bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PS2-25: Cell-free DNA based detection of mono-allelic versus bi-allelic loss of function for essential genes in breast cancer
Authors: Xie Feng , Tang Haoran , Zhang Yue , Huang Yong 
Published: February 2021

Abstract
Background: Breast cancer is the top cancer in women, accounting for over 30% of new cancer cases in women worldwide. Breast cancer is a highly heterogenous disease. Treatment of breast cancer is a very active area in cancer research with significant progresses in recent years. Despite of recent progress in liquid biopsy molecular profiling, blood-based detection of mono-allelic versus bi-allelic loss of function for essential genes such as BRCA, PTEN etc. remains an unmet clinical need for targeted therapy in breast cancer.
Methods: We tested over 1000 plasma samples of breast cancer patients using PredicneCARE, a proprietary cell-free DNA (cfDNA) assay, which covered the DNA Damage Repair (DDR) genes in addition to most genes under research in cancer pathways. This blood-based cfDNA assay has a well-tuned capability to reliably detect copy number gain and loss, discriminating bi-allelic versus mono-allelic gene deletions. The assay also has an HRD (Homologous Recombination Deficiency) add-on for the generation of HRD score.
Results: PredicineCARE was used to test over 1000 breast cancer patients. The most frequently mutated genes include TP53(59.7%), PIK3CA(47.6%), BRCA2(16.1%), ATM(12.9%), ESR1(12.1%), and ARID1A(10.1%), with cancer variant detection capability down to 0.1% for hotspots; for copy number gain at ≥2.23 and for copy number loss at ≤1.75; and for rearrangements at 0.375%. Interestingly, cfDNA-based gene amplifications were founded in ERBB2, PIK3CA, FGFR1, MYC, etc. and gene deletions were found in important genes such as PTEN, RB, BRCA1/2 etc. Interestingly, we observed significant difference in mutations of key driver genes such as PIK3CA in Chinese versus Caucasian mBC cohorts.
Conclusion: The PredicineCARE assay detects blood-based cancer alterations including copy number loss, fusion detection and somatic status evaluation, providing a non-invasive approach to profile important targets including HER2, EGFR, VEGFR, DNA damage repair (BRCA1/2), cell cycle and growth regulations (CDK4/6-RB and PTEN/PI3K/AKT/mTOR), and TRK/ROS1/RET fusions for the treatment of breast cancer.
Citation Format: Feng Xie, Haoran Tang, Yue Zhang, Yong Huang. Cell-free DNA based detection of mono-allelic versus bi-allelic loss of function for essential genes in breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS2-25.
Abstract PS2-27: Benefits of a rapid diagnostic centre for breast cancer care during the COVID-19 pandemic
Authors: Ko Gary , Sarvanantham Sharmy , Sequeira Sangita , Prajapati Vrutika , McCready David R. , Freitas Vivianne , Cil Tulin D. 
Published: February 2021

Abstract
BACKGROUND: Changes in access to breast imaging and suspension of mammographic screening during the COVID-19 pandemic had the potential to significantly delay breast cancer diagnostic pathways. The Gattuso Rapid Diagnostic Centre (GRDC) is an innovative clinic that provides a patient-centered approach for investigation of suspicious breast abnormalities and sees approximately 1200 patients per year. The aim of this study was to assess the impact of the pandemic on patient volumes and imaging at this high-volume breast rapid diagnostic centre.
METHODS: A retrospective review of consecutive patients who presented to the GRDC from the start of the pandemic (March 12, 2020) until May 31, 2020 was performed. The number of patients, reason for referral, cancer detection rate (CDR), and waiting time from appointment to diagnosis were evaluated and compared to a corresponding time period in 2019.
RESULTS: A total of 168 new patients presented to the GRDC during the study period, corresponding to a 32.3% decrease in the number of patients compared to 2019 (n=248). Seventy-eight patients (46.4%) were referred due to the presence of a clinical palpable abnormality, which represented an increase of 13.8% (n=81 [32.7%] in 2019; p=0.005). Out of 168 patients, 69 were diagnosed with a breast malignancy, yielding a CDR of 41.1% during the pandemic versus 111 patients in 2019 (CDR of 44.8%; p= 0.456). The average time from appointment at GRDC to diagnosis was lower at 0.76 days vs 1.21 days in 2019. The rate of same day diagnosis was significantly higher at 39.5% vs 27.0% in 2019 (p=0.008). Twenty-five patients (14.9%) received neoadjuvant systemic therapy compared to 16 patients (6.5%) in 2019 (p=0.005). CONCLUSION: There were fewer patients presenting for breast investigations during the pandemic period and a significant increase in the percentage of patients with palpable masses as the cause for referral with no appreciable change in the CDR. The presence of a rapid diagnostic breast center enabled patients with concerning breast symptoms to access and receive expedited assessment. This ensured patients did not undergo diagnostic delays despite the health care restrictions that emerged during the COVID-19 pandemic.
