bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PS9-55: Subcutaneous fixed-dose combination of pertuzumab and trastuzumab for the treatment of metastatic breast cancer in Canada - a budget impact analysis
Authors: Sripada Kaushik , Manjrekar Siddhi , Klein-Panneton Kristoph , Coombes Megan , Ferrario Cristiano 
Published: February 2021

Abstract
Background: Recently, the FeDeriCa trial investigated a fixed-dose combination (FDC) of Perjeta and Herceptin (PH), administered by subcutaneous (SC) injection, and demonstrated non-inferior pharmacokinetics of serum Perjeta and Herceptin levels compared to PH IV, along with a similar efficacy and safety profile to the intravenous (IV) administration of PH. In Canada, the standard of care for first-line HER2-positive metastatic breast cancer (mBC) is PH plus taxane chemotherapy with PH until disease progression. Currently, PH are administered as sequential IV infusions. SC administration of PH FDC has the potential to relieve pressure on the healthcare system, decrease treatment burden, and improve the patient experience.
Objective: To estimate the incremental costs/savings, including time savings, associated with the use of PH FDC SC for the treatment of HER2+ mBC, if reimbursed with the same provincial funding criteria as PH IV in Ontario and Quebec, Canada.
Methods: An Excel-based budget impact model was developed to determine the economic impact of PH FDC SC in comparison to PH IV in Ontario and Quebec. Direct medical costs in the analysis included drug acquisition, drug preparation and administration, and systemic therapy infusion chair/suite costs. Nurse and pharmacist wages were obtained from the Government of Canada’s Job Bank. Systemic therapy infusion chair/suite costs were derived from literature. Data related to time associated with preparation and administration of PH FDC SC and PH IV were collected through a survey completed by nurses and pharmacists involved in the FeDeriCa clinical trial in Canada.
Results: HER2+ mBC patients treated with PH FDC SC generate net cost savings to the health system compared to treatment with PH IV. These cost savings to the health system are generated due to fewer costs associated with drug acquisition, pharmacist and nurse wages directed towards drug preparation and administration respectively, as well as fewer overhead costs associated with the infusion chair/suite for PH FDC SC compared to PH IV. The use of PH FDC SC provides the healthcare payer with the opportunity to optimize drug and medical resources appropriately while offering a therapy that is aligned with patient and clinician preferences.
Citation Format: Kaushik Sripada, Siddhi Manjrekar, Kristoph Klein-Panneton, Megan Coombes, Cristiano Ferrario. Subcutaneous fixed-dose combination of pertuzumab and trastuzumab for the treatment of metastatic breast cancer in Canada - a budget impact 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 PS9-55.
Abstract PS9-60: Insomnia is the most disturbing symptom during breast cancer treatment: Results from a Brazilian cohort using a patient-reported outcomes: PRO tool - Tummi App
Authors: Morelle Alessandra Menezes , Venero Fernando Castilho , Ferreira Rafael DalPonte , Silva Rommel FabricioPereirada , Sant'Anna Pedro Tofani 
Published: February 2021

Abstract
Background: PRO have been shown to enhance our ability to communicate with patients and to control their symptoms. There are data that suggest a positive impact on survival when there is active participation of the patient in the reporting of symptoms. However, PRO data are not commonly collected in routine cancer care due to challenges like cost and due to the obsolete technology of many existing electronic health records. Methods: in an effort to bridge the unmet needs of PRO collection and integration into routine cancer care, we developed a symptom monitoring and management system that was launched as a free mobile app in August, 2018. Tummi app is designed for reporting 28 symptoms based on the National Cancer Institute’s Common Terminology Criteria for Adverse Events. Symptoms are reported in a 3-point scale (mild, moderate, severe) and patient reported an overall well-being scale represented by emojis. Tummi has the ability to record symptoms, summarize the reporting in physical printout, and automatically store and analyze the input symptoms into graphical interpretations. Results: since august 2018, 281 patients with the diagnosis of invasive breast cancer, during their treatment, downloaded and enjoyed the app. The most common side effect registered was back pain. When assessing the most intense symptoms reported by patients (grade 3), insomnia appears as the most remembered, followed by headache. Regarding general well-being reports, patients totaled 4501 records. Of these, at 62.40% of the time the patients were well, while at 33.16% they were average and at 4.44% they felt bad. Conclusions: in this group of patients evaluated by the Tummi App, insomnia is the most disturbing symptom. Although it appears in the literature as quite prevalent in this scenario, we see that its approach to day-by-day oncology clinics is far from ideal. We believe that the monitoring by a PRO tool can lead to a greater effort to improve this symptom that has such an impact on the quality of life of our patients.
Citation Format: Alessandra Menezes Morelle, Fernando Castilho Venero, Rafael DalPonte Ferreira, Rommel FabricioPereirada Silva, Pedro Tofani Sant'Anna. Insomnia is the most disturbing symptom during breast cancer treatment: Results from a Brazilian cohort using a patient-reported outcomes: PRO tool - Tummi App [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 PS9-60.
Abstract SP111: Interpreting reports
Authors: Park B 
Published: February 2021

