bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract PS17-57: Breast cancer patients have reduced levels of short chain fatty acid producing beneficial gut bacteria
Authors: Vikas Praveen , Cady Nicole , Knobbe Jessica , Hoang Jemmie , Yadav Meeta , Curry Melissa , Cherwin Cathernine , Sugg Sonia , Phadke Sneha , Filardo Edward , Mangalam Ashuthosh
Published: February 2021

The role of the human gut microbiome has been increasingly appreciated in respect to its influence on human health and disease. It has been proposed that dysbiosis in the gut microbiome and subsequent induction of chronic inflammatory state might have an influence on breast cancer development and prognosis. Therefore this study was undertaken to determine the role of gut microbiome in breast cancer. The Breast Molecular Epidemiology Resource (BMER) resources of the Holden Comprehensive Cancer Center (HCCC) were used to recruit 23 women with breast cancer. Fecal samples were used to characterize the gut microbiome of our patient population using 16S rRNA amplification and Illumina sequencing. Reads were then mapped back to amplicon sequence variant using DADA2 pipeline and compared to a cohort of race, age, and gender matched cohort of regional healthy controls. In our preliminary analysis, we observed that breast cancer patients have distinct microbiota compared to age and gender matched healthy controls. We identified depletion of the anti-inflammatory short chain fatty acid producing bacteria specifically Faecalibacterium, Anaerostipes, Parabacteroides and Phascolarctobacterium in feces from BC patients. Additionally, breast cancer cohort showed enrichment of the pro-inflammatory bacteria such as Eubacterium (dolichum), Bifidobacterium, and Blautia. These bacteria have been previously been identified to change with clinical disease stage and/or BMI, as has genus Bifidobacterium (increased in BC cohort). Within BC group, patients with high grade showed lower levels of Eggerthella lenta and Desulfovibrio whereas patients receiving chemotherapy showed depletion of Sulphur reducing Desulfovibrio and methane producing archaea Methanobrevibacter. Further analysis may lead to insights into the interplay between gut microbiome and breast cancer, as well as the feasibility of therapeutic strategies in the form of novel and existing probiotics.

Citation Format: Praveen Vikas, Nicole Cady, Jessica Knobbe, Jemmie Hoang, Meeta Yadav, Melissa Curry, Cathernine Cherwin, Sonia Sugg, Sneha Phadke, Edward Filardo, Ashuthosh Mangalam. Breast cancer patients have reduced levels of short chain fatty acid producing beneficial gut bacteria [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 PS17-57.
Abstract PS18-17: Mdm2 inhibition synergises with endocrine therapy or cdk4/6 inhibition for the treatment of estrogen receptor-positive breast cancer
Authors: Portman Neil , Milioli Heloisa , Alexandrou Sarah , Coulson Rhiannon , Yong Aliza , Fernandez Kristine , Chia KeeMing , Halilovic Ensar , Segara Davendra , Parker Andrew , Haupt Sue , Haupt Ygal , Tilley Wayne , Swarbrick Alex , Caldon Liz , Lim Elgene
Published: February 2021

Background: Resistance to endocrine therapy is a major clinical challenge in the management of estrogen receptor (ER)-positive breast cancer. In this setting p53 is frequently wildtype and its activity may be suppressed via upregulation of its key regulator MDM2. This underlies our rationale to evaluate MDM2 inhibition as a therapeutic strategy in treatment resistant ER-positive breast cancer.

Methods: We used the MDM2 inhibitor NVP-CGM097 to treat in vitro and in vivo models alone and in combination with fulvestrant or palbociclib. We perform cell viability, cell cycle, apoptosis and senescence assays to evaluate antitumor effects in p53 wildtype and p53 mutant ER positive cell lines (MCF-7, ZR75-1, T-47D) and MCF-7 lines resistant to endocrine therapy and to CDK4/6 inhibition. We further assess the drug effects in patient-derived xenograft (PDX) models of endocrine-sensitive and -resistant ER positive breast cancer.

Results: We demonstrate that MDM2 inhibition results in cell cycle arrest and increased apoptosis in p53-wildtype in vitro and in vivo breast cancer models, leading to potent anti-tumour activity. We find that endocrine therapy or CDK4/6 inhibition synergises with MDM2 inhibition but does not further enhance apoptosis. Instead, combination treatments result in profound regulation of cell cycle-related transcriptional programmes, with synergy achieved through increased antagonism of cell cycle progression. Combination therapy pushes cell lines resistant to fulvestrant or palbociclib to become senescent and significantly reduces tumour growth in a fulvestrant resistant patient derived xenograft model.

Conclusions: We conclude that MDM2 inhibitors in combination with ER degraders or CDK4/6 inhibitors represent a rational strategy for treating advanced, endocrine resistant ER-positive breast cancer, operating through synergistic activation of cell cycle co-regulatory programs.

Citation Format: Neil Portman, Heloisa Milioli, Sarah Alexandrou, Rhiannon Coulson, Aliza Yong, Kristine Fernandez, KeeMing Chia, Ensar Halilovic, Davendra Segara, Andrew Parker, Sue Haupt, Ygal Haupt, Wayne Tilley, Alex Swarbrick, Liz Caldon, Elgene Lim. Mdm2 inhibition synergises with endocrine therapy or cdk4/6 inhibition for the treatment of estrogen receptor-positive 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 PS18-17.
Abstract PS18-35: Disparities in reporting of race and participation by race in genomic studies
Authors: Khanna Niloufar R , Dixit Niharika
Published: February 2021

Background: Black/African American(B/AA) women are more likely to die of breast cancer as compared to White (Wh) women but are underrepresented in genomic research. Current genomic research that aims to classify breast cancer in order to personalize treatment in early breast cancer or to identify targets for therapy in advanced breast cancer fails to adequately represent B/AA women and other minority groups. This negatively impacts our current knowledge of breast cancer in non-Wh women and raises questions about the applicability of such testing in minority groups.

