bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thromboembolism (TE) and adjuvant endocrine therapy (AET) in hormone receptor positive (HR+) early breast cancer (EBC): Did the evolution of treatment change the incidence of the adverse event? A metanalysis.
Authors: Moscetti Luca , Omarini Claudia , Sperduti Isabella , Canino Fabio , Barbolini Monica , Nasso Cecilia , Toss Angela , Dominici Massimo , Piacentini Federico 
Published: June 2021

e12516 Background: The AET of HR+ EBC has been changing in the recent years. Aromatase inhibitors (AI) as upfront, or in a planned switch strategy after Tamoxifen (T), have been added to the choice of T alone. An increased risk of TE is well known in the T treated patients while AIs have showed a reduced rate of TE. Recently, adding the cyclin dependent kinase 4/6 inhibitors (CDK4/6) abemaciclib to AIs, has showed a positive impact in the high risk HR+ EBC subgroups, but we are seeing an increase of the TE rate. We conducted this meta-analysis to evaluate the impact of the new AETs on the incidence of TE if compared to the standard monotherapy. Methods: We performed a meta-analysis of the randomized phase III trials comparing the experimental AETs and the endocrine standard therapy. A random-effect model to find differences in the rate of TE events between the experimental treatments and the standard therapy has been used. Results: Twelve phase III trials were included. Five trials evaluated the upfront strategy, 6 studies the switch and one the combination with a CDK4/6inhibitor (i.e. abemaciclib). Overall, the new AETs did not significantly modify or affect the rate of TE events (OR 0.708, 0.444-1.130, p = 0.148) with high heterogeneity among studies (I2 87, p < 0.0001). Excluding the abemaciclib trial, the incidence of TE is reduced (OR 0.609, 0.462-0.802, p < 0.0001) with a moderate heterogeneity among the studies (I2 59, p < 0.006). Considering the upfront strategies with AIs, the TE events are reduced (OR 0.507, 0.394-0.651, p < 0.0001) but they are not if we consider the trials in which T is used upfront before AIs (OR 0.762, 0.546-1.065, p = 0.112). Conclusions: Overall, the new treatments (AIs alone or plus CDK4/6 inhibitors) did not affect the rate in TE events. AIs as upfront strategy is the safest AETs of HR+ EBC, being associated to the lowest incidence of TE. The switch strategy increases the TE rate whereas the addition of abemaciclib to the standard AET showed to significantly increase the TE events. The results of the currently ongoing trials with the CDK4/6 inhibitors will help to obtain additional data to evaluate any differences among the different CDK4/6 inhibitors and to clarify the weight of the TE adverse events in the balance of benefit/risk of this new adjuvant strategy.
Comparing practice patterns and outcomes for early-stage hormone receptor-positive and node-positive breast cancer patients with high-intermediate-risk Oncotype Dx scores in the National Cancer Database.
Authors: Tamragouri Keerthi , Ritz Ethan M. , Rao Ruta D. , O'Donoghue Cristina 
Published: June 2021

