bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PS13-13: The value of shear-wave elastography for prediction of treatment response to neoadjuvant chemotherapy in patients with breast cancer
Authors: Bae Soong June , Kim Min Ji , Cha Yoon Jin , Eun Na Lae , Kim Dooreh , Lee Janghee , Ahn Sung Gwe , Son Eon Ju , Jeong Joon 
Published: February 2021

Abstract
Introduction Recently, Shear-wave elastography (SWE) has been known to be useful for the diagnosis of breast cancer and lymph node metastasis. However, little is known about whether SWE can predict the response to neoadjuvant chemotherapy in patients with breast cancer. This study aimed to investigate the relationship between treatment response and elasticity values. Method Pre-treatment shear-wave elastography was performed in 394 patients who underwent neoadjuvant chemotherapy followed by surgery at Gangnam Severance Hospital from January 2012 to May 2020. We evaluated the pathologic complete response (pCR, defined as ypTis/T0, No) according to elasticity values such as ‘Mean stiffness’, ‘Minimum stiffness’, ‘Maximum stiffness’, and ‘Ratio’. Results A total of 394 patients, 147 (37.3%) achieved pCR. All elasticity values were significantly lower in patients with pCR after neoadjuvant chemotherapy than those with the residual invasive tumor. In the multivariable analysis, the mean stiffness (OR 0.995; 95% CIs, 0.989-1.000; P=0.039) and the maximum stiffness (OR 0.995; 95% CIs, 0.990-0.999; P=0.024) were independent predictive factors for pCR after adjusting clinic-pathologic factors. Besides, the tumor-infiltrating lymphocytes (TILs) evaluated in biopsy samples were inversely correlated with pre-treatment mean stiffness (CC -0.053, P=0.044), and elasticity ratio (CC-0.288, P=0.033). Conclusion In this study, pre-treatment elasticity values measured by SWE were significantly associated with pCR in breast cancer. Our results suggest that SWE can be a useful diagnostic tool for predicting treatment response in patients with breast cancer who will receive neoadjuvant chemotherapy.
Citation Format: Soong June Bae, Min Ji Kim, Yoon Jin Cha, Na Lae Eun, Dooreh Kim, Janghee Lee, Sung Gwe Ahn, Eon Ju Son, Joon Jeong. The value of shear-wave elastography for prediction of treatment response to neoadjuvant chemotherapy in patients with breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-13.
Abstract PS13-15: Impact of neoadjuvant chemotherapy on breast reconstruction - systematic review and meta-analysis
Authors: Varghese Jajini Susan , Gohari Shireen , Shawky Michael , Hyun Faith , Johnson Laura , Schmid Peter 
Published: February 2021

Abstract
BackgroundImpact of neoadjuvant chemotherapy (NACT) on breast reconstruction outcomes remain unclear. We did a systematic review and meta-analysis to assess the effect of NACT on post-operative complications and delay to adjuvant therapy among women undergoing immediate breast reconstruction.
MethodsIn this systematic review and meta-analysis, we searched medical databases from inception of this technique to May 2, 2020 to identify articles that assessed the impact of NACT on separate techniques of immediate breast reconstruction. Studies reporting on at least one of our pre-defined major post-operative complications were included. Study authors were contacted for individual patient-level data which was not available. Study quality and risk of bias are reported through NOS Scores and GRADE table. PROSPERO registration CRD42020183761.
FindingsOf 477 identified articles, 17 studies (3249 patients) were eligible for inclusion. NACT did not increase the risk of overall complications after immediate breast reconstructions RR: 0.91(95% CI 0.74 to 1.11, p = 0.34). There was no large increase in flap losses (total and partial) in patients receiving NACT compared to control group (RR:1.23, 95% CI 0.70 to 2.18, p = 0.47; I2 = 0%). There was however, some evidence of increased risk of implant/expander loss after NACT treatment (RR:1.50, 95% CI 1.03 to 2.20, p = 0.04; I2 = 34%). NACT treatment was not associated with increase in haematomas, seromas or wound complications or significant delay to adjuvant therapy access; RR:1.59, 95% CI 0.66 to 3.87, p = 0.30
InterpretationImmediate breast reconstruction after treatment with NACT remains a safe procedure. Careful patient selection may play a bigger role when planning implant-based reconstructions after NACT.
