bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract BS1-2: A new perspective on androgen receptor action in estrogen receptor-α positive breast cancer
Authors: Tilley W 
Published: March 2022

Abstract
Resistance to estrogen receptor alpha (ER) target therapies is the major cause of breast cancer death. Therapeutic engagement of steroid receptors that impinge on, but do not ablate, ER signalling is an emerging new treatment strategy. The AR is expressed in the majority of breast tumors and represents an exceptional therapeutic target, especially as a range of drugs including AR agonists, antagonists and selective AR modulators (SARMs) are available. Interest in targeting AR for treatment of breast cancer has escalated over the past decade. Despite clinical correlations and preclinical studies supporting a protective role for AR in breast cancer, especially in ER-positive disease, enthusiasm was largely directed toward antagonizing AR with anti-androgenic drugs used to treat men with prostate cancer, a disease definitively driven by oncogenic AR activity. While some pre-clinical studies supported use of an AR antagonist for ER-positive breast cancer, this strategy has had minimal success in clinical trials. Our most recent preclinical studies using a diverse range of in vivo breast cancer models (Hickey et al, Nature Medicine 2021) provides compelling evidence for (i) AR being a tumor suppressor in ER+ breast cancer, and (ii) an AR agonist, not an antagonist, treatment strategy being the optimal therapeutic approach.
Citation Format: W Tilley. A new perspective on androgen receptor action in estrogen receptor-α positive breast cancer. [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr BS1-2.
Abstract DEB2-2: Con - One Week of Whole Breast RT is the New Standard of Care
Authors: White J 
Published: March 2022

Abstract
The dual role of breast irradiation post lumpectomy for conservative treatment is to yield local cancer control comparable to that achieved with mastectomy while maintaining a sensate and cosmetically acceptable breast. Through application of a linear quadratic equation that characterizes the radiobiological relationship of total dose and dose per fraction to predict efficacy as well as tissue specific toxicity, breast radiation that is equally effective can be delivered with fewer treatments. This has allowed standard post lumpectomy breast radiation to be reduced to 15 -16 treatments from 25-28 with similar efficacy and toxicity confirmed in multiple clinical trials. The recent Fast Forward trial (Lancet 2020; 395: 1613-26) has now further advanced the application of this radiobiological model evaluating breast irradiation delivered in 5 treatments. This resulted in non-inferior recurrence events compared to 15-treatment breast irradiation. When using fewer treatments of larger radiation dose, small changes can result in significant toxicity effects. For example, with 1 Gy difference between 26 Gy and 27 Gy total dose treatment arms on the Fast Forward trial, significantly higher rates of breast adverse outcomes were seen. Additional experience with the 5-fraction breast irradiation is needed prior to its replacing the current 15-16 treatment standard.
Citation Format: J White. Con - One Week of Whole Breast RT is the New Standard of Care [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr DEB2-2.
Abstract ES10-2: Immune therapy in the (neo) adjuvant setting
Authors: McArthur H 
Published: March 2022