e12520 Background: Oncotype Dx (ODX) is a commercial diagnostic test primarily used to predict the likely benefit from chemotherapy in ER+, HER2-, and node negative breast cancer. The prognostic value (recurrence risk) has also been demonstrated to apply to early stage lymph node positive (LN+) disease in a number of retrospective and prospective studies. The ongoing RxPONDER trial aims to clarify the predictive value of RS in LN+ population. In light of the initial results, we analyzed the practice patterns and outcomes for HR+/Her2 -/node positive breast cancer patients receiving ODX testing in the years from 2010-2017 with RS 14-25 in a retrospective observational study of the NCDB. Methods: Women with HR+/Her2 -/node positive breast cancer receiving ODX testing from 2010-2017 were identified in the NCDB using TAILORx and RxPONDER patients’ inclusion criteria: ages 18-75, 6-50mm invasive tumors, N1, M0, ER+/HER2 -. The impact of ODX results in the high-intermediate range (14-25) and other clinico-pathologic variables on the receipt of chemotherapy were compared. Additionally, we examined the impact of chemotherapy on overall survival (OS). Frequencies, Kaplain-Meier analysis, and changepoint analysis using the Contal and O’Quigley method were utilized. Results: There were 109,652 T1-2 and N1 patients of whom 32,506 (29.6%) received ODX testing. 13,461 (41.4%%) women had scores in the high-intermediate (14-25) range. The majority tended to have only 1 LN involved (1LN: 77.2%, 2LNs: 17.5%, 3LNs: 5.3%), had a mean age of 57.8y, were Caucasian (86.4%), and were preferentially tested at academic or comprehensive community cancer programs (79.2%). 6,610 (49.3%) patients were recommended chemotherapy, the median ODX score for all women who were recommended chemotherapy was 20 compared to 17 for those whom chemotherapy was not recommended. 5,068 (76.7%) women had documentation of receiving chemotherapy which correlated with improved OS regardless of age. Conclusions: In the group of women with HR+/Her2 -/node positive breast cancer, clinicians appear to utilize ODX testing in less than one-third of patients, possibly finding RS to be most useful in guiding adjuvant therapy recommendations when only 1LN is involved. Both the recommendation and receipt of chemotherapy correlated linearly with increasing RS, as expected based on the current NCCN guideline recommendations. We identified an OS benefit when chemotherapy was administered, regardless of patient age. Long-term follow-up in the RxPONDER trial will likely continue to clarify the predictive value of RS < 25 in the ER+/HER2-/node positive breast cancer population.
Trends in use of ovarian suppression (OS) for premenopausal patients with early-stage hormone positive breast cancer and Intermediate Risk (IR) Oncotype Recurrence Scores (RS) from 2006-2020: A retrospective database analysis.
Authors: Hovstadius Sara Malin , Zimmerman Brittney Shulman , Berwick Shana , Blanter Julia , Berger Natalie F , Moshier Erin , Berkalieva Asem , Jaffer Shabnam , Cascetta Krystal Pauline , Tiersten Amy 
Published: June 2021

e12522 Background: Oncotype RS is a 21-gene assay used to predict the risk of recurrence and benefit from chemotherapy in early-stage, hormone positive (HR+), node-negative breast cancer (BC). The TAILORx trial showed that many patients with RS<25 can avoid chemotherapy and the small absolute benefit may be due to chemotherapy-induced menopause in premenopausal patients. The SOFT-TEXT trials found that premenopausal women have higher rates of freedom from recurrence and 8-year survival when receiving OS with endocrine therapy (ET). These studies suggest that premenopausal women with IR RS (16-25) benefit from aggressive ET with OS but trends in OS use have not been adequately studied. We predict that OS use has increased in premenopausal patients over time. Methods: We identified 87 premenopausal patients with early-stage, HR+ BC with IR Oncotype RS (16-25) who were treated with ET between 2006-2020 at our large NYC academic cancer center. The Cochran-Armitage test was used for trends in the proportions of patients receiving OS and chemotherapy over time. The log-rank test was used to compare distributions of recurrence rates between RS groups. Results: Median age was 46 years and median RS was 19. Overall, 23 (26%) patients received chemotherapy and 30 (34%) received OS (via leuprolide, goserelin or surgical oophorectomy) with ET. 55 (63%) received tamoxifen alone, 10 (11%) tamoxifen + OS, and 20 (23%) aromatase inhibitor (AI) + OS. Between 2006-2010, 2 (17%) patients received OS and 2 (17%) received chemotherapy compared to 9 (24%) and 12 (32%) between 2011-2015, and 19 (51%) and 9 (24%) between 2016-2020, respectively (Table). There was a significant increasing proportion of patients receiving OS; p=0.0064, but no significant trend in chemotherapy receipt; p=0.8910. There were 8 (9%) patients that recurred, with a borderline significant difference in secondary invasive breast event rates in patients receiving tamoxifen alone (8, 15%) compared to those on tamoxifen + OS or AI + OS (0, 0%), (p=0.0520). There were no significant differences in recurrence rates based on chemotherapy receipt (p=0.1868) or RS group 16-20 vs 21-25 (p= 0.1836). Conclusions: There has been a significant increase in the use of OS with ET in premenopausal women with IR RS in our study population. This study shows how the results of the SOFT-TEXT trial have been adapted into current practice. Future studies are needed to evaluate real-world recurrence rates with the use of increased OS and whether chemotherapy rates have decreased over time.[Table: see text]
Impact of RxPONDER on breast cancer treatment in an academic-community hospital.
Authors: Saito Be , Johnson Cathryn , Sizer Lina , Carruthers Catherine , Lamb Elena , Carter W. Bradford , Frazier Thomas G. 
Published: June 2021

