bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adherence to different adjuvant endocrine therapies in HR+ HER2-breast cancer and its relation to real-world progression rates.
Authors: Durutovic Ivana , Gendy Shady , Kumar Deepa , Amioka Elise 
Published: June 2022

e12507 Background: Adjuvant hormonal therapy (Adj.) has significantly improved long-term survival of breast cancer (BC) patients with hormone receptor-positive (HR+) disease1. Despite proven efficacy, many breast cancer patients fail to adhere to treatment2. This study aims to assess patient adherence to different Adj. regimens by observing Proportion Days Covered (PDC) in relation to Real-World Data Overall Response Rate (RWD-ORR), Event Free Survival (EFS) & Adverse Events Rates (AEs). Methods: ICON US Medical & Prescription data was used. Analysis was limited to female BC patients who started Adj. [July’13 - June’14] & further refined to HR+ & HER2 negative patients by drug proxy. Patients were followed for 72 months. RWD-ORR was defined as percent of patients with no evidence of progression during follow-up. EFS was defined as time from Adj. start to first observed progression. PDC was calculated as (days on drug/duration on Adj.). AEs evaluated were endometrial & bone density changes. Chi square, t-tests & Fisher exact tests were used to examine Adj. regimen associations with age & adherence. General linear models (GLMs) were used to examine the effect of adherence on RWD-ORRs and AEs by treatment group, adjusting for patient age at diagnosis. Results: 1,498 patients met study criteria & data integrity procedures. Mean age was 60 years. Adherent patients were significantly older (57.8 vs 60.4 p < 0.001). RWD-ORR was 70.4%, median EFS was not reached, median Duration on Therapy was 52 months and overall AEs was 9%; highest in leuprolide group but no statistical difference across groups. RWD-ORR was observed to be highest among the AI group. High treatment adherence (PDC 80%+) was the strongest indicator of ORR (p < 0.001). RWD-ORR among those treated with AI or Tamoxifen were found to be more sensitive to adherence compared to AI/Tamoxifen. Conclusions: This study offers evidence to support provider´s messaging to patients that adherence improves outcomes when prescribing treatments. While adherence is important for positive outcomes for all regimens, some regimens appear to be more sensitive to adherence changes with respect to RWD-ORR. Further analysis including disease risk factors is needed to explain ORR - PDC relationship.[Table: see text]
The population characteristic analysis in RecurIndex for clinical decision-making on adjuvant therapy for early breast cancer: Results of a real-world study.
Authors: Wang Xiaojia , Lei Lei , Fu Peifen , Wang Ouchen , Xie Xiaohong , Xu Haibin , Feng Weiliang , Yang Hongjian , Hu Guinv , Li Shuguang , Dai Zhijun , Guo Guilong , Lv Xiaoai , Zheng Ya-bing , Chen Zhan-hong , Shao Xi-Ying 
Published: June 2022