Citation Format: Gary Ko, Sharmy Sarvanantham, Sangita Sequeira, Vrutika Prajapati, David R. McCready, Vivianne Freitas, Tulin D. Cil. Benefits of a rapid diagnostic centre for breast cancer care during the COVID-19 pandemic [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 PS2-27.
Abstract PS2-43: Innovating a magnetic experience on wirral peninsula in the United Kingdom- our experience with magseed localisation of impalpable breast tumours and axillary node for therapeutic surgery and staging
Authors: Arif Tahera , Absar Mohammed Shameem , Lund Jonathan Michael 
Published: February 2021

Abstract
INTRODUCTION Magseed is a novel localization technology in which a tiny seed is inserted to accurately mark the site of breast tumour. These can be detected intra-operatively by sentimag localization system. These can be implanted days prior to surgery and do not require use of radioactive material. It aids localization of impalpable breast lesions improving margin clearance rates. METHODS A study was undertaken of 50 patients undergoing Magseed localization of non-palpable breast lesions in rural and urban areas of Wirral Peninsula in the UK. Data including age, mode of localization (Stereo-guided/ Ultrasound guided), presentation (Symptomatic/Screen detected), and time to surgery after localization, size and weight of specimen, histology and re-excision rates was collected between June 2019 and November 2019. RESULTS A total of 50 patients had 52 Magseed inserted. n=14 were symptomatic, n=35 were screen detected and n=1 was an incidental finding on surveillance mammogram for a B3 lesion. All 50 patients had therapeutic surgery. 30 seeds were inserted on the right and 22 were inserted on the left (two were bilateral). 44 seeds were inserted under Ultrasound guidance and the rest were targeted under stereo guidance (n=8).Deployment of 2 Magseed resulted in malposition requiring wire localization. Mean age of subjects was 59.76 (range 31-81) years. Mean time to surgery after Magseed insertion was 8.04 (range 1-27) days. Mean weight of the specimen was 48.57(range 10-264) gm. Mean size of the lesions was 20.32 (range 8-65) mm. Redo surgery for margin clearance was performed bringing the re-excision rate to 15.38% (n=8). CONCLUSION We conclude that Magseed localization of breast tumours is a safe and reliable technique in terms of accuracy, localization and clearance of margins without any radiation concerns. Our re-excision rate for margin clearance is comparable to the national average. The only caveat we observed was localization of impalpable lesions prior to surgery in bulky breasts where we had to utilize wire guided localization on the day of surgery. Large scale data are lacking to compare Magseed localization with other localization techniques for non-palpable breast lesions.
Citation Format: Tahera Arif, Mohammed Shameem Absar, Jonathan Michael Lund. Innovating a magnetic experience on wirral peninsula in the United Kingdom- our experience with magseed localisation of impalpable breast tumours and axillary node for therapeutic surgery and staging [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 PS2-43.
Abstract PS3-30: Peri-operative diagnostic accuracy of magnetic resonance imaging and ultrasonography in breast cancer: A meta-analysis
Authors: Mouabbi Jason A , Sako Zeyad , Abdalla Ahmed , Hadid Tarik , Rimawi Mothaffar F 
Published: February 2021

Abstract
Background: Accurate determination of the extent of tumor is essential when a breast-conserving therapy (BCT) is considered. Due to its high sensitivity, breast magnetic resonance imaging (MRI) is increasingly used for the accurate diagnosis and surgical planning of breast cancers. However, a recent meta-analysis showed that peri-operative evaluation with MRI leads to higher mastectomy rates in patients that could have potentially underwent BCT.
Objective: The aim of this study is to compare the pre-operative diagnostic accuracy of MRI to ultrasonography (US) in breast cancer.
