bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomized trial of pegylated recombinant human granulocyte-colony stimulating factor to prevent febrile neutropenia in breast cancer after chemotherapy.
Authors: Zhang Lina , Li Yuntao , Fan Zhonglin , Wang Meiqi , Hui Tianli , Zhang Yanshou , Gao Chunhui , Zhang Jing , Zhang Guoshuan , Kong Xiangshun , Geng Cuizhi 
Published: June 2022

e12516 Background: The purpose of this study was to evaluate the incidence of febrile neutropenia (FN) in breast cancer patients with pegylated recombinant human granulocyte-colony stimulating factor (PEG-rhG-CSF) administration at 48 or 24 hours after chemotherapy for primary prevention. Methods: Patients with stage I-III invasive breast cancer who were scheduled to receive 4 cycles of adjuvant chemotherapy with EC regimen (epirubicin combined with cyclophosphamide) were eligible for this multicenter, open-label, randomized trial. Patients were randomized (1:1) to receive PEG-rhG-CSF (Jinyouli) 48 hours (48h group) or 24 hours (24h group) after the end of each cycle of chemotherapy. The primary endpoint was the incidence rate of FN. The secondary endpoints included the incidence rates of grade 3/4 neutropenia, chemotherapy dose reduction and chemotherapy delay due to neutropenia, antibiotic administration, the pain (bone, muscle, or joint), and the relative dose intensity (RDI) of the chemotherapy. Results: The preliminary results enrolled 197 patients including 96 in the 48h group and 101 in the 24h group. 78.1% of 48h group patients and 73.3% of 24h group patients completed four cycles of chemotherapy. The incidence rates of FN were 2.1% in the 48h group and 4.0% in the 24h group respectively. FN occurred in the first two cycles in the 48h group, while in the 24h group, it occurred only in the first cycles. The incidence rate of grade 3/4 neutropenia was 27.1% in the 48h group and 51.5% in the 24h group respectively. There was no delay in chemotherapy due to neutropenia in the two groups. The incidence rate of chemotherapy dose reduction due to neutropenia was 2.1% in the 48h group and 1.0% in the 24h group respectively. 2 (2.1%) patients in the 48h group and 4 (4.0%) patients in the 24h group received antibiotics. The mean RDI of each cycle of chemotherapy was 91.3% in the 48h group and 91.5% in the 24h group, respectively. The incidence rate of all grades pain (bone, muscle, or joint) was 25.0% in the 48h group, and 20.8% in the 24h group. With regard to 3 or higher grade pain, 1 (1.0%) patient in the 48h group experienced bone pain and 1 (1.0%) patient in the 24h group experienced muscle pain. Conclusions: Preliminary results suggest a similar effect of PEG-rhG-CSF administration at 48 or 24 hours after chemotherapy in primary prevention of FN in breast cancer patients receiving EC chemotherapy regimen. Recruitment is ongoing and updated data will be presented. Clinical trial information: ChiCTR1800019516. [Table: see text]
Prognostic role of the stromal tumor-infiltrating lymphocytes (TILs) in women with early ER+/HER2+ breast cancer (BC) in whom adjuvant chemotherapy (ChT) was omitted.
Authors: Jeric Horvat Valentina , Manevski Damjan , Gazic Barbara , Drev Primoz , Matos Erika , Ribnikar Domen , Seruga Bostjan 
Published: June 2022

