bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract PS7-67: Breast cancer subtype differences according to race/ethnicity
Authors: Fukui Jami , Bansil Surbhi , Silva Anthony , Killeen Jeffrey , Pagano Ian
Published: February 2021

Background:Breast cancer incidence and mortality rate differ across racial/ethnic population in the US, little is known about Asian and Pacific Island subpopulations. For the Asian subgroups (Japanese, Chinese, Korean, Filipino, Vietnamese, etc.) in the U.S., overall incidence has increased over recent decades. From 2012-2016 Hawai’i incidence rates were significantly higher than the US overall for breast cancer, although cancer mortality rates in Hawai’i were significantly lower than the US overall for breast cancer. Significant disparities in breast cancer incidence and mortality exist, with Native Hawaiian and Filipino women particularly affected. Native Hawaiian women have the highest incidence and also have a 50% higher risk of breast cancer mortality compared to White women. In addition, there are dramatic racial/ethnic differences in mortality rates in the state, with Native Hawaiians having the highest mortality rates compared to all other major racial/ethnic groups.

Methods:We examined unique breast cancer cases in a major health system in Hawai’i from 2013-2019 according to race/ethnicity. We found statically significant differences in breast cancer subtype according to race/ethnicity and menopausal status.

Results:In 561 premenopausal breast cancer cases, we found that Native Hawaiians were less likely to have triple negative breast cancer (OR 0.2, p=0.02) and Japanese were less likely to have triple positive breast cancer (OR 0.17, p=0.002) compared to other race/ethnicities. In 1,954 postmenopausal breast cancer cases, we found that Filipino women were more likely to have hormone negative/HER2 positive breast cancer (OR 2.38, p=0.006) compared to other race/ethnicities.

Table 1-Breast cancer subtype according to race/ethnicity in premenopausal women

Table 2-Breast cancer subtype according to race/ethnicity in postmenopausal women

Summary:Although behavioral, environmental, social, economic, and biological factors have been shown to influence risk and survival for breast cancer, they do not entirely explain the differences observed across populations. These findings show the need to characterize the underlying differences in breast tumor biology of breast cancer patients from different racial/ethnic groups to better understand known health disparities. Our hypothesis is that molecular characteristics are key contributors to the disparities in disease outcome across the different racial/ethnic groups. We have previously shown the importance of the tumor microenvironment differences in racial/ethnic groups in our population.

Citation Format: Jami Fukui, Surbhi Bansil, Anthony Silva, Jeffrey Killeen, Ian Pagano. Breast cancer subtype differences according to race/ethnicity [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 PS7-67.
Abstract PS7-77: Pathological response after neoadjuvant chemotherapy and long-term outcomes among very young women with HER2 negative breast cancer
Authors: Valencia Fernando , Laboriano Jorge , Chirinos Luis A. , Gomez Henry L.
Published: February 2021

Purpose: To describe the pathological response rates (according to the MD Anderson RCB score) achieved by patients with 35 years old or younger, with HER2 negative breast cancer, who received neoadjuvant chemotherapy (NAC) and long term outcomes according to the response. Methods: A retrospective review of 526 medical records of women aged less than or equal to 35 years at diagnosis between 2009 and 2014 at INEN in Lima-Peru, who received NAC for invasive breast cancer, was performed. HER2 positive patients were excluded because of a lack of access to neoadjuvant anti-HER2 therapy during this period in our hospital. Descriptive statistics were used to describe baseline characteristics. OS was calculated from the date of diagnosis to death or last follow-up and presented as Kaplan-Meier curves. The comparison among patients who achieved pCR (RCB-0) and those with residual disease, was based on a log-rank test. Results: Seventy women (One with synchronous bilateral disease) were selected according to selection criteria, median age: 31.7 years old (IQR: 30.0-33.2). Hormone receptor-positive: 38 (53.5%). Clinical stage: IIA: 13(18.3%), IIB: 8(11.3%), IIIA: 25(35.2%), IIIB: 21 (29.6%) and IIIC: 4 (5.6%). Type of NAC: Anthracyclines 6 (8.6%), Anthracyclines and taxanes 55 (78.6%), Platin 5 (7.1%), Taxanes 4 (5.7%). Type of surgery: Conservative 16 (22.5%), radical 50 (70.4%), toilet 5 (7.0%). Type of pathological response RCB-0: 9(12.7%), RCB-I: 2(2.8%), RCB-II:29(40.8%), RCB-III: 24(33.8%), non-pCR: 7(9.9%). With a median follow-up of 46.5m, 5y OS: 100/100/79.3/45.8% according to RCB-0/I/II/III respectively (p=0.004). Conclusions: "Very young" women reach fewer pCR rates than reported for "young" and older women. Even so, RCB-0 can be considered as a biomarker of excellent prognosis and could be used as a surrogate biomarker to evaluate the efficacy of neoadjuvant therapy even in very young women who receive NAC.

