bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract ES4-4: Dietary modification to impact both tumor progression and treatment response
Authors: Simone NL 
Published: March 2022

Abstract
As the landscape of medicine changes to a precision approach to treating patients based on novel therapeutic interventions, the metabolic landscape of our country's population has also been changing at a rapid pace. As rates of metabolic disorders such as obesity and diabetes continues to increase in this country, so will the incidence of cancer. It is well established that patients who present with metabolic disorders such as obesity or diabetes often have increased recurrence rates, poor survival and increase toxicity despite standard treatments of chemotherapy and radiation. Unfortunately, this has created a new type of health disparity. To date, there has been no emphasis on creating novel therapeutics to address the metabolic profile created by an interplay of the patient, or the host, and the tumor. To begin to evaluate if metabolic processes can be altered to enhance radiation and chemotherapy, we began to employ caloric restriction as a concurrent treatment with cytotoxic therapy. Preclinical models demonstrated that caloric restriction could increase local control and overall survival and decrease distant metastases. We have now completed clinical trials to determine that caloric restriction could be used as a therapeutic option in patients undergoing radiation or chemotherapy and noted this treatment to be tolerated well by patients while decreasing typical toxicities of treatment. The preclinical and clinical effects of modulating the metabolic landscape of the patient and the tumor will be discussed as well as future directions.
Citation Format: NL Simone. Dietary modification to impact both tumor progression and treatment response [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 ES4-4.
Abstract ES5-1: Genomic and transcriptomic landscape of TNBC
Authors: Shao Z 
Published: March 2022

Abstract
Triple-negative breast cancer (TNBC) is highly heterogeneous. Due to the limited number of TNBCs that have been analyzed, molecular events driving subtypes and prognosis are not firmly established, and little is known regarding TNBC in non-Caucasian patients. Our findings advance the understanding of TNBC subtypes, subdivide the established transcriptome-based subtypes in search of more targeted therapeutic strategies, and offer potential insights to guide subtype-specific therapy. We further conducted a phase Ib/II subtyping-based and genomic biomarker guided umbrella trial to evaluate the efficacy of these targets. Objective response rate (ORR) of these 69 refractory metastatic TNBC patients was 29.0%, while the ORR of arm C (immunotherapy) was 52.6%. Still, genomic and transcriptomic-based target mining do not solve all the problems in TNBC treatment, for example the poor treatment efficacy in luminal androgen receptor (LAR) and basal-like immune-suppressed (BLIS) subtypes. Increasing the dimensions of omics to look for potential therapeutic targets would hopefully solve this problem.
Citation Format: Z Shao. Genomic and transcriptomic landscape of 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 ES5-1.
Abstract ES6-1: Approving New Therapies for Early Breast Cancer
Authors: Wedam S 
Published: March 2022

Abstract
The approval of a therapy by the US Food and Drug Administration (FDA) for the treatment of early breast cancer (EBC) requires substantial evidence of efficacy and an acceptable benefit-to risk evaluation from adequate and well-controlled investigations. There are two different regulatory pathways by which the FDA may approve drugs and biologics for the treatment of cancer. Regular or traditional approvals are based on the demonstration of direct clinical benefit, such as an improvement in survival or disease-related symptoms, or an improvement in an established surrogate. Examples of endpoints used for regular approval in EBC include invasive disease-free survival (IDFS) and event free survival (EFS). In 1992, new regulations were implemented, allowing for the accelerated approval (AA) of drugs for serious or life-threatening diseases in which the drugs seem to provide benefit over available therapy. AA is based on a surrogate or intermediate endpoint that is reasonably likely to predict clinical benefit. A post marketing requirement to confirm the effect on a direct clinical benefit is required. An example of an endpoint used for AA in EBC is pathologic complete response (pCR). Pertuzumab, neratinib, ado-trastuzumab emtansine and pembrolizumab have all received approvals for treatment of breast cancer in the neo/adjuvant setting over the last decade. Some of these approvals will be discussed to highlight various efficacy endpoints and clinical trial design features that may be used in the early breast cancer setting.
Citation Format: S Wedam. Approving New Therapies for Early 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 ES6-1.
Abstract ES7-1: Harnessing Lifestyle Interventions via Diet and Exercise for Cancer Risk Reduction
Authors: Iyengar NM 
Published: March 2022