Abstract
Although next generation sequencing (NGS) has become commonplace for breast and other cancers, interpretation of reports remains a challenging unmet need. This is further confounded by the therapeutic importance of understanding and interpreting whether pathogenic variants/mutations are germline versus somatic. Here we will discuss and provide examples of how molecular tumor boards can aid clinicians in providing interpretation of NGS results for optimal patient benefit.
Citation Format: B Park. Interpreting reports [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 SP111.
Abstract SP112: Spatial variance signatures/Intra-tumor zonation in TNBC
Authors: Park M , Martínez Ramirez C , Yang Y , Blanchet-Cohen A , Kuasne H , Fortier A , Ragoussis J , Savage P , Omeroglou A , Meterissian S , Costantino S , Kleinman C 
Published: February 2021

Abstract
It is increasingly clear that triple negative breast cancer (TNBC) is a heterogeneous disease with variable clinical presentation, histological features and response to therapy. While these differences have been partially explained by inter- and intra-tumoral heterogeneity, spatial heterogeneity represented by the tumor architecture plays a critical role in clonal evolution and displays a landscape for different compartment-specific processes and cell-to-cell specific interactions. To better understand the impact of spatial heterogeneity on gene-expression-defined cell populations, we have coupled single-cell RNA sequencing with multiplex immunofluorescence (IF). Multiplex immunofluorescence using specific markers for each cell cluster, integrated with computational image analyses and neighborhood maps, has revealed spatial zonation of single cell subpopulations. Zonation of single cell populations was coupled to hypoxia and overlayed distinct metabolic tumor zones and defined areas of differential stress and cell plasticity that give rise to tumor cells with enhanced fitness and aggressivity.
Citation Format: M Park, C Martínez Ramirez, Y Yang, A Blanchet-Cohen, H Kuasne, A Fortier, J Ragoussis, P Savage, A Omeroglou, S Meterissian, S Costantino, C Kleinman. Spatial variance signatures/Intra-tumor zonation in TNBC [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 SP112.
Abstract SP125: Rescue DNA repair pathway and tumor immunity
Authors: Rao M 
Published: February 2021

Abstract
Defects in DNA damage response (DDR) is a major factor that predispose normal cells to acquire oncogenic mutations. However, after a tumor develops, cancer cells manage their survival by repairing DNA damage resulting from unchecked DNA replication. Cancer cells can use the alternative or backup (rescue) DNA repair programs to overcome their DDR defects and cope with genotoxic lesions. For example, breast cancer cells with deficiency in homologous recombination (HR) can repair their DNA by either relying on other highly expressed HR-related proteins (such as RAD51 or PARP1), or by using other DNA repair mechanisms such as break-induced replication, alternative nonhomologous end joining (ALT-NHEJ) and basal excision repair (BER). Since DNA repair pathways operate in related networks in cancers in general and breast cancers in particular, it is likely that factor/s that play important roles in multiple DNA repair pathways may serve as a critical component of backup DNA repair pathways that breast cancer cells get addicted to survive and to become therapy resistant. One way these rescue DNA repair pathway factor/s may promote breast cancer progression is by shaping tumor immune microenvironment. Consistent with that, DNA damage and DNA repair pathways in general have been shown to regulate multiple arms of the immune response including antigenicity or tumor mutational burden (TMB) and regulation of immune checkpoint protein levels. Our studies suggest that rescue DNA repair pathways may support tumor progression and therapy response by promoting tumor cell intrinsic and extrinsic mechanisms of immunosuppression. Our results reveal that factors associated with backup DNA repair pathwaysmay promote immunosuppression by altering cGAS-STING and Type I Interferon (IFN) signaling pathways. Furthermore, using a specific inhibitor that targets rescue DNA repair pathway signaling, we show altered levels of several proteins involved in antigen processing and presentation, including proteasome/Immunoproteasome subunits and MHC I protein subunits, which are essential for the detection of cancer cells by cytotoxic T cells. Importantly, our pre-clinical and clinical data suggest that approaches aimed at successfully targeting rescue DNA repair factor(s) may promote anti-tumor immunity and will have promising clinical outcomes for treating breast cancer patients.
Citation Format: M Rao. Rescue DNA repair pathway and tumor immunity [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 SP125.
Abstract SP133: Oncofertility
Authors: Ruddy K 
Published: February 2021

