bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P4-07-19: Eribulin enhances STING-dependent induction of type I interferons in immune and triple-negative breast cancer cells
Authors: Takahashi-Ruiz Leila , Fermaintt Charles , Wilkinson Nancy , Mooberry Susan , Risinger April 
Published: March 2023

Abstract
Triple-negative breast cancer (TNBC) is a heterogenous subtype of breast cancer that lacks effective targeted treatment options. However, TNBC typically has a higher mutational burden and greater degree of immunogenicity than other breast tumors, making immunotherapy a viable strategy for effective treatment of this disease. Strategies to improve the response of TNBC patients to immunotherapy include the upregulation of the cGAS-STING innate immune sensing pathway and STING agonists are in clinical development for the treatment of TNBC. We demonstrate that eribulin, a microtubule destabilizer currently used in the treatment of TNBC, functions as an indirect STING agonist because it promotes the release of mitochondrial DNA into the cytoplasm. Eribulin also enhances type I interferon expression induced by STING agonists through a second TBK1-dependent mechanism downstream of STING activation that is shared by the RIG/MAVS RNA sensing pathway. Both mechanisms of eribulin-mediated activation of interferon expression occur in immune and TNBC cells and are shared with other microtubule destabilizers, including vinorelbine, but not with the microtubule stabilizing agent paclitaxel. These effects of eribulin on innate immune sensing pathways in vitro prompted further evaluations of the impact of eribulin on the in vivo immunological response to mammary tumors. We found that eribulin, but not paclitaxel, promotes the activation of CD4+ T-cells in the spleens and draining lymph nodes of tumored animals. This activation required tumor priming but was independent of any direct effect on tumor growth inhibition, demonstrating a specific role of eribulin as a tumor immune modulator. These data contribute to accumulating evidence that there are important mechanistic differences between the microtubule targeted chemotherapeutics currently used in the treatment of TNBC and suggest that eribulin elicits a more favorable innate immunological signature than paclitaxel. Research supported by Eisai Inc.
Citation Format: Leila Takahashi-Ruiz, Charles Fermaintt, Nancy Wilkinson, Susan Mooberry, April Risinger. Eribulin enhances STING-dependent induction of type I interferons in immune and triple-negative breast cancer cells [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-19.
Abstract P4-07-63: Local delivery of immunotherapeutics as an in situ vaccine in triple negative breast cancer
Authors: Mantooth Siena , Zaharoff David 
Published: March 2023

Abstract
Introduction. Breast cancer (BC) is among the most common types of cancer among women, with an estimated 287,850 new cases and 43,250 deaths in 2022 [1]. Triple negative breast cancer (TNBC), characterized by lack of ER/PR/HER2 receptors, constitutes 10-15% of diagnosed BC and correlates with the worst prognosis and most aggressive form of the disease [2]. Additionally, compared to the other BC subtypes, TNBC have higher rates of recurrence and highest therapy resistance [2]. Because TNBC lacks a clearly defined target, in situ vaccination may pose a viable therapy option, to locally stimulate an immune response and thereby reduce the tumor burden and prevent recurrence and metastasis. To this end, we developed an injectable delivery medium to effectively localize immune agonists at the site of the tumor. Materials and methods. Hydrogel delivery medium: Low-viscosity, high-deacetylated chitosan was crosslinked with 1-ethyl-3-(-3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide at room temperature overnight. The mixture was dialyzed and freeze-dried. A hydrogel was formed by dissolving the chitosan in deionized water at concentrations from 25-50 mg/mL. In vivo tumor treatment: 1e5 E0771 breast cancer cells were implanted subcutaneously in the right flank of C57BL/6 mice. When tumors were 50-100mm3, mice were treated intratumorally with 50ug Poly(I:C) + 50ug CpG in 30 mg/mL chitosan gel, with 50ug Poly(I:C) + 50ug CpG in saline, or with gel alone. In the second experiment, to enhance the anti-tumor effect of the immunotherapeutic, 2ug of the cytokine interleukin-12 in the chitosan gel will be delivered intratumorally. All experiments involving laboratory animals were approved by the Institutional Animal Care and Use Committee at North Carolina State University. Results and Discussion. The gel was effectively localized within the tumor environment upon injection. The localized Poly(I:C) + CpG in the gel demonstrated an enhanced anti-tumor effect, compared to gel alone. Ongoing work will determine the efficacy of administering the cytokine IL-12. Acknowledgements. This work is supported by an NSF Graduate Research Fellowship. References. [1] Siegel R, et al. CA A Cancer J Clin (2022) 72(1):7-33. [2] Retecki K, et al. Cancers (2021) 13(23):6012
Citation Format: Siena Mantooth, David Zaharoff. Local delivery of immunotherapeutics as an in situ vaccine in triple negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-63.
