Pub Date : 2019-02-15DOI: 10.1158/1538-7445.SABCS18-P6-02-14
W. Xing, Q. Li, G. Sun, R. Cao, B. Chen, C. Jiang, L. Ma, K. Wang
{"title":"Abstract P6-02-14: Not presented","authors":"W. Xing, Q. Li, G. Sun, R. Cao, B. Chen, C. Jiang, L. Ma, K. Wang","doi":"10.1158/1538-7445.SABCS18-P6-02-14","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-P6-02-14","url":null,"abstract":"","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82966992","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-P3-08-09
J. Boughey, T. Hoskin, D. Cocco, C. Day, R. Leon-Ferre, E. Habermann, M. Goetz
{"title":"Abstract P3-08-09: The 21-gene recurrence score and chemotherapy use in triple negative breast cancer (TNBC) and HER2 positive breast cancer: A National Cancer Database study","authors":"J. Boughey, T. Hoskin, D. Cocco, C. Day, R. Leon-Ferre, E. Habermann, M. Goetz","doi":"10.1158/1538-7445.SABCS18-P3-08-09","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-P3-08-09","url":null,"abstract":"","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":"60 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85532378","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-P2-09-15
H. Han, H. Khong, R. Costa, L. Loftus, D. Goodridge, T. Henry, H. Soliman, R. Ismail-Khan, B. Fridley, B. Czerniecki
Background: IFN-γ, a cytokine that plays diverse roles in innate and adaptive immunity, has been shown to be essential in anti-tumor immune response. In vitro and in vivo studies have shown the synergistic effect of IFN-γ in combination with HER2-targeting monoclonal antibodies with or without taxane chemotherapy. We have conducted a phase 1 clinical trial of systemic IFN-γ in combination with trastuzumab, pertuzumab, and paclitaxel in HER2-positive metastatic breast cancer. Methods: Two dose levels (DL) of IFN-γ, 50 (DL1) and 75 mcg/m2 (DL2), were evaluated. IFN-γ was given as subcutaneous injection three times weekly starting on day 1 of therapy for 12 weeks. Paclitaxel was administered intravenously (IV) weekly at 80mg/m2 in combination with trastuzumab IV (8 mg/kg loading dose, then 6 mg/m2 q 21 days) and pertuzumab IV (840 mg loading dose, then 420 mg q 21 days). Eligible patients had measurable metastatic HER2-positive breast cancer, were candidates to receive paclitaxel chemotherapy, and had an ECOG PS 0-1. The primary objective of this study was to evaluate the safety and tolerability of the combination therapy during the 12 weeks of treatment and to determine the recommended phase II dose (RP2D). Dose-limiting toxicity (DLT) during cycle one was defined as follows: Non-hematologic or hematologic toxicities that are ≥ grade 3 and probably or definitely related to study therapy which lead to chemotherapy treatment delays > 14 days. Results: A total of nine patients (3 on DL1 and 6 on DL2) were enrolled between 2/2017 and 11/2017. No DLT was observed. For DL1, no serious adverse events (SAE) or significant adverse events (AE) were observed among 3 patients who completed 12 weeks of treatment. For DL2, two out of 6 patients had SAEs including grade 3 pneumonitis (at week 8; treatment was subsequently discontinued) and grade 3 non-neutropenic fever (at week 6), which were possibly related to study treatment. These toxicities, however, did not meet the protocol definition of DLT. Based on these findings suggesting an improved tolerability of DL1 (50 mcg/m2), DL1 was selected as the RP2D. The most frequently observed grade 1 and 2 AEs that were at least possibly related to IFN-γ were fatigue (45%) nausea (36%), myalgia (36%), and fever (27%) diarrhea (18%). No grade 4 AE was noted. Grade 3 AEs included diarrhea, nausea, pneumonitis, non-neutropenic fever. Three out of 9 patients achieved partial response and 6 patients had stable disease per RECIST criteria. Conclusion: IFN-γ in combination with trastuzumab, pertuzumab, and paclitaxel was well tolerated in patients with HER2-positive metastatic breast cancer. Updated results will be presented and the phase 2 neoadjuvant trial is ongoing to further assess the efficacy of this approach. Citation Format: Han HS, Khong H, Costa R, Loftus L, Goodridge D, Henry T, Soliman H, Ismail-Khan R, Fridley B, Czerniecki B. A phase I study of interferon-gamma (γ)plus weekly paclitaxel, trastuzumab and pertuzum
