防和治疗乳腺癌的有效药物，但其引起子宫内膜癌和静脉血栓栓塞的风险限制了其广泛应用。我们在生物标志物试验中反复表明，他莫昔芬的最小有效剂量低于20mg /天，但关于疗效和安全性的明确答案需要进行三期试验。导管原位癌(DCIS)的最佳治疗方法仍存在争议。方法:我们对手术后激素敏感性乳腺上皮内瘤变(DCIS或LCIS)的女性进行了他莫昔芬(T) (5mg /天)与安慰剂(P)的III期试验。G3、边缘阳性或有粉刺/坏死的DCIS患者接受放疗。随机分组后，妇女每6个月进行一次年度乳房x光检查，持续5年。最初的统计计算根据低于预期的应计数进行了修订，独立数据安全监测委员会建议披露结果，因为观察到80%的最初预期事件。结果:在2008年11月1日至2015年3月31日期间，共有500名女性被随机分为T、5mg /天或P组，持续3年。共有10名患者因同意撤回或退出而无法评估。各兵种之间的主体特征平衡得很好。截至2018年5月31日，在中位随访5.1年(四分位数范围3.9-6.3)后，T组有14例复发，P组有29例复发(风险比=0.48,95% CI, 0.25-0.89, P =0.02)。T组的事件发生率为11.8/1000 py, P组为24.9/1000 py。大多数复发为浸润性乳腺癌:T组为11/14 (78%)，P组为16/29(55%)。T组有8例严重不良事件，P组有12例，其中每组2例动脉事件，T组有2例浅表性静脉炎，T组有1例子宫内膜癌(年发病率0.85/1000 py)。T组和P组分别有6例和4例第二原发癌症，P组有2例死亡。绝经期症状在T组更常见，会议将详细报道。结论:他莫昔芬5mg /天的剂量可使手术后激素敏感性DCIS或LCIS患者的复发率减半，且毒性有限，为女性患者提供了一种有效的治疗选择。此外，本研究对高危未受影响妇女的预防性治疗具有重要意义。ClinicalTrials.gov标识符:NCT01357772;由意大利卫生部(RFPS-2006-1-339898)和意大利癌症研究协会(AIRC) (IG 2008资助号:5611. 引用本文: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.低剂量他莫西芬预防激素敏感性乳腺导管原位癌或小叶原位癌复发的随机对照III期试验[摘要]。2018年圣安东尼奥乳腺癌研讨会论文集;2018年12月4-8日;费城(PA): AACR;癌症杂志，2019;79(4增刊):摘要nr GS3-01。
{"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}
Pub Date : 2019-02-15DOI: 10.1158/1538-7445.SABCS18-GS2-07
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
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
{"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}
Pub Date : 2019-02-15DOI: 10.1158/1538-7445.SABCS18-GS6-03
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
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.
背景:从患者的角度出发，TAILORx患者报告结局(PRO)从C+E而不仅仅是E来量化症状和健康相关生活质量(HRQL)，因此可以为中等风险组中仍可能考虑化疗的妇女提供决策依据。方法:将OncoType DX复发评分为11-25分的TAILORx参与者随机分为E组或C+E组。所有入选的受试者(N=612)在基线、3、6、12、24和36个月完成了疲劳、内分泌症状、认知障碍(PCI)和复发恐惧的PROs测量。在基线、12个月和36个月时评估HRQL。线性回归(LR)检查每个方案样本的PRO分数。结果:总体而言，与基线相比，参与者在3、6、12、24和36个月时报告的疲劳、内分泌症状和PCI明显增加，随机分配到C+E组的参与者在基线-3个月时报告的变化幅度大于随机分配到E组的参与者(表1)。总体而言，12个月时各组之间的症状具有可比性。绝经前妇女在24个月和36个月时也有类似的症状。绝经后妇女随机分为C+E组，在第24和36个月时内分泌症状加重，在第6和24个月时疲劳加重。在治疗和随访期间，两组患者对复发的恐惧程度具有可比性。多元线性回归发现疲劳增加(LR斜率β=0.67)、内分泌症状(β= 0.14)和PCI (β=0.11)是各组HRQL下降的重要预测因子(p)。结论:TAILORx是第一个在随机分配到单独内分泌治疗与化疗内分泌治疗的乳腺癌患者中检查患者报告的疲劳、内分泌症状、PCI和HRQL的试验，从而使我们能够量化化疗引起的急性和长期症状。正如预期的那样，化疗与治疗期间更严重的疲劳、内分泌症状和PCI急性相关，并且对于绝经后妇女有更大的长期内分泌症状。症状加重与较差的HRQL相关。两组间长期HRQL具有可比性。引用格式:Wagner LI, Gray RJ, Garcia S, Whelan TJ, Tevarweerk A, Yanez B, Carlos R, Gareen I, mccasgill - stevens W, Cella D, Sparano JA, Sledge, Jr. GW，代表TAILORx研究团队。单独内分泌治疗(E)与化学内分泌治疗(C+E)的症状和健康相关生活质量:TAILORx患者报告的结果[摘要]。2018年圣安东尼奥乳腺癌研讨会论文集;2018年12月4-8日;费城(PA): AACR;癌症杂志，2019;79(4增刊):摘要nr GS6-03。
{"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}
Pub Date : 2019-02-15DOI: 10.1158/1538-7445.SABCS18-GS1-02
Tk Seth, S. Bai, M. Hu, Emi Sei, Al Wood, J. Wiley, Huiqin Chen, A. Contreras, M. Teshome, B. Lim, N. Navin
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.