Abstract P5-01-09: Evaluation of the efficacy of using fluorescence-associated indocyanine green in sentinel lymph node biopsies from breast cancer patients
Authors: Sá Rafael , Nazário Afonso , Sanvido Vanessa M. , Giordano Roberto , Rodrigues Raquel , Bugalho Luiz , Silva Suelen 
Published: March 2023

Abstract
Introduction: Sentinel lymph node biopsy is the technique of choice for axillary staging in patients with breast cancer. Although it is already a widespread technique, its history is relatively recent. Three techniques are globally used to detect sentinel lymph nodes: the patent blue, described by Giuliano et al. (1994); the technetium-99 radiopharmaceutical with gamma probe, published by Krag et al. (1993); and the combination of these two techniques. Objective: This study aims to evaluate sentinel lymph node detection rate using the innovative fluorescence-associated indocyanine green technique in breast cancer patients, and to compare it with that of patent blue and with a combination of the two dyes. Method: A randomized trial was conducted on 99 patients who were equally divided into three arms, each one undergoing sentinel lymph node detection using either patent blue, indocyanine green, or a combination of the two dyes. The study was conducted at Hospital de Esperança, Presidente Prudente, SP, Brazil, in partnership with the Breast Department of Paulista School of Medicine, Federal University of São Paulo. Results: The accuracy rate in identifying sentinel lymph nodes was 78.8% with patent blue, 93.9% with indocyanine green, and 100% with patent blue + indocyanine green. Two sentinel nodes (48.5%) were mostly identified in the combined group; however, only one sentinel node was identified in the other groups. The mean time for sentinel lymph node identification was 20.6 minutes with the traditional dye, 8.6 minutes with indocyanine green, and 10 minutes with the combination of the two methods (p &lt; 0.001). The mean surgical time was 69.4 minutes with patent blue, 55.1 minutes with indocyanine green, and 69.4 minutes with their combination (p &lt; 0.001). Conclusion: Sentinel lymph node detection rate by fluorescence-associated indocyanine green was considered effective. The comparison of sentinel lymph node detection rates between patent blue, indocyanine green, and a combination of patent blue + indocyanine green revealed statistically significant differences (p = 0.030), with the combined method being the most effective. Keywords: breast neoplasm, sentinel lymph node biopsy, fluorescence, indocyanine green
Citation Format: Rafael Sá, Afonso Nazário, Vanessa M. Sanvido, Roberto Giordano, Raquel Rodrigues, Luiz Bugalho, Suelen Silva. Evaluation of the efficacy of using fluorescence-associated indocyanine green in sentinel lymph node biopsies from breast cancer patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-01-09.