Abstract
Historically, the treatment of early-stage triple negative breast cancer (TNBC) has hinged on the administration of conventional cytotoxics. However, the curative-intent treatment landscape has recently evolved with the successful development of checkpoint blockade inhibitor (CPI) strategies. Specifically, on July 27, 2021, the United States FDA approved the PD-1 directed antibody, pembrolizumab, for high-risk early-stage TNBC together with chemotherapy as neoadjuvant treatment and then continued as a single agent as adjuvant treatment after surgery based on the results of the randomized, phase 3 KEYNOTE-522 study. In this study, the addition of pembrolizumab to a platinum-, taxane- and anthracycline-based regimen conferred an absolute 13.6% improvement in pathologic complete response (pCR) in the intention-to-treat population at the first interim analysis, with benefits observed irrespective of PD-L1 status. Although the absolute benefit subsequently decreased to 7.5% at the third interim analysis, the event free survival (EFS) benefit was maintained. In fact, with a median follow-up of 39.1 months at the fourth interim analysis, the EFS was 15.7% versus 23.8% (HR 0.63, p= 0.00031) in favor of the CPI containing regimen. The Geparnuevo study, a modestly powered study in which randomized patients with early stage TNBC to receive neoadjuvant chemotherapy with or without durvalumab, a PD-L1 targeting CPI, did not meet its pCR primary endpoint; however, in a recent update reporting on secondary endpoints, improvements in invasive disease free survival (85.6% vs 77.2%), distant disease free survival (91.7% vs 78.4%) and overall survival (95.2% vs 83.5%) were reported in favor of the CPI-containing regimen. EFS data from the IMpassion031 study of neoadjuvant chemotherapy with or without the PD-L1 targeting CPI, atezolizumab, are anticipated after an absolute 16.5% improvement in pCR was reported in the intention-to-treat population with the addition of the CPI, with benefits observed regardless of PD-L1 status. Studies evaluating the role of CPI strategies in the adjuvant setting are also underway. For example, pembrolizumab is being evaluated as monotherapy for patients with residual TNBC after neoadjuvant chemotherapy in the SWOG 1418 study and atezolizumab is being administered with adjuvant chemotherapy after upfront surgery for early-stage TNBC in the IMpassion030/ALEXANDRA study. Studies evaluating curative-intent CPI and targeted therapies and/or local therapies are underway or planned. Available data, current controversies and future directions will be discussed.
Citation Format: H McArthur. Immune therapy in the (neo) adjuvant setting [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr ES10-2.
Abstract ES13-3: Novel epigenomic targets in TNBC
Authors: Cescon DW 
Published: March 2022

Abstract
Triple negative breast cancer is a heterogenous disease, characterized by a dearth of recurrent actionable genetic alterations. Epigenetic alterations have been implicated in the pathogenesis of triple negative breast cancer, as well as in the acquisition of drug resistance, which is a commonly observed phenomenon and persisting clinical challenge. An expanding array of tools for epigenomic characterization, together with novel selective inhibitors of epigenetic regulators are enabling new opportunities to identify and target these processes in triple negative breast cancer. Examples of recent and emerging therapeutic strategies using conventional therapies and epigenetic-targeted agents to exploit these vulnerabilities in triple negative breast cancer will be discussed.
Citation Format: DW Cescon. Novel epigenomic targets in TNBC [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr ES13-3.
Abstract ES8-3: Refining axillary management after neoadjuvant chemotherapy - what does the evidence support
Authors: Mamounas P 
Published: March 2022

Abstract
The surgical management of the axilla in patients with operable breast cancer has undergone significant evolution over the past 25 years. Axillary lymph node dissection (ALND), the undisputed standard since the end of the 19th century, has largely been replaced by sentinel lymph node biopsy (SLNB) in most patients with clinically negative axilla with considerable reduction in axillary morbidity. Neoadjuvant chemotherapy (NAC) has been increasingly used in early-stage breast cancer, particularly in patients with triple-negative and HER-2 neu positive tumors. Rates of sterilization of involved axillary lymph nodes with NAC in appropriately selected patients have been steadily increasing with the adoption of more effective NAC regimens. Adoption of SLNB after NAC has lagged behind that of upfront SLNB. Recent data support the feasibility and accuracy of the procedure after NAC in patients who present with clinically negative axilla. Although the accuracy of SLNB is lower after NAC in patients who present with documented involvement of the axilla, identification and removal of the previously biopsied axillary lymph node(s) in addition to performing SLNB (“targeted axillary dissection”) greatly improves the accuracy to levels equivalent to those with upfront SLNB.
Citation Format: P Mamounas. Refining axillary management after neoadjuvant chemotherapy - what does the evidence support [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr ES8-3.
Abstract MS1-3: Targeting DNA damage response and HRD in breast cancer
Authors: Yap TA 
Published: March 2022