e12514 Background: 28-gene signature (RecurIndex) is the first multi-gene panel for recurrence risk prediction after surgery developed from the Asian breast cancer population. In this study, we aimed to report the clinical and genomic characteristics of Chinese early-stage breast cancer patients whose primary lesions have been evaluated by 28-gene signature testing. Methods: In this study, 363 patients were assessed by 28-gene signatures between November 2019 and August 2021. Of these, 330 (90.9%) had stage I-II, hormone receptor-positive, HER2-negative breast cancer, 16 (4.4%) had triple-negative breast cancer (TNBC), and 17 (4.7%) had HER2-enriched breast cancer. The genomic risks of local and distant recurrence were determined by 28-gene signature respectively; the clinical risk was evaluated by the modified Adjuvant! Online. The molecular subtyping of the 28-gene signature was also compared with immunohistochemistry (IHC) status. In the future analysis, we will report the clinical decisions and outcomes of these patients. Results: The 28-gene signature classified 86.8% (n = 315/363) of patients as genomic Low Risk (LR) and 13.2% (n = 48/363) as genomic High Risk (HR) for local recurrence; 83.7% (n = 304/363) and 16.3% (n = 59/363) for distant recurrence. Among clinical HR patient, a total of 72 patients (64.9%) were deemed to be genomic LR of distant recurrence, and a total of 88 patients (79.3%) were deemed to be genomic LR of local recurrence. The concordance of luminal type identified by IHC or 28-gene based molecular subtyping was 99.1% (n = 327/330); TNBC type was 25% (n = 4/16), and HER2 enriched was 70.6% (n = 12/17). Conclusions: This study showed that in clinical HR patients, 64.9% 28-gene LR patients who could waive their adjuvant chemotherapy and 79.3% who could have the adjuvant radiotherapy adjusted. Additionally, the results of IHC and 28-gene signature-based molecular subtyping were highly consistent in luminal type, while the potential value of TNBC and HER2 enriched subtyping identified by the 28-gene signature needs to be further explored in the future.[Table: see text]
The use of clinical impact of the breast cancer intrinsic subtype-Prosigna assay for adjuvant treatment decision in early breast cancer with hormone receptor positive and HER-2 negative Middle East women.
Authors: Zidan Jamal , Leviov Michelle , Kuchuk Iryna , Bar-Sela Gil , Shai Ayelet , Kazarin Olga , Suheil Nasralla 
Published: June 2022

e12527 Background: Clinico-pathological evaluations of intrinsic subtypes by immunohistochemistry (IHC) are routinely used for treatment decision in patients with early-stage breast cancer (EBC). The Prosigna (PAM50) gene signature, is validated test measures the expression levels of 50 genes from formalin-fixed paraffin-embedded (FFPE) tumor samples. It permits intrinsic subtype classification of tumor and prognostic test of risk of recurrence (ROR) score. The objectives of this study were to evaluate the impact of Prosigna results on type of adjuvant treatment in EBC, to overcome disparities by comparing the results on different ethnicity groups in Israel and to asses physicians treatment decision before and after Prosigna results. Methods: This prospective, observational study was carried out in 7 Medical Centers at Northern Israel. Postmenopausal women with hormone-receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative invasive EBC were enrolled. Physicians completed treatment confidence questionnaires prior to and after receiving Prosigna test results. Only EBC : T 1-2, N0 and N1 were included. Results: Between May 2018 and April 2021, 238 women were enrolled, 204 patients are eligible for this analysis. Ashkenazi Jews were 38%, Sephardi Jews 32% and 30% were Palestinian Arab women. Mean age was 65.28 years. T1 was diagnosed in 82.3%, T2 in 17.3% and N1 in 22.4% of pts. At time of diagnosis tumor subtypes were categorized based on IHC as Luminal A in 50%, 54.4%, 59.5% and Luminal B in 50%, 44.6% and 40.5% of Sephardi, Ashkenazi and Arab patients retrospectively. Intrinsic tumor subtypes detected by the Prosigna test were Luminal A in 63.8%, 71%, 74.3% and Luminal B in 34.5% (+1.7% basal like), 29% and 25.7% respectively. No significant different between these groups. Overall 50.5% of pts were low risk, 26% intermediate risk and 23.5% high risk due to Prosigna results. Following Prosigna results 23.4% of the physicians changed their treatment recommendation. Conclusions: To our knowledge this is the first study using Prosigna test in Middle East women with early breast cancer. The use of Prosigna results led to a 23.4% change in adjuvant treatment decision. The results of this prospective study is similar to the data published in other studies in the literature. The intrinsic tumor subtypes and risk of recurrence detected by Prosigna adds to the physicians' confidence in the choice of treatment type. Prosigna test was additive for understanding the biology and for adjuvant treatment choice in both Jewish and Palestinian women in Israel.
Assessing adherence to adjuvant hormone therapy in breast cancer patients in routine clinical practice.
Authors: Camejo Natalia , Castillo Cecilia , Tambasco Clara , Strazzarino Noelia , Requena Nicolás , Peraza Silvina , Boronat Anna , Herrera Guadalupe , Esperon Patricia , Cuello Toledo Mauricio , Krygier Gabriel David 
Published: June 2022