{"title":"Abstract P2-09-15: A phase I study of interferon-gamma (γ)plus weekly paclitaxel, trastuzumab and pertuzumab in patients with HER-2 positive breast cancer","authors":"H. Han, H. Khong, R. Costa, L. Loftus, D. Goodridge, T. Henry, H. Soliman, R. Ismail-Khan, B. Fridley, B. Czerniecki","doi":"10.1158/1538-7445.SABCS18-P2-09-15","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-P2-09-15","url":null,"abstract":"Background: IFN-γ, a cytokine that plays diverse roles in innate and adaptive immunity, has been shown to be essential in anti-tumor immune response. In vitro and in vivo studies have shown the synergistic effect of IFN-γ in combination with HER2-targeting monoclonal antibodies with or without taxane chemotherapy. We have conducted a phase 1 clinical trial of systemic IFN-γ in combination with trastuzumab, pertuzumab, and paclitaxel in HER2-positive metastatic breast cancer. Methods: Two dose levels (DL) of IFN-γ, 50 (DL1) and 75 mcg/m2 (DL2), were evaluated. IFN-γ was given as subcutaneous injection three times weekly starting on day 1 of therapy for 12 weeks. Paclitaxel was administered intravenously (IV) weekly at 80mg/m2 in combination with trastuzumab IV (8 mg/kg loading dose, then 6 mg/m2 q 21 days) and pertuzumab IV (840 mg loading dose, then 420 mg q 21 days). Eligible patients had measurable metastatic HER2-positive breast cancer, were candidates to receive paclitaxel chemotherapy, and had an ECOG PS 0-1. The primary objective of this study was to evaluate the safety and tolerability of the combination therapy during the 12 weeks of treatment and to determine the recommended phase II dose (RP2D). Dose-limiting toxicity (DLT) during cycle one was defined as follows: Non-hematologic or hematologic toxicities that are ≥ grade 3 and probably or definitely related to study therapy which lead to chemotherapy treatment delays > 14 days. Results: A total of nine patients (3 on DL1 and 6 on DL2) were enrolled between 2/2017 and 11/2017. No DLT was observed. For DL1, no serious adverse events (SAE) or significant adverse events (AE) were observed among 3 patients who completed 12 weeks of treatment. For DL2, two out of 6 patients had SAEs including grade 3 pneumonitis (at week 8; treatment was subsequently discontinued) and grade 3 non-neutropenic fever (at week 6), which were possibly related to study treatment. These toxicities, however, did not meet the protocol definition of DLT. Based on these findings suggesting an improved tolerability of DL1 (50 mcg/m2), DL1 was selected as the RP2D. The most frequently observed grade 1 and 2 AEs that were at least possibly related to IFN-γ were fatigue (45%) nausea (36%), myalgia (36%), and fever (27%) diarrhea (18%). No grade 4 AE was noted. Grade 3 AEs included diarrhea, nausea, pneumonitis, non-neutropenic fever. Three out of 9 patients achieved partial response and 6 patients had stable disease per RECIST criteria. Conclusion: IFN-γ in combination with trastuzumab, pertuzumab, and paclitaxel was well tolerated in patients with HER2-positive metastatic breast cancer. Updated results will be presented and the phase 2 neoadjuvant trial is ongoing to further assess the efficacy of this approach. Citation Format: Han HS, Khong H, Costa R, Loftus L, Goodridge D, Henry T, Soliman H, Ismail-Khan R, Fridley B, Czerniecki B. A phase I study of interferon-gamma (γ)plus weekly paclitaxel, trastuzumab and pertuzum","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85693002","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-P6-09-12
D. Desa, B. Turner, B. Buscaglia, Rl Hill, R. Strawderman, D. Hicks, E. Brown
Background : Over-expression of Human Epidermal Growth Factor receptor-2 (HER2) in breast cancer is associated with an aggressive clinical course and poor prognosis. Targeting HER2 over-expression has been shown to be a remarkably effective therapeutic modality in the metastatic, adjuvant and neoadjuvant setting and the pathologic response to neoadjuvant treatment in HER2-positive breast cancer has been shown to be an excellent surrogate for a good outcome. The stromal tumor microenvironment is implicated in fostering tumor growth, facilitating cell migration and ultimately resulting in metastatic disease. Specifically, the collagenous extracellular matrix, which includes fibrillar collagen, has been suggested to play a role in the migration of malignant breast epithelial cells within the surrounding stroma. We have developed a novel methodology which uses an intrinsic optical signature to quantitatively evaluate fibrillar collagen (Burke et al. BMC Cancer 15 (2015): 929). Here, we evaluate the ability of this quantitative methodology to predict the pathologic response after neoadjuvant HER2-targeted treatment as assessed by the Residual Cancer Burden score/class (RCB). This quantitative evaluation in pre-treatment biopsies is then correlated with the pathologic response to treatment in the post-therapy resection. Material and Methods : Clinical pathologic variables for 29 cases of HER2-positive breast cancer that had undergone neoadjuvant chemotherapy plus HER2-targeted therapy were retrieved from the medical record database at URMC, including the post-treatment RCB score and ER/PR/HER2 status. Second harmonic generation (SHG) is an intrinsic optical signal produced by fibrillar collagen. To quantify collagen microstructure in the pre-treatment core biopsy, we used SHG imaging to determine the average forward to backward-light scattering ratio (F/B). The F/B ratio is sensitive to structural properties of collagen fibers. Results: Logistic regression was used to assess the association between F/B and the binary response variable RCB class (0/1 or 2/3). A likelihood ratio test was used to calculate the p-value to test whether the regression coefficient for F/B was zero (i.e. no effect) in the tumor-stromal interface. The average F/B ratio at the leading edge of the tumor stratified by RCB class is shown in Table 1. When evaluated in the bulk of the tumor tissue, F/B was not correlated with RCB status; however, when evaluated at the leading edge of the tumor stromal interface, F/B was significantly correlated with RCB status (p=0.035). Conclusions : We have previously shown that the measurement of F/B in the primary tumor after resection is an independent prognostic indicator of metastasis-free survival in breast cancer. Our results in the current study furthers these observations and suggests that the evaluations of the microstructure of collagen fibers by F/B measurement from the pre-treatment biopsy, specifically at the leading edge of the tumor
背景:人表皮生长因子受体-2 (HER2)在乳腺癌中的过度表达与侵袭性临床病程和不良预后相关。靶向HER2过表达已被证明是一种非常有效的治疗方式，在转移性、辅助性和新辅助性的情况下，HER2阳性乳腺癌对新辅助治疗的病理反应已被证明是一个很好的替代结果。间质肿瘤微环境与促进肿瘤生长、促进细胞迁移并最终导致转移性疾病有关。具体来说，胶原细胞外基质，包括纤维性胶原，已被认为在恶性乳腺上皮细胞在周围基质内的迁移中发挥作用。我们已经开发了一种新的方法，它使用内在光学特征来定量评估纤维性胶原蛋白(Burke等人)。中国医学杂志，2015，(3):929。在这里，我们通过残余癌症负担评分/分类(RCB)评估该定量方法预测新辅助her2靶向治疗后病理反应的能力。治疗前活检的定量评估与治疗后切除的病理反应相关。材料与方法:从URMC病历数据库中检索29例接受新辅助化疗加HER2靶向治疗的HER2阳性乳腺癌患者的临床病理变量，包括治疗后RCB评分和ER/PR/HER2状态。二次谐波产生(SHG)是纤维性胶原蛋白产生的固有光信号。为了量化预处理前核心活检中的胶原微结构，我们使用SHG成像来确定平均正反光散射比(F/B)。F/B比对胶原纤维的结构特性很敏感。结果:采用Logistic回归评估F/B与二元反应变量RCB分级(0/1或2/3)之间的关系。采用似然比检验计算p值，检验F/B在肿瘤-基质界面的回归系数是否为零(即无影响)。按RCB分级的肿瘤前缘平均F/B比率见表1。当在大部分肿瘤组织中进行评估时，F/B与RCB状态无关;然而，当在肿瘤间质界面前沿进行评估时，F/B与RCB状态显著相关(p=0.035)。结论:我们之前已经表明，原发肿瘤切除术后F/B的测量是乳腺癌无转移生存的独立预后指标。我们目前的研究结果进一步证实了这些观察结果，并表明通过治疗前活检的F/B测量来评估胶原纤维的微观结构，特别是在肿瘤-间质界面的前沿，可能有助于预测基于曲妥珠单抗的新辅助治疗的病理反应。需要在更大的患者群体中进行进一步的研究。引用格式:Desa DE, Turner BM, Buscaglia B, Hill RL, Strawderman RL, Hicks DG, Brown EB。使用多光子激光扫描显微镜评估核心针活检的新辅助治疗结果:一种新的方法[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;中国癌症杂志，2019;79(4增刊):P6-09-12。
{"title":"Abstract P6-09-12: Using multiphoton laser scanning microscopy to assess neoadjuvant therapy outcome in core needle biopsies: A novel methodology","authors":"D. Desa, B. Turner, B. Buscaglia, Rl Hill, R. Strawderman, D. Hicks, E. Brown","doi":"10.1158/1538-7445.SABCS18-P6-09-12","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-P6-09-12","url":null,"abstract":"Background : Over-expression of Human Epidermal Growth Factor receptor-2 (HER2) in breast cancer is associated with an aggressive clinical course and poor prognosis. Targeting HER2 over-expression has been shown to be a remarkably effective therapeutic modality in the metastatic, adjuvant and neoadjuvant setting and the pathologic response to neoadjuvant treatment in HER2-positive breast cancer has been shown to be an excellent surrogate for a good outcome. The stromal tumor microenvironment is implicated in fostering tumor growth, facilitating cell migration and ultimately resulting in metastatic disease. Specifically, the collagenous extracellular matrix, which includes fibrillar collagen, has been suggested to play a role in the migration of malignant breast epithelial cells within the surrounding stroma. We have developed a novel methodology which uses an intrinsic optical signature to quantitatively evaluate fibrillar collagen (Burke et al. BMC Cancer 15 (2015): 929). Here, we evaluate the ability of this quantitative methodology to predict the pathologic response after neoadjuvant HER2-targeted treatment as assessed by the Residual Cancer Burden score/class (RCB). This quantitative evaluation in pre-treatment biopsies is then correlated with the pathologic response to treatment in the post-therapy resection. Material and Methods : Clinical pathologic variables for 29 cases of HER2-positive breast cancer that had undergone neoadjuvant chemotherapy plus HER2-targeted therapy were retrieved from the medical record database at