Abstract
A growing body of evidence indicates the importance of maintaining optimal metabolic health to reduce the risk of developing cancer and to improve outcomes after cancer diagnosis. Classical and normal weight obesity are states of metabolic dysfunction, and highly prevalent risk factors for the development and growth of several cancers. Classical obesity (defined as a body mass index (BMI) ≥ 30) is a risk factor for at least 13 different types of cancer. Recent data indicate that up to one third of normal weight individuals have metabolic obesity and, subsequently, increased risk for several cancers including breast and colon. Methods to risk-stratify metabolic health and subsequent cancer risk beyond traditional anthropometric metrics such as BMI could improve the efficacy of lifestyle interventions aimed at reducing cancer risk and improving cancer outcomes. In this educational session, the molecular mechanisms linking classical and normal weight obesity to cancer growth will be presented. Obesity-related dysfunction can contribute to cancer pathogenesis and treatment resistance through various mechanisms, including those mediated by insulin, leptin, adiponectin, pro-inflammatory mediators, and hormone signaling pathways, particularly in women. Furthermore, adiposity-related changes can influence tumor vascularity and inflammation in the tumor microenvironment, which can support tumor development and growth. Building upon these mechanistic findings, several clinical trials testing “precision lifestyle” interventions targeted at specific biologic pathways are ongoing. Several randomized control trials testing diet, exercise, and weight loss interventions in cancer populations have demonstrated the feasibility of such interventions. Here, the next generation of lifestyle interventions, such as digital interventions, that target specific pathway dysregulation will be presented. Additionally, pharmacologic interventions that target host metabolism are under study as adjuncts to standard cancer therapy. As rates of classical and normal weight obesity continue to increase, the development of individualized and biologically rational lifestyle interventions could represent an impactful strategy to reduce the worldwide cancer burden.
Citation Format: NM Iyengar. Harnessing Lifestyle Interventions via Diet and Exercise for Cancer Risk Reduction [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 ES7-1.
Abstract ES8-1: Options for reducing risk for lymphedema when ALND/regional nodal XRT are needed
Authors: Sbitany H 
Published: March 2022

Abstract
Upper extremity lymphedema following axillary lymph node harvest or radiation therapy, can be extremely debilitating and symptomatic in breast cancer patients, and significantly reduces quality of life. In recent years, surgical procedures to reduce the development and progression of lymphedema have become more prevalent. These surgical procedures carry the aim of restoring lymphatic flow in the extremity following disruption of native channels. The most common procedures include vascularized lymph node transfer (VLNT) to the axilla, and lymphaticovenous bypass (LV bypass). The goal of both procedures is to restore flow, and reduce symptoms (infections, cellulitis, and reduced range of motion). VLNT involves harvest and transfer of autologous lymph node packets from a separate area of the body (most frequently the groin or supraclavicular region), and placement into the involved axilla, followed by microsurgical revascularization of the lymph nodes. Through cell signaling, this allows development of new lymphatic channel pathways, and resumption of drainage. LV bypass involves localized microsurgical anastomosis of lymphatic channels in the downstream affected extremity, directly to superficial veins in their vicinity. This allows lymphatic channels, proximal to the site of obstruction, to still drain their collected lymphatic fluid, directly into the systemic venous circulation in the extremity. In most cases, multiple LV bypass anastomoses are performed, to enhance lymphatic outflow. Due to the safety and efficacy of both procedures, they continue to be incorporated more frequently and routinely as part of breast reconstruction treatment plans.
Citation Format: H Sbitany. Options for reducing risk for lymphedema when ALND/regional nodal XRT are needed [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 ES8-1.
Abstract ES9-2: Special indications where local therapy should be considered
Authors: Lucci A 
Published: March 2022