Methods: We identified eligible studies that examined peri-operative tumor size using MRI and US and compared it to its pathological counterpart. Databases of PubMed, Embase and Google Scholar were reviewed. To keep the study homogenous, only studies evaluating invasive ductal carcinoma were included and studies evaluating ductal carcinoma in-situ and lobular ductal carcinoma were excluded. An accurate tumor estimation by MRI or US was defined as within 10 mm from the pathological tumor size. An overestimation was defined as imaging tumor size more than 10 mm larger than its pathological counterpart. Odds ratios (ORs) were calculated using a random-effects model with 2-sided p-value of 0.05 set as the significance level.
Results: Twenty-five studies with 3,562 patients were included in the final analysis. MRI was 1.6-fold more accurate than US in preoperative diagnostic evaluation of breast cancer (OR 1.65; 95% confidence interval (CI) 1.24-2.18, p-value &lt;0.00001). However, MRI was 20 folds more likely to overestimate the tumor size compared to US (OR 20.25; 95% CI 9.46-43.33; p-value &lt;0.0001).
Conclusion: MRI remains the most accurate modality for the diagnosis of breast cancer. However, it is highly likely to overestimate tumor size and can result in unnecessary mastectomies. US is a reasonable diagnostic option for most patients with breast cancer.
Citation Format: Jason A Mouabbi, Zeyad Sako, Ahmed Abdalla, Tarik Hadid, Mothaffar F Rimawi. Peri-operative diagnostic accuracy of magnetic resonance imaging and ultrasonography in breast cancer: A meta-analysis [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS3-30.
Abstract PS4-39: Efficacy of combined CDK4/6 inhibitor and PARP inhibitor in the treatment of BRCA1 mutant triple negative breast cancer
Authors: Zhu Xiuzhi , Chen Li , Wang Zhonghua 
Published: February 2021

Abstract
Background: PARP inhibitors (PARPi) benefit only a fraction of breast cancer with BRCA mutation, and are even more limited in triple negative breast cancer (TNBC), due to clinical primary and acquired resistance. Here we found that the efficacy of PARPi in TNBC can be expanded with CDK4/6 inhibitors (CDK4/6i). Methods: We screened sensitive and resistant PARPi cell lines from existing TNBC cell lines and cultured PARPi-resistant strains by gradient concentration increase method. The effects of PARP inhibitor Olaparib and CDK4/6 inhibitor Palbociclib on TNBC cells lines were examined in vitro and in vivo. Combination index (CI) was used to evaluate the synergistic effects of drug combination. Results: We screened out the cell line MDA-MB-436, which was the most sensitive to PARPi, and the cell lines HCC1937 and SUM149, which were relatively resistant to PARPi, all of which were BRCA1 mutants. We demonstrated for the first time that the combination of PARPi and CDK4/6i has synergistic effects against some TNBCs both in vitro and in vivo, and was verified by CI&lt;0.9. Further experiments confirmed that PARPi combined with CDK4/6i inhibited cell proliferation and migration, and increased apoptosis and DNA damage. In the PARPi sensitive BRCA-/TNBC cell (MDA-MB-436), the inhibitory effect of monotherapy PARPi was obvious; In the PARPi resistant BRCA-/TNBC cells (HCC1937 and SUM149), CDK4/6i was added to achieve significant growth inhibition. In the timing of medication, PARPi followed by CDK4/6i had better inhibitory effect.Conclusions: In some BRCA-/ TNBCs, PARPi combined with CDK4/6i had a synergistic effect. Even in PARPi-resistant cells, combined treatment could enhance the efficacy and might reverse the drug resistance to some extent.
The combination index index of HCC1937 at different drug concentrations (uM)The combination index index of HCC1937 at different drug concentrations (uM)OlaparibPalbociclib25.0016.6711.117.414.943.292.191.460.980.65P-25.000.459110.668320.866540.869640.993450.989890.97841.003221.073741.00809P-20.000.537090.851131.022651.149561.231561.270271.189071.145021.14811.25795P-15.000.594121.018141.134481.056960.928140.955670.889760.842040.81060.81348P-10.000.475540.860580.77190.717480.62330.615880.561390.52960.510250.49752P-5.000.509450.762230.746560.683340.56030.499410.467390.41490.390670.37502P-2.500.573130.706410.714750.661230.519270.455960.350980.29340.319310.2756
Citation Format: Xiuzhi Zhu, Li Chen, Zhonghua Wang. Efficacy of combined CDK4/6 inhibitor and PARP inhibitor in the treatment of BRCA1 mutant 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 PS4-39.