Objective: To evaluate the frequency of race reporting and representation of non-White women in genomic studies.

Methods: This a database study of all PubMed reported genomic testing studies to classify breast cancer for prognostic or predictive purposes. A PubMed search was conducted with articles from inception to the present with the following keyword search terms: “Breast Cancer Gene Expression Assay” AND “Race”, “PAM50” AND “Race”, “MammaPrint” AND “Race”, “Oncotype Dx” AND “Race”, “76 gene prognostic score” AND “Race”, Intrinsic Subtype” AND “Breast Cancer” AND “Race”. This search yielded 129 articles. 31 articles were removed due to lack of relevance.

Results: Of the 98 articles remaining after applying inclusion/exclusion criteria, 39 (40%) failed to report race in their analysis. Of the remaining 59 articles, 57 (96.61%) included Wh participants in their study, 54 (91.53%) included B/AA participants, 13 (22.04%) included Hispanics/Latinos, and 20 (33.90%) included Asians. Two of the major clinical trials of widely used testing such as Oncotype Dx and MammaPrint but did not report race in the pivotal studies. The genomic studies that included B/AA women were more likely to be health services research studies. The genomic studies that focused on triple-negative breast cancer (TNBC) were also more likely to have B/AA participants that ranged from 6%-52% of participants. For Oncotype Dx testing, B/AA women were more likely to have a later stage at diagnosis. While the number of patients with low risk was similar in all race groups, B/AA women were more likely to have high Ki-67 with uncertain significance of these findings.

Conclusions: A significant number of genomic studies did not report race and ethnicity. Racial and ethnic minorities continue to be under-represented in genomic research and this raises questions about the wider applicability of this research in these populations. Large clinical studies should specifically report the race and ethnicity of participants to inform decision making. In addition, funders should require reporting of race in genomic studies.

Citation Format: Niloufar R Khanna, Niharika Dixit. Disparities in reporting of race and participation by race in genomic studies [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 PS18-35.
Abstract PS18-45: Association between tumor mutation profile and clinical outcomes among Hispanic Latina women with triple-negative breast cancer
Authors: Philipovskiy Alexander , Dwivedi Alok , Gamez Roberto , McCallum Richard , Nahleh Zeina , Aguilera Renato , Gaur Sumit
Published: February 2021

Triple-negative breast cancer (TNBC) represents approximately 15-20% of all breast cancer types. It is more common among African American (AA) and Hispanic-Latina (HL) women and has more aggressive course. The biology of TNBC in HL women has been poorly characterized, but some data suggest that molecular drivers of breast cancer might be different. Chemotherapy remains the only option for those patients. There is no clinical tool to help medical oncologist with the decision about appropriate individual chemotherapy, as well as no way to predict long-term outcomes. The aim of the study was to characterize individual patient gene expression profiles and to identify the relationship with clinical outcomes.Patients and Methods: From 2012-2019, we collected formalin-fixed paraffin-embedded tumors (FFPE) from women with TNBC. All specimens were carefully examined by pathologists for adequacy and for a hormonal status. We analyzed gene mutation profiles of collected tumors and associated results with individual patient’s clinical history and outcomes.Results: Of 25 patients with TNBC, 24 (96%) identified as HL, one patient as NHL. Twenty-one (84%) had stage III/IV disease, and four (16%) had stage II at the diagnosis. Most commonly mutated genes were: TP53, Notch, AKT, MEP3K, PIK3CA and EGFR. Compared to other international cancer databases mostly included NHW, AA and Asian women, our study demonstrated statistically significant higher frequencies of those among HL women. With TNBC. Also a worse clinical course was among those patients whose tumor had mutations in Notch and PIK3CA. Conclusion: In conclusion, this study is the first to identify the most common genetic alterations among HL women with TNBC. Our data strongly support the notion that molecular drivers of breast cancer could be different in HL women. Therefore, a deeper understanding of the biological mechanisms behind Notch, PIK3CA mutation, might lead to a new treatment approach.

Citation Format: Alexander Philipovskiy, Alok Dwivedi, Roberto Gamez, Richard McCallum, Zeina Nahleh, Renato Aguilera, Sumit Gaur. Association between tumor mutation profile and clinical outcomes among Hispanic Latina women with triple-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 PS18-45.
Abstract PS18-48: Comprehensive analysis of solute carriers to characterise differential expression in breast cancer cell lines and human tissue
Authors: Sutherland Rachel Jane , Meeson Annette , Lowes Simon
Published: February 2021