URMC, including the post-treatment RCB score and ER/PR/HER2 status. Second harmonic generation (SHG) is an intrinsic optical signal produced by fibrillar collagen. To quantify collagen microstructure in the pre-treatment core biopsy, we used SHG imaging to determine the average forward to backward-light scattering ratio (F/B). The F/B ratio is sensitive to structural properties of collagen fibers. Results: Logistic regression was used to assess the association between F/B and the binary response variable RCB class (0/1 or 2/3). A likelihood ratio test was used to calculate the p-value to test whether the regression coefficient for F/B was zero (i.e. no effect) in the tumor-stromal interface. The average F/B ratio at the leading edge of the tumor stratified by RCB class is shown in Table 1. When evaluated in the bulk of the tumor tissue, F/B was not correlated with RCB status; however, when evaluated at the leading edge of the tumor stromal interface, F/B was significantly correlated with RCB status (p=0.035). Conclusions : We have previously shown that the measurement of F/B in the primary tumor after resection is an independent prognostic indicator of metastasis-free survival in breast cancer. Our results in the current study furthers these observations and suggests that the evaluations of the microstructure of collagen fibers by F/B measurement from the pre-treatment biopsy, specifically at the leading edge of the tumor","PeriodicalId":20307,"journal":{"name":"Poster 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":"84017225","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-P5-07-05
N. Iyengar, B. Siegel, M. Malik, D. Giri, J. Tsai, M. Hughes, A. Adam, Samantha Williams, X. Zhou, W. Rodgers, P. Ginter, A. Patel, F. Yong, A. Cherian, P. August, A. Dannenberg
Background: Elevated body mass index (BMI) is associated with increased risk of estrogen receptor-positive postmenopausal breast cancer. Mechanistically, most individuals with elevated BMI have breast white adipose tissue inflammation (WATi) which confers increased breast cancer risk, particularly in those with existing benign breast disease. Individuals with WATi have elevated in-breast expression of aromatase and several systemic changes that increase breast cancer risk, including hyperinsulinemia and higher levels of C-reactive protein. However, women with normal BMI but high levels of body fat are also likely to harbor WATi and are at increased risk of postmenopausal breast cancer. The accuracy of BMI for assessing adiposity and predicting obesity-related disorders, including cancer, varies across race and ethnicity. Whether the association between BMI and WATi varies by race is unknown. Here we aimed to characterize relationships among breast WATi and clinicopathologic features in a racially diverse cohort undergoing mastectomy for breast cancer treatment. Methods: Non-tumorous breast tissue and fasting blood were collected from women undergoing mastectomy for breast cancer treatment or prevention at a single center serving a racially diverse patient population. Breast WATi was detected by the presence of crown-like structures in the breast (CLS-B), which are composed of a dead/dying adipocyte surrounded by CD68+ macrophages. Clinicopathologic data were abstracted from electronic medical records. Associations among categorical variables were examined using Fisher9s exact test. Relationships between continuous variables were examined using the Spearman correlation. Results: As of May 18, 2018 62 patients have been accrued; median age 55 (range 32 to 84). Self-reported race distribution was: 36 (58%) Asian, 5 African American (8%), 20 (32%) Caucasian, and 1 (2%) unknown. Breast tissue has been analyzed for WATi in 60 cases thus far. Clinicopathologic features stratified by the presence or absence of breast WATi are presented in. Breast WAT inflammation was associated with obesity (P=0.02) and a trend to association was observed with dyslipidemia (P Conclusions: Breast adipose inflammation is associated with elevated BMI and possibly metabolic syndrome disorders in a racially diverse population. These findings are consistent with observations from predominantly Caucasian cohorts. Race-specific characteristics will also be examined. Study accrual is ongoing and updated results will be presented. Citation Format: Iyengar NM, Siegel B, Malik M, Giri DD, Tsai J, Hughes M, Adam A, Williams S, Zhou XK, Rodgers W, Ginter P, Patel A, Yong F, Cherian A, August P, Dannenberg AJ. Obesity, adipose inflammation, and race in patients with early stage 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 P5-07-05.