Abstract PS5-39: Tumour cellularity size as a biomarker to predict response after neoadjuvant endocrine therapy: Correlation analysis between Ki67 expression and PEPI score
Authors: Velazco Joanna Ines Lopez , Otaño María , Larburu Lide , Lahuerta Ainhara , Elorriaga Kepa , Segur Virginia , Irizabal Juan Carlos , Martínez Ana , Jáuregui Lourdes , Caffarel Maria M. , Urruticoechea Ander 
Published: February 2021

Abstract
Background: Neoadjuvant endocrine therapy (NET) is an approach that allows real-time evaluation of drug efficacy as well as investigation of the biological and molecular changes that occur after estrogenic deprivation. This evaluation is mainly performed in surgical specimens after NET and it has been used as a research tool to obtain prognostic and predictive information using tumour response to decide adjuvant treatment. In this setting, there are not many validated biomarkers to predict response beyond Ki67 expression and Preoperative Prognostic Index (PEPI score) in NET. The aim of this study is to determine if the tumour cellularity size (TCS) in surgical specimen after NET correlates with PEPI score and Ki67 expression. Methods: Retrospective study of postmenopausal patients with estrogen receptor (ER) positive/HER2 negative resectable breast cancer, treated with an aromatase inhibitor for at least 4 months prior to surgery. Pathological characterization of tumour specimens: Evaluation of the percentage of residual tumour cellularity of formalin fixed paraffin embedded surgical specimens and immunohistochemistry characterization of ER and Ki67. Tumour cellularity size: calculated by combining the percentage of residual tumour cellularity and tumour pathological size. Results: N=104. Tumour characteristics at surgery and breakdown for the calculated PEPI score: table 1. Correlation between the percentage of Ki67 positive cells at surgery and TCS: (r=0.2503) p=0.04 (95% CI, 0.0014 to 0.4700). Correlation between TCS and PEPI score: (r=0.2582) p=0.05 (95% CI, -0.0131 to 0.4940).
Conclusions: Tumour cellularity size is a promising biomarker to determine response and prognosis after NET. There is a need to find other biomarkers to predict response after NET.
Table 1Pathology/Biomarker statusPEPI score RFS pointsNo. of patientspTNot available (NA)1pT1/T20102pT3/T431pNNA7Negative075Positive322KI67 levelNA10%-2.7%039&gt;2.7%-7.3%131&gt;7.3%-19.7%119&gt;19.7%-53.1%213&gt;53.1%31ER-status Allred scoreNA120-2303-8092PEPI scoreNA190281342533495561PEPI groupNot calculated19I (0 score)28II (1-3 score)42III (≥4 score)15
Citation Format: Joanna Ines Lopez Velazco, María Otaño, Lide Larburu, Ainhara Lahuerta, Kepa Elorriaga, Virginia Segur, Juan Carlos Irizabal, Ana Martínez, Lourdes Jáuregui, Maria M. Caffarel, Ander Urruticoechea. Tumour cellularity size as a biomarker to predict response after neoadjuvant endocrine therapy: Correlation analysis between Ki67 expression and PEPI score [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 PS5-39.
Abstract PS6-59: Impact of Cholecystectomy in Breast Cancer Recurrence
Authors: Madeka Isheeta , Gawdi Rohin , Cook Katherine L , Chiba Akiko 
Published: February 2021

Abstract
Background: Several published studies demonstrate that bile acid metabolites may influence the growth of breast cancer cells in vitro. Our group has shown reduced plasma concentrations of cholic acid and chenodeoxycholic acid (primary bile acids) and deoxycholic acid and lithocholic acid (secondary bile acids) in breast cancer patients that later on develop tumor recurrence. Cholecystectomy reduces the circulating bile acid pool. In patients with prior cholecystectomy, changes in bile acid metabolites may contribute to breast cancer tumorigenesis and recurrence. This study investigates our institutional rate of cholecystectomy in women diagnosed with breast cancer and its impact on breast cancer recurrence.
Methods: A retrospective review of patients with an invasive breast cancer diagnosis between 2014-2015 was conducted. Demographics, preoperative variables, surgical history and clinical outcome data was collected. 5-year disease-free survival (DFS) was compared using a Log-rank (Mantel-Cox) test.