Essential nutrient uptake required for cell growth and survival is mediated by Solute Carrier (SLC) transporters both physiologically and in cancers. The SLC super-family encompasses sub-families of transport proteins including organic anion transporters (OAT), organic cation transporters (OCT) and organic anion transporting polypeptides (OATP). SLCs transport a vast array of endogenous and exogenous substances, including estrogen, its conjugates, and clinically relevant anti-cancer drugs. Accumulating evidence suggests that SLC transporters are differentially expressed in hormone-responsive and hormone non-responsive breast cancers, which could influence breast cancer pathogenesis, both in disease progression and treatment resistance. We investigated whether SLC transporters are differentially expressed in different breast cancer cell lines and in human breast cancer tissue. First, bulk cells from the breast cancer cell lines MCF-7 (hormone responsive) and MDA-MB-231 (hormone non-responsive) were analysed for differential expression of SLCs using sq-PCR and RT-PCR. 8 of 11 SLCO and 10 of 14 SLC22 transporters were expressed in at least one cell line. Transporter expression was either similar or lower in MCF-7 cells compared to MDA-MB-231 cells, with the exception of SLCO2A1, SLCO4C1, SLCO5A1 and SLC22A5 which were higher in MCF-7 cells. mRNA expression of SLCs was then compared between both cell lines and human breast cancer tissue. The latter showed an expression pattern largely reminiscent of the MCF-7 cells. Because these techniques measure the average level of expression shown by a pooled cell population, there is the potential disadvantage that cell heterogeneity is masked. To help address this, Single Cell RNA Sequencing (scRNA-Seq) was performed using the 10x Genomics Chromium Single Cell 3’ platform and NovaSeq Technologies to compare SLC transporter expression between the cell lines. Together these results provide evidence for differences in SLC transporter expression between cell lines and cancer tissues that may contribute to cancer progression.

Citation Format: Rachel Jane Sutherland, Annette Meeson, Simon Lowes. Comprehensive analysis of solute carriers to characterise differential expression in breast cancer cell lines and human tissue [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 PS18-48.
Abstract PS18-51: Leptin receptor expression in breast tumors and chromatin modulators: A comparative study
Authors: Pacheco Sara , Juarez Maria E. , Nandy Sushmita
Published: February 2021

Metabolic dysregulation and carcinogenesis are strongly linked. Leptin signaling acts as a metabolic switch that maintains body weight and energy homeostasis and gets impacted during metabolic dysregulation. Leptin signaling mediates its effect on breast cancer cells through downstream effectors like JAK-STAT, MAPK and PI3K pathways. At the molecular level, leptin exerts its effects through its receptor, LEPR, encoded by LEPR gene. Leptin signaling has been shown to contribute towards progression of breast cancer. Obese post-menopausal women are considered to be a high-risk category for breast cancer and dysregulated leptin signaling contributes towards it. We in this study focused on comparative molecular analysis of Leptin high (LEPRhi) and low (LEPRlow) expressing breast tumors.Breast cancer data from METABRIC (Molecular Taxonomy of Breast Cancer International Consortium) study was used through the cBioPortal (http://cbioportal.org) platform for cancer genomics. The METABRIC study includes clinical and molecular data from over 2500 breast cancer cases. The LEPRhi and LEPRlow expressing breast tumors in RNA-seq dataset were queried using cBioPortal embedded SQL feature as LEPR: EXP>1 and LEPR: EXP<-1 respectively. This query enabled us to create LEPRhi and LEPRlow expressing breast tumor cohorts from 243 and 234 patients respectively. Comparative analysis of LEPRhi and LEPRlow expressing breast tumors was performed for mRNA expression profiles. The mRNA data was further analyzed for integrated networks using GSEA pathway enrichment and CR2-cancer algorithms.The analysis indicated unique mRNA expression signature for LEPRhi and LEPRlow breast tumors. CR2-Cancer analysis of the mRNA dataset revealed chromatin modulators like- EZH2 (Enhancer of Zeste homolog 2), MEN1 (Menin), UHRF1 (Ubiquitin Like with PHD And Ring Finger Domains 1), TTF2 (Transcription termination factor 2), LMNB2 (Lamin B2), and RUVBL2 (RuvB Like AAA ATPase 2) had significantly higher mRNA expression in LEPRlow compared to LEPRhi tumor group. GSEA pathway enrichment analysis indicated PLK1 and Aurora A signaling as the most significant signaling pathways with an FDR q-value of less than 0.05.This preliminary study provides us with mechanistic insight into the unique molecular signatures of LEPRhi and LEPRlow expressing breast tumors. The results of this study leads to the basis of our hypothesis that leptin receptor signaling in breast cancer mediates epigenetic modifications of key genes that impact promotion and progression of breast cancer through chromatin modulators.

Citation Format: Sara Pacheco, Maria E. Juarez, Sushmita Nandy. Leptin receptor expression in breast tumors and chromatin modulators: A comparative study [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 PS18-51.
Abstract PS19-13: Palmitate exacerbates breast tumorigenesis in vitro via induction of a senescent-like phenotype in fibroblasts
Authors: Harlow Brittany Susanne , Davalos Albert , Brenner Andrew , Jolly Christopher , Tiziani Stefano , Hursting Steve , deGraffenried Linda
Published: February 2021