Abstract
Many young women have not completed their desired childbearing when they are diagnosed with breast cancer. This is increasingly true as the average age of first birth rises such that more premenopausal breast cancers are diagnosed in nulliparous women. Even women who already have one or more children at the time of their cancer diagnosis may be hoping to become pregnant again. Because chemotherapy is gonadotoxic and endocrine therapy is contraindicated during pregnancy(allowing natural ovarian aging over the 5-10 years of adjuvant therapy recommended for those with endocrine-sensitive stage 1-3 tumors), breast cancer treatments can impair fertility. Fertility preservation strategies including oocyte cryopreservation and embryo cryopreservation should be considered prior to initiation of systemic therapy for young women with fertility concerns, often using modified ovarian stimulation protocols to minimize delays in cancer treatment. The administration of a gonadotropin-releasing hormone agonist before and during chemotherapy to help maintain ovarian function is more controversial, but can also be considered. It is critical that we offer reproductive counseling and access to fertility preservation techniques at the time of diagnosis, and that we also continue to discuss contraception and fertility planning during and after cancer treatment. Results from the POSITIVE trial, which is assessing pregnancy and cancer outcomes of young women who wished to take a break from adjuvant endocrine therapy to attempt conception, are eagerly awaited to inform these discussions. This talk will address current knowns and unknowns related to the optimal management of reproductive concerns in premenopausal women with breast cancer.
Citation Format: K Ruddy. Oncofertility [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 SP133.
Abstract SP151: BRCA and homologous recombination deficiency mediated mutagenesis in breast cancer
Authors: Tutt A 
Published: February 2021

Abstract
The genes BRCA1, BRCA2 and PALB2 genes are the major high penetrance risk alleles in breast cancer have function in a DNA repair mechanism called homologous recombination (HR). These and a wider group of other genes including the RAD51 paralogues and kinase regulators of HR can also be subject to somatic mutation or epigenetic modification in cancer and, usually in the setting of bi-allelic inactivation, effect the use of HR. The dysregulation of BRCA1 by methylation of its regulatory region is frequent occurring, in approximately 30% of sporadic basal-like breast cancers. While there is evidence that BRCA1 silencing causes functional HR deficiency, there is also evidence suggesting this may be more “plastic” and subject to change to maintain cell fitness and DNA replication capacity under the evolutionary pressures that cancer cells are subjected to during progression and therapyexposure.HR deficient cancers change to use of other DNA break and DNA replication fork repair mechanisms that are mutagenic. A number of methods based on tumor genome sequencing have been developed to assesssomatic mutational signatures. These methods have revealed pathognomonic “scars” or “tattoos” indicating exposure to HR deficiency during breast cancer evolution and the variable performance of mutational signatures in the contexts of genetic and epigenetic loss of HR function. HR deficiency induced mutagenesis can also inactivate genes that negatively regulate HR, or re-activate (reversion mutation) the previously inactivated HR gene, driving a reversal of HR deficiency. As this changes a cell’s DNA repair phenotype and its ability to handle to therapeutic damage, these are increasingly found to be relevant to the development of resistance to DNA interacting drugs such as platinums and PARP inhibitors as well as to emerging DNA damage response (DDR) targeting therapeutics. In the setting of resistance both the residual HR deficiency induced genome landscape or the altered use of the DNA damage response in breast cancer cells may offer new vulnerabilities, enhanced in tumor cells, that are subject to targeted DDR directed or immunotherapy therapy and inform combination or sequential therapy approaches and associated patient selection biomarkers now being assessed in the clinic.
Citation Format: A Tutt. BRCA and homologous recombination deficiency mediated mutagenesis 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 SP151.
Abstract SP021: Understanding current platforms
Authors: Burkard M 
Published: February 2021

Abstract
Next-generation sequencing (NGS) of breast cancer is becoming increasingly integrated into clinical practice. The fast pace of advances coupled with the dizzying array of technologies and platforms challenges the oncologist to select the right test for each patient. The choice could depend on a host of factors including the accessibility of clinical trials, clinical scenario and sample type, and the interest in turning up improbable but profoundly useful findings. Here, I will review the various types of clinical NGS platforms—including tumor and circulating-tumor DNA—particularly highlighting the unique features of commercial platforms that are widely available. Performance characteristics differ by technology: amplification technologies can detect mutations with smaller specimens, whereas capture-based NGS platforms may perform better for detecting novel genomic alterations. Assays integrating RNA-based analysis may enhance detection of rare but impactful gene fusions, such as of FGFR1-3 and NTRK1-3. Some potentially actionable genomic alterations only emerge after therapy, and are detected only with repeat tumor biopsy or cell-free DNA. Some assays include parallel germline testing which can clearly distinguish inherited from somatic (tumor-specific) findings, but may offer logistical challenges. An ever expanding set of ‘genomic phenotypes’ may be captured in these updated assays, with their limitations, including tumor mutational burden, microsatellite instability and homologous recombination. Newer platforms are now including exome and whole-genome sequencing, which may require more tissue and offer research insights, but currently add little to directing clinical care. New technologies, such as long-read and single-cell platforms of the future, may elucidate genomic features that are undetectable with current bulk short-read platforms, and will enable new genomic biomarkers. Despite the differences in genomics platforms, practical matters such as reimbursement, ease of use, and turn-around-time will likely govern platform selection for most oncologists in the near future.
Citation Format: M Burkard. Understanding current platforms [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 SP021.
Abstract SP027: Treatment differences and consequences
Authors: Chavez Mac Gregor M 
Published: February 2021