e12526 Background: Adjuvant systemic therapy in women with early ER+/HER2+ BC usually includes ChT, trastuzumab (T) and endocrine therapy (ET). High level of TILs is associated with better outcome in HER2+ disease. Here we explore the outcome and prognostic role of TILs in women with early ER+/HER2+ BC in whom ChT was omitted. Methods: Women with ER+ (IHC ≥ 1%) and HER2+ (IHC3+ and/or FISH ratio ≥ 2.0) early BC who underwent surgery between years 2006 and 2016 at the Institute of Oncology Ljubljana and did not receive adjuvant ChT were eligible for this study. Hematoxilin and eosin slides of primary tumors were retrieved and evaluated for the percentage of stromal TILs. Distant disease-free survival (DDFS) was estimated by the Kaplan-Meier method. The association between DDFS and TILs level was explored in the Cox proportional hazard model. Relative survival was used for estimating the probability of dying due to the breast cancer or other causes. Results: During the 10-year period 86 (29.4%) out of 292 women with early ER+/HER2+ BC who underwent surgery did not receive adjuvant ChT. ChT was omitted due to the stage I disease (n=30), comorbidities (n=25), older age (n=19), refusal of treatment (n=9) and other causes (n=3). Five (5.8%) and 81 (94.1%) women received T and ET, respectively. Their median age was 65.8 yrs (IQR 55.7, 75.6 yrs) and 45 (52.3%) had stage I disease. There were 53 (61.6%), 24 (27.9%) and 9 (10.4%) women with low (<10%), intermediate (≤10% to <40%) and high (≥ 40%) level of TILs, respectively. After median follow-up of 10 years 28 events (distant recurrence or death) occurred. The 10-year DDFS for those who did not receive ChT due to the stage I disease, comorbidities and older age was 91% (95% CI, 0.79 to 1.00), 38% (95% CI, 0.18 to 0.75]) and 26% (95% CI, 0.10 to 0.66) (p˂0.0001), respectively. After excluding women with stage I disease the estimated probability of dying due to the breast cancer and due to other causes was 26.7% and 26.5%, respectively. Overall, for every 10% increase in TILs the risk of distant recurrence or death was reduced for 18% (HR=0.82; 95% CI, 0.64 to 1.05) (p=0.11). In the multivariable Cox model, higher TILs level was a significant predictor of better DDFS (HR 0.75; 95% CI, 0.57 to 0.98) (p=0.041) (Table). Conclusions: Women with stage I ER+/HER2+ BC who do not receive adjuvant ChT and T but do receive adjuvant ET may still have a very good outcome. In contrast, survival of women who do not receive adjuvant ChT and T for other reasons is poor; however, only a half of those deaths are related to BC. TIL is a favourable prognostic biomarker which might be helpful when de-escalation of systemic therapy in women with ER+/HER2+ BC is considered.[Table: see text]
Clinical audit of breast cancer patients under 40 years of age: A single institution experience.
Authors: Kate Shruti , Patil Roshan , Nagarkar Rajnish Vasant , Randive Makarand Arun , Valame Shaunak , Ramesh Yasam Venkata 
Published: June 2022

e12533 Background: Age is an important risk factor for breast cancer (BC). The younger age (< 40 years) is associated with unfavorable tumor biology. This is a retrospective analysis of young breast patients treated from 2012-2020 at a comprehensive cancer centre. Methods: Data regarding demography, clinical presentation, histopathological features, molecular profiling, treatment details, and outcomes were retrieved from medical records. All time-to event outcomes were analyzed using Kaplan-Meir method. Results: A total of 134 patients (< 40 years) with BC were included. Median age of the study cohort was 37 years (range: 22-40 years) with a female predominance (98.5%). Most of the patients presented with locally advanced BC (51%) followed by early BC (43%) and metastatic BC (6%). The mean tumor size and positivity lymph nodes of our non-metastatic patients were 3.86±1.90 cm and 3.3±3.98, respectively. The molecular classification revealed most of the patients were of Basal-like BC (TNBC, 40%) followed by Luminal A (33%), Luminal B (14%) and Her-2 (13%), respectively. Germline BRCA testing was positive in 22% patients (10/45). At a median follow-up of 51 months, 3 and 5-year Kaplan-Meier estimates of overall survival were 67.2% and 44.7%, respectively. Conclusions: Breast cancer is a heterogeneous disease with varied survival depending on multiple factors. Early diagnosis and timely appropriate management, as per clinical and molecular profile provides acceptable outcome.
Bisphenol A exposures and hormone concentrations in a cohort of women receiving aromatase inhibitor therapy for breast cancer.
Authors: Robien Kimberly , Kirstein Mark N. , Pawloski Pamala A. , Shapiro Alice C. 
Published: June 2022

