bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P3-14-08: The influence of metabolic factors, migration, and ethnic disparities on breast cancer risk and treatment
Authors: Lofterød Trygve , Frydenberg Hanne , Veierød Marit , Jenum Anne Karen , Reitan Jon B , Wist Erik , Thune Inger 
Published: March 2022

Abstract
Background: Migrant studies have shown an increase in breast cancer incidence rates among immigrants moving from a breast cancer low-incidence to a high-incidence country. However, 30 years after immigration, it remains equivocal to what degree metabolic factors and ethnic disparities affect breast cancer development and treatment. Methods: Using Cox regression models, we examined the association between ethnicity and breast cancer development, and whether this association varied by pre-diagnostic metabolic profiles among 13 802 women, aged 20-75 years, participating in the population-based Oslo Ethnic Breast Cancer Study. Ethnicity was categorized into: women of Western European descent (reference population) and women of non-western ethnicity (ethnic minority). The ethnic minority women were further subclassified into three groups: 1) South Asian, 2) Middle East and North African, and 3) all other non-western origin women. We defined four pre-diagnostic unfavorable metabolic factors (above median body mass index (&gt;24.6 kg/m2), waist:hip ratio (&gt;0.79), triglyceride:HDL-cholesterol ratio (&gt;0.73), and blood pressure (&gt;96.5 mmHg)), which were combined to define three metabolic profiles: (0-2, 3, and 4 unfavorable metabolic factors). A total of 557 women developed invasive breast cancer during a mean 16.5 years of follow-up. Detailed medical records were obtained. Results: Among women with an unfavorable metabolic profile, South Asian women, compared with Western European women, had a 2.3 times higher breast cancer risk (HR 2.30, 95% CI 1.18-4.49). Furthermore, the ethnic minority women, compared with the Western European women, were suggestively more likely to present with triple-negative breast cancer (OR 2.11, 95% CI 0.97-4.61), and less likely to complete all courses of planned taxane treatment (OR 0.26, 95% CI 0.08-0.82). No differences by ethnicity were observed in physicians’ decisions of planned breast cancer treatment, Conclusions: Our results support that metabolic factors, including body composition, serum lipids and blood pressure, are important when balancing breast cancer prevention and disease management among non-western women migrating from a breast cancer low-incidence to a high-incidence country. However, larger studies are needed.
Citation Format: Trygve Lofterød, Hanne Frydenberg, Marit Veierød, Anne Karen Jenum, Jon B Reitan, Erik Wist, Inger Thune. The influence of metabolic factors, migration, and ethnic disparities on breast cancer risk and treatment [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-14-08.
Abstract P3-19-28: The impact of PM2.5 on the radiation-induced pneumonitis in patients with breast cancer
Authors: Kim Dong-Yun , Kim In Ah , Jang Bum-Sup 
Published: March 2022

Abstract
Purpose: Exposure to particulate matter (PM) air pollution has been associated with adverse effect on respiratory disease, but no study has investigated its impact on radiation-induced pneumonitis (RIP) in patients with breast cancer who received adjuvant radiation therapy (RT). Materials and Methods: We conducted a retrospective review of 2,762 breast cancer patients who received postoperative RT between 2017 and 2020 in a single institution. Particulate matter data including PM2.5 and PM10 were retrieved from the open dataset in the ‘Gyeonggi Data Dream’. We used the average, median and maximum values of the PM2.5 and PM10 measured during daytime when a patient visited to the hospital for RT. We excluded the patients when missing PM data exceeded 50% of the total treatment period (N=26). Finally, altogether 2,736 patients were analyzed. Results: Overall incidence rate of RIP was 1.74%. There were no significant differences in average value of PM2.5 and number of RT fractions between RIP (+) and RIP (-) groups, but marginal differences were found in RT techniques (3-dimentional conformal RT vs. intensity modulated RT, P=0.053) and proportion of PM2.5 value ≥ 35 (μg/m3) (P=0.053) between the two groups. After adjusting for age, RT technique, regional irradiation, fractionation and boost, the average value of PM2.5 was significantly associated with a higher risk of RIP (Odds ratio [OR] 1.05, 95% confidential incidence [CI] 1.00-1.10, P=0.047) when patients received ≥ 20 fractions of RT. Especially, PM2.5 ≥ 35 (μg/m3) showed significant higher risk of RIP (OR 4.32, 95% CI 1.34-13.87, P=0.014) in patients with ≥ 20 fractions of RT after adjustment of aforementioned covariates. Other PM data (median, maximum value of PM2.5 and all PM10 values) were not related to the RIP regardless of the number of RT fractions. Conclusion: This is the first study to reveal the association between PM2.5 and RIP in breast cancer patients who received 20 fractions or more of postoperative RT.
Citation Format: Dong-Yun Kim, In Ah Kim, Bum-Sup Jang. The impact of PM2.5 on the radiation-induced pneumonitis in patients with breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-28.
Abstract P4-01-09: The WAVE3 phosphorylation/β-catenin oncogenic signaling axis promotes chemoresistance and cancer stemness in triple negative breast cancer
Authors: Wang Wei , Rana Priyanka , Alkrekshi Akram , Markovic Vesna , Sossey-Alaoui Khalid 
Published: March 2022