FundingNone.
Citation Format: Jajini Susan Varghese, Shireen Gohari, Michael Shawky, Faith Hyun, Laura Johnson, Peter Schmid. Impact of neoadjuvant chemotherapy on breast reconstruction - systematic review and meta-analysis [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-15.
Abstract PS13-45: Radiological response pattern predicts disease-free survival in breast cancer patients undergoing neoadjuvant chemotherapy
Authors: Ahn Juneyoung , Yoo Tae-kyung , Paik Pill Sun , Cho Min Kyung , Yoon Chang Ik , Park Woo Chan 
Published: February 2021

Abstract
Purpose Pathological complete response (pCR) predicts improved survival in breast cancer patients undergoing neoadjuvant chemotherapy (NAC). However, the prognosis of patients with non-pCR remains unclear. The aim of this study was to evaluate the effect of radiological response pattern on breast cancer patients’ outcome.
Method A total of 396 breast cancer patients who underwent neoadjuvant chemotherapy between 2010-2017 at Seoul St. Mary’s Hospital were retrospectively reviewed. Among them, patients who underwent 4-6 cycles of neoadjuvant chemotherapy and underwent response evaluation every 2 cycles using breast MRI were included for analysis. Early and late response ratio was calculated from breast MR images using the longest diameter of the main tumor. Early response ratio was calculated as post-2 cycle NAC / pre-NAC ratio. Late response ratio was calculated as post-4 cycle NC / post-2 cycle NAC ratio. Radiological response pattern was divided into three groups; fast-slow responder meaning early response ratio &gt; late response ratio + 20%, slow-fast responder meaning late response ratio &gt; early response ratio + 20% and constant responder meaning the difference between initial response ratio and later response ratio is lower than 20%. Survival analysis was done using the Kaplan-Meier method and multivariate analysis by Cox regression. Disease-free survival (DFS) was defined as locoregional recurrence, contralateral breast recurrence and distant metastasis.
Result A total of 177 patients were included for analysis. Among them 19 (10.7%) patients were pCR, 122 (68.9%) patients had partial response, 29 (16.4%) patients had stable disease and 7 (4.0%) patients had progressive disease. Median follow-up period was 50 months (range, 3-112 months). Radiological response pattern was significantly associated with disease-free survival in univariate analysis (p=0.042). Fast-slow responders had significantly worse disease-free survival (DFS) in univariate analysis compared to slow-fast responders and constant responders (p=0.042, 5-year DFS 67.6%, 88.3% 67.6%). Radiological response pattern continued to be statistically significant by multivariable analysis (p=0.037).
Conclusion Our results showed that fast-slow responders have worse survival compared to constant or slow-fast responders. Radiological response patterns may be useful to more accurately assess prognosis, especially when considering adjuvant chemotherapy.
Citation Format: Juneyoung Ahn, Tae-kyung Yoo, Pill Sun Paik, Min Kyung Cho, Chang Ik Yoon, Woo Chan Park. Radiological response pattern predicts disease-free survival in breast cancer patients undergoing neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-45.
Abstract PS14-24: Multi-center trial in the treatment of ductal carcinoma in situ of breast using intra-operative electronic brachytherapy technique, results
Authors: Syed Alam M.Nisar 
Published: February 2021

Abstract
Purpose: To report on the technique of intra-operative electronic brachytherapy, local control, side effects and complications after a single fraction of 2000 cGy at the time of partial mastectomy.