背景:身体质量指数(BMI)升高与雌激素受体阳性绝经后乳腺癌的风险增加有关。从机制上讲，大多数BMI升高的个体都有乳房白色脂肪组织炎症(WATi)，这增加了患乳腺癌的风险，特别是那些已有良性乳房疾病的人。WATi患者的乳腺内芳香化酶表达升高，以及一些增加乳腺癌风险的全身变化，包括高胰岛素血症和更高水平的c反应蛋白。然而，身体质量指数正常但体脂水平高的女性也可能患有WATi，绝经后患乳腺癌的风险也会增加。BMI在评估肥胖和预测肥胖相关疾病(包括癌症)方面的准确性因种族和民族而异。BMI和WATi之间的关系是否因种族而异尚不清楚。在这里，我们的目的是在一个接受乳房切除术治疗乳腺癌的不同种族队列中描述乳房WATi与临床病理特征之间的关系。方法:在单一中心为不同种族的患者群体提供服务，从接受乳腺癌治疗或预防的乳房切除术的妇女中收集非肿瘤乳腺组织和空腹血液。乳腺WATi是通过乳腺中存在的冠状结构(CLS-B)来检测的，CLS-B由CD68+巨噬细胞包围的死亡/垂死脂肪细胞组成。临床病理资料从电子病历中提取。分类变量之间的关联使用fish9s精确检验。使用Spearman相关检验连续变量之间的关系。结果:截至2018年5月18日，已累计62例患者;中位年龄55岁(32 - 84岁)。自我报告的种族分布为:亚裔36人(58%)，非裔美国人5人(8%)，白种人20人(32%)，未知1人(2%)。到目前为止，已经对60例乳腺组织进行了WATi分析。临床病理特征分层的存在或不存在乳房WATi提出。乳腺脂肪炎症与肥胖相关(P=0.02)，且与血脂异常相关(P)。结论:在不同种族的人群中，乳腺脂肪炎症与BMI升高以及可能的代谢综合征疾病相关。这些发现与主要来自高加索人群的观察结果一致。种族特征也将被检查。研究项目正在进行中，并将提供最新的结果。引用格式:Iyengar NM, Siegel B, Malik M, Giri DD, Tsai J, Hughes M, Adam A, Williams S，周晓光，Rodgers W, Ginter P, Patel A, Yong F, Cherian A, August P, Dannenberg AJ。早期乳腺癌患者的肥胖、脂肪炎症和种族[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;中国癌症杂志2019;79(4增刊):P5-07-05。
{"title":"Abstract P5-07-05: Obesity, adipose inflammation, and race in patients with early stage breast cancer","authors":"N. Iyengar, B. Siegel, M. Malik, D. Giri, J. Tsai, M. Hughes, A. Adam, Samantha Williams, X. Zhou, W. Rodgers, P. Ginter, A. Patel, F. Yong, A. Cherian, P. August, A. Dannenberg","doi":"10.1158/1538-7445.SABCS18-P5-07-05","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-P5-07-05","url":null,"abstract":"Background: Elevated body mass index (BMI) is associated with increased risk of estrogen receptor-positive postmenopausal breast cancer. Mechanistically, most individuals with elevated BMI have breast white adipose tissue inflammation (WATi) which confers increased breast cancer risk, particularly in those with existing benign breast disease. Individuals with WATi have elevated in-breast expression of aromatase and several systemic changes that increase breast cancer risk, including hyperinsulinemia and higher levels of C-reactive protein. However, women with normal BMI but high levels of body fat are also likely to harbor WATi and are at increased risk of postmenopausal breast cancer. The accuracy of BMI for assessing adiposity and predicting obesity-related disorders, including cancer, varies across race and ethnicity. Whether the association between BMI and WATi varies by race is unknown. Here we aimed to characterize relationships among breast WATi and clinicopathologic features in a racially diverse cohort undergoing mastectomy for breast cancer treatment. Methods: Non-tumorous breast tissue and fasting blood were collected from women undergoing mastectomy for breast cancer treatment or prevention at a single center serving a racially diverse patient population. Breast WATi was detected by the presence of crown-like structures in the breast (CLS-B), which are composed of a dead/dying adipocyte surrounded by CD68+ macrophages. Clinicopathologic data were abstracted from electronic medical records. Associations among categorical variables were examined using Fisher9s exact test. Relationships between continuous variables were examined using the Spearman correlation. Results: As of May 18, 2018 62 patients have been accrued; median age 55 (range 32 to 84). Self-reported race distribution was: 36 (58%) Asian, 5 African American (8%), 20 (32%) Caucasian, and 1 (2%) unknown. Breast tissue has been analyzed for WATi in 60 cases thus far. Clinicopathologic features stratified by the presence or absence of breast WATi are