Abstract
Acquisition of the metastatic phenotype is responsible for the death of ~90% of breast cancer (BC) patients. In fact, metastatic BC is the 2nd leading cause of cancer-related deaths in women in the United States, annually accounting for more than 40,100 deaths and 266,000 new cases of invasive BC. Amongst individual BC subtypes, those classified as TNBCs are especially lethal due to their highly metastatic behavior and propensity to recur rapidly. As a group, TNBCs lack expression of hormone receptors (ER-α and PR) and ErbB2/HER2, which has prevented the development of FDA-approved targeted drug therapies that are effective against this BC subtype. Likewise, recurrent TNBCs frequently acquire resistance to standard-of-care chemotherapeutic agents (e.g., doxorubicin, cyclophosphamides, and taxanes) through mechanisms that remain incompletely understood. We established Wiskott-Aldrich Syndrome Protein-3 (WAVE3) as a novel promoter of TNBC development and metastatic progression. Our recently published studies have shown that WAVE3 phosphorylation regulates the interplay between PI3K, TGF-β, and EGF signaling pathways. In this study, we show that WAVE3 phosphorylation promotes chemotherapy-resistance and cancer stemness in TNBC, both in vitro and in in vivo mouse models. CRISPR/Cas9-mediated inactivation of WAVE3 resulted in inhibition of 2D growth and 3D tumorspheres’ invasion of TNBC cells in vitro, as well as tumor growth and metastasis in vivo. In addition, while re-expression of phospho-active WAVE3 in the WAVE3-deficient TNBC cells restored the oncogenic activity of WAVE3, re-expression of phospho-mutant WAVE3 or the pharmacologic inhibition of WAVE3 phosphorylation did not. Further studies revealed that dual blocking WAVE3 expression or phosphorylation with chemotherapy treatment inhibited the activity and expression of β-catenin. Importantly, a combination of WAVE3-deficiency and chemotherapy suppressed the oncogenic behavior of chemo-resistant TNBC cells, both in vitro and in vivo. This study suggests that a targeted therapeutic strategy against WAVE3 could be effective for the treatment of chemoresistant TNBC tumors.
Citation Format: Wei Wang, Priyanka Rana, Akram Alkrekshi, Vesna Markovic, Khalid Sossey-Alaoui. The WAVE3 phosphorylation/β-catenin oncogenic signaling axis promotes chemoresistance and cancer stemness in triple negative breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-01-09.
Abstract P4-02-07: Lasofoxifene as a potential treatment for aromatase inhibitor resistant ER positive breast cancer
Authors: Laine Muriel , Greene Marianne E , Leng Tiffany , Kurleto Justyna D , Li Sophia , Komm Barry , Greene Geoffrey L 
Published: March 2022