Abstract
Genomic instability is a key hallmark of cancer that arises owing to defects in the DNA damage response (DDR) and/or increased replication stress. These alterations promote the clonal evolution of cancer cells via the accumulation of driver aberrations, including gene copy-number changes, rearrangements and mutations; however, these same defects also create vulnerabilities that are relatively specific to cancer cells, which could potentially be exploited to increase the therapeutic index of anticancer treatments and thereby improve patient outcomes. The discovery that BRCA-mutant cancer cells are exquisitely sensitive to inhibition of poly(ADP-ribose) polymerase has ushered in a new era of research on biomarker-driven synthetic lethal treatment strategies for breast and other cancers. The therapeutic landscape of antitumor agents targeting the DDR has rapidly expanded to include inhibitors of other key mediators of DNA repair and replication, such as ATR, WEE1, ATM, PK-MYT1, DNA-PK, POLQ and USP1. Efforts to optimize these therapies are ongoing across a range of cancers, involving the development of predictive biomarker assays of responsiveness (beyond BRCA mutations), assessment of the mechanisms underlying intrinsic and acquired resistance, and evaluation of rational, tolerable combinations with standard-of-care treatments, novel molecularly targeted agents and immune-checkpoint inhibitors.
Citation Format: TA Yap. Targeting DNA damage response and HRD in breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr MS1-3.
Abstract P1-01-02: Pathologic nodal status is a predictor for metastatic disease in lymph nodes identified by axillary reverse mapping
Authors: Saengphongchawan Rak , Manasnayakorn Sopark 
Published: March 2022

Abstract
Background Breast cancer is the most common cancer in female patients worldwide. Although axillary management in breast cancer has been de-escalated to reduce untoward effects, breast cancer-related lymphedema (BCRL) is still not uncommon. Axillary reverse mapping (ARM) emerges as a novel technique that identifies the lymphatic system draining the upper extremities. Preservation of this system and associated lymph nodes theoretically reduces the chance of BCRL. However, concerns regarding oncologic safety have limited the adoption of the technique. Objective To identify factors associated with metastatic disease in lymph nodes identified by ARM in breast cancer patients. Materials and methods Breast cancer patients treated at King Chulalongkorn Memorial Hospital from October 2018 to January 2021 who underwent axillary lymph node dissection (ALND) underwent concurrent ARM whereby five milliliters of 1% isosulfan blue dye was injected at the medial aspect of the arm as previously described elsewhere. Patient demographics and clinical data such as clinical staging, pathological staging, cancer subtype, and whether neoadjuvant chemotherapy was administered were collected and analyzed. Result Thirty-six patients with a median age of 57 were included in this prospective study. ARM lymph node identification success rate was 83% (30 of 36 patients) with a median of 2 identified ARM lymph nodes (range 0-11 nodes). Metastatic disease in ARM nodes was present in 30% of patients. ARM success rate did not depend on whether preoperative chemotherapy had been given (ARM lymph nodes identified in 7 out of 8 patients without preoperative chemotherapy and 23 out of 28 in patients with preoperative chemotherapy; p=0.36). There was no statistically significant difference in metastatic disease in ARM-identified nodes and clinical stage (stage II=13.3%, stage III=33.3%, and stage IV=50.0%; p=0.18). However, higher pathologic N stage was associated with finding metastasis in ARM-identified lymph nodes (N0=0%, N1=15.8%, N2=33.3%, and N3=80%; p=0.005). Conclusions ARM is a novel technique which can potentially reduce BCRL. However, a significant number of ARM lymph nodes were found to have pathologically-proven metastatic disease, especially in higher pathologic N stages (pN2 and pN3). Therefore, for oncologic safety, consideration should be given to removal of all ARM lymph nodes in breast cancer patients undergoing formal axillary dissection. Keywords: Axillary Reverse Mapping, Axillar dissection, Lymphedema, Breast Cancer
Citation Format: Rak Saengphongchawan, Sopark Manasnayakorn. Pathologic nodal status is a predictor for metastatic disease in lymph nodes identified by axillary reverse mapping [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-01-02.
Abstract P1-01-04: RUFY3 as a predictive intratumor biomarker for lymph node metastasis in older women with invasive breast cancer
Authors: Angarita Fernando A. , Oshi Masanori , Yamada Akimitsu , Yan Li , Matsuyama Ryusei , Edge Stephen B. , Endo Itaru , Takabe Kazuaki 
Published: March 2022