Material & Methods: 1200 patients with early stage invasive ductal carcinoma and carcinoma in situ were enrolled in the Multi-Center Trial. 246 (20.5%) patients among these 1200 patients had carcinoma in situ and were treated by a single fraction of 2000 cGy dose by intra-operative irradiation to the lumpectomy cavity using Xoft system of electronic brachytherapy at the time of partial mastectomy. 80% of the patients were Caucasian, 7% African American, 7% Hispanic and 6% others. Estrogen receptor was positive in 211 patients, negative in 28 patients and unknown/not assessed in 7 patients. Progesterone receptor was positive in 190 patients, negative in 45 patients and unknown/not assessed in 11 patients. All patients were BRCA negative. 34 (14%) patients had low grade tumors, 109 (44%) intermediate grade tumors, and 103 (42%) high grade tumors. Seroma occurred in 9.8%, induration in 7.6%, and significant fibrosis in 3.5% of the patients. 2/246 (1%) developed ipsilateral recurrence and one patient developed a gastrointestinal cancer. 118 (48%) patients had characteristics of ASTRO criteria being suitable, 108 (44%) cautionary and 20 (8%) unsuitable.
Conclusion: The relatively early 2.3 year results of a single fraction of 2000 cGy by IORT to the lumpectomy cavity at the time of partial mastectomy using Xoft Axxent electronic brachytherapy in the treatment of carcinoma in situ of the breast is safe and associated with low morbidity and local recurrence with good to excellent cosmesis in 80% of the patients.
Citation Format: Alam M.Nisar Syed. Multi-center trial in the treatment of ductal carcinoma in situ of breast using intra-operative electronic brachytherapy technique, results [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-24.
Abstract PS15-06: The distribution of radiosensitivity index differs by PAM50 subtype in primary breast tumors
Authors: Fahey Matthew , Russo Nicholas , Liveringhouse Casey , Mills Matthew , Ahmed Kamran , Diaz Roberto 
Published: February 2021

Abstract
Background: Prior studies identified radiosensitive and radioresistant breast tumor phenotypes and demonstrated that gene-expression signatures such as the radiosensitivity index (RSI) can be used to derive biologically rational radiation dose selection. In this study, we assessed the RSI of primary breast tumor samples and its association with PAM50 subtype.Materials/Methods: Primary breast tumor samples were identified from a multi-institutional tissue biorepository. Tumors were excluded if they were treated with neoadjuvant therapy or had distant metastatic disease at the time of sample collection. The RSI gene signature and PAM50 subtype were assessed through transcriptomic profiling performed on Affymetrix microarray chips. Distribution of RSI values across PAM50 subtypes was assessed with the Kruskal-Wallis test. Differences in proportions of radioresistant and radiosensitive tumors among PAM50 subtypes were assessed with the Chi-squared test, where radioresistant was defined as RSI&gt;0.3745 based on prior studies. Clinicopathologic characteristics were obtained through clinical chart review. Results: A total of 637 primary breast tumors with available genomic profiling and clinical information were included for analysis. HIstologies were predominantly invasive ductal carcinoma (81.5%) and invasive lobular (11.6%). Most tumors were T1-T2 (91.7%) while 35.9% had pathologically positive lymph nodes. The distribution of RSI significantly differed by PAM50 classification (Kruskal-Wallis p &lt; 0.001). Proportions of radioresistant vs radiosensitive tumors varied significantly according to PAM50 subtype and are included in the accompanying table (Chi-squared p &lt; 0.001). Median follow-up was 89 months.
Conclusion: Breast tumor PAM50 subtypes demonstrate significant variation in radiosensitivity. Further studies are needed to determine if genomic subtyping can refine the ability to predict clinical radiation response and further optimize individual therapy.
PAM50TotalBasalHer2LumALumBNormalRSI PhenotypeRadioresistantn (%)50 (60.2%)32 (42.1%)146 (54.4%)82 (45.3%)24 (82.8%)334 (52.4%)Radiosensitive n (%)33 (39.8%)44 (57.9%)122 (45.6%)99 (54.7%)5 (17.2%)303 (47.5%)Total837626818129637
Citation Format: Matthew Fahey, Nicholas Russo, Casey Liveringhouse, Matthew Mills, Kamran Ahmed, Roberto Diaz. The distribution of radiosensitivity index differs by PAM50 subtype in primary breast tumors [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS15-06.