Abstract
Postmenopausal patients with estrogen receptor positive (ERα+) primary invasive breast cancer are typically treated with aromatase inhibitors (AIs) as first line adjuvant therapy. Patients who become resistant to AIs are treated with fulvestrant and/or CDK4/6 inhibitors, such as palbociclib, as second line therapy. Lasofoxifene, a selective estrogen receptor modulator (SERM), was developed for the treatment of vaginal atrophy and osteoporosis. Our previous studies, performed in an MCF-7 xenograph metastatic breast cancer mouse model with activating ERα mutations, showed that lasofoxifene, both alone and in combination with palbociclib, was more effective than fulvestrant at inhibiting tumor growth and metastasis to the liver, lung, bone and brain. In the current study, we compared the efficacy of lasofoxifene +/- palbociclib to fulvestrant +/- palbociclib combinations in a letrozole-induced, AI-resistant breast tumor model (MCF-7 LTLT cells) that does not express ERα activating mutations. Luciferase-GFP tagged LTLT cells were injected into the mammary ducts of NSG mice (MIND model) and tumor progression was monitored by live luminescence imaging of primary tumors, as well as ex vivo imaging and histochemical analysis of metastatic sites at study endpoint. Primary tumor area was also measured at study endpoint. Lasofoxifene +/- palbociclib was significantly more effective than fulvestrant +/- palbociclib at inhibiting primary tumor growth. In addition, all treatments, except fulvestrant, inhibited bone metastasis versus vehicle. These data show that lasofoxifene is more effective than fulvestrant in this tumor model and suggest that lasofoxifene has potential as an effective therapy for AI resistant breast cancers that do not express ERα activating mutations.
Citation Format: Muriel Laine, Marianne E Greene, Tiffany Leng, Justyna D Kurleto, Sophia Li, Barry Komm, Geoffrey L Greene. Lasofoxifene as a potential treatment for aromatase inhibitor resistant ER positive breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-02-07.
Abstract P4-04-02: A clinical-stage toll-like receptor 5 agonist, entolimod, boosts chemo-immunotherapy in pre-clinical TNBC by generating durable antitumor immunity
Authors: Brackett Craig M , Aldrich Alyssa R , Greene Kellee F , Kandar Bojidar , Veith Jean , Burdelya Lyudmila G , Abrams Scott I. , Gudkov Andrei V 
Published: March 2022

Abstract
Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast cancer diagnoses, is the most aggressive form of the disease, and has the poorest clinical outcomes. Effective or durable therapies are lacking because these tumors lack targets for therapeutic intervention and rapidly develop resistance to chemotherapy (CTx). The FDA has now approved chemo-immunotherapy (CTx-I) regimens (αPD-L1/nab-Paclitaxel, αPD-1/CTx) as standard-of-care for early-stage, locally advanced, and metastatic TNBC. Despite these advancements, overall response rates remain relatively low and survival outcomes are extended for only a few months especially in the case of locally advanced or metastatic disease. Thus, the need exists to develop additional or alternative strategies to potentially build upon and improve CTx-I protocols for TNBC. To this end, our laboratory has explored the importance of engaging the innate immune response to augment the efficacy of CTx-I. Previously, we demonstrated that toll-like receptor (TLR) 5 signaling can elicit antitumor immunity against a preclinical model of metastatic TNBC. In particular, systemic administration of the TLR5 agonist, entolimod, stimulated durable CD8+ T cell immunity against 4T1, the prototypical preclinical PD-L1+ metastatic TNBC model. Here, using primary 4T1 tumors to mirror the clinical setting of locally advanced disease, we show that entolimod boosts the efficacy of CTx-I (αPD-L1/Paclitaxel) by causing tumor regression. Moreover, these mice completely reject a subsequent tumor challenge, highlighting that the entolimod/αPD-L1/Paclitaxel combination generates durable antitumor immunity in such advanced preclinical settings. Importantly, systemically administered entolimod was shown to be safe in Phase I clinical trials cumulatively involving nearly 200 subjects in both healthy volunteers and advanced cancer patients. Thus, this work will aid in formulating a more effective CTx-I treatment regimen with potentially important clinical implications for patients with locally advanced or metastatic TNBC.
Citation Format: Craig M Brackett, Alyssa R Aldrich, Kellee F Greene, Bojidar Kandar, Jean Veith, Lyudmila G Burdelya, Scott I. Abrams, Andrei V Gudkov. A clinical-stage toll-like receptor 5 agonist, entolimod, boosts chemo-immunotherapy in pre-clinical TNBC by generating durable antitumor immunity [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-04-02.
Abstract P4-04-12: Macrophage migration inhibitory factor regulates triple-negative breast cancer progression by enhancing the recruitment of immune suppressive cells
Authors: Charan Manish , Das Subhadip , Mishra Sanjay , Varikuti Sanjay , Satoskar Abhay R , Ganju Ramesh K 
Published: March 2022