e12532 Background: Adjuvant hormone therapy (HT) in patients with hormone receptor-positive breast cancer (BC) increases overall survival (OS). Adherence to HT in routine clinical practice is still poorly reported. Many BC patients are treated for other diseases and experience polypharmacy. Methods: Objective To assess adherence to HT in routine clinical practice.Materials and Methods: Adjuvant hormone therapy (HT) in patients with hormone receptor-positive breast cancer (BC) increases overall survival (OS). Adherence to HT in routine clinical practice is still poorly reported. Many BC patients are treated for other diseases and experience polypharmacy. Results: A total of 118 patients were included; 65.2% were treated with aromatase inhibitors (AI) and the rest with tamoxifen, with 36% presenting polypharmacy. Treatment adherence was observed in 81% of the patients, and it was associated with age (p=0.03, OR=0.96 for non-adherence), with adherent and non-adherent patients having a median age of 66 and 61.5 years, respectively; however, adherence was not associated with polypharmacy, territory of origin, marital status, living alone, level of education, occupation, or stage. The adherence profile was similar for both drugs, but homemakers and retired women showed greater adherence to AI. Conclusions: Adherence to HT was assessed in real life, with 19% of the patients not adhering to the treatment, despite the known benefit for OS, being a well-tolerated treatment, and being provided free of charge. The most adherent patients were the oldest. The results show the need to investigate the reasons for discontinuing HT, with Pharmacy and Medical Oncology fields combining efforts to develop coordinated strategies and interventions to increase adherence, given the impact that this may have on patients' OS.
Use of breast MRI to distinguish treatment failure versus new primary tumor following single fraction breast intraoperative radiotherapy for breast cancer (SF-IORT).
Authors: Payne Shelby , Payne Sydney , Horst Kathleen C. , Ikeda Debra M. , Dirbas Frederick M. 
Published: June 2022

e12534 Background: Single-fraction, intraoperative radiation therapy (SF-IORT) can replace whole breast radiotherapy (WBT) in select patients after lumpectomy for breast cancer. By combining histology review with co-registration of breast MRI at diagnosis and following an in-breast tumor recurrence, we sought to characterize IBTR as: missed on initial MRI, treatment failure, or new primary tumor. This has important implications for both breast MRI and understanding the effectiveness of SF-IORT. Methods: We reviewed our IORT database for patients with IBTR. Three radiologists recorded findings on DCE-MRI, mammograms and ultrasound, pathology at initial diagnosis and IBTR, and time to IBTR. Results: 90 women received SF-IORT between 12/6/2002 - 4/10/2019. There were 6 IBTRs (average age at recurrence 63, range 49-71 years). For these 6 patients, initial diagnostic mammograms showed fatty (1), scattered (4) or extremely dense (1) breasts with suspicious masses (4), calcifications (1), or asymmetry (1), average size 1.4 cm: range 0.3 - 2.0 cm. On MRI, background parenchymal enhancement was minimal (2), mild (2), moderate (1), or marked (1), showing a mass (4), mass/distortion (1), or post-biopsy marker/no abnormal enhancement (1). Initial pathology showed 2 IDC, 3 IDC/DCIS, and 1 DCIS, (average size 1.7 cm, range 1.1 - 2.4 cm) with 6/6 ER +, 5/6 PR + and 6 HER2 negative. IDC Ki-67 ranged from 5-25%. 5/6 patients had sentinel lymph node biopsy (SLNB) with 1/5 having a positive SLN. 4/6 received endocrine therapy. One patient declined follow-up mammography. After IORT, IBTR (average size 1.4 cm, range 0.7 - 3.6 cm) was diagnosed by mammography (3), palpable breast lump (2), or palpable axillary lymph node (LN) (1) shown as mass (4), mass/calcifications (1), or abnormal LN (1). IