bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P3-09-01: MYC dysregulates mitotic spindle function in triple-negative breast cancer creating a dependency on TPX2
Authors: Goga A , Rohrberg J , Corella A , Taileb M , Kilinc S , Jokisch M-L , Camarda R , Zhou A , Balakrishnan S , Chang AN , Klein-Connolly H 
Published: May 2019

Abstract
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.
Abstract P3-09-05: Withdrawn
Authors: Chakladar M , Nair MG , Prabhu JS , Cohen S , Srinivas ST , Lingadahalli SS 
Published: May 2019

Abstract
This abstract was withdrawn by the authors.
Citation Format: Chakladar M, Nair MG, Prabhu JS, Cohen S, Srinivas ST, Lingadahalli SS. Withdrawn [abstract].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 P3-09-05.
Abstract P3-10-21: Withdrawn
Authors: Manai MM , Thomassin-Piana JJ , Finetti PP , Gammoudi AA , Manai MM , Rahal KK , Birnbaum DD , Boussen HH , Bertucci FF 
Published: May 2019

Abstract
This abstract was withdrawn by the authors.
Citation Format: Manai MM, Thomassin-Piana JJ, Finetti PP, Gammoudi AA, Manai MM, Rahal KK, Birnbaum DD, Boussen HH, Bertucci FF. Withdrawn [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 P3-10-21.
Abstract P3-11-01: Interaction between molecular subtype and stromal immune infiltration dynamics in breast cancer patients treated with neoadjuvant chemotherapy
Authors: Hamy A-S , Bonsang-Kitzis H , De Croze D , Laas E , Darrigues L , Topciu L , Menet E , Vincent-Salomon A , Lerebours F , Pierga J-Y , Brain E , Feron J-G , Benchimol G , Lam G-T , Laé M , Reyal F 
Published: May 2019

Abstract
Purpose: High levels of tumor-infiltrating lymphocytes (TILs) before neoadjuvant chemotherapy (NAC) are associated with higher pathological complete response (pCR) rates, and better survival in TNBC and HER2-positive breast cancers (BCs). We investigated the value of changes in TIL levels and final TIL levels after treatment, by evaluating lymphocyte infiltration before and after NAC in a real-life BC cohort.
Patients and methods: We assessed stromal TIL levels in 716 pre- and post-treatment matched paired specimens, according to the guidelines of the international TIL working group.
Results: Pre-NAC TIL levels were higher in tumors for which pCR was achieved than in cases of residual disease (33.9% versus 20.3%, p=0.001), in luminal tumors and TNBCs, but not in HER2-positive BCs, (pInteraction =0.001). The association between pre-NAC TIL levels and pCR was non-linear in TNBCs (p=0.005). Mean TIL levels decreased during NAC (pre-NAC TILs: 24.1% versus post-NAC TILs: 13.0%, p&lt;0.001). This decrease was strongly associated with high pCR rates, and TIL level variation was strongly inversely correlated with pre-NAC TIL levels (r=-0.80, p&lt;0.001). Pre-NAC TILs and disease-free survival (DFS) were associated in a non-linear manner (p&lt;0.001). High post-NAC TIL levels were associated with aggressive tumor characteristics and with impaired DFS in HER2-positive BCs (HR=1.04, CI [1.02-1.06], p=0.001), but not in luminal tumors or TNBCs (pInteraction =0.04).
Conclusion: The associations of pre, post-NAC TIL levels with response to treatment and DFS differ between BC subtypes and may deviate from linearity. The characterization of immune subpopulations may improve our understanding of the complex interactions between pre- or post-NAC setting, BC subtype, response to treatment and prognosis.
Citation Format: Hamy A-S, Bonsang-Kitzis H, De Croze D, Laas E, Darrigues L, Topciu L, Menet E, Vincent-Salomon A, Lerebours F, Pierga J-Y, Brain E, Feron J-G, Benchimol G, Lam G-T, Laé M, Reyal F. Interaction between molecular subtype and stromal immune infiltration dynamics in breast cancer patients treated with neoadjuvant chemotherapy [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 P3-11-01.
Abstract P3-11-09: Not presented
Authors: Bownes RJ , Turbull A , Martínez-Pérez C , Sims AH , Oikonomidou O 
Published: May 2019

Abstract
This abstract was not presented at the conference.
Citation Format: Bownes RJ, Turbull A, Martínez-Pérez C, Sims AH, Oikonomidou O. Not presented [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 P3-11-09.
Abstract P3-12-02: Intraoperative radiotherapy outcomes in early-stage breast cancer: A study in elderly Canadian women
Authors: Elmi M , Tigert A , Escallon J , Zagorski B , Leong W , Vranic M , Fyles A , Vitkin A , Cil T , McCready D 
Published: May 2019