Abstract
Background: Sentinel lymph node biopsy (SLNB) is omitted in older women (≥ 70 years old) with clinical lymph node (LN)-negative hormone receptor-positive breast cancer as it does not influence adjuvant treatment decision-making. However, older women are heterogenous in frailty while the chance of recurrence increase with improving longevity. Therefore, a biomarker that identifies LN metastasis may facilitate treatment decision-making. RUFY3 is associated with cancer progression. We evaluated RUFY3 expression level as a biomarker for LN-positive breast cancer in older women. Methods: Clinical and transcriptomic data of breast cancer patients were obtained from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC, n=1,903) and The Cancer Genome Atlas (TCGA, n=1,046) Pan-Cancer study cohorts. Results: A total of 510 (METABRIC) and 211 (TCGA) older women were identified. LN-positive breast cancer, which represented 51.4% (METABRIC) and 48.4% (TCGA), demonstrated worse disease-free, disease-specific, and overall survival. RUFY3 levels were significantly lower in LN-positive tumors regardless of age. The area under the curve for the receiver operator characteristic (AUC-ROC) curves showed RUFY3 predicted LN metastasis. Low RUFY3 enriched oxidative phosphorylation, DNA repair, MYC targets, unfolded protein response, and mtorc1 signaling gene sets, was associated with T helper type 1 cell infiltration, and with intratumor heterogeneity and fraction altered. Low RUFY3 expression was associated with LN-positive breast cancer and with worse disease specific survival amongst older women. Conclusion: Low RUFY3 expression is associated LN-positive in breast cancer. Intratumor RUFY levels can be used for selection of older breast cancer patients for LN staging.
Citation Format: Fernando A. Angarita, Masanori Oshi, Akimitsu Yamada, Li Yan, Ryusei Matsuyama, Stephen B. Edge, Itaru Endo, Kazuaki Takabe. RUFY3 as a predictive intratumor biomarker for lymph node metastasis in older women with invasive breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-01-04.
Abstract P1-02-01: Deep learning identifies morphological changes in whole slide images of treatment-resistant TNBC
Authors: Pour Ali Foroughi , Wu Te-Chia , Martinek Jan , Kumar Swarup , Anzeneder Tobias , Torkler Stephanie , Sommermeyer Franziska , Palucka Karolina , Chuang Jeffrey 
Published: March 2022