Background: Obesity is associated with a worse breast cancer prognosis, conferring an increased risk of recurrence and mortality. At the same time, recent evidence suggests that obesity is also correlated with development of cellular senescence, an inflammatory state associated with exacerbation of breast tumorigenesis in preclinical models. As obese individuals present greater levels of inflammation at baseline, research efforts are warranted to examine the means by which obesity promotes the development of a senescent phenotype, which may further exacerbate inflammation. Additionally, studies have yet to determine whether obesity-induced senescence modulates the tumorigenic process in the context of breast cancer specifically. Methods: To this end, we exposed fibroblasts to the obesity-associated circulating factor palmitate and used qPCR and western immunoblotting to assess the expression of genes and proteins involved in the senescent state, including interleukin (IL)-1a, IL-6, IL-8, senescence-associated beta-galactosidase (SA-beta-gal), and matrixmetalloproteinase (MMP)-9. As a mechanistic investigation, we next assessed the impact of palmitate on activation of NF-kB signaling using western immunoblotting, immunofluorescence, and NF-kB luciferase reporter assays. Finally, we utilized cell counting, MTT, wound healing, and colony formation assays to examine the impact of these palmitate-exposed fibroblasts on breast cancer cell proliferation, viability, motility, and survival, respectively. Results: We found that palmitate induced fibroblast gene expression of IL-1a, IL-6, and IL-8, major components of the senescent secretome, as well as expression of the senescent markers SA-beta-gal and MMP-9. The mechanism at least partially involved activation of NF-kB, responsible for production of about 75% of senescent secretome components. More importantly, these palmitate-exposed fibroblasts were of pathological impact, exacerbating in vitro measures of breast cancer cell aggressiveness. Conclusions: These findings contribute to our understanding of the impact of obesity-associated factors on breast tumorigenesis, demonstrating a mechanistic link between palmitate and the pro-tumorigenic effects of senescent cells. Our studies will ultimately aid in the identification of a therapeutic target that can be used to improve the comparably worse outcomes of the obese breast cancer patient.

Citation Format: Brittany Susanne Harlow, Albert Davalos, Andrew Brenner, Christopher Jolly, Stefano Tiziani, Steve Hursting, Linda deGraffenried. Palmitate exacerbates breast tumorigenesis in vitro via induction of a senescent-like phenotype in fibroblasts [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 PS19-13.
Abstract PS19-23: Effect of Wnt5a on drug resistance in estrogen receptor-positive breast cancer
Authors: Amioka Ai , Kadoya Takayuki , Sueoka Satoshi , Kobayashi Yoshie , Sasada Shinsuke , Emi Akiko , Masumoto Norio , Ito Masaoki , Okada Morihito
Published: February 2021

Purpose: We previously showed that Wnt5a-positive breast cancer belongs to a subgroup of estrogen receptor (ER)-positive breast cancers and its prognosis is worse than that of Wnt5a-negative breast cancer. In this study, we aimed to investigate the molecular mechanisms underlying the poor prognosis of patients with Wnt5a-positive breast cancer.Methods: A total of 151 patients with ER-positive invasive breast cancer were recruited for this study between January 2011 and February 2014. The association between Wnt5a expression and recurrence rate was examined. To identify the pathways associated with Wnt5a-positive breast cancer, we established a Wnt5a-expressing cell line (MCF-7/Wnt5a cells) and conducted DNA microarray analysis of MCF-7/Wnt5a cells. We also performed pathway analysis associated with Wnt5a expression, and evaluated the effects of Wnt5a in vitro using MCF-7/Wnt5a cells.Results: Data showed poorer relapse-free survival of patients with Wnt5a-positive breast cancer (P = 0.047). The median length of follow-up was 6.08 years (range, 0.027 to 8.47 years) for all patients. According to DNA microarray data, only the cytochrome P450 (CYP) pathway was significantly upregulated and related with Wnt5a (P = 0.0440). Moreover, MCF-7/Wnt5a cells were less sensitive to tamoxifen and paclitaxel, which are metabolic substrates of CYP (P < 0.05). Although the PI3K-AKT-mTOR signaling pathway is involved in the poor prognosis of ER-positive breast cancer, it was not associated with Wnt5a.Conclusions: In ER-positive breast cancer, Wnt5a expression upregulated the CYP metabolic pathway and decreased the sensitivity to tamoxifen and paclitaxel, the standard treatment options for ER-positive breast cancer.

Citation Format: Ai Amioka, Takayuki Kadoya, Satoshi Sueoka, Yoshie Kobayashi, Shinsuke Sasada, Akiko Emi, Norio Masumoto, Masaoki Ito, Morihito Okada. Effect of Wnt5a on drug resistance in estrogen receptor-positive 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 PS19-23.
Abstract PS2-22: The sensitivity and specificity of routine breast cancer pathology based on breast core biopsies compared with pathology based on surgical resections
Authors: Lundgren Claudia , Sjöberg Fanny , Olofsson Helena , Lindman Henrik
Published: February 2021

Background: Several studies have reported good or reasonable concordance of biomarker panel based on core needle biopsies (CNB) and the pathology based on the surgical specimen (SS). However, as neoadjuvant therapy (NAC) is becoming more common, the result from the preoperative CNB is crucial as it is the only source for the subtyping of the breast tumor. Incorrect results of subtype could result in suboptimal choice of NAC. The aim of this study was to estimate the sensitivity and specificity of biomarkers and surrogate subtypes based on CNB compared with the surgical specimen (SS) in a three-year cohort of primary breast cancer patients diagnosed at Uppsala University Hospital.

Patients and Methods: We collected data from all patients diagnosed with breast cancer at the University Hospital Uppsala, between 1st of September 2015 and 31st of August 2018 (n=837). Of these, 319 primary operated tumors were available with full biomarker information on CNB and SS. An additional 71 tumors from patients treated with NAC could be identified (not reported). Histopathological results from CNB and SS (n= 319) were used to divide the tumors in five subtypes; luminal A, luminal B, triple negative (TNBC), HER2-luminal and HER2 non-luminal.

Results: The sensitivity/specificity of CNB for the expression of estrogen receptor was 100%/100%, progesterone receptor 96%/77%, HER2 by IHC3+ 77%/99%, Grade 3 49%/89% and high Ki67 72%/78%. The sensitivity and specificity of CNB and SS in subtype TNBC and HER2 non-luminal subtypes was 100%. Out of 37 cases with HER2-luminal subtype, 27 were correctly diagnosed by CNB (sensitivity 73%, specificity 100%). The sensitivity for correct diagnosis of luminal A was 76% with a specificity of 83% and luminal B subtype had a sensitivity of 74% and 99% specificity.

Conclusions CNB was very reliable in defining TNBC and HER2 non-luminal subtypes, but less accurate in diagnosing luminal subtypes. There is a clear risk for underdiagnosis of HER2-luminal tumors. These patients might therefore receive suboptimal treatment when treated with NAC.

Citation Format: Claudia Lundgren, Fanny Sjöberg, Helena Olofsson, Henrik Lindman. The sensitivity and specificity of routine breast cancer pathology based on breast core biopsies compared with pathology based on surgical resections [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 PS2-22.
Abstract PS3-24: Using big data to gauge effectiveness of breast cancer awareness month
Authors: Gathers Diamone A. , Pankratz Vernon S. , Tawfik Bernard
Published: February 2021

Introduction: Breast Cancer Awareness Month (BCAM) has been used for decades to increase awareness and screening for breast cancer but it’s reach and effectiveness is difficult to judge. Using Internet Search Interest (ISI) could allow better evaluation of BCAM effects.Methods: Using Google Trends, we evaluated the ISI of a given term(s) as compared to that cancer’s awareness month. The ISI represents population level Google internet searches relative to the highest number of searches for the United States from 2004-2019 with a max number of 100. The ISI for breast cancer and mammogram in October, which is BCAM, was compared against all other months during this period. Results: The BCAM of October was associated with statistically significant more ISI for breast cancer 77.0 vs. 34.6 (95% CI 69.5-84.5, CI 32.9-35.3, p < 0.0005) as compared to the rest of the year. ISI for mammogram was similar (41.6 vs. 60.2, 95% CI 39.4-43.7, 48.5-71.9, p = 0.007). There was significant differences between the top half of states with Mississippi (100), Delaware (97) and West Virginia (95) having the highest ISI while Nevada (60), Oregon (60) and Utah (57) the lowest (87.6 vs 71.8, 95% CI, 85.5-89.7, 69.0-74.6, p < 0.0005). There was significant differences between the top half of 208 United States metro areas with Rochester MN (100), Greenwood MS (85) and Jackson MS (80) having the highest ISI while Salt Lake City UT (43), Idaho Falls UT (41) and Roanoke VA (40) the lowest (67.5 vs 54.4, 95% CI, 66.4-68.6, 53.4-55.4, p < 0.0005). Conclusion: ISI suggests that BCAM is effective at increasing breast cancer awareness with significant heterogeneity across states and metro areas. This publicly available free tool can be used to assess penetrance of awareness campaigns in a time sensitive manor for future targeting of populations with low breast cancer awareness. Future research is needed to correlate outcomes and ISI.

Citation Format: Diamone A. Gathers, Vernon S. Pankratz, Bernard Tawfik. Using big data to gauge effectiveness of breast cancer awareness month [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 PS3-24.
Abstract PS3-27: 18F-FDG-PET/CT and MRI in the assessment of neoadjuvant chemotherapy treatment response in breast cancer. Correlation with pathological response
Authors: Guarin Marco , Azar M. Eugenia , Tinetti Carolina , Mansilla F. M. Dolores , Namias Mauro , Carballo Pilar , Santamarina Lucia , Cavallero Jorgelina , Moreau Romina , Gonzalez Christian , Caceres Valeria , Gonzalez Eduardo , Bruno Gabriel
Published: February 2021

Introduction: Residual cancer burden (RCB) after neoadjuvant chemotherapy (NAC) can accurately predict disease recurrence and survival in breast cancer. In this context, end of treatment (EOT) image-guided response assessment could be useful to adapt treatment for individual patients. Our main objective was to assess the effectiveness of 18F-FDG PET/CT and MRI in determining NAC response. Methods: Patients with surgically resectable breast cancer (stages II-III) were prospectively included and evaluated with 18F-FDG-PET/CT and MRI before and after standard-of-care neoadjuvant chemotherapy (NAC). Ultrasound guided breast biopsy was performed before NAC and pathologic examination with residual cancer burden (RCB) scoring was performed after surgery. Standard uptake values (SUVmax and SUVmean) from baseline PET scans were measured. EOT images results were compared with RCB scores to assess the sensitivity and specificity of (EOT) 18F-FDG-PET/CT and MRI images. A multinomial logistic regression was performed to assess predictors of pathological response. A p-value of 0.05 was considered significant. Results: 30 patients were included, with 25% showing complete pathological response. EOT 18F-FDG-PET/CT images had a sensitivity of 55% and specificity of 100% to predict RCB > 0, while EOT MRI had a sensitivity of 65% and specificity of 66,6%. Luminal tumors showed significant lower baseline SUVmean and SUVmax values than triple-negative tumors. Ki67 expression didn´t correlate with treatment outcome. High estrogen receptor expression level was significantly associated with non-complete pathological response and higher false negative rates in both EOT 18F-FDG-PET and MRI images (7/8 in PET and 6/7 in MRI). Conclusions: 18F-FDG-PET / CT could be a useful diagnostic tool to assess neoadjuvant chemotherapy treatment response in breast cancer, showing greater specificity than MRI to predict pathological response. A high expression of estrogen receptors could lead to a high rate of false negative findings, both in PET and MRI. A greater number of cases is required to validate these findings.