Abstract P5-03-11: The impact of single nucleotide polymorphisms on return-to-work after taxane-based chemotherapy in breast cancer
Authors: Hjorth Cathrine , Damkier Per , Stage Tore B. , Feddersen Søren , Hamilton-Dutoit Stephen , Ejlertsen Bent , Lash Timothy L. , Bøggild Henrik , Sørensen Henrik , Cronin-Fenton Deirdre 
Published: March 2023

Abstract
Background Return-to-work (RTW) after breast cancer may be challenging for breast cancer survivors, especially those who experience adverse effects. Neuropathies are common adverse effect of taxane-based chemotherapy. Single nucleotide polymorphisms (SNPs) in genes related to taxane metabolism and transport, neural function, and neural- or DNA-repair may influence the risk of taxane-induced adverse effects, potentially impacting patient recovery and RTW. We examined the association of such SNPs with RTW in premenopausal breast cancer survivors. Methods We used Denmark’s nationwide population-based health registries to ascertain data on premenopausal women aged 18‒55 years diagnosed with non‒distant metastatic breast cancer during 2007‒2011, who were candidates for adjuvant combination chemotherapy including cyclophosphamide and docetaxel. Only women employed at diagnosis were included. We collected archived tumor tissue from nationwide pathology departments and genotyped 26 SNPs in 20 genes using TaqMan assays. For each SNP, we categorized the women as wildtype, homozygote or heterozygote. Follow-up continued from the date of primary surgery to the first of RTW (defined as 4 consecutive weeks of work), recurrence, maternity leave/childbirth, other malignancy, retirement, death, emigration or 25th September 2017. We computed the cumulative incidence of RTW and used Cox regression models to calculate unadjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of RTW. Results We included 1,963 women. Women who were homozygotes for the phase 1 metabolizer CYP3A5 rs776746 (n=15) had lower cumulative incidence of RTW than wildtypes (n=1,600) and heterozygotes (n=249), 7%, 25% and 17% at six months, 57%, 87% and 88% at two years, and 82%, 94% and 94% at end of follow-up, respectively. Compared with wildtypes, CYP3A5 rs776746 homozygotes had delayed RTW throughout follow-up (HR 0-10 years: 0.48, 95% CI: 0.26, 0.86). No other SNPs were associated with RTW. Conclusions Among 26 SNPs, CYP3A5 rs776746 was associated with delayed RTW after breast cancer among premenopausal women. Our findings may help identify women at risk of a poor clinical course, who may benefit from enhanced supportive care during treatment and follow-up.
Citation Format: Cathrine Hjorth, Per Damkier, Tore B. Stage, Søren Feddersen, Stephen Hamilton-Dutoit, Bent Ejlertsen, Timothy L. Lash, Henrik Bøggild, Henrik Sørensen, Deirdre Cronin-Fenton. The impact of single nucleotide polymorphisms on return-to-work after taxane-based chemotherapy in breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-03-11.
Abstract P5-15-01: Rediscovering IRF5: A prognostic indicator with novel roles in mammary gland development, ribosome biogenesis, tumor initiation, and metastasis
Authors: Barnes Betsy , Brune Zarina , Rice Matthew , Somerville Carter 
Published: March 2023

Abstract
Breast cancer is the second leading cause of death for women in the United States. However, only 10% of breast cancers have been linked to inherited genomic mutations. Thus, identifying biomarkers to predict cancer progression and metastasis remains a clear need in the research and medical world. Here, we report a novel role for Interferon Regulatory Factor 5 (IRF5) in mammary gland development, tumorigenesis, and metastasis. Historically, IRF5 has been studied as a transcription factor in the context of genetic risk for autoimmune diseases. However, mining of The Cancer Genome Atlas revealed that loss of IRF5 expression in human breast cancer is significantly linked with progression to high grade carcinoma, increased metastasis, and decreased overall and recurrence-free survival. Supporting these analyses, we demonstrated that female Irf5-/- BALB/c mice have higher incidence of spontaneous atypical ductal hyperplasia (ADH), increased progression to DCIS, and ultimately, increased incidence of IDC. Using qPCR, FISH and IHC, we confirmed that IRF5 is expressed in both luminal and basal myoepithelial cells, but expression is higher in basal cells. Histologic analysis of whole mount preparations of Irf5-/- mammary glands revealed aberrant ductal morphogenesis, characterized by expansion of luminal and basal myoepithelial cells with a loss of organized glandular structure. RNAseq of primary mammary epithelial cells from wild type and Irf5-/- littermate mice showed Irf5-/- mammary epithelial cells to be enriched in ribosome biogenesis pathways, the physiologic consequences of which were demonstrated through increased rates of protein synthesis. Transferring our studies in vivo, we demonstrated that loss of tumor IRF5 expression resulted in decreased tumor-infiltrating lymphocytes and increased pulmonary metastasis in the murine orthotopic 4T1 implantation model. Mechanistically, we found that—as in our studies utilizing primary mammary epithelial cells—IRF5 expression in tumors regulated protein translation and ribosome biogenesis. In light of these findings, we propose IRF5 as a novel prognostic biomarker, loss of which alters mammary gland development, drives tumor initiation and metastasis, and dysregulates mammary epithelial cell protein synthesis.