e12535 Background: Bisphenol A (BPA), a widely used chemical in plastics production, has been shown to have estrogenic activity, although it is unclear whether BPA exposure alters effectiveness of aromatase inhibitor (AI) treatment among women with breast cancer. In vitro studies have indicated that at higher concentrations (≥10-4 μM), BPA inhibits aromatase expression and activity, whereas at environmentally relevant concentrations (≤10-8 μM), BPA increases aromatase expression and activity. Few in vivo studies have investigated the association between BPA exposure and estrogen concentrations among non-pregnant women. This pilot study among post-menopausal women receiving AI therapy evaluated whether BPA is detectable in participants’ urine, and the association between BPA and hormone concentrations. Methods: This study was ancillary to a larger intervention study (ClinicalTrials.gov NCT01509079), and participants provided informed consent for this ancillary study under a protocol approved by the institutional review boards of Park Nicollet Institute/HealthPartners and the University of Minnesota. AI adherence during the 4 weeks prior to the baseline visit was monitored through weekly diaries. Participants were instructed to collect spot urine collections in sterile, BPA-free polypropylene containers in the 24 hours prior to the baseline study visit. Serum hormone concentrations were measured using serum collected at the baseline study visit. The Breast Cancer Prevention Trial - Musculoskeletal Symptom (BCPT-MS) scale was used to assess AI-associated musculoskeletal syndrome symptoms at the baseline study visit. Results: Fourteen women agreed to participate in the pilot study, however one participant’s data was excluded due to substances interfering with BPA measurement. BPA was detected in urine from all 13 remaining participants. Geometric mean urinary BPA concentration (1.55 mcg/g creatinine, 95% confidence interval (CI): 0.98-2.45) was higher than concentrations reported for females (1.36 mcg/g creatinine, 95% CI: 1.23-1.51) in the 2013-14 National Health and Nutrition Examination Survey biomonitoring data. Age, body mass index, and percent body fat did not differ between women above or below the study median urinary BPA concentrations (1.49 ng/mL). Women with BPA concentrations >1.49 ng/mL had consistently lower serum estrone (5.0 vs. 7.0 pg/mL, p=0.15), estradiol (2.8 vs. 3.6 pg/mL, p=0.04), and testosterone (21.5 vs 23.8 ng/dL, p=0.28) concentrations compared to women with lower BPA concentrations. No statistically significant differences in BCPT-MS scores were observed between women with higher vs. lower urinary BPA concentrations. Conclusions: These preliminary findings suggest that BPA exposures may work in concert with AIs to lower serum estrogen levels. However, further research is needed to confirm these findings.
Decreased bile acid metabolism and association with prognosis reflecting microbiome in tumor microenvironment involved in cancer cell proliferation in breast cancer.
Authors: Wu Rongrong , Yu Irene , Tokumaru Yoshihisa , Asaoka Mariko , Oshi Masanori , Ishikawa Takashi , Takabe Kazuaki 
Published: June 2022

e12539 Background: Bile acids are metabolized by the gut microbiome and are involved in fat absorption. Contrary to their carcinogenic role in gastrointestinal cancers, bile acids have been reported to inhibit cancer cell proliferation in breast cancer. We hypothesized that activation of bile acid metabolism is associated with a better prognosis based on previous reports regarding the antitumor effects of bile acids in breast cancer cells. Methods: A total of 6050 patients from three large open primary breast cancer cohorts (GSE96058, METABRIC, and TCGA) were analyzed by bile acid metabolism scores calculated by gene set variation analysis, and the association with the microbiome of the breast cancer tumor microenvironment in TCGA was also investigated. Results: We found that disease free, disease specific and overall survival was significantly improved in the high bile acid metabolism group, which was validated by three large breast cancer cohorts. However, apoptosis, ROS, and unfolded protein response gene sets were not found to be enriched in the high bile acid metabolism group, despite the expectation that oxidative stress-induced apoptosis would lead to improved survival. Several metabolic pathways and pathways associated with bile acid production and regulation were enriched in this group. On the other hand, Ki67 and nuclear grade were higher, and several cell proliferation-related gene sets were upregulated in the low bile acid metabolism group, especially the G2M checkpoint in all cohorts. In association with the higher cell proliferation, the low bile acid metabolism group showed higher mutation load, immune activation, and infiltration of anti-cancer immune cells. We further investigated that the composition of the microbiome in each group and four species that demonstrated significant abundance in the high bile acid metabolism group and three species in the low bile acid metabolism group. Surprisingly, almost all the cell proliferation-related gene sets from Hallmark were enriched in the three microorganisms-rich groups specific for low bile acid metabolism breast cancer. This was not the case for the microorganisms specific to high bile acid metabolism. Conclusions: Clinical relevance of bile acid metabolism in breast cancer is that low bile acid metabolism with abundant Lactobacillus, Ruegeria, and Marichromatium is associated with highly proliferative cancer and worse survival, rather than the growth suppression effect of bile acids.
Artificial intelligence-powered human epidermal growth factor receptor 2 (HER2) analyzer in breast cancer as an assistance tool for pathologists to reduce interobserver variation.
Authors: Jung Minsun , Song Seung Geun , Cho Soo Ick , Jung Wonkyung , Oum Chiyoon , Song Heon , Ma Minuk , Park Seonwook , Pereira Sergio , Song Sanghoon , Paeng Kyunghyun , Yoo Donggeun , Ock Chan-Young , Sung Ji-Youn , Kim So-Woon 
Published: June 2022