presented in. Breast WAT inflammation was associated with obesity (P=0.02) and a trend to association was observed with dyslipidemia (P Conclusions: Breast adipose inflammation is associated with elevated BMI and possibly metabolic syndrome disorders in a racially diverse population. These findings are consistent with observations from predominantly Caucasian cohorts. Race-specific characteristics will also be examined. Study accrual is ongoing and updated results will be presented. Citation Format: Iyengar NM, Siegel B, Malik M, Giri DD, Tsai J, Hughes M, Adam A, Williams S, Zhou XK, Rodgers W, Ginter P, Patel A, Yong F, Cherian A, August P, Dannenberg AJ. Obesity, adipose inflammation, and race in patients with early stage 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 P5-07-05.","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77834952","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-p2-13-06
S. Ellegård, M. Asowed, K. Engvall, Anna-Lotta Hallbeck, Nils Elander, O. Stål
Background: The prognosis for patients with HER2-positive early breast cancer (EBC) has improved dramatically since the introduction of adjuvant trastuzumab therapy. With the addition of pertuzumab the prognosis has improved further. However, there is a need to study how these results from clinical controlled trials are transferred to the real-world clinical setting. In this study we aim to investigate all patients with early HER2-positive breast cancer in our region since the introduction of adjuvant trastuzumab to evaluate the implementation of trastuzumab treatment regarding treatment coverage, prognosis and survival. Method: All patients with HER2-positve EBC, diagnosed between 2006 and 2014 in South-east Sweden were included in the study. The patients were identified using the Swedish national breast cancer register and then cross-referenced with data from the pathology department at each hospital in order to obtain complete coverage in a retrospective clinical follow up. In addition, data were collected from medical records for each patient to verify the actual given treatments and survival data. Results: Preliminary data is available. 611 patients were included with a median follow-up time of 5 years. During the follow-up period the number of patients diagnosed with HER2-positive EBC cancer doubled. 73% of all patients received trastuzumab treatment; however the coverage increased successively from 56% in 2006 to 83% in 2013. ER-positive patients did receive trastuzumab therapy to the same extent as ER-negative patients. Local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS) and breast cancer specific survival (BCSS) at 5 years were 85%, 76%, and 75% for patients not receiving trastuzumab. In the trastuzumab treated group LRFS, DRFS and BCSS was 95%, 85% and 83% respectively. The group not receiving trastuzumab was significantly older, had more frequently node negative disease and was not treated with chemotherapy to the same extent. Conclusion: A significant amount of early HER2-positive breast cancer patients did not receive adjuvant trastuzumab therapy between 2006 and 2014. In this group fewer patients received chemotherapy and despite less nodal involvement LRFS, DRFS and BCSS were poor for these patients. Citation Format: Ellegard S, Asowed M, Engvall K, Hallbeck A-L, Elander N, Stal O. Long term clinical follow up of real world HER2-positive patients since the introduction of trastuzumab [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 P2-13-06.