Abstract
Deep learning has become an important methodology for analyzing hematoxylin and eosin (H&E) stained whole slide images (WSIs), with high accuracy in detecting tumors, distinguishing cancer subtypes, and stratifying patients by survival risk in certain cancers [1,2,3]. However, machine-learning based evaluations of post-treatment tumors have been limited, e.g. focusing on user-defined features such as cellularity [4] rather than data-driven approaches. We analyzed 80 WSIs to determine if treatment-naïve TNBC, treatment-resistant TNBC, and treatment resistant growth factor and hormone receptor expressing tumors could be distinguished from each other (36 treatment naïve TNBC, 25 resistant TNBC, and 19 resistant non-TNBC WSIs corresponding to 31, 22, and 16 patients, respectively). All resistant patients received chemotherapy, except for one ER+ patient who only received medication to block hormone production. Our deep learning image-based models were able to separate treatment naive and treatment resistant TNBC tumors with high accuracy (AUC=0.85). We further developed a 3-way classifier that was able to distinguish resistant non-TNBC tumors from TNBC treatment-resistant and treatment-naïve samples (AUC=0.74). Removing deep learning features differentiating between TNBC and non-TNBC resistant samples, we find treatment-naïve and resistant samples can be separated irrespective of breast cancer subtype (AUC=0.77). Our results show that post chemotherapy, breast tumors are morphologically distinguishable by machine learning methods from treatment naïve tumors. While some treatment-related morphological changes are present across subtypes, some are unique to TNBC. References:[1] Noorbakhsh, Javad, et al. "Deep learning-based cross-classifications reveal conserved spatial behaviors within tumor histological images." Nature communications 11.1 (2020): 1-14.[2] Wulczyn, Ellery, et al. "Interpretable survival prediction for colorectal cancer using deep learning." NPJ digital medicine 4.1 (2021): 1-13.[3] Cui, Lei, et al. "A deep learning-based framework for lung cancer survival analysis with biomarker interpretation." BMC bioinformatics 21.1 (2020): 1-14.[4] Peikari, Mohammad, et al. "Automatic cellularity assessment from post-treated breast surgical specimens." Cytometry Part A 91.11 (2017): 1078-1087.
Citation Format: Ali Foroughi Pour, Te-Chia Wu, Jan Martinek, Swarup Kumar, Tobias Anzeneder, Stephanie Torkler, Franziska Sommermeyer, Karolina Palucka, Jeffrey Chuang. Deep learning identifies morphological changes in whole slide images of treatment-resistant TNBC [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-02-01.
Abstract P1-08-23: Androgen receptor as predictive marker for pathologic complete response in breast cancer with neoadjuvant chemotherapy
Authors: Lee Eun-Gyeong , Lee Dong-Eun , Han Jai Hong , Lee Seeyoun , Kang Han-Sung , Lee Eun Sook , Kwon Youngmee , Kim Hyun Hee , Chae Hee Jung , Sim Sung Hoon , Lee Keun Seok , Jung So-Youn 
Published: March 2022

Abstract
Background: Androgen receptors (AR) has emerged as a prognostic factor predicting survival and recurrence in breast cancer. However, the role of AR as a predictor of pathological complete response (pCR) rate after neoadjuvant chemotherapy by subtypes is unclear. This study aimed to investigate according to AR in breast cancer patients undergoing neoadjuvant chemotherapy as a predictor. Furthermore, we estimated the relationship between AR expression and clinicopathological factors. Method: We identified 624 breast cancer patients who underwent surgery after neoadjuvant chemotherapy at the National Cancer Center from April 2016 to October 2019. We retrospectively collected the medial records that the clinicopathologic information and AR expression analyzed according to cancer stage, hormonal receptor status, HER2 status, tumor subtype, pCR. Results: Among the 624 breast cancer patients, 529 (84.8%) were AR positive patients and 95 (15.2%) were AR negative patients. The mean age of the patients was 50.0 years. The rate of pCR was 31.4% (196/624). AR negative patients had significantly high rate of pCR than AR positive patients. (AR (-) 43.2% vs. AR (+) 29.3%, p = 0.0074). AR positive patients showed more ER positivity, PR positivity, HER2 positivity and luminal A subtype. A higher proportion of AR positive patients compared to AR negative patients received target therapy and hormonal therapy (target therapy, AR (-) 15.8% vs. AR (+) 43.9%, hormonal therapy, 14.7% vs. 71.0%, p &lt;.0001). The tumor factors associated with pCR were early stage, histologic grade 3, ER negativity, PR negativity, AR positivity, HER2 positivity, and high ki-67%. According to subtypes of tumor, the correlation between AR expression and pCR was. significantly higher in AR negative luminal A type (AR (-) 28.57% vs. AR (+) 7.26%, p =0.0215). The other subtypes did not show a statistically significant difference. Conclusion: This study shows that AR expression is predominant in luminal A subtype. When determining neoadjuvant chemotherapy in luminal A subtype, AR expression can be considered as a pCR predictive marker.
Citation Format: Eun-Gyeong Lee, Dong-Eun Lee, Jai Hong Han, Seeyoun Lee, Han-Sung Kang, Eun Sook Lee, Youngmee Kwon, Hyun Hee Kim, Hee Jung Chae, Sung Hoon Sim, Keun Seok Lee, So-Youn Jung. Androgen receptor as predictive marker for pathologic complete response in breast cancer with neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-08-23.