Citation Format: Fernando Valencia, Jorge Laboriano, Luis A. Chirinos, Henry L. Gomez. Pathological response after neoadjuvant chemotherapy and long-term outcomes among very young women with HER2 negative 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 PS7-77.
Abstract PS9-48: Depression, sexual dysfunction and quality of life among breast cancer patients with ovarian function suppression: A cross sectional study between ovarian ablation verse GnRH agonists
Authors: Xu Junnnan , Sun Tao
Published: February 2021

Background: Ovarian function suppression is being widely utilized as endocrine therapy to reduce estrogen release in premenopausal breast cancer patients and was achieved either by medical treatment with the Gonadotropin releasing hormone (GnRH) agonist or bilateral oophorectomy. This study aimed to examine the difference between GnRHa and ovarian ablation on depression, sexual dysfunction and quality of life.Methods: The premenopausal breast cancer patients who received ovarian function suppression were enrolled from seven hospital between June 2019 and February 2020. Our independent variable was the type of ovarian suppression, categorized as Ovarian Ablation (OA cohort, n=62) and medical GnRH agonist (GnRHa cohort, n=260). The self-administered questionnaire (OFS-Q5) developed and used in this study aimed to assess the depression (PHQ-9), sexual dysfunction (FSFI) and quality of life (EORTC QLQ-BR23), as well as the contributing factors.Results: In this cross-sectional study, 322 patients with ovarian function suppression completed surveys were collected. The mean sum score of the PHQ-9 in GnRHa cohort tend to be lower than that in ovarian ablation (OA) cohort (9.6 ±5.2 vs. 11.0 ±5.8, OR=1.495, P=0.080). Patients with major depression (PHQ-9≧15) was indicated significantly fewer in GnRHa cohort. Less patients met the criteria for sexual dysfunction (66.1%, FSFI< 26.55) in OA cohort compared with 81.5% of patients with GnRHa (P = 0.008). The ratio of sexual dysfunction remained lower for ovarian ablation women in long-term ovarian suppression (duration of ovarian suppression > 2 years: OA vs GnRHa, 36.7% vs 78.4%, P=2.4E-05). The differences of most subscales of QLQ-BR23 were insignificant in both cohorts.Conclusions: Our finding demonstrate here for the first time that ovarian ablation resulted in worse depression, favour sexual function than those with medical GnRHa, with similar quality of life. More attention need to paid on adverse effect in patients with diverse ovarian function suppression.

Citation Format: Junnnan Xu, Tao Sun. Depression, sexual dysfunction and quality of life among breast cancer patients with ovarian function suppression: A cross sectional study between ovarian ablation verse GnRH agonists [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 PS9-48.
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

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

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

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

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

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

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

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

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

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

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.
Abstract SP066: Omitting radiotherapy in select situations
Authors: Jagsi R
Published: February 2021

Advances in breast imaging, surgery, pathology, and systemic therapy have rendered certain patients with breast cancer at sufficiently low risk of local recurrence that they may reasonably consider the omission of radiation therapy to reduce toxicity and burden. For decades, clinical trials have been conducted to try to identify the population of patients in whom the risk of recurrence in the absence of radiotherapy is sufficiently small that omission of radiotherapy might reasonably be considered after breast conserving surgery. Although trials to date, including ER+ patients selected based upon clinicopathologic characteristics alone, have largely proven unsuccessful, guidelines do currently identify older women with early-stage, node-negative, hormone receptor-positive disease to be candidates for radiotherapy omission after lumpectomy. This talk will review historical trials evaluating the role of radiotherapy after breast conserving surgery as well as exciting ongoing trials leveraging our growing appreciation of tumor biology to identify a population of patients who may reasonably consider omitting radiotherapy after breast conserving surgery.