背景:自引入辅助曲妥珠单抗治疗以来，her2阳性早期乳腺癌(EBC)患者的预后显著改善。随着帕妥珠单抗的加入，预后进一步改善。然而，有必要研究这些临床对照试验的结果如何转移到现实世界的临床环境中。在本研究中，我们旨在调查自引入辅助曲妥珠单抗以来本地区所有早期her2阳性乳腺癌患者，以评估曲妥珠单抗治疗在治疗覆盖率、预后和生存率方面的实施情况。方法:纳入2006年至2014年间在瑞典东南部诊断为her2阳性EBC的所有患者。这些患者是通过瑞典国家乳腺癌登记处确定的，然后与每家医院病理部门的数据交叉参考，以便在回顾性临床随访中获得完整的覆盖范围。此外，从每位患者的医疗记录中收集数据，以验证实际给予的治疗和生存数据。结果:获得初步资料。611例患者纳入研究，中位随访时间为5年。在随访期间，诊断为her2阳性EBC癌的患者数量翻了一番。73%的患者接受了曲妥珠单抗治疗;然而，覆盖率从2006年的56%上升到2013年的83%。er阳性患者接受曲妥珠单抗治疗的程度与er阴性患者相同。未接受曲妥珠单抗治疗的患者5年局部无复发生存率(LRFS)、远处无复发生存率(DRFS)和乳腺癌特异性生存率(BCSS)分别为85%、76%和75%。在曲妥珠单抗治疗组，LRFS、DRFS和BCSS分别为95%、85%和83%。未接受曲妥珠单抗治疗的患者明显年龄较大，淋巴结阴性疾病发生率更高，且未接受相同程度的化疗。结论:2006年至2014年间，大量早期her2阳性乳腺癌患者未接受曲妥珠单抗辅助治疗。在该组中，接受化疗的患者较少，尽管淋巴结受累较少，但这些患者的LRFS、DRFS和BCSS较差。引用格式:Ellegard S, asow M, Engvall K, Hallbeck A-L, Elander N, Stal O.曲妥珠单抗引入后真实世界her2阳性患者的长期临床随访[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):P2-13-06。
{"title":"Abstract P2-13-06: Long term clinical follow up of real world HER2-positive patients since the introduction of trastuzumab","authors":"S. Ellegård, M. Asowed, K. Engvall, Anna-Lotta Hallbeck, Nils Elander, O. Stål","doi":"10.1158/1538-7445.sabcs18-p2-13-06","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs18-p2-13-06","url":null,"abstract":"Background: The prognosis for patients with HER2-positive early breast cancer (EBC) has improved dramatically since the introduction of adjuvant trastuzumab therapy. With the addition of pertuzumab the prognosis has improved further. However, there is a need to study how these results from clinical controlled trials are transferred to the real-world clinical setting. In this study we aim to investigate all patients with early HER2-positive breast cancer in our region since the introduction of adjuvant trastuzumab to evaluate the implementation of trastuzumab treatment regarding treatment coverage, prognosis and survival. Method: All patients with HER2-positve EBC, diagnosed between 2006 and 2014 in South-east Sweden were included in the study. The patients were identified using the Swedish national breast cancer register and then cross-referenced with data from the pathology department at each hospital in order to obtain complete coverage in a retrospective clinical follow up. In addition, data were collected from medical records for each patient to verify the actual given treatments and survival data. Results: Preliminary data is available. 611 patients were included with a median follow-up time of 5 years. During the follow-up period the number of patients diagnosed with HER2-positive EBC cancer doubled. 73% of all patients received trastuzumab treatment; however the coverage increased successively from 56% in 2006 to 83% in 2013. ER-positive patients did receive trastuzumab therapy to the same extent as ER-negative patients. Local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS) and breast cancer specific survival (BCSS) at 5 years were 85%, 76%, and 75% for patients not receiving trastuzumab. In the trastuzumab treated group LRFS, DRFS and BCSS was 95%, 85% and 83% respectively. The group not receiving trastuzumab was significantly older, had more frequently node negative disease and was not treated with chemotherapy to the same extent. Conclusion: A significant amount of early HER2-positive breast cancer patients did not receive adjuvant trastuzumab therapy between 2006 and 2014. In this group fewer patients received chemotherapy and despite less nodal involvement LRFS, DRFS and BCSS were poor for these patients. Citation Format: Ellegard S, Asowed M, Engvall K, Hallbeck A-L, Elander N, Stal O. Long term clinical follow up of real world HER2-positive patients since the introduction of trastuzumab [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 P2-13-06.","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77953649","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-P6-20-05
Bing Na, Xin Yu, T. Wither, John Gilleran, M. Yao, T. K. Foo, Chunxia Chen, D. Moore, B. Xia, Yong Lin, D. Kimball, S. Ganesan, D. Carpizo