Abstract
Objective. Breast-conserving therapy with external beam radiotherapy (EBRT) is currently the standard of care for women with early breast cancer. Our aim was to determine if early-stage breast cancers treated with lumpectomy and primary intraoperative radiotherapy (IORT) have comparable local recurrence rates. This is the first study examining the Canadian experience with IORT.
Methods. Patients who underwent breast-conserving therapy with pre-pathology IORT between 2007- 2017 were retrospectively identified. The primary outcome measure was ipsilateral breast tumor recurrence (IBRT). A time to event analysis was performed; Kaplan-Meier estimates report the fraction of patients living free of recurrence. Secondary outcomes included acute and chronic wound complications.
Results. 106 patients with a median age of 70 (IQR 65-75) were included. Median follow-up was 33 months. The majority of patients had screen-detected (94.3%), estrogen-receptor positive (96.2%), HER2neu negative (93.4%), invasive ductal carcinomas (92.5%). Only 50 (47.6%) were prescribed adjuvant endocrine blockade. IBTR occurred in 5 (4.7%) patients. Five and ten-year local recurrence-free rates were 0.95 and 0.81, respectively. The superficial skin infection rate was 9.4%. Acute symptomatic seromas occurred in 23 (21.7%), while only 10 (9.4%) persisted chronically.
Conclusion. In this cohort of Canadian post-menopausal women treated with breast-conserving surgery and IORT, the IBTR approached 5%. Despite selection of low-risk patients, the local recurrence rate is higher than what is reported in the literature with EBRT. The low rates of prescribed adjuvant systemic therapy may have contributed to this outcome.
Citation Format: Elmi M, Tigert A, Escallon J, Zagorski B, Leong W, Vranic M, Fyles A, Vitkin A, Cil T, McCready D. Intraoperative radiotherapy outcomes in early-stage breast cancer: A study in elderly Canadian women [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 P3-12-02.
Abstract P3-12-12: Impact of regional nodal irradiation for breast cancer patients with supraclavicular and/or internal mammary lymph node involvement: A multicenter, retrospective study (KROG 16-14)
Authors: Kim K , Jeong Y , Shin KH , Kim JH , Ahn SD , Kim SS , Suh C-O , Kim YB , Choi DH , Park W , Cha J , Chun M , Lee DS , Lee SY , Kim JH , Park HJ 
Published: May 2019

Abstract
Purpose: To evaluate the treatment outcomes of radiotherapy (RT) for breast cancer with ipsilateral supraclavicular (SCL) and/or internal mammary (IMN) lymph node involvement.
Methods: A total of 353 patients from 11 institutions were included. One hundred and thirty-six patients had SCL involvement, 148 had IMN involvement, and 69 had both. All patients received neoadjvant systemic therapy followed by breast conserving surgery or mastectomy, and postoperative RT to whole breast/chest wall. As for regional lymph node irradiation, SCL RT was given to 344 patients, and IMN RT to 236 patients. The median RT dose was 50.4 Gy.
Results: The median follow-up duration was 61 months (range, 7-173). In-field progression was present in SCL (n=20) and/or IMN (n=7). The 5-year disease-free survival (DFS) and overall survival rates were 57.8% and 75.1%, respectively. On multivariate analysis, both SCL/IMN involvement, number of axillary lymph node ≥4, triple negative subtype, and mastectomy were significant adverse prognosticators for DFS (p = 0.022, 0.001, 0.001, and 0.004, respectively). Regarding the impact of regional nodal irradiation, SCL RT dose ≥54 Gy was not associated with DFS (5-yr rate, 52.9% vs. 50.9%, p = 0.696) in SCL-involved patients, and the receipt of IMN RT was not associated with DFS (5-yr rate, 56.1% vs. 78.1%, p = 0.099) in IMN-involved patients.
Conclusion: Neoadjuvant chemotherapy followed by surgery and postoperative RT achieved an acceptable in-field regional control rate in patients with SCL and/or IMN involvement. However, a higher RT dose to SCL or IMN RT was not associated with the improved DFS in these patients.
Citation Format: Kim K, Jeong Y, Shin KH, Kim JH, Ahn SD, Kim SS, Suh C-O, Kim YB, Choi DH, Park W, Cha J, Chun M, Lee DS, Lee SY, Kim JH, Park HJ. Impact of regional nodal irradiation for breast cancer patients with supraclavicular and/or internal mammary lymph node involvement: A multicenter, retrospective study (KROG 16-14) [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 P3-12-12.
Abstract P3-13-09: Increased mortality with repeat lumpectomy alone after ipsilateral breast tumor recurrence: A propensity-adjusted, population-based SEER analysis
Authors: Su Y , Guo R , Xue J , Chi Y , Wu J 
Published: May 2019