Abstract
Breast cancer is the deadliest cancer among women worldwide, with a total of over half a million deaths annually impacting both developed and developing countries. With an estimated 276,480 breast cancer cases projected to occur in women in the U.S., it is estimated that 42,170 women will die in 2020 due to this devastating disease. Despite the decrease in breast cancer mortality rates seen in recent years, the magnitude of that decrease in not similar across populations. In the U.S the burden of cancer is not shouldered equally. It is well known that racial and ethnic minority populations are more likely to experience cancer health disparities. While potential contributing factors associated with this phenomenon include the fact that certain groups of patients are more likely to be diagnosed with more advanced stages and to have tumors with more aggressive biology, sociodemographic factors and difficulty accessing medical care play an important role. Unfortunately, cancer care delivery is not the same for all and this can seriously hinder the cancer outcomes of those affected. Across the cancer care continuum -from screening, diagnosis, and all the way to treatment, survivorship or end-of life care-, important disparities exist leading to worse outcomes. It has been well described that Black and Hispanic women are less likely to receive appropriate and timely breast cancer treatment. Furthermore, the complex, and in many cases long treatments needed to achieve the desired outcomes, force patients to face issues associated with navigating the health care system, making life changes to accommodate treatment, and ensuring continuation and treatment adherence. In this presentation, we will review the complexities of breast cancer diagnosis and treatment and review some of the data regarding the detrimental impact associated to treatment delays. Improving cancer care delivery and ensuring access to timely and high-quality care should be a priority. We will briefly revise some of the strategies designed to overcome health disparities and hopefully, improve breast cancer outcomes.
Citation Format: M Chavez Mac Gregor. Treatment differences and consequences [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 SP027.
Abstract SP057: Mechanisms Controlling Expression of the Breast Cancer Genomic DNA Deaminase APOBEC3B
Authors: Harris R 
Published: February 2021

Abstract
Introduction: APOBEC3B (A3B)-catalyzed DNA cytosine deamination contributes to the overall mutational landscape in primary and metastatic breast cancer. While low in normal tissues, A3B expression and activity are elevated in many primary tumors and increase further in metastases. Prior studies have implicated the RB/E2F signaling pathway in A3B overexpression in breast cancer but a detailed molecular mechanism has yet to be described.
Methods: A combination of genetic, biochemical, proteomic, and bioinformatic approaches were used to investigate whether dysregulation of the RB/E2F signaling pathway is a molecular trigger for A3B overexpression in breast cancer.
Results: First, an A3B promoter-driven luciferase reporter was used to demonstrate functional repression by one of five predicted E2F binding sites. Disruption of this single E2F site both phenocopied and prevented further induction by BK polyomavirus T antigen, which was known from prior studies to induce A3B expression. Second, targeted disruption of the endogenous E2F binding site caused strong A3B upregulation and confirmed the importance of this cis-regulatory element. Third, proteomics experiments showed that members of the DREAM and PRC1.6 complexes are able to bind to wildtype but not to mutant E2F promoter sequences. Additional biochemical, genetic, and cell biological studies implicated both the E2F4/DREAM complex and E2F6/PRC1.6 complex in endogenous A3B repression. Last, bioinformatic analyses of breast cancer data sets showed A3B overexpression and higher levels of APOBEC signature mutations in tumors with coordinately overexpressed E2F target genes.
Conclusions: These studies combine to demonstrate that A3B expression is suppressed in normal cells by repressive E2F complexes and that disruption of this regulatory network triggers overexpression in breast cancer and provides fuel for tumor evolution. These studies raise the possibility that overexpression of an E2F gene set in breast tumors may be a biomarker for APOBEC mutability.
Citation Format: R Harris. Mechanisms Controlling Expression of the Breast Cancer Genomic DNA Deaminase APOBEC3B [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 SP057.