Citation Format: R Jagsi. Omitting radiotherapy in select situations [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 SP066.
Abstract SP069: Strategies to reduce cardiac toxicity
Authors: Jimenez R
Published: February 2021

Approximately 60-70% of breast cancer (BC) patients receive radiation therapy (RT) as part of their care. Breast or chest wall RT improves locoregional control for BC and also improves BC survival in select populations. However, RT to the cardiac silhouette can be cardiotoxic and radiation induced cardiac toxicity (RIC) affects many breast cancer survivors. The likelihood of RIC is radiation dose dependent and can manifest in multiple forms including cardiovascular disease, heart failure, and/or pericarditis. The risk of cardiovascular disease among patients receiving RT for breast cancer increases linearly with mean heart dose exposure, with no minimum safe threshold. Prior studies have shown an increased risk of both major coronary events and heart failure within 5 years of RT among women with breast cancer, though the latency can be pronounced (10-20 years from exposure) and is further influenced by patient age at treatment as well as pre-existing cardiac risk factors. Therefore, the purpose of this talk is to: 1) discuss the nature and timing of RIC, including those patients most at risk of developing RIC, 2) review national and international cardiology-based guidelines for patient management after chest radiotherapy and 3) detail advances in cardiac sparing radiation techniques intended to reduce the risk of RIC. Ongoing research regarding novel detection and prevention strategies will be highlighted.

Citation Format: R Jimenez. Strategies to reduce cardiac toxicity [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 SP069.
Abstract SP087: Epigenetic therapy against high-risk breast cancer
Authors: Lupien M
Published: February 2021

Standard-of-care therapy in high-risk stage II-III ER+/HER2-negative and Triple-Negative Breast Cancer (TNBC) includes neoadjuvant chemotherapy (NAC) prior to surgery, which is then followed by adjuvant endocrine (for ER+) +/- salvage chemotherapy (for TNBC). These treatments are delivered with limited stratification by disease histology and, while many patients are cured, more than one third of those in whom invasive disease remains in the breast at the time of surgery experience early relapses of metastatic disease within the first few years. The poor survival rate stems from incomplete response to NAC and the lack of alternative tailored therapy against the chemo-resistant disease that recurs. Hence, there is an urgent need for new therapies to treat recurrence and improve outcome. Tumor progression following standard-of-care therapy arises from pre-existing resistant and/or adapting persister cancer cells committing to an expansion phase. These differ from treatment sensitive cells in the epigenetic landscape of their genome, regulating the on/off state of genes for instance. This underlies epigenetic variants, akin to genetic variants, that define vulnerabilities to new treatment strategies. Here, we demonstrate the value of epigenetic therapy in preclinical settings against high-risk breast cancer, putting forward new treatment options to be tested in clinical trials.

Citation Format: M Lupien. Epigenetic therapy against high-risk 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 SP087.
Maturation Block in Childhood Cancer
Authors: Behjati Sam , Gilbertson Richard J. , Pfister Stefan M.
Published: February 2021

The key differences between tumors arising in children and those in adults stem from the cellular origin of cancer at different ages, with adult cancers arising within aging cell hierarchies, as a consequence of accumulated damage and mutagenesis, in contrast to childhood tumors that are born in aberrantly developing tissues. A distinct biological property of childhood tumor cells—a block of developmental maturation—may hold the key to advancing the treatment of childhood cancer beyond cytotoxic strategies.
Coexistence of Hereditary Spastic Paraplegia Type 4 and Narcolepsy: A Case Report
Authors: Nagai Takahiro , Sunami Yoko , Kato Risa , Sugai Megumi , Takahara Makoto , Ohta Kentaro , Fujinaka Hidehiko , Goto Kiyoe , Okanura Osamu , Nakajima Takashi , Ozawa Tetsuo
Published: February 2021