Abstract
Clarity for the clinical issue of which patients with metastatic breast cancer should undergo local/regional therapy (LRT) was provided by the recent presentation of the prospective randomized ECOG-ACRIN 2108 trial data. This study, which randomized Stage IV breast cancer patients (initially treated with optimal systemic therapy for 4-8 months) to early local therapy or to continued systemic therapy alone, failed to demonstrate an improvement in overall survival for patients who had early local therapy compared to continued systemic therapy alone. However, there are some special indications that fall outside of this trial, and which remain areas of controversy. For instance, the subset of patients with inflammatory breast cancer (IBC) were not included in the ECOG trial, and therefore there are no prospective randomized clinical trial data available to determine if LRT improves survival in de novo stage IV IBC patients. To further confound the issue, several retrospective studies show clear survival benefit for Stage IV IBC patients who complete LRT, versus those who do not. While we all recognize that some differences could be attributed to selection bias, the differences in outcome are so striking that we believe that it warrants further discussion of the possible value of LRT in the IBC group. Furthermore, patients with IBC are more likely to be found to have Stage IV disease at presentation, complicating the discussion of whether complete trimodal therapy (neoadjuvant chemotherapy, mastectomy, and post-mastectomy radiation therapy) should still be considered at initial treatment planning, or whether LRT should be omitted altogether. Finally, due to the skin involvement and rapid progression inherent to IBC, these patients often require LRT for palliation of advanced disease (to control fungating tumors, brachial plexus involvement, etc.), so palliative surgery plays an important role in the management of the patient with IBC. During this presentation, we plan to discuss the available data regarding optimal LRT decisions for patients with de novo Stage IV IBC. Beyond the subset of IBC patients, several studies have identified non-IBC patients with Stage IV disease who might benefit from LRT. We will also discuss subsets of Stage IV breast cancer patients, including those with HR+ tumors, those with bone-only oligometastasis, and younger age patients, where LRT has shown survival benefit, based mainly on longer follow-up data from the randomized MF07-01 trial. Our objective is to improve knowledge of the local/regional treatment recommendations of select subgroups of Stage IV patients, where the use of LRT could translate to not only improved local control, but possibly to improved survival in carefully selected patients.
Citation Format: A Lucci. Special indications where local therapy should be considered [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 ES9-2.
Abstract ES9-3: Oligo-progressive disease. Treating locally more than systemically
Authors: Xu A 
Published: March 2022

Abstract
Advances in cancer therapies and technologies have shifted the paradigm for treating metastatic disease. Patients with stage IV disease are living longer and technologic advances enable us to deliver local therapies, such as surgical resection, radiofrequency ablation, or stereotactic radiosurgery, with lower toxicities. Genetic deep sequencing has helped us understand metastases to be genetically heterogeneous with independent subpopulations evolving in response to environmental pressures. We currently understand metastatic progression from primary tumor to disseminated disease to involve multiple stages, raising the possibility of an intermediate, curable, oligometastatic state with limited metastatic potential. The clinical relevance of oligometastases has been validated in multiple, recent randomized clinical trials. Metastasis directed therapies have been demonstrated to improve overall survival, however, this benefit is not seen in all patients, and breast specific data are lacking. This educational presentation will review randomized evidence supporting local treatment of oligometastases. We will also review evidence specific to breast cancer and highlight the critical need to define when local therapies can be effective at disrupting metastatic progression in breast cancer patients.
Citation Format: A Xu. Oligo-progressive disease. Treating locally more than systemically [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 ES9-3.
Abstract P1-05-06: Establishment of novel BRCA1ness score to quantify BRCAness in breast cancer
Authors: Oshi Masanori , Wu Rongrong , Yamada Akimitsu , Yan Li , Ishikawa Takashi , Endo Itaru , Takabe Kazuaki 
Published: March 2022