人类乳房组织由小叶组成，这些小叶连接着一个复杂的导管网络，在进化过程中，这些导管被设计用来生产和输送乳汁，以滋养后代。组织病理学已经根据形态学特征确定了10种主要的细胞类型，但在细胞状态(反映不同生物学功能的细胞类型的转录程序)方面提供的信息有限。在这项研究中，我们利用单细胞RNA测序方法生成了正常人类乳房的无偏细胞图谱，以确定细胞类型和细胞状态。我们对11名乳腺切除术后病理正常的女性的31442个间质细胞进行了39个基于微滴的单细胞RNA测序。无偏表达分析鉴定出三种主要的细胞类型:上皮细胞(管状细胞和基底细胞)、成纤维细胞和内皮细胞，此外还有几种次要的细胞类型:巨噬细胞、t细胞、自然杀伤细胞、周细胞和平滑肌细胞。这些细胞类型的细胞状态分析揭示了不同的转录程序在管腔上皮细胞(激素受体阳性和分泌)，基底上皮细胞(肌上皮或基底样)，内皮细胞(淋巴或血管)，巨噬细胞(M1或M2)和成纤维细胞(三个亚群)，并提供了了解每种细胞类型的祖细胞。这些数据为研究界提供了有价值的参考，并将为正常细胞类型如何在肿瘤微环境中转化以促进或抑制乳腺癌的进展提供新的见解。引用格式:Seth TK, Bai S, Hu M, Sei E, Wood A, Wiley J, Chen H, Contreras A, Teshome M, Lim B, Navin NE。迈向人类乳腺细胞图谱[摘要]。2018年圣安东尼奥乳腺癌研讨会论文集;2018年12月4-8日;费城(PA): AACR;癌症杂志，2019;79(4增刊):摘要nr GS1-02。
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Pub Date : 2019-02-15DOI: 10.1158/1538-7445.SABCS18-GS4-03
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
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.
背景乳房肿瘤切除术后全乳照射(WBI)可降低局部复发的风险，从而避免后续的乳房切除术。它是保乳治疗的关键组成部分。WBI通常在3-6周内按日分次给予。在加速部分乳房照射(APBI)中，辐射在一周或更短的时间内传递到具有正常组织边缘的手术腔。它的引入是为了以更短、更方便的方式提供治疗。3D-CRT是一种有吸引力的方法，因为它是非侵入性的，并且使用了广泛可用的外部束RT的标准技术。RAPID试验的目的是确定保乳手术(BCS)后使用3D-CRT的APBI是否优于WBI。方法女性≥40岁，腋窝淋巴结阴性的浸润性导管癌，或导管原位癌(DCIS)≤3cm，行BCS治疗，切除边界明确。结果2006年2月至2011年7月，来自加拿大、澳大利亚和新西兰的2135名患者被随机分配:1070名患者被分配到APBI, 1065名患者被分配到WBI。中位随访时间为8.6年。研究人群的平均年龄为61岁;82%的患者患有浸润性乳腺癌，18%的患者仅患有DCIS。结论:在我们的试验中，APBI方案在预防局部复发方面并不亚于WBI方案。虽然APBI与较低的急性毒性相关，但观察到APBI后期正常组织毒性和不良美容的增加。引用格式: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.快速:三维共形放疗加速部分乳房放疗的随机试验[摘要]。2018年圣安东尼奥乳腺癌研讨会论文集;2018年12月4-8日;费城(PA): AACR;癌症杂志，2019;79(4增刊):摘要nr GS4-03。
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