Abstract
Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast cancers and lacks the expression of estrogen, progesterone, and Her2 receptors. TNBC is a highly aggressive subtype of breast cancer that has been associated with poorer prognosis and worse overall survival rate. Macrophage migration inhibitory factor (MIF) is a multipotent pro-inflammatory cytokine, highly expressed in various cancers and reported to enhance tumor growth and metastasis. However, its role in influencing the anti-tumor immunity is unexplored. We have previously shown that MIF promotes TNBC growth and metastasis. In addition, CPSI-1306 (MIF inhibitor), reduces its oncogenic effects. Here, we have shown that MIF downregulation in human TNBC xenografts correlate with reduced infiltration of myeloid derived suppressor cells (MDSCs). Furthermore, using a MIF knockout mouse model, we detected reduced MDSC population in the tumor microenvironment. In addition, we observed higher recruitment and increased proliferation of CD3+ T cells. Furthermore, we utilized a syngeneic mouse model to study the effect of MIF inhibition on infiltration of different immune cells in-vivo. CPSI-1306 treatment decreased the recruitment of MDSCs in both the tumor and spleen. In addition, CPSI-1306 treatment promotes the infiltration of CD8+ T cells in both the tumor and spleen. However, CPSI-1306 treatment did not influence the recruitment of CD4+ T cells. We further analyzed the expression of various cytokines and chemokines in blood sera of control and CPSI-1306 treated mice groups using a cytokine array kit. We observed that CPSI-1306 treatment group showed reduced levels of GCSF, GMCSF, IL-2 and IL-4 levels compared to vehicle control groups. Overall, our data strongly suggests that small molecular weight MIF inhibitors could be a potential strategy against TNBC.
Citation Format: Manish Charan, Subhadip Das, Sanjay Mishra, Sanjay Varikuti, Abhay R Satoskar, Ramesh K Ganju. Macrophage migration inhibitory factor regulates triple-negative breast cancer progression by enhancing the recruitment of immune suppressive cells [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-04-12.
Abstract P4-04-13: S100a7/rage signaling promotes breast tumorigenesis through modulating tumor-associated macrophages
Authors: Verma Ajeet K , Wilkie Tasha , Mishra Sanjay , Charan Manish , Ganju Ramesh K 
Published: March 2022

Abstract
S100A7 has been shown to be associated with breast cancer growth and metastasis. However, the molecular mechanism through which S100A7 promotes breast tumorigenesis is not completely understood. In this study, we revealed that S100A7 enhanced Stat3-mediated secretion of Serpin-E1 in triple negative breast cancer (TNBC) cell lines. Serpin-E1 has been shown to promote recruitment and polarization toward a pro-tumorigenic phenotype of tumor-associated macrophages through activating the Stat3 pathway. Importantly, we reported that the inhibition of Stat3 led to reduction of S100A7-mediated invasiness of TNBC cells and also significantly decreased the secretion of Serpin-E1 by cancer cells. We also revealed that Stat3 inhibition in TNBC cells or Serpin-E1 neutralization significantly reduced the migration of human monocytes/macrophages by transwell migration assay. We further demonstrate that murine ortholog of S100A7, mS100a7a15 enhanced mammary hyperplasia, tumor growth and metastasis through Stat3 activation. Previously, we reported that S100A7 mediated its tumorigenic effects through RAGE in breast cancer cells. Therefore, we also discovered that combinatorial treatment of Stat3 and RAGE inhibitors in mammary tumor bearing mS100a7a15 overexpression mouse model strongly decreased the tumor burden and enhanced the recruitment of tumor-suppressing M1-macrophages. We also found that combined inhibition of RAGE and Stat3 significantly increased the infiltration of CD4 T cells in the tumor microenvironment (TME). Collectively, these findings suggest S100A7/RAGE signaling pathway could be used as a novel therapeutic target to inhibit breast cancer growth and metastasis through modulating the TME.
Citation Format: Ajeet K Verma, Tasha Wilkie, Sanjay Mishra, Manish Charan, Ramesh K Ganju. S100a7/rage signaling promotes breast tumorigenesis through modulating tumor-associated macrophages [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-04-13.
Abstract P4-10-11: Eyebrow/eyelash loss among survivors
Authors: Cathcart-Rake Elizabeth , Loprinzi Charles L , Couch Fergus , Olson Janet , Dulmage Brittany , Lustberg Maryam , Larson Nicole , Ruddy Kathryn J 
Published: March 2022