Abstract
Germline mutations in the loci of BRCA1 or BRCA2 genes with loss of heterozygosity or additional somatic truncation at the WT allele in breast cancer result in characteristic clinicopathological features of homologous recombination deficiency, also known as “BRCAness.”. Although clinical genetic testing for mutations of BRCA1 and BRCA2 has increased the chances of identifying pathogenic variants, we speculated that there may be a difference in cancer biology by the degree of BRCAness. To address this question, we sought to develop a means to estimate the amount of BRCAness using a score consists of BRCA1-mutation-related genes. Thirty-four BRCA1-mutation related genes were selected by high area under the curve (AUC) levels in receiver operating characteristic (ROC) curve between BRCA1 mutation and non-mutation breast cancer, consistently in two large breast cancer cohorts, TCGA and METABRIC. The score was established by using gene set variation analysis (GSVA) algorithm on 34 genes. We found that the BRCA1ness score was the highest in triple negative breast cancer (TNBC) among subtypes consistently in both cohorts (both p &lt; 0.001). Although BRCA1ness score did not correlate with mRNA expression of BRCA1 nor BRCA2 at all (spearman’s rank correlation coefficient (r) = 0.191 and 0.093, respectively), high BRCA1ness score was significantly associated with high rate of BRCA1 mutation (AUC = 0.735 and 0.709, respectively) in both cohorts. This level of AUC for BRCA1ness mutation score was highest compared to other factors, including BRCA1 expression (AUC = 0.323), DNA repair gene set score (AUC = 0.553 and 0.543), nor homologous recombination deficient (HRD) (AUC = 0.659), which are known as the characteristics of BRCAness. Furthermore, the score was significantly correlated with DNA repair gene set score (r = 0.593 and 0.323, both p &lt; 0.01) as well as MKI67 expression (r = 0.655 and 0.626, both p &lt; 0.01) in both cohorts. HRD score was also strongly correlated with BRCA1ness score in the TCGA cohort (r = 0.633). Interestingly, high BRCA1ness was significantly associated with worse disease-free survival (DFS) (p = 0.037 and p &lt; 0.001, respectively) and disease-specific survival (DSS) (p = 0.012 and p &lt; 0.001, respectively) in both cohorts. In conclusion, we established novel BRCA1ness score using mRNA expression of BRCA1-mutation-related genes, and found that it associate with DNA repair and worse survival.
Citation Format: Masanori Oshi, Rongrong Wu, Akimitsu Yamada, Li Yan, Takashi Ishikawa, Itaru Endo, Kazuaki Takabe. Establishment of novel BRCA1ness score to quantify BRCAness 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 P1-05-06.
Abstract P1-08-11: Clinical relevance of host immunity in patients with breast cancer who received neoadjuvant chemotherapy
Authors: Bae Soong June , Ji Jung Hwan , Chu Chihhao , Cha Yoon Jin , Kim Jee Hung , Ahn Sung Gwe , Jeong Joon 
Published: March 2022