Citation Format: Marco Guarin, M. Eugenia Azar, Carolina Tinetti, M. Dolores Mansilla F., Mauro Namias, Pilar Carballo, Lucia Santamarina, Jorgelina Cavallero, Romina Moreau, Christian Gonzalez, Valeria Caceres, Eduardo Gonzalez, Gabriel Bruno. 18F-FDG-PET/CT and MRI in the assessment of neoadjuvant chemotherapy treatment response in breast cancer. Correlation with pathological response [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 PS3-27.
Abstract PS4-32: Tim3 expression on tumor infiltrating lymphocytes is associated with poor response to neoadjuvan chemotherapy in patients with locally advanced triple negative breast cancer
Authors: Cabioglu Neslihan , Onder Semen , Oner Gizem , Karatay Hüseyin , Tukenmez Mustafa , Muslumanoglu Mahmut , Igci Abdullah , Eralp Yesim , Aydiner Adnan , Saip Pinar , Yavuz Ekrem , Ozmen Vahit
Published: February 2021

Background: Expression of immune checkpoint receptors (ICR) on tumor infiltrating lymphocytes (TILSs) is associated with better response to immunotherapies via immune checkpoint inhibitors. Therefore, we investigated various ICR expressions on TILs in patients with locally advanced triple negative breast cancer (TNBC) after neoadjuvant chemotherapy (NAC). Methods: Expressions of ICRs were examined immunohistochemically by staining surgical specimen (n=61) using specific monoclonal antibodies for PDL-1, PD-1, TIM-3, LAG-3, CTLA-4. Positivity was defined staining >1% on TILs. Results: Median age was 49 (24-76) years. The majority patients were clinically T3-4 (n=31, 50.8%), and clinically N1-3 (n=58, 95.1%) before NAC. Of those, 82% were found to have CTLA-4 positivity, whereas TILs associated positivites for PD1, PDL-1, LAG3 and TIM-3 were 62.3%, 50.9%, 26.2%, 68.9%. High expression of CTLA-4 was found to be associated with a better chemotherapy response (OR=7.94, 95%CI: 0.9-70.12, p=0.06), whereas TIM-3 positivity was contrarly associated with a worse chemotherapy response (OR=0.253, 95%CI: 0.066-0.974, p=0.047) as measured by MDACC Residual Cancer Burden Index. At a 47-month follow-up, patients with ypN0 disease (DFS; HR=0.31, 95% CI: 0.12-0.83, p=0.02 and DSS; HR=0.21, 95% CI:0.07-0.62, p=0.005) and CTLA-4 high expression on TILs (DFS; HR=0.38, 95% CI=0.17-0.85, p=0.019 and DSS; HR=0.34, 95% CI:0.15-0.78, p=0.01) were found to have improved survival. Conclusions: These findings demonstrate that CTLA-4, PD-1, PDL-1 and TIM-3 were highly expressed in TNBC after NAC. Our results more favor an immuncheckpoint inhibitor therapy via CTLA-4 alone or in combination with other immune check point inhibitors against PDL-1 and/or TIM-3 in addition to NAC in advanced TNBC.

Citation Format: Neslihan Cabioglu, Semen Onder, Gizem Oner, Hüseyin Karatay, Mustafa Tukenmez, Mahmut Muslumanoglu, Abdullah Igci, Yesim Eralp, Adnan Aydiner, Pinar Saip, Ekrem Yavuz, Vahit Ozmen. Tim3 expression on tumor infiltrating lymphocytes is associated with poor response to neoadjuvan chemotherapy in patients with locally advanced triple 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 PS4-32.
Abstract PS4-46: Homologous recombination deficiency score predicts patient characteristics and outcomes of triple negative breast cancer in China
Authors: Wang Xue , Du Feng , Yue Jian , Si Yiran , Cui Lina , Yuan Peng
Published: February 2021

BackgroundPrevious studies found homologous recombination deficiency (HRD) score could predict response to platinum-containing neoadjuvant chemotherapy in patients with triple negative breast cancer (TNBC), but its predictive effects of adjuvant chemotherapy is unexplored.

Methods We developed the 3DMed-HRD algorithm, which combines loss of heterozygosity score (LOH), telomeric allelic imbalance score (TAI) and large-scale state transition score (LST) to characterize genomic instability using over 10000 SNPs, adjusted by tumor ploidy and purity. HRD positive is defined by deleterious mutation in BRCA1/2 or HRD score above the threshold (cut-off ≥30). Tumor samples were retrospectively obtained from 149 TNBC patients who received platinum-based (paclitaxel and cisplatin, TP) or platinum-free (cyclophosphamide and adriamycin, EC) adjuvant chemotherapy after surgery. All patients underwent the 3DMed-HRD testing.

ResultsIn 25.5% (38/149) of TNBC patients deleterious germline or somatic mutation in BRCA 1/2 was detected. HRD results were available for all patients and 81of the 149 patients (54.4%) were defined as HRD positive. HRD-positive patients had younger age at diagnosis (median 46.7 years vs 51.5 years, P=0.002), higher differentiated (59.8% vs 39.5%; p=0.037), lower N-stage (55.7% vs 33.3%; p=0.006) and more common at high expression of Ki67 (64.7% vs 39.0%; p=0.015). In TP treatment group, patients with HRD positive tumors had a lower 5-year recurrence rate although the difference was not statistically significant (8.82% vs 16.1%; p=0.463). Patients in EC treatment cohort, 5-year recurrence rate was comparable between HRD positive and negative subgroups (15.4% vs 13.3%; p=1.0). In the 81 patients in HRD-positive cohort, patients in TP treatment group showed a numerical lower 5-year recurrence rates compared with patients in EC treatment group (8.82% vs 15.4%; p=0.489).