e12543 Background: Human epidermal growth factor receptor 2 (HER2) expression is a predictive marker for HER2-targeted therapy in breast cancer patients. Interobserver variation in the interpretation of HER2 levels exists among pathologists, thus a method to increase the consistency of evaluation is needed. This study aimed to evaluate the performance of the artificial intelligence (AI)-based Lunit SCOPE HER2 in assisting pathologists to evaluate HER2 expression levels in breast cancer. Methods: Lunit SCOPE HER2 was developed with a 1.04 x 1010 μm2 area and 7.31 x 105 tumor cells from 1,133 HER2 immunohistochemistry stained whole-slide images (WSI) of breast cancer, annotated by 113 board-certified pathologists. The AI model was developed based on a semantic segmentation algorithm, which consists of two atrous spatial pyramid pooling blocks for tissue level classification and for tumor cell level classification. To validate the model, a total of 209 HER2 WSIs diagnosed with breast cancer were obtained from Kyung Hee University Hospital in Korea and were assigned as an external validation set. Three board-certified pathologists evaluated slide level HER2 expression (3+, 2+, 1+, and 0) twice, first without AI assistance and second, with it. The second reading was performed for WSIs where the pathologist's reading showed discrepancy with the AI model. Results: In the external validation set, all pathologists scored the same HER2 grade in 103 WSIs (49.3%), and the Fleiss kappa value was 0.512. The HER2 grade from the AI model and pathologists was the same in 151 WSIs (72.2%), and the weighted kappa value was 0.844. The pathologists re-evaluate 43, 63, and 83 WSIs, respectively. After AI assistance, all pathologists scored the same HER2 grade in 156 WSIs (74.6%), and the Fleiss kappa value increased to 0.762 (Table). Conclusions: This study demonstrates that an AI-powered HER2 analyzer can help achieve consistent HER2 expression level evaluation in breast cancer by reducing interobserver variability. Thus, the AI model can be applied as an assistance tool for pathologists in HER2 grade evaluation.[Table: see text]
Association of pre-treatment hemoglobin levels with survival outcomes among Indian women with triple negative breast cancer.
Authors: Sagiraju Hari Krishna Raju , Gogia Ajay , Sharma Rakesh Kumar , Deo S.V.S. , Sharma Dayanand , Gupta Ritu , Mathur Sandeep 
Published: June 2022

e12549 Background: Prevalence of Triple Negative Breast Cancer (TNBC), which has utterly poor prognosis and higher recurrence rate, is high among Indian women ranging from 20-43% across different regions of India. Previous studies from other countries have shown that pretreatment hemoglobin and hematocrit values influence treatment outcomes among breast cancer patients. Recent 2019-2020 National Family Health Survey (NFHS) of India reported that 66.4% of women suffer from anemia. This study examined the association of pre-treatment hemoglobin levels with survival outcomes among Indian women with TNBC. Methods: We retrospectively analyzed the medical records of 435 women registered at our institute with a diagnosis of TNBC between the years 2013-2021. Pre-treatment hemoglobin levels i.e. either before the start of neoadjuvant chemotherapy (NACT) or prior to surgery among those who received adjuvant chemotherapy were retrieved from the medical records along with clinical and tumor characteristics. Primary outcomes were relapse free survival (RFS) and overall survivals (OS). Cox-regression and Kaplan-Meier survival analysis were used to examine the association of pre-treatment anemia with survival outcomes in these patients. Results: Fifty-one percent (n=221) of the 435 TNBC patients in our study cohort had pretreatment hemoglobin level of <12.0 g/dL (based on the World Health Organization criteria). 278 patients received NACT and pathological complete response (pCR) rates were similar in anemic (31.5%) and non-anemic groups (30.1%). When adjusted for clinical and other hematological parameters, anemia was not associated with pCR. Median follow-up of the study cohort was 22.9 months (Range: 2.6 to 92.7 months). Pre-treatment anemia was significantly associated with poor RFS when adjusted for clinical and hematological parameters [adjusted Hazard ratio (aHR) (95%CI): 1.53 (1.02-2.31)]. Median RFS was 52.5 months among the anemic group and was not reached in non-anemic group. Effect of anemia on RFS did not vary by age category or menopausal status. However, the effect of anemia on OS varied significantly by menopausal status. Menopausal women with anemia at time of diagnosis had significantly higher hazard of death compared to menopausal women without anemia [aHR (95%CI): 5.0 (1.15-21.66)] and this association was not observed in pre-menopausal women [aHR (95%CI): 0.53 (0.19-1.44)]. Conclusions: Pretreatment hemoglobin level of <12g/dL was associated with poor survival outcomes among Indian women with TNBC and the effect of anemia on overall survival of these patients varied by menopausal status. Evaluation of hemoglobin levels during chemotherapy, pre-post surgery, and at various stages of follow-up is needed to determine the independent association of hemoglobin level trajectories with treatment outcomes and long-term survival among these TNBC patients.
CD45-positive tumor infiltrating lymphocytes in early-stage hormone-positive, HER2-negative (ER+/HER2-) breast cancer: Correlation with proliferation and prognostic signature scores.
Authors: Lucas Mairi , Kinsella Zak , Gonzalez Claudia Aura , Hurley Camille , Blümel Anna , Fay Joanna , O'Grady Anthony , Murphy Verena , Jahangir Chowdhury Arif , Burke Caoimbhe , Rahman Arman , Crown John , Kelly Catherine Margaret , Gallagher William M. , O'Connor Darran 
Published: June 2022