{"title":"Abstract P6-20-05: Therapeutic targeting ofBRCA1andTP53mutant breast cancer through mutant p53 reactivation","authors":"Bing Na, Xin Yu, T. Wither, John Gilleran, M. Yao, T. K. Foo, Chunxia Chen, D. Moore, B. Xia, Yong Lin, D. Kimball, S. Ganesan, D. Carpizo","doi":"10.1158/1538-7445.SABCS18-P6-20-05","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-P6-20-05","url":null,"abstract":"","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":"76 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72853091","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-P1-16-05
N. LeVasseur, L. Fiorino, C. Speers, M. Aparicio, C. Lohrisch, S. Chia
{"title":"Abstract P1-16-05: Prognosis and survival in metastatic breast cancer – Ten years in review, a population-based analysis","authors":"N. LeVasseur, L. Fiorino, C. Speers, M. Aparicio, C. Lohrisch, S. Chia","doi":"10.1158/1538-7445.SABCS18-P1-16-05","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-P1-16-05","url":null,"abstract":"","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73115071","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-p3-12-10
S. Misra, G. Lee, M. Maganti, C. A. Koch
{"title":"Abstract P3-12-10: Utilization patterns and temporal trends of internal mammary nodal irradiation (IMNI) at a tertiary cancer centre","authors":"S. Misra, G. Lee, M. Maganti, C. A. Koch","doi":"10.1158/1538-7445.sabcs18-p3-12-10","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs18-p3-12-10","url":null,"abstract":"","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73313289","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-P3-09-01
A. Goga, Julia Rohrberg, Alexandra Corella, Moufida Taileb, S. Kilinc, Marie-Lena Jokisch, Roman Camarda, A. Zhou, S. Balakrishnan, An-Chen Chang, H. Klein-Connolly
Tumors that overexpress the MYC oncogene, including most receptor triple-negative breast cancers, frequently demonstrate aneuploidy, numerical chromosome alterations associated with highly aggressive cancers. Aneuploidy is also associated with rapid tumor evolution and poor patient outcome. We identify that MYC overexpression induces reversible defects in microtubule nucleation and mitotic spindle assembly, in TNBCs and other epithelial cells, promoting chromosome segregation defects, micronuclei and chromosomal instability (CIN). High TPX2 expression is permissive for mitotic spindle assembly and chromosome segregation in cells with MYC overexpression; whereas TPX2 depletion blocks mitotic progression, induces cell death and prevents tumor growth. Attenuating MYC expression reverses mitotic defects, even in established breast tumor cell lines, implicating an ongoing role for high MYC in the persistence of CIN in cancers. Our studies implicate the MYC oncogene as a regulator of spindle assembly and identify a new MYC-TPX2 synthetic-lethal interaction in TNBC that could represent a future therapeutic strategy in MYC-overexpressing cancers. Moreover, our studies suggest that blocking MYC activity can attenuate the emergence of CIN and tumor evolution. Citation Format: Goga A, Rohrberg J, Corella A, Taileb M, Kilinc S, Jokisch M-L, Camarda R, Zhou A, Balakrishnan S, Chang AN, Klein-Connolly H. MYC dysregulates mitotic spindle function in triple-negative breast cancer creating a dependency on TPX2 [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 P3-09-01.
过度表达MYC癌基因的肿瘤，包括大多数受体三阴性乳腺癌，经常表现出非整倍体，与高度侵袭性癌症相关的数字染色体改变。非整倍体还与肿瘤的快速演变和患者预后差有关。我们发现MYC过表达诱导tnbc和其他上皮细胞中微管成核和有丝分裂纺锤体组装的可逆缺陷，促进染色体分离缺陷、微核和染色体不稳定性(CIN)。在MYC过表达的细胞中，TPX2的高表达有利于有丝分裂纺锤体组装和染色体分离;而TPX2缺失阻断有丝分裂进程，诱导细胞死亡并阻止肿瘤生长。降低MYC表达可逆转有丝分裂缺陷，即使在已建立的乳腺肿瘤细胞系中也是如此，这意味着高MYC在癌症中CIN的持续存在中起着持续的作用。我们的研究表明MYC癌基因是纺锤体组装的调节因子，并在TNBC中发现了一种新的MYC- tpx2合成致死相互作用，这可能代表未来MYC过表达癌症的治疗策略。此外，我们的研究表明，阻断MYC活性可以减轻CIN的出现和肿瘤的发展。引用格式:Goga A, Rohrberg J, Corella A, Taileb M, Kilinc S, Jokisch M- l, Camarda R, Zhou A, Balakrishnan S, Chang AN, Klein-Connolly H.三阴性乳腺癌MYC有丝分裂纺锤体功能异常产生TPX2依赖[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;中国癌症杂志2019;79(4增刊):P3-09-01。
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