e12524 Background: The introduction of Oncotype Dx set the stage for targeting chemotherapy treatment to only patients who would derive a benefit. RxPONDER trial then demonstrated that postmenopausal women with 1-3 positive lymph nodes, could forego chemotherapy if the recurrence score (RS) was ≤25. The most common chemotherapy regimens for breast cancer are taxotere and cytoxan or dose dense adriamycin/cytoxan followed by taxol. Chemotherapy can have many side effects and can increase risk of hospitalization due to complications. In addition, the financial cost can be considerable. Four cycles of TC will approximately cost $59,000, and most patients likely receive doses of growth factor support (neulasta is $12,565 per dose), totaling at minimum to $100,000 per patient. The purpose of this study was to look at the impact of RxPONDER on our patients. We reviewed patients who had RS at our institution in the last 5 years to see if we were appropriately treating patients with chemotherapy and hormonal therapy, or if a large group could be treated with hormonal therapy alone. Methods: This was an IRB approved retrospective chart review of patients at an academic-community hospital from 2015-2019. We identified patients ≥50 years old diagnosed with ER+/HER2- node positive breast cancer. Exclusion criteria included: M1, pN2, pN3. Univariate analysis used to compare patients that had RS vs those that did not. Student’s t-test was used to analyze whether there was a difference in rate of patients getting chemotherapy based on RS. Results: 216 patients were identified with ER+/Her2- breast cancer and 1-3 positive lymph nodes. 142 had RS (65.7%). Of those with RS, 140 were T1-T2 (98.6%), 131 had 1-2 positive LNs (92.3%), 115 had RS≤25 (80.9%), and 56 received chemotherapy (39.4%). Of the 74 patients without RS, 60 were T1-T2 (94.6%), 69 had 1-2 positive LNs (93.2%), and 51 received chemotherapy (68.9%). 30 patients who met the RxPONDER criteria (postmenopausal, 1-3 positive lymph nodes, and RS ≤25) still received chemotherapy. Conclusions: If we apply the RxPONDER trial recommendations, 30 patients would have been spared chemotherapy. In addition, 54.2% RxPONDER patients had RS ≤25. Extrapolated by percentage, 40 of the 74 patients who did not get RS in our study may have also been spared the side effects and cost of chemotherapy. This would be a savings of at least $3-7 million dollars to the health care system. RxPONDER makes a significant impact, not only in appropriately deescalating breast cancer treatment, but also to counter the increasing cost of medical care.[Table: see text]
An analysis of lines of treatment and survival analysis in older Indigenous and Nonindigenous women of Western Australia with breast cancer.
Authors: Khan Azim , Spalding Lisa , Martin Hilary Laura , Redfern Andrew David 
Published: June 2021

e12529 Background: Indigenous women with breast cancer (BrCa) have markedly higher mortality and are more likely to be diagnosed with more advanced disease compared with non-indigenous women. However, it is unknown if Indigenous older adults receive same lines of treatment as non-indigenous older adults with breast cancer. Methods: We retrospectively examined data from WA cancer registry from 2001 to 2016 with BrCa by Indigenous status. Indigenous were considered older adults aged above 55 years and non-indigenous aged above 65 years. Cases with confirmed breast cancer, where chemotherapy was indicated in adjuvant and metastatic setting were included for analysis. Overall survival was compared between treatment arms of indigenous and non-indigenous cohort using log-rank analysis and demonstrated by Kaplan Meier curve. Chi-square was employed as well. Results: At time of writing, results were available for 75 indigenous and non-indigenous older adults identified for analysis from cohort of 315 older adults. 79% Indigenous received treatment in adjuvant setting, 14% was not offered and 7% declined adjuvant treatment compared to 89% non-indigenous patients received adjuvant chemotherapy, 7% were not offered and 4% declined therapy. In first line metastatic setting, only 65% older indigenous group received chemotherapy compared to 76% non-indigenous patients. In second line, only 48% patients received treatment compared to 61% non-indigenous patients. In third line, 23% indigenous women received chemotherapy compared to 51% non-indigenous women with significant p-value 0.012. The rate of decline was higher in indigenous cohort. Kaplan meier curve of 10-year survival analysis favors the Non-Indigenous group. The difference between groups was 55 vs 68%. When comparing groups, the median survival of Indigenous group was 79 months and mean survival of Non-Indigenous cohort was 97 months. Log-rank testing p value 0.0025. Conclusions: In this study, indigenous patients have shown reduced survival outcomes and with drop in lines of treatment in the course of disease, highlighting a potential area to address and improve survival outcomes, along with addressing barriers that lead to treatment disparity in older adults.
Association of blood inflammatory/immune markers with outcomes in (neo)adjuvant breast cancer: A large single institutional study.
Authors: Mohd Ishak Hanis Mariyah , Nitar Phyu , Wong Fuh-Yong , Kusumawidjaja Grace , Leong Lester , Sim Yirong , Hakim Mohamed , Chay Wen Yee , Wong Ru Xin 
Published: June 2021