Conclusions54.5% patients were characterized as HRD positive in TNBC patients in our cohort. HRD was associated with clinicopathologic characteristics. Our results suggested that HRD status mightguide chemotherapy treatment decisions. Prospective validation with larger sample size is needed.

Citation Format: Xue Wang, Feng Du, Jian Yue, Yiran Si, Lina Cui, Peng Yuan. Homologous recombination deficiency score predicts patient characteristics and outcomes of triple negative breast cancer in China [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 PS4-46.
Abstract PS6-26: Recurindex® predicts local regional recurrence for n1 breast cancer after mastectomy
Authors: Zhang Li-Na , Liu Yue-Ping , Li Chun-Xiao , Song Chao , Wang Ning , Tang Ji-Yu , Zhou Meng-Li , Chen Ting-Hao , Chen Ming-Shuo , Cheng Skye Hung-Chun , Geng Cui-Zhi
Published: February 2021

Background: Post-mastectomy radiation therapy (PMRT) is part of standard regimen in the management of breast cancer. It has been shown to decrease the incidence of local regional recurrence (LRR) and improve breast cancer survival. Yet, its role in patients with 1-3 positive lymph nodes (N1) remains unclear. The lack of biological markers to evaluate the efficacy of PMRT for N1 patients leads to excessive treatment of low-risk patients and ignore of those at high risk. A clinical-genomic model RecurIndex® (RI-LR), based on a genomic database from mRNA expression as well as clinical factors (lymph node involvement, ER status,age at diagnosis, and lymphovascular invasion), is mainly developed for predicting the LRR in early stage breast cancer patients.

Method: The preliminary result enrolled 107 breast cancer patients with N1 involvement in a retrospective study atthe fourth hospital of Hebei Medical University. Kaplan Meier method is used to calculate the survival rates in terms of LRR-free interval (LRFI). The log rank test and cox regression model are applied for the survival difference between two independent groups, and for investigating prognostic factors related to high-risk patients. The primary endpoint is LRFI.

Results: With a median follow-up of 84 [IQR 64-84] months, RI-LR partitioned these N1 patients into 70% high-risk group and 30% low-risk group. LRR rate was 14.7% in the high-risk group whereas only 3.1% in the low-risk group. The survival curve clearly showed a partitioned trend of two groups (5-year LRFI 87.5%vs 100%, p = 0.085). Patients identified in the RI-LR high-risk group showed significantly higher LRFI if they had PMRT compared to those without PMRT (5-year LRFI 94% vs 70%, p =0.043), suggesting that higher radiosensitive patients could be identified by RI-LR. Multivariate analysis revealed that high-risk patients treated with PMRT has a 71 % reduction of LRR compared to those without PMRT (HR 0.29, 95%CI: 0.08-1.00, p = 0.051).

Conclusions:The present study provided robust evidence that RI-LR could partition N1 breast cancer patients into good and poor prognosis of LRR. RI-LR is capable of identifying high-risk patients who would benefit from PMRT. This observation warrants to validate in a larger cohort.

Key words: Early breast cancer, genomic assay, recurrence index (RI), local-regional recurrence (LRR), post mastectomy radiotherapy (PMRT)

Citation Format: Li-Na Zhang, Yue-Ping Liu, Chun-Xiao Li, Chao Song, Ning Wang, Ji-Yu Tang, Meng-Li Zhou, Ting-Hao Chen, Ming-Shuo Chen, Skye Hung-Chun Cheng, Cui-Zhi Geng. Recurindex® predicts local regional recurrence for n1 breast cancer after mastectomy [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 PS6-26.
Abstract PS6-37: Clinical stage is the only predictor of survival in breast cancer patients with a complete pathological response
Authors: Acevedo Francisco , Walbaum Benjamin , Merino Tomas , Petric Militza , Sanchez Cesar
Published: February 2021

INTRODUCTION In breast cancer (BC) patients, achieving a complete pathological response (pCR) after neoadjuvant chemotherapy (NCT) is associated with better prognosis. Despite this, some of these patients will experience recurrences of the disease and will eventually die of BC. We identified clinical factors that can affect recurrence and survival in BC patients who achieve pCR.METHODSRetrospective analysis of a Chilean BC database including patients treated in public and private hospitals in Santiago, Chile from 2010 to 2019. pCR was defined as the absence of residual invasive disease in the breast and in the axillary lymph nodes (ypT0/is N0) at the completion of the NCT. Invasive Disease-Free Survival (IDFS), Distant Disease-Free Survival (DDFS) and BC-specific survival (BCS) was measured from the time of diagnosis to the event or lost to follow-up. We performed Cox regression analysis to identify factors associated with prognosis.RESULTSFrom 855 patients who received NCT, 195 (22.8%) achieved pCR and were included in this study. Clinical characteristics are shown in table 1. 76 (37.9%) patients had hormone receptor positive (HR+) and 113 (57.4%) had Human epidermal growth factor 2 (HER2) positive tumors. 88.7% were treated with a regimen that included anthracyclines and taxanes. With a median follow-up of 36 months, three-year IDFS, DDFS and BCS and their 95% confidence intervals were 90.9% (84.7 - 94.6), 91.8% (86.0 - 95.3) and 93.8% (87.8 - 97.5); respectively. The stage at diagnosis was the only predictor associated with IDFS (Hazard ratio (HR) = 5.6; p = 0.02), DDFS (HR = 4.1, p = 0.07), and BCS (HR = 8.3, p = 0.04). Body mass index (BMI), age, hospital, HR or HER2 status, lymph node involvement, or the presence of an in-situ component, were not associated with prognosis in the multivariate analysis.CONCLUSIONThe clinical stage at diagnosis was the only predictor of survival in patients who achieved pCR after NCT. Short follow-up and few events may have affected these results. This data is consistent with previously published work.