Abstract
Background Host immunity plays a key role in breast cancer progression. It seems that the neutrophil-to-lymphocyte ratio (NLR) may reflect the systemic host immunity, and tumor-infiltrating lymphocytes (TILs) may reflect the localized host immunity. This study aimed to analyze the clinical relevance of host immunity combining NLR and TILs to treatment efficacy and survival.Methods We assessed the pre-treatment NLR and TILs from core-biopsy samples in 461 patients with breast cancer who received neoadjuvant chemotherapy. The patients were assigned into two groups: the intact host immunity group (NLR &lt; 2.75 and TILs ≥ 30%) and the defective host immunity group (the remainder; NLR &gt; 2.75 or TILs &lt; 30%). We investigated the pathologic complete response (pCR) and recurrence-free survival (RFS) according to host immunity.ResultsOf the total, 141 (30.6%) patients belong to the intact host immunity group, and 320 (69.4%) patients belong to the defective host immunity group. A pCR was achieved in 76 (53.9%) of 141 patients in the intact host immunity group, whereas a pCR was achieved in 96 (30.0%) of 320 patients in the defective host immunity group (P&lt;0.001). The intact host immunity was an independent predictor for high pCR (adjusted odds ratio [OR], 2.65; 95% confidence interval [CI], 1.74-4.03). Furthermore, the Cox proportional hazards regression models revealed that the intact host immunity obtained an independent prognostic value for favorable RFS after adjusted for clinicopathologic factors including pCR (adjusted hazard ratio [HR], 0.33; 95% CI, 0.11-0.98; P=0.045).ConclusionHost immunity based on the combined analysis of NLR and TILs provides information regarding the treatment response and prognosis in patients with breast cancer receiving neoadjuvant chemotherapy. There is a need for a new therapeutic strategy to activate the immune system in patients with defective host immunity. 2
Citation Format: Soong June Bae, Jung Hwan Ji, Chihhao Chu, Yoon Jin Cha, Jee Hung Kim, Sung Gwe Ahn, Joon Jeong. Clinical relevance of host immunity in patients with breast cancer who received 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 P1-08-11.
Abstract P1-24-02: Genetic variants and tumor microenvironment in inflammatory breast cancer: Clues for targeted therapies
Authors: Arisi Maria F. , Gong Yulan , Nagarathinam Rajeswari , Gerratana Lorenzo , Pei Jianming , Cai Kathy Q. , Winn Jennifer , Hasse Zachary , Obeid Elias , Noriega Julio , Sebastiano Christopher , Ross Eric , Alpaugh R. Katherine , Cristofanilli Massimo , Fernandez Sandra V 
Published: March 2022

Abstract
Background: Inflammatory breast cancer (IBC) is characterized by a young age at diagnosis, high metastatic potential, and poor overall survival. To better understand the etiology of this aggressive disease, we performed a retrospective study to evaluate genomic alterations and tumor microenvironment in IBC patients. Methods: Targeted next generation sequencing (NGS) was performed using blood cell-free DNA (cfDNA) (n=32), paired DNA from tumor tissues (n=29) and DNA from whole blood or normal tissue (n=20). We also characterized the tumor infiltrating lymphocytes (TILs) in tumor tissue biopsies by studying several markers (CD4, CD8, FoxP3, CD20, PD-1 and PD-L1) through immunohistochemistry (IHC) staining. Results: Our results shown a high incidence of germline variants in patients with IBC that could be associated with an increased risk of developing the disease. Germline variants were found more frequently in patients with TN (38.9%) than non-TN IBC (28.6%). IHC staining revealed that in 7 of 24 (29%) patients, tumor biopsies were positive for PD-L1 and PD-1 expression on TILs. Patients with PD-L1&PD-1 positive biopsies had a lower OS (31 months) than patients with PD-L1&PD-1 negative (38 months) tumors, though the difference was not statistically significant. PD-L1&PD-1 positive tumors had significantly more CD8+ (cytotoxic T-cells), CD20+ (B-cells) and FoxP3+ (Tregs) cells than PD-L1&PD-1 negative ones. Furthermore, most IBC patients showed to have deficiencies in the homologous recombination repair (HRR) pathway (BRCA1, BRCA2, PALB2, RAD51C, ATM, BARD1) making them sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors. All tumor biopsies showed positive staining for p-FAK1(Tyr 397). Conclusion: A subset of IBC patients (29%) expressed both PD-L1 and PD-1 on tumor immune cells infiltrates, providing rationale for testing PD-1/PD-L1 blocking therapies. IBC patients could have benefits from PD-1/PD-L1 blocking therapies alone or in combination with PARP or FAK (Tyr397) kinase inhibitors, both having the capacity of altering the tumor microenvironment.
Citation Format: Maria F. Arisi, Yulan Gong, Rajeswari Nagarathinam, Lorenzo Gerratana, Jianming Pei, Kathy Q. Cai, Jennifer Winn, Zachary Hasse, Elias Obeid, Julio Noriega, Christopher Sebastiano, Eric Ross, R. Katherine Alpaugh, Massimo Cristofanilli, Sandra V Fernandez. Genetic variants and tumor microenvironment in inflammatory breast cancer: Clues for targeted therapies [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 P1-24-02.