e12540 Background: An inflammatory state in various cancer populations may correlate with mortality. Neutrophil-lymphocyte ratio is a surrogate marker of an inflammatory state. A recent meta-analysis showed the predictive value of neutrophil to lymphocyte ratio in breast cancers, but series are generally small. We aim to study the associations of Neutrophil-Lymphocyte Ratio (NLR) with outcomes in stage I–III breast cancer in patients who received neo-adjuvant chemotherapy (NAC) or upfront surgery. The endpoints are overall survival (OS) and breast cancer-specific survival (BCSS). In the NAC group, association with pathological complete response (PCR) rate was also studied. Methods: Data of patients with stage I–III breast cancer treated from 2011–2017 were extracted from a prospectively maintained registry and merged with full blood count (FBC) results from a clinical management software. FBC were performed within one-month pre-chemo for NAC patients and one-month pre-surgery for upfront surgery patients. PCR is defined as stage ypT0/isN0M0. OS is defined as death from any cancer from diagnosis date, censored at last follow-up. BCSS is defined as death from breast cancer from diagnosis date, censored at last follow up or death from any cause. The NLR values with the maximal Youden’s indexes calculated for each outcome were used as cut-off, logistic regression was used to determine PCR association and cox regression and log rank for OS and BCSS. Results: A total of 2,479 eligible patients were analysed. Overall, treatment compliance was high (87.6% of ER+ patients received endocrine treatment, and 94.1% of HER2+ NAC patients had targeted therapy). In the NAC group (n = 357), 23% achieved PCR. NLR did not show any statistically significant association with PCR. In unadjusted analysis, high NLR was associated with worse BCSS (log-rank p = 0.003 figure 1). In multivariable analysis (MVA), only triple negative and HER-enriched cancers were significantly associated with PCR. In NAC patients, NLR was associated with OS (cut-off 2.63; OR 1.6, p = 0.077) and BCSS (cut-off 3.58; OR 2.2, p = 0.003) in MVA. In patients treated with up-front surgery (n = 2122), unadjusted analysis showed high NLR was associated with worse BCSS (OR 1.55, p = 0.05; figure 2). In MVA, NLR (cut-off 2.13, OR 1.57, p = 0.005), triple negative histology, stage and age were significant predictors of OS. BCSS was not significantly associated with NLR (OR 1.38 95%CI 0.90-2.12 p = 0.145). Conclusions: Using a large cohort of patients, a high NLR was found to be associated with worse outcomes in NAC and upfront surgery breast cancer patients.
Genetic instabilities as potential biomarkers for pregnancy-associated breast cancer.
Authors: Suelmann B.B.M. Berendine , Moelans Cathy B. , Rademaker Aniek , Bakhuis Carsten , Dooijeweert Carmen , van Diest Paul J. , Van Der Wall Elsken 
Published: June 2021

e12559 Background: Pregnancy associated breast cancer (PABC), defined as breast cancer diagnosed during or within one year after pregnancy, occurs approximately once in every 3,000 pregnancies and accounts for up to 6.9% of all breast cancers in women ≤ 45 years. Compared to age-matched non-PABC patients, PABC is generally characterized by a particularly aggressive histopathologic profile (more ER-, PR- and HER2 negative tumors and tumors of higher grade) with a higher mortality rate. Whether these cancers arise before or during pregnancy, and whether their genetic profile differs from non-PABC tumors, is currently unknown. This study assesses the genetic background of PABC by detection of specific DNA copy number alterations (CNA). Methods: We assembled 29 triple-negative PABC patients from the Dutch nationwide pathology database (PALGA). From their formalin-fixed and paraffin embedded (FFPE) tumor tissue blocks, DNA was extracted. Multiplex Ligation-Dependent probe Amplification (MLPA) analysis was performed for detection of CNAs in 20 oncogenes and 2 tumor suppressor genes using the P078-D2 kit (MRC Holland). Individual gene copy number loss (MLPA ratio < 0.7), gain (ratio 1.3-2.0) and amplification (ratio > 2.0) was determined and unsupervised hierarchical cluster analysis was performed to identify differences in copy number (CN) patterns between PABC patients. Chi square statistics were used to interrogate associations with clinicopathologic characteristics. Log-Rank test was used to compare Kaplan Meier survival curves between CN subgroups. Results: Triple negative PABC tumors showed frequent copy number loss on chromosome 17q ( CPD, MED1, TOP2A, MAPT, PPM1D) and 8p ( ZNF703 and ADAM9), as well as frequent copy number gain/amplification of MYC (8q) and CCND1 (11q). Cluster analysis identified 2 clusters of PABC patients based on their tumor copy number patterns: a CN-neutral cluster and a CN-high cluster, the latter demonstrating significantly lower chromosome 17 copy numbers than the former (for PPM1D, ERBB2, CPD, MED1, TOP2A, CDC6 and MAPT). Patients with CN-neutral tumors more often showed lymph node metastases (p = 0.028), were of significantly higher stage (p = 0.031), and demonstrated a worse overall survival (p = 0.036) compared with PABC patients harboring CN-high tumors. Conclusions: We demonstrate different tumor CN patterns within a small group of triple negative PABC-patients, associated with distinct aggressiveness. This will form the basis for further in-depth genetic profiling within a larger Dutch PABC cohort, rendering insight in the disease progression and contributing to the development of more targeted and personalized treatments.
Oncotype Dx score associated to pathological features to better prognosticate the risk of recurrence for breast cancer patients.
Authors: Namuche Fernando , Ruiz Rossana , Morante Zaida , Flores Claudio J. , Gomez Henry Leonidas 
Published: June 2021