Spastic paraplegia type 4 (SPG4) is the most common type of hereditary spastic paraplegia (HSP) caused by the mutations in the SPAST gene, which encodes a microtubule-severing protein named spastin. Spastin regulates the number and mobility of microtubules and is essential for axonal outgrowth and neuronal morphogenesis. Herein, we report a patient with SPG4 harboring a novel donor splice site mutation in the SPAST gene (c.1616+1dupG). Although SPG4 usually manifests itself as a pure form of HSP, this patient exhibited a slow progressive cognitive decline and also developed narcolepsy type 2 (narcolepsy without cataplexy) prior to the onset of SPG4. Recently, cognitive decline has attracted attention as a main non-motor symptom of SPG4. However, this is the first reported case of a patient developing both SPG4 and narcolepsy, although it remains unclear whether the manifestation of the two diseases is a coincidence or an association. In this report, we describe the clinical symptoms and genetic background of the patient.
Pre-Admission CHADS2 and CHA2DS2-VASc Scores on Early Neurological Worsening
Authors: Nam Ki-Woong , Kim Chi Kyung , Yu Sungwook , Chung Jong-Won , Bang Oh Young , Kim Gyeong-Moon , Jung Jin-Man , Song Tae-Jin , Kim Yong-Jae , Kim Bum Joon , Heo Sung Hyuk , Park Kwang-Yeol , Kim Jeong-Min , Park Jong-Ho , Choi Jay Chol , Park Man-Seok , Kim Joon-Tae , Choi Kang-Ho , Hwang Yang Ha , Oh Kyungmi , Seo Woo-Keun
Published: February 2021

Background: Stroke risk scores (CHADS2 and CHA2DS2-VASc) not only predict the risk of stroke in atrial fibrillation (AF) patients, but have also been associated with prognosis after stroke. Objective: The aim of this study was to evaluate the relationship between stroke risk scores and early neurological deterioration (END) in ischemic stroke patients with AF. Methods: We included consecutive ischemic stroke patients with AF admitted between January 2013 and December 2015. CHADS2 and CHA2DS2-VASc scores were calculated using the established scoring system. END was defined as an increase ≥2 on the total National Institutes of Health Stroke Scale (NIHSS) score or ≥1 on the motor NIHSS score within the first 72 h of admission. Results: A total of 2,099 ischemic stroke patients with AF were included. In multivariable analysis, CHA2DS2-VASc score (adjusted odds ratio [aOR] = 1.17, 95% confidence interval [CI] = 1.04–1.31) was significantly associated with END after adjusting for confounders. Initial NIHSS score, use of anticoagulants, and intracranial atherosclerosis (ICAS) were also found to be closely associated with END, independent of the CHA2DS2-VASc score. Multivariable analysis stratified by the presence of ICAS demonstrated that both CHA2DS2-VASc (aOR = 1.20, 95% CI = 1.04–1.38) and CHADS2 scores (aOR = 1.24, 95% CI = 1.01–1.52) were closely related to END in only patients with ICAS. In patients without ICAS, neither of the risk scores were associated with END. Conclusions: High CHA2DS2-VASc score was associated with END in ischemic stroke patients with AF. This close relationship is more pronounced in patients with ICAS.
Sleep Apnea as a Cardiorenal Risk Factor in CKD and Renal Transplant Patients
Authors: Zoccali Carmine , Roumeliotis Stefanos , Mallamaci Francesca
Published: February 2021