Table 1. Tumor and patient characteristicsMedian age49 (24 – 78)HospitalPublic57.4%Private43.6%BMIMedian27.2 (18.5 – 44.7)Overweight38.0%Obese31.9%Receptor StatusRH+/HER2-16.4%RH+/HER2+21.5%RH-/HER2+35.9%RH-/HER2-26.2%Clinical StageI2.1%II47.4%III50.5%Lymph Node +69.7%ypT0/N078.1%ChemotherapyAnthracycline5.1%Taxane6.2%Anthracycline-Taxane88.7%

Citation Format: Francisco Acevedo, Benjamin Walbaum, Tomas Merino, Militza Petric, Cesar Sanchez. Clinical stage is the only predictor of survival in breast cancer patients with a complete pathological response [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 PS6-37.
Abstract PS6-39: A novel prognostic nomogram for 2-year survival in HER2-positive patients
Authors: Zhu Li , Chen Mengdi , Wu Jiayi
Published: February 2021

Background: Targeted therapies have largely improved prognosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Yet, disease can still progress rapidly for some patients in the first two years after diagnosis. Our study aimed to establish a nomogram model to predict 2-year breast cancer-specific survival (BCSS) in early HER2-positive breast cancer patients. Patients and Methods: A total of 32,481 HER2-positive patients derived from Surveillance, Epidemiology, and End Results (SEER) database were included in the construction of nomogram. Concordance index (C-index) and calibration curve were used to evaluate the discrimination ability and predictive accuracy. We also tested the model in 804 patients from Shanghai Jiao Tong University Breast Cancer Data Base (SJTU-BCDB).Results: Age, estrogen receptor (ER) status, progesterone receptor (PR) status, histologic type, T stage and N stage were selected to construct the nomogram according to multivariable analysis. The 2-year BCSS rate was 95% and 60% for patients at low risk (<8 points) and high risk (>13 scores) respectively. The C-index of model derived from SEER database is 0.81 (95%CI 0.79-0.83). Sensitivity analysis was performed in patients undergoing breast surgeries with the C-index of 0.81 (95%CI 0.79-0.83). Validation in 804 patients from SJTU-BCDB showed respective C-index of 0.77 (95%CI, 0.62-0.92) in total population, 0.67 (95%CI 0.44-0.90) in patients receiving anti-HER2 therapy and 0.90 (95%CI 0.81-0.90) in those without targeted therapy.Conclusions: The novel nomogram can predict 2-year survival outcome in HER2-positive patients independent of receiving anti-HER2 therapy or not and help clinicians to adjust therapeutic strategies for those patients with higher risk.

Citation Format: Li Zhu, Mengdi Chen, Jiayi Wu. A novel prognostic nomogram for 2-year survival in HER2-positive patients [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 PS6-39.
Abstract PS6-47: Breast cancer and COVID-19: Impact of active treatment on severe outcomes
Authors: Tawagi Karine , Burton Jeff , Lunski Michael , Maslov Diana , Cole John
Published: February 2021

Background: Several reports have observed that cancer patients who recently underwent chemotherapy or surgery had a higher risk of severe events compared with patients without cancer. Limited data is available on outcomes in specific cancer types, as well as the impact of non-cytotoxic systemic treatment, such as targeted therapy and hormonal therapy on severe outcomes. We aim to identify whether active treatment impacts severe outcomes (rate of hospitalization, ICU admission, intubation, and death) in breast cancer patients. Methods: We conducted a multicenter study in the state of Louisiana, throughout the Ochsner Health System, in both tertiary and non-tertiary centers. Patients must carry a diagnosis of breast cancer, and have a completed SARS-CoV-2 test between March 1st and April 30th, 2020. Chi-squared and Fisher’s exact tests were performed to compare the proportion of patients experiencing severe outcomes between treatment groups. Results: As of April 30, 2020, a total of 70 patients with breast cancer who had a positive SARS-COV-2 test were identified. Median age 64.5, median BMI 30.8, 62.9% (n=44) black, 27.1% (n=19) current/former smokers, HTN (n=52) and DM2 (n=22) were the most common comorbidities, and 12.9% (n=9) of patients had stage IV disease. Of these patients, 58.6% (n=41) were on hormonal treatment, and another 12.9% (n=9) were receiving other forms of systemic therapy (cytotoxic chemotherapy or targeted therapy). In terms of severe outcomes, 32.9% (n=23) of patients required hospitalization, 8.6% (n=6) required ICU admission with 7.1% (n=5) patients requiring intubation, 11.4% (n=8) of patients died. There was not a statistical difference in rate of severe outcomes (rate of hospitalization, ICU admission, intubation, and death) among breast cancer patients receiving active treatment (chemotherapy, targeted therapy, or hormonal therapy) vs those receiving no active treatment. There was also no difference in terms of severe outcomes by race. Conclusion: With an ongoing global COVID-19 pandemic, it is important to identify how the treatment and management of cancer impacts COVID-19 outcomes. This small cohort does not identify active treatment as a risk factor for increased rate of severe outcomes in patients with breast cancer. Further analyses describing impact of specific hormonal and chemotherapy regimens on risk of hospitalization and death will be completed by time of presentation.

Citation Format: Karine Tawagi, Jeff Burton, Michael Lunski, Diana Maslov, John Cole. Breast cancer and COVID-19: Impact of active treatment on severe outcomes [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 PS6-47.