Results: The study included 264 patients with mean age of 60.9. Most were Caucasian (83.5%). The majority were diagnosed at Stage II or lower (80.3%) and had hormone receptor positive, HER2 negative breast cancer (72.9%). Approximately 22.7% of patients had prior cholecystectomy surgery. The only statistically significant heterogeneity in demographic data between patients with and without cholecystectomy was body mass index (BMI). Patients with cholecystectomy had a mean BMI of 33.3, versus 29.1 in patients with intact gallbladders. The 5-year DFS in breast cancer patients with cholecystectomy was 91.6%, versus 97.1% in patients with intact gallbladders (p=0.06).
Conclusion: Women with breast cancer who had a history of cholecystectomy had increased rates of breast cancer recurrence over a 5-year period compared to women with breast cancer with intact gallbladders. Although this result was not statistically significant, a trend was seen. Future study of a larger patient sample size sample may lead to a statistical significant difference. The statistically significant difference in BMI between the two patient groups is likely a confounding factor, given increased BMI is a known risk factor for developing cholecystitis and breast cancer. This data supports existing in vitro studies that bile acids may influence the growth of breast cancer cells. There may be utility in closer follow-up of women with breast cancer and a history of cholecystectomy given the increased rate of breast cancer recurrence in this population.
Citation Format: Isheeta Madeka, Rohin Gawdi, Katherine L Cook, Akiko Chiba. Impact of Cholecystectomy in Breast Cancer Recurrence [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 PS6-59.
Abstract PS7-05: Estrogen-based hormone replacement therapy [E-HRT] reduces all-cause, breast cancer, and Alzheimer's dementia mortality
Authors: Ragaz Joseph , Shakeraneh Shayan , Qian Hong , Wong Hubert , Spinelli John J. , Wilson Kenneth S. 
Published: February 2021

Abstract
OBJECTIVES. To evaluate the long-term population-level impact of E-HRT on cause-specific and all-cause mortality in postmenopausal women in the USA, using the results of the 2017 Women’s Health Initiative HRT Trial 2 update.1 Of particular interest was the significantly reduced Breast Cancer [BrCa] mortality rates [RR=0.55, 95% C.I.=0.33-0.92].1
METHODOLOGY. In the WHI HRT Trial 2, women were randomized to receive estrogen (E) or placebo (P).1 For our analyses, the Annualized mortality rates (AR) were extracted for women aged 50-59, 60-69, 70-79, for breast cancer, Alzheimer's dementia, and all-cause mortality. The Median follow-up was 18 years. The Annualized Mortality Rate Difference (ARD) between the two groups was calculated as a difference of the AR between the P vs. E (AR in P - [minus] AR in E), expressed per 100,000 person-years. Subsequently, the Number of Avoided Deaths per year (NAD/year) was calculated using the number of women in each age group from the 2010 US census data.
RESULTS. The annualized number of deaths avoided by the use of E-HRT in the US population was estimated as follows: BrCa, 9,292; Alzheimer’s dementia: 18,966; and all cause-mortality: 50,008 (Table).
CONCLUSIONS. These data show a major beneficial impact of E-HRT, with over 50,000 deaths/year prevented in the USA alone. While these gains, sustained throughout the follow-up, represent undoubtedly major multi-organ metabolic benefits of estrogen, the most striking and unexpected findings involve BrCa, with over 9,000 BrCa deaths potentially avoided each year, just in the USA alone.
RECOMMENDATION. Adoption and implementation of E-based HRT to the current HRT medical guidelines, to extend the health benefits to millions of women, and to prevent thousands of deaths each year in the USA alone.
REFERENCE.1.Manson JE et al. Menopausal Hormone Therapy and Long-term All-Cause and Cause-Specific Mortality: The Women’s Health Initiative Randomized Trials. J Am Med Assoc 2017; 318(10): 927-938.
AgesAge 50 – 59(N=21,506,008)Age 60 – 69(N=15,323,140)Age 70 – 79(N=9,169,601)ALL ages(N=45,998,749)ARD / 100,000NAD / YearARD / 100,000NAD / YearARD / 100,000NAD / YearNAD / YearBreast Cancer204,301233,524161,4679,292Alzheimer’s Dementia00406,12914012,83718,966All-Cause Mortality15032,259507,66211010,08750,008
Citation Format: Joseph Ragaz, Shayan Shakeraneh, Hong Qian, Hubert Wong, John J. Spinelli, Kenneth S. Wilson. Estrogen-based hormone replacement therapy [E-HRT] reduces all-cause, breast cancer, and Alzheimer's dementia mortality [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-05.