e12555 Background: Tumour infiltrating lymphocytes (TILs), have been associated in higher responses to treatment and are thought to be a prognostic marker in a number of cancer types. The role of TILs in breast cancer varies depending on the molecular subtype of the disease. In hormone positive, HER2-negative breast cancer, the significance of TILs is less clear, partly due to the paucity of data in this area. We aim to assess overall TILs in early-stage, hormone-positive, HER2-negative (ER+/HER2-) breast cancer and its relationship with proliferation index, Ki67, and the 21-gene recurrence score. Methods: Archival patient tissue samples of early-stage, ER+/HER2- breast cancer from the Irish arm of the TAILORx clinical trial were used. Full-face sections of these tumours were stained with anti-CD45 antibody (DAKA clone M0701) via the automated Leica Bond III system. A watershed cell-detection algorithm from the open-source digital pathology software, QuPath, was fine-tuned to identify true cell objects and positive immune markers. Optimised detection parameters were used to calculate the percentage of overall CD45+ cells (CD45%) within the tumour area. Patient TIL categories were dichotomised into High v Low CD45%, with 10% chosen as the threshold. CD45% was further correlated with proliferation index, clinical data, and 21-gene recurrence score. Results: 409 samples were included in the analysis. The mean CD45% was 5.96, with samples ranging from 0.13 to 78.86. The majority of samples were in the range of 0-10% of CD45% positivity with 89% (n = 367) patients in this category. Stratification of the cohort by 21-gene-recurrence score (RS) into Low, Intermediate and High, showed a statistically significantly high CD45% in patients with a High RS compared to Low RS (p = 0.0015). When divided by recurrence score group, high CD45% trended toward a lower disease free survival (DFS) when compared to low CD45%, with statistical significance found in those in the Intermediate RS chemotherapy treatment arm (p = 0.009). Conclusions: The role of TILs in ER+/HER2- breast cancer is still undefined. While a High RS was associated with a higher percentage of CD45-positive lymphocytes, the impact on recurrence and response to treatment remains unclear. Further studies to assess the role of different tumour infiltrating lymphocyte phenotypes, and the spatial distribution of assessed markers, are needed.
Prognostic value of circulation tumor DNA dosing in patients in neoadjuvant breast neoplasia (GIRO-ctDNA).
Authors: Giro Camila , Cruz Felipe Melo , De Rêgo Barros Lilian Arruda , Fonseca Fernando Luiz Affonso , Del Giglio Auro , Yamada Alayne Magalhaes Trindade Domingues 
Published: June 2022

e12559 Background: Pathologic Complete Response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer is strongly associated with a favorable prognosis. We evaluated whether there is a correlation between serum levels of circulating tumor DNA (ctDNA) during neoadjuvant therapy with obtaining pCR and detection of residual disease after treatment. Methods: ctDNA was isolated from 310 plasma samples of 27 patients diagnosed with localized and/or locally advanced breast cancer treated with standard NAC alone or combined with immunotherapy and/or anti-HER 2- targeted therapy when indicated. Blood was collected at pretreatment, every 15 days during treatment and before surgery. Results: Eight (29%) of the 27 patients presented pCR, 4 triple negative (50%, 3 HER2+ (37%) and 1 (13%) luminal B. We observed that throughout the neoadjuvant treatment in the seventh collection the ctDNA levels were significantly higher in patients who did not presented pCR in relation to those who achieved it, p-value = 0.014. 62% of patients who presented pCR in the surgical specimen also had a complete radiological response, with a significant correlation, p-value = 0.02492. Although we did not find statistical significance, we did note that patients who presented pCR had a tendency towards an initial increase in their ctDNA levels after the first cycle of chemotherapy. Conclusions: ctDNA dosage in the third month (seventh collection) of neoadjuvant treatment is inversely correlated with the achievement of tumor pCR. The tendency we saw of an increased ctDNA levels soon after the initiation neoadjuvant chemotherapy could indicate tumor sensitivity by the increase in cell death with release of ctDNA into the circulation. Clinical trial information: NCT05050890.