Background: Chronic kidney disease (CKD) is a public health priority of increasing concern worldwide. Sleep apnea (SA) of moderate-to-severe degree has a 3–9% prevalence in women and 10–17% in men in the general population. Summary: In CKD patients, the prevalence of SA parallels the decline of the GFR being 27% in CKD patients with a GFR of >60 mL/min/1.73 m2 and 57% in patients with end-stage kidney disease (ESKD). In the early CKD stages, fluid overload is probably the sole risk factor for SA in this population. At more severe CKD stages, disturbed central and peripheral chemosensitivity and the accumulation of uremic toxins might contribute to SA. Still, there is no direct evidence supporting this hypothesis in human studies. Observational studies coherently show that SA is a risk factor for CKD incidence and CKD progression as well as for cardiovascular disease and death in this population. However, there is no randomized clinical trial testing continuous positive airway pressure or other interventions documenting that attenuation of SA may have a favorable effect on renal and cardiovascular outcomes in CKD and ESKD patients. However, most likely, the causal nature of the association between SA and cardiorenal outcomes remains unproven. Renal transplantation is the most effective treatment of SA in patients with ESKD, but this disturbance re-emerges on long-term observation in this population. However, after renal transplantation, SA does not seem to be a predictor of adverse health outcomes.
Odour Retrieval Processing in Mice: Cholinergic Modulation of Oscillatory Coupling in Olfactory Bulb-Piriform Networks
Authors: Ahnaou Abdallah , Chave Lucile , Manyakov Nikolay V. , Drinkenburg Wilhelmus H.I.M.
Published: February 2021

Background/Aims: Olfactory dysfunction can provide valuable insight into early pathophysiological processes of brain disorders. Olfactory processing of chemosensory and odour sensitivity relies on segregating salient odours from background odours cues. Odour-evoked fast oscillations in the olfactory bulb (OB) are hypothesized to be an important index of odour quality coding. The present preclinical work aimed at better understanding connectivity associated with odour coding and behavioural odour discrimination. Methods: Network oscillations and functional connectivity (FC) were measured in C57BL/6 mice performing the olfactory associative odour learning (OL) test, using multichannel local field potential recordings in key olfactory networks. Cholinergic modulation of odour processing was investigated using the muscarinic antagonist scopolamine. Results: At the behavioural level, olfactory memory, which refers to the acquisition and recollection of a reference odour by reduced exploration time, was observed in animals that correctly learned the task. Significant decrease in mean investigation and retrieval time of the associated odour-food reward was observed between trials. At the network level, the associated odour during sniffing behaviour was associated with enhanced coherence in the β and γ frequency oscillations across the olfactory pathway, with marked changes observed between the OB and anterior piriform cortex (PC). The enhanced phase-amplitude cross-frequency coupling in the OB and the weak coupling index in the hippocampal CA1 suggests a role of the OB network in olfaction encoding and processing. Scopolamine impaired behavioural and FC underlying recall and retrieval of the associated odour. Conclusion: The results suggest that the acquisition and formation of odour reference memory rely primarily on FC at the OB-PC network and confirm the role of muscarinic receptors in olfactory retrieval processing.
Sleep Disturbance in Inflammatory Bowel Disease Is Associated with Disease Activity and Adverse Outcome
Authors: Leal Tiago , Gonçalves Margarida , Antunes Pedro , Costa Dalila , Mendes Sofia , Soares João Bruno , Rebelo Ana , Gonçalves Bruno , Arroja Bruno , Gonçalves Raquel
Published: February 2021

Background: There is growing evidence about the relationship between sleep quality (SQ) and disease activity in inflammatory bowel disease (IBD). This study aimed to identify the prevalence of sleep disturbance in IBD and its predictive factors and to assess its association with worse outcome. Methods: IBD patients were prospectively enrolled. Clinical activity, inflammatory activity (high C-reactive protein or fecal calprotectin), and SQ (assessed using the Pittsburgh Sleep Quality Index) were evaluated, and logistic regression was used to identify predictors of poor SQ at baseline. The development of disability or disease progression at 6 months (surgery, hospitalization, development of stenosis, penetrating or perianal disease, steroid dependency, or start/change immunosuppression) was compared between patients with and without poor SQ. Results: Two hundred and five patients were enrolled, with 44.9% (n = 92) reporting poor SQ. On multivariate analysis, current smoking (OR 2.80), extraintestinal manifestations (OR 2.68), clinical activity (OR 3.31), and inflammatory activity (OR 4.62) were predictive factors of poor SQ. Cox proportional hazards model showed that poor SQ was predictive of worse prognosis at 6 months (HR 2.470). Conclusion: There is a high prevalence of poor SQ in IBD patients, highlighting the importance of its inclusion in patient-reported outcomes. Sleep disturbance seems to have prognostic value in IBD.