Citation Format: Betsy Barnes, Zarina Brune, Matthew Rice, Carter Somerville. Rediscovering IRF5: A prognostic indicator with novel roles in mammary gland development, ribosome biogenesis, tumor initiation, and metastasis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-15-01.
Abstract P6-02-16: Breast cancer prognosis of germline BRCA1/BRCA2 mutation carriers of young women: a retrospective hospital-based cohort
Authors: HEGO Florent , BARTHOULOT Maël , PIERARD Charles , Mailliez Audrey 
Published: March 2023

Abstract
Background Studies evaluating prognostic impact of germline BRCA1/2 mutations (gBRCAm) on breast cancer patients reported controversial results. The primary aim of this study was to investigate outcomes of young gBRCAm patients with very early onset of breast cancer (&lt; 30 years) compared with noncarriers. Methods In this retrospective study, 149 patients 30 years aged or younger at early breast cancer diagnosis between 2005 and 2019 were included in Oscar Lambret Center. Outcomes were overall survival (OS) and disease-free survival (DFS), defined as time from first diagnosis to first recurrence, second cancer or death from any cause, at 2 years, 5 years, and 10 years. Key patient data, kaplan-meier plots and outcomes were described by BRCA mutation status. Hazard ratios (HR) were calculated using Cox proportional-hazards models. Results Twenty-eight (18.8%) patients were gBRCAm carriers. The median follow-up was 6.5 years (IQR 0.25-16.5). Twenty-three deaths, 41 recurrences and 2 second cancers were reported. OS was 89.3% [70.4–96.4] in gBRCAm patients vs 99.1% [95% CI 93.9–99.9] in non-carriers patients at 2 years; 85.0% [64.7–94.1] vs 92.3% [85.1–96.1] at 5 years and 75.3% [52.5–88.3] vs 80.2% [66.6–88.7] at 10 years. There was no difference in OS between groups in multivariable analysis (HR=1.63 [0.55–4.77], p=0.37). Similar results were noted when comparing disease-free survival (HR=1.42 [0.64–3.11], p=0.38). Conclusions In this cohort of 149 patients with very early onset breast cancer, outcomes of gBRCAm mutation carriers did not differ from non-carriers when adjusted for others prognostic factors.
Citation Format: Florent HEGO, Maël BARTHOULOT, Charles PIERARD, Audrey Mailliez. Breast cancer prognosis of germline BRCA1/BRCA2 mutation carriers of young women: a retrospective hospital-based cohort [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-02-16.
Abstract P6-05-32: Does Aggregation Hide Place of Death Disparities for Asians with Breast Cancer?
Authors: Lall Naveena , Noveihed Alexandra , Hussaini Qasim S. , Blackford Amanda L. , Gupta Arjun , Sedhom Ramy 
Published: March 2023

Abstract
Introduction: Place of death (PoD) studies are often used to motivate and monitor progress on health inequities for persons with cancer. It remains unclear whether aggregation of Asian race masks disparities in health equity for care at the end of life.