Abstract
Background: The benefit of repeat lumpectomy for ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery (BCS) is currently inconclusive. This issue has become even more important as small and isolated recurrent tumors were frequently diagnosed.
Methods: IBTR patients with definitive surgery were identified in the Surveillance, Epidemiology, and End Results registry between 1973 and 2013. The effect of different IBTR surgeries on overall and cancer-specific mortality was assessed using risk-adjusted Cox proportional hazard regression modeling and stratified propensity score matching analysis (PSMA).
Results: Based on the selection criteria, 5098 patients were recruited. Of those, 4048 (79.4%) women underwent mastectomy and 1050 (20.1%) underwent repeat lumpectomy after IBTR. Patients who received repeat lumpectomy had lower grade (23.7% vs 15% for well-differentiated) and smaller recurrent tumor (47% vs 36.2% for ≤ 1 cm) but earlier recurrence (23.9% vs 11.2% for interval times &lt; 48 months) than those who underwent mastectomy. A minority of each group (24.7% of those undergoing repeat lumpectomy and 3% of the mastectomy group) underwent RT after surgery. In multivariable Cox regression analysis, repeat lumpectomy was associated with increased overall mortality (Hazard ratio (HR) = 1.58, 95% CI = 1.353 to 1.844, P &lt; 0.001) and cancer-specific mortality (HR = 1.721, 95% CI = 1.345 to 2.202, P&lt; 0.001). Similar HRs were derived from the PSMA cohort. However, we found no significant difference in overall mortality for women who underwent repeat lumpectomy followed by RT compared with that for those who underwent mastectomy (P= 0.411). Moreover, IBTR patients with small tumors (≤ 1 cm) who underwent repeat lumpectomy with RT rather than without had similar overall and cancer-specific survival rates to those who underwent mastectomy (P= 0.189 and P= 0.604, respectively).
Conclusions: Our investigation suggests that compared with mastectomy, repeat lumpectomy for IBTR is associated with higher overall and cancer-specific mortality under real-world observational conditions. Furthermore, repeat lumpectomy with RT is equivalent to mastectomy with respect to overall mortality and may influence treatment decision making for patients with small IBTR.
Citation Format: Su Y, Guo R, Xue J, Chi Y, Wu J. Increased mortality with repeat lumpectomy alone after ipsilateral breast tumor recurrence: A propensity-adjusted, population-based SEER analysis [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 P3-13-09.
Abstract P3-13-10: Factors impacting surgical option in patients who achieved complete response in the breast after neoadjuvant systemic therapy
Authors: Kou H-W , Shen S-C , Chen S-C 
Published: May 2019

Abstract
Background:
Neoadjuvant systemic therapy (NST) is the standard treatment for locally advanced breast cancer. Early studies have demonstrated that the rate of breast conservation was significantly increased and NST is now widely applied to operable breast cancer to increase breast conservation rate and to achieve better cosmetic outcome after breast conservative surgery (BCS). For patients who achieved pathologic complete response (pCR), they were perfect candidate for BCS. However, data from prospectively randomized trials have shown that, with the significantly increase of pCR by adding new drugs in the neoadjuvant regimen, BCS rate does not significantly increased. The purpose of current study is to identify factors that have influence on surgical option in patients that have achieved complete response in the breast after NST.
Methods:
From January 2009 to July 2016, 1150 patients with breast cancer received NST in our institute. There were 103 patients achieved complete response (CR) in the breast and were included in current analysis. Medical records were reviewed regarding to individual surgeon, pre-NST clinicopathologic characteristics, and post-NST image findings. Risk factors for mastectomy were assessed by univariate and multivariate analyses.
Results:
Of the 103 patients who achieved CR in the breast, 40 of them (38.8%) received mastectomy. In univariate analysis, physician factor, larger initial tumor size, advanced clinical stages, as well as post-NST image findings including skin change, residual tumor ≥3 cm, short nipple-tumor distance, and residual axillary lymph node(LN) on ultrasound and segmental/diffuse distribution of malignant calcification on mammography were associated with more mastectomy. In multivariate analysis, physician factor (OR=5.192, CI [1.562 – 17.257], p=0.021), residual axillary LN on echography (OR=4.000, CI [1.552 – 10.319], p=0.004), and segmental/diffuse distribution of malignant calcification on mammography (OR=7.500, CI [1.819 – 30.916], p=0.018) were independently related to mastectomy in patients who achieved CR in the breast after NST.
Conclusion:
Physician factor, residual axillary LN and segmental/diffuse malignant calcifications were risk factors for mastectomy in patients who achieved CR in the breast after NST. In addition to embrace current treatment guidelines of surgical management after NST, our data provide valuable additional information to avoid unnecessary mastectomy.
Citation Format: Kou H-W, Shen S-C, Chen S-C. Factors impacting surgical option in patients who achieved complete response in the breast after neoadjuvant systemic therapy [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 P3-13-10.
Abstract P3-13-12: The margin of breast-conserving surgery when ductal carcinoma in situ is present within invasive ductal carcinoma
Authors: Chen J , Ro A , Tan Q-W , Wang Z , Chang HR 
Published: May 2019

Abstract
Objective: The presence of ductal carcinoma in situ (DCIS) in invasive ductal carcinoma (IDC) may increase the rates of positive margins and re-excision. Literature addressing this association is limited. This study aimed to explore the factors that are associated with positive margins and re-excision, as well as to evaluate the influence of positive margins on the survival of patients with breast cancer containing both invasive and in situ ductal carcinoma.
Methods: A retrospective medical chart review of patients diagnosed with DCIS within IDC who underwent BCS at the Revlon/UCLA Breast Center between January 2003 and December 2008 was performed.
Results: Of the 488 eligible patients, 267 patients (53.9%) underwent re-excision. The presence of residual disease upon re-excision was the highest in patients who initially had positive margins involved by both DCIS and IDC. In multivariate analysis, calcifications, tumor size, positive lymph nodes, and the presence of extensive intraductal component (EIC) were significantly associated with initial positive margins, with the latter having the highest hazard ratio (HR, 5.5–5.7, P = 0.000). Tumor size, molecular subtype, and final margin status were associated with disease-free survival. The final margin and regional lymph node status are significant prognosticators for breast cancer-specific survival.
Conclusions: In patients with ductal carcinoma of the breast containing both invasive and in situ components, the rate of initial positive margin after BCS was high and was significantly associated with calcifications, tumor size, regional lymph node status, and the presence of EIC.
Citation Format: Chen J, Ro A, Tan Q-W, Wang Z, Chang HR. The margin of breast-conserving surgery when ductal carcinoma in situ is present within invasive ductal carcinoma [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 P3-13-12.
Abstract P4-01-13: Molecular characterization of circulating tumor DNA in Chinese metastatic breast cancer (mBC) patients
Authors: Yu J , Li H , Zhang S , Wang A , Zhao Z , Liu X-R 
Published: May 2019

Abstract
Background: Circulating tumor DNA (ctDNA) have been increasingly used as a minimal invasive test to detect genomic alterations of cancer patients.
Methods: We performed a retrospective analysis of blood samples from mBC patients (pts) collected at baseline, on-treatment, and disease progression. A highly sensitive, plasma-derived ctDNA-based NGS assay (PredicinePLUS, a comprehensive 180 key cancer gene panel) was used to detect somatic mutations and copy number variations in ctDNA with an in-house propriety algorithm.
Results: In this study, we evaluated 162 blood samples from 109 mBC pts who underwent systematic therapy at Beijing Cancer Hospital with approval from Research Ethics Committee. 129 samples from 92 pts passed NGS quality check, and were included in the analysis. Among these pts, the percent of HR+, HER2+ and Triple-Negative pts is 36.8%, 29.5% and 31.5%, respectively. About 86% samples contain somatic mutations and/or copy number variations. Collectively, 372 somatic mutations (SNV and Indels) were detected on 76 genes, among which TP53 (44.2%), PIK3CA (25.3%), BRCA2(10.5%) and ATM (10.5%) were frequently altered with frequency varying across different subtypes. ESR1 hotspot mutations ((D538G and Y537S/N/C) were also detected in a subset of HR+ patients. Copy number gain or loss was detected on 32 genes, including amplification of ERBB2, PIK3CA, FGFR1 and deletion of CDKN2A, ATM, RB1 etc. Importantly, ERBB2 copy number amplifications were only detected in HER2 IHC positive cases for base-line samples, leading to 68% sensitivity and 100% specificity. Interestingly, ctDNA yield increased as disease progressed, suggesting ctDNA yield may serve as a potential biomarker for predicting treatment response and monitoring disease progression. Additional genomic alterations that change dynamically along with the course of treatment or associate with drug response and/or resistance were also identified.
Conclusions: This study demonstrated ctDNA-based genomic analysis was highly sensitive and specific in detecting various genomic alterations, consistent with other published studies. It also suggests that HER2 copy number amplification could be robustly assessed in a non-invasive manner.
Citation Format: Yu J, Li H, Zhang S, Wang A, Zhao Z, Liu X-R. Molecular characterization of circulating tumor DNA in Chinese metastatic breast cancer (mBC) patients [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 P4-01-13.