Abstract
Background: Eyebrow and eyelash loss are widely recognized as consequences of some chemotherapies, but prevalence and predictors are understudied. The purpose of this study was to evaluate real world experiences of eyebrow and eyelash loss during treatment for breast cancer. Methods: Breast cancer survivors participating in the ongoing prospective Mayo Clinic Breast Disease Registry (MCBDR) were mailed a survey one year after diagnosis. Respondents were asked to recall their severity of eyebrow and eyelash loss since diagnosis, measured from “no loss” to “a little loss” to “a lot of loss” to “complete loss”. Results: 524 participants were mailed a survey including these questions between May 2020 and November 2020; the median time from diagnosis to survey completion was 12 months (range 6 months). Of the 265 participants whose responses were available for analysis (median age 60.8 years), 88 (33%) had received chemotherapy, including 39 (44%) who received doxorubicin and cyclophosphamide, 16 (18%) who received docetaxel and cyclophosphamide, 56 (64%) who received paclitaxel, and 11 (13%) who received carboplatin. 173 (65%) had received endocrine therapy: 56 (32%) of patients who received endocrine therapy received tamoxifen, and 115 (66%) received aromatase inhibitors. 124 (47%) reported at least a little eyebrow loss, and 22 (8%) reported complete loss. Forty-seven percent reported at least a little eyelash loss, and 27 (10%) reported complete loss (Table 1). In the subgroup of 88 patients who received chemotherapy, the rates of at least a little eyebrow and eyelash loss were 50% and 55%, respectively, and rates of complete loss were 8% and 9%. Rates of eyebrow and eyelash loss did not appear to differ significantly by age. Conclusion: Eyebrow and eyelash loss are frequently reported during breast cancer-directed therapy. Future investigations into the incidence and treatment of this side effect are needed.
Table 1.&lt;55 years old55+ years oldEyebrow Loss (N)%Eyelash Loss (N)%Eyebrow Loss (N)%Eyelash Loss (N)%No Loss4551%4753%9655%9353%A Little Loss2629%2225%3922%3922%A lot of loss1011%1112%2715%2514%Complete Loss89%910%148%1810%Funding Source: Breast Cancer Research Foundation (CLL) Clinic
Citation Format: Elizabeth Cathcart-Rake, Charles L Loprinzi, Fergus Couch, Janet Olson, Brittany Dulmage, Maryam Lustberg, Nicole Larson, Kathryn J Ruddy. Eyebrow/eyelash loss among survivors [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-10-11.
Abstract P4-10-13: Area deprivation index and rurality in relation to financial toxicity among breast cancer surgical patients - Investigating geospatial differences in risk profiles
Authors: Corkum Joseph P , Zhu Victor , Agbafe Victor , Chu Carrie , Colen Jessica Suarez , Greenup Rachel , Offodile Anaeze C. 
Published: March 2022

Abstract
Background: Financial toxicity (FT) depicts the burden of cancer treatment-costs and is associated with lower quality-of-life and survival in breast cancer survivors. We examined the relationship between geospatial location, represented by rurality and Area Deprivation Index (ADI), and risk of FT.Study Design: A single-institution, cross-sectional study was performed on adult female surgical breast cancer patients. Chart reviews were used to obtain patient information while FT was identified using a validated instrument. Patients’ home addresses were used to determine rurality using the Rural Urban Continuum Codes and linked to national ADI score. Tertile ADI groups enabled statistical analysis and multivariate logistic regression models were developed to determine the independent effects of geospatial location and FT.Results: A total of 568 surgical breast cancer patients were included. Univariate analyses showed significant differences across ADI tertiles with respect to race/ethnicity, marital status, insurance type, education, and rurality. Following multivariate analysis, advanced cancer stage (OR 2.26, CI: 1.15-4.44), and escalating ADI (OR 1.012, CI:1.005-1.020) were associated with worsening FT. Increasing age (OR 0.976, CI: 0.96- 0.992), marital status (OR 0.458, CI: 0.299-0.699), receipt of bilateral mastectomy (OR 0.558, CI: 0.323-0.964) were protective of FT. Increasing ADI was also significantly associated with use of coping strategiesConclusion: FT was significantly associated with areas of higher socioeconomic deprivation as measured by the ADI. However, rurality was not found to be a significant predictor of FT. ADI may be used to facilitate pre-operative screening of at-risk populations and the deployment of community-based interventions to alleviate FT.
Multivariate logistic regression analysis results.
Citation Format: Joseph P Corkum, Victor Zhu, Victor Agbafe, Carrie Chu, Jessica Suarez Colen, Rachel Greenup, Anaeze C. Offodile. Area deprivation index and rurality in relation to financial toxicity among breast cancer surgical patients - Investigating geospatial differences in risk profiles [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-10-13.