Methods: De-identified death certificate data were obtained via the National Center for Health Statistics. All adult (&gt;18 years of age) breast cancer deaths from 2018 to 2019 were included. Multinomial logistic regression was used to test for differences in place of death associated with sociodemographic variables.
Results: From 2018 through 2019, 81,772 died from breast cancer in the United States. Overall, persons of Asian descent were less likely to die at home compared to White patients. Disaggregation noted significant differences in likelihood of hospice facility use. For example, Filipino race was approximately 5 times more likely to utilize hospice facilities (CI 3.764, 8.718; p&lt; 0.001) compared to Whites, whereas Chinese race was significantly less likely (OR 0.49, 95% CI 0.307 to 0.627, p&lt; 0.001). American Indian (OR 0.006), Asian Indian (OR 0.016), and Samoan (0.011) were the least likely to die in a nursing facility. While trends were overall similar when compared to White, Black and Hispanics, the likelihood of PoD among Asian subgroups were significantly different.
Conclusion: Our data highlights notable differences in PoD only apparent with disaggregation of Asian race. While this study remains exploratory in nature, and reasons to explain these disparities are necessary, disaggregation of the Asian Pacific Island category is imperative to unmask disparities to improve health equity among all indigenous populations.
Association Between Race and Place of Death for Patients with Breast Cancer
Table 1. Number of deaths due to breast cancer in 2018 and 2019, by race. Odds ratios for the association between race and place of death from multinomial regression.
Citation Format: Naveena Lall, Alexandra Noveihed, Qasim S. Hussaini, Amanda L. Blackford, Arjun Gupta, Ramy Sedhom. Does Aggregation Hide Place of Death Disparities for Asians with Breast Cancer? [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-05-32.
Abstract P6-05-59: Clinical Characteristics and Prognosis of Postpartum Breast Cancer
Authors: Bae Soo Youn , Paik Pill Sun , Lee Young Joo , Kang Young-Joon 
Published: March 2023

Abstract
Background: Postpartum breast cancer (PPBC) is a not well-established subset of breast cancer, and only few studies address its poorer prognosis. However, there are previous studies that PPBC is associated with worse outcome with higher rates of metastasis than in young women’s breast cancer (YWBC). The purpose of this study was to analyze the clinical characteristics and prognosis according to the onset period of PPBC, Materials and methods: 208,780 breast cancer patients from the online Korean Breast Cancer Society (KBCS) registry database between January 2000 and December 2014 were reviewed retrospectively. Premenopausal women aged 20 to 50 years who underwent breast cancer surgery were included. According to the diagnosis period of breast cancer, it was classified into groups diagnosed within 5 years (PPBC&lt; 5) after delivery, between 5-10 years((5≤PPBC&lt; 10), and after 10 years(PPBC≥10). Results: The patients in PPBC &lt; 5 group showed a younger and more advanced stage compared to other groups, and the expression of estrogen receptor (ER) and progesterone receptor (PR) was lower and the HER2 positive rate was higher. PPBC&lt; 5 group had worse survival rate compared to nulliparous and other group (5-year cumulative survival; PPBC&lt; 5 group, 89% vs. nulliparous group, 97.3% vs. 5≤ PPBC&lt; 10 group 93%). In multivariate analysis, PPBC&lt; 5 group was associated with worse survival rate (Hazard ratio 1.55, 95% CI 1.148-2.094, p=0.004) after adjustment for age at diagnosis, breast cancer stage, ER and HER2 status, Ki-67 level, and chemotherapy. Conclusion: We demonstrated that patients with breast cancer diagnosed within first five years after delivery had aggressive characteristics and a worse survival rate. In order to improve the survival rate of PPBC, the cause should be identified and new therapeutic strategy should be established.
Citation Format: Soo Youn Bae, Pill Sun Paik, Young Joo Lee, Young-Joon Kang. Clinical Characteristics and Prognosis of Postpartum Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-05-59.