e12562 Background: Oncotype Dx (ODX) prognosticates the risk of recurrence and predicts the benefit of adjuvant chemotherapy in estrogen-receptor-positive breast cancer (BC). However, it puts aside important clinical features. Our objective is to develop a model that uses routine clinical parameters associated with Oncotype Dx score to estimate the recurrence rate in our population. Methods: We retrospectively reviewed ODX and pathology reports from 371 early BC patients diagnosticated between 2014 and 2016 in a specialized cancer center, with a 5 year follow up. Variables were selected first with a univariate cox regression, then the statistically significant variables underwent a multivariate cox regression. The β coefficients from selected variables were used to create the prediction formula. Results: Among the tested variables, ki67, estrogen receptor (ER) and ODx score were significantly associated with Recurrence. The linear predictor is: (0.1331 x Ki67) + (0.4232 x ER)+(0.2112xODx score). The threshold score for this equation was set on 33 (median value) to discriminate low and high estimated risks for recurrence. The correct classification rate (CCR) for the training and validation sets was 76% and 68%, respectively. Conclusions: It is possible to optimize the Oncotype Dx to better determine a recurrence score with selected pathological features.
Study on relationship between chemokines and immune activation phenotype of breast cancer.
Authors: Wang Yanru , Wang Senming , Li Yingqiang , Lai Guorong 
Published: June 2021

e12564 Background: Breast cancer is one of the most common malignant tumors in women. The incidence rate and mortality rate are increasing year by year. Studies have shown that chemokines may act as an important driver in the immune microenvironment of breast cancer. Understanding the potential immunobiological driving effect in breast cancer is important for the early diagnosis of breast cancer, which is helpful to determine the immunotherapy strategy for patients. Methods: Gene expression data of 1050 cases of breast cancer were downloaded from TCGA database. Cluster analysis was applied to investigate the level of immunity of the observations using ssGESA software. The observations were divided into three groups according to their immune score. The expression of CXCL9, CXCL10, CCL4 and CCL5 chemokines were checked for the three groups using PHEATMAP software. The differential expression analysis for the three groups was performed using Edger software. The enrichment analysis was conducted using clusterprofiler software. Results: Cluster analysis showed that the observations could be divided into three subgroups according to their immunity score, and the heatmap proved that expression level of CXCL9, CXCL10, CCL4 and CCL5 chemokines of the subgroup with high immune score were apparently higher than that of the other two subgroups. The differential expression analysis revealed that the expressions of T cell exhaustion genes were markedly different between high-level group and low-level group. A total of 402 differentially expressed genes were identified, among which 380 were up-regulated in high-level group, comparing to low-level group, and 22 were down-regulated in high-level group, comparing to low-level group. Enrichment analysis indicated they were enriched in T cell-related pathway, such as th17, th1, th3 cell differentiation and so on. Conclusions: Our study showed that the expression of four chemokines were obviously different between the groups with high immune score and low immune score. Observations with high expression of four chemokines had more active levels of immune infiltration. Differentially expressed genes were enriched in T cell-related pathway. These four chemokines could be potential biomarkers for breast cancer patients through their unique immune characteristics.