Abstract PS16-21: Apc control of taxane resistance in breast cancer
Authors: Prosperi Jeni , Astarita Emily , Hoover Camden , Maloney Sara 
Published: February 2021

Abstract
Adenomatous Polyposis Coli (APC) is a multi-domain tumor suppressor with multiple binding partners, including β-catenin, axin, and microtubules. APC is lost in many epithelial cancers, including up to 70% of sporadic breast cancers, with a tendency towards triple negative breast cancers (TNBCs). We previously demonstrated that APC knockdown in the human TNBC cell line, MDA-MB-157, resulted in resistance to Paclitaxel (PTX), a chemotherapeutic agent of the Taxane family that inhibits mitotic progression. Further studies have confirmed this finding in the MDA-MB-231 cells with CRISPR-mediated APC knockout. To understand the mechanism(s) by which APC controls response to PTX, we have taken two approaches. We first performed an unbiased analysis of transcriptomic changes downstream of APC loss to identify potential therapeutic targets to overcome PTX resistance. In this, a group of transcripts involved in regulation of the cell cycle were identified, including LBH, GLI1, RGS4, and NUPR1. These results have been validated by qRT-PCR and western blot, leading to studies in the laboratory to investigate their specific effects on the response to PTX in breast cancer. Along with the broad exploration studies, molecular studies have focused on whether APC controls expression of cell cycle proteins, leading to PTX resistance. While we observed changes in multiple cell cycle proteins, our focus was on the G2/M transition, given that both PTX and APC impact microtubule dynamics and the G2/M phase of the cell cycle. We examined the effect of APC loss on expression of G2/M proteins, identifying a significant upregulation of CDK1 in APCKD cells. Despite no changes in phosphorylation status of CDK1, we found that Cyclin B1 and CDK1 are only complexed in the APCKD cells, suggesting increased activation. Further studies showed that while the majority of CDK1 and Cyclin B1 are localized to the cytoplasm, there is a small amount in the nucleus. Based on these findings, we sought to investigate whether PTX sensitivity would be altered in response to CDK1 inhibitor, RO-3306. We have shown that PTX resistant APCKD cells are more sensitive (IC50 = 25.5uM) to RO-3306 compared the parental control (IC50 = 78uM). Future studies will use combination and sequential treatments to monitor PTX response in vitro and in vivo. Combined, these studies are elucidating the mechanisms by which loss of APC controls sensitivity to PTX in TNBC, with the long-term goal of designing treatment regimens to improve patient health and survival.
Citation Format: Jeni Prosperi, Emily Astarita, Camden Hoover, Sara Maloney. Apc control of taxane resistance in breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS16-21.
Abstract PS16-23: Elucidating the role of APC resulting in doxorubicin resistance in breast cancer
Authors: Prosperi Jeni , Stefanski Casey 
Published: February 2021

Abstract
Chemoresistance is a leading cause of breast cancer related deaths. Therefore, understanding the molecularbasis for chemoresistance is essential for novel therapeutic advancement improving patient outcome. TheAdenomatous Polyposis Coli (APC) tumor suppressor is lost in up to 70% of sporadic breast cancer; however,little is known about how APC loss contributes to chemoresistance. Using mammary tumor cells isolated fromthe Apc Min/+ mouse crossed to the Polyoma middle T antigen (PyMT) transgenic model, we werethe first to show that APC loss decreased doxorubicin (DOX) induced apoptosis. Therefore, we investigatedthe mechanisms contributing to DOX resistance with APC loss to identify combination therapy options. DOX, acommonly used chemotherapeutic in breast cancer, inhibits topoisomerase IIa (Topo IIa), causing doublestranded breaks (DSBs), the most lethal form of DNA damage, and APC has been shown to affect Topo IIaactivity. DSB repair is mediated through HRR (homologous recombination repair) or NHEJ (nonhomologousend joining), which are regulated by the repair serine/threonine kinases: ataxia telangiectasia mutated (ATM)or ataxia telangiectasia and Rad3 related (ATR), but only NHEJ activates DNA-dependent protein kinase(DNA-PK). We hypothesized that APC loss prevents DOX-mediated apoptosis through alterations in HRR andNHEJ. To investigate the effect of APC loss on DNA damage repair pathways, we monitored damagerecognition pathways after 24-hour DOX treatment. The MMTV-PyMT;Apc Min/+ cells exhibited decreaseddamage as measured by γH2AX expression and comet assay. We also observed decreased ATMphosphorylation in MMTV-PyMT;Apc Min/+ following DOX treatment compared to control. Decreasedphosphorylation of Chk1 and Chk2 was also observed in DOX-treated MMTV-PyMT;Apc Min/+ cells. Using theATM inhibitor (KU55933) or the DNA-PK inhibitor (NU7441), we observed increased DOX-induced apoptosis inMMTV-PyMT;Apc Min/+ cells. These data suggest enhanced DNA repair in MMTV-PyMT;Apc Min/+ cells and will beconfirmed by measuring repair efficiency via reporter plasmids. In addition, knowing that APC affects activitiesby Topo IIa, we measured the amount of Topo IIa: DNA cleavage complexes following DOX treatment.Taken together, APC loss mediates DOX resistance via increasing DNA repair demonstrating the potential useof combination therapy to overcome chemoresistance.
Citation Format: Jeni Prosperi, Casey Stefanski. Elucidating the role of APC resulting in doxorubicin resistance in breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS16-23.
Abstract PS16-24: Mechanisms underlying obesity-induced enrichment of stem-like breast cancer cells
Authors: Mayberry Shannon , Harlow Brittany , Eichman Elizabeth , Hsu Christopher , deGraffenried Linda 
Published: February 2021

Abstract
Background: Breast cancer represents the most common nonskin malignancy in women worldwide, and most deaths result from metastatic dissemination of the disease. At the same time, studies indicate that obesity induces a stem cell-like phenotype, required for tumor metastases and associated with cancer progression and mortality. Although the precise mechanism behind this reprogramming event remains to be elucidated, preliminary data from our lab demonstrate that the epithelial-mesenchymal transition (EMT) associated with obese conditions is linked to IL-6 mechanistically. Because IL-6 cannot be targeted clinically, it will be of the utmost importance to identify downstream effectors of this IL-6-mediated response. This said, we hypothesize that increased levels of IL-6 in obese conditions are at least partially responsible for inducing a stem cell-like phenotype in breast cancer cells through activation of the Akt-mTOR pathway.Methods: MCF-7 and T47D breast cancer cells will be exposed to sera pooled from normoweight (BMI&lt;25 kg/m2) or obese (BMI≥30 kg/m2) women as an in vitro model of the systemic inflammation present in obesity. The cells will then be assessed for changes in expression of genes and proteins involved in induction of EMT using qPCR and western immunoblotting, respectively. Finally, flow cytometry will be used to confirm establishment of an EMT phenotype with measurement of the stem cell markers CD24 and CD44.Results: Our gene expression analyses confirm that obese conditions increase expression of EMT-related genes, including those encoding the transcription factors Snail and Twist. Our flow cytometric analyses also indicate an increase in the stem cell population following a 10-day IL-6 exposure. Additionally, supplementation of IL-6 to non-obese sera increased expression of Twist and Snail in breast cancer cells, while inhibition of IL-6 in obese sera reduced expression of these transcription factors. Finally, western blot analyses demonstrate mechanistic involvement of the Akt-mTOR pathway.Conclusions: These data contribute to our understanding of the means by which obesity induces a stem-like phenotype in breast cancer cells and will ultimately bring light to a therapeutic target that can be used to modulate IL-6-induced activation of the Akt-mTOR signaling pathway leading to an EMT phenotype in obese conditions.
Citation Format: Shannon Mayberry, Brittany Harlow, Elizabeth Eichman, Christopher Hsu, Linda deGraffenried. Mechanisms underlying obesity-induced enrichment of stem-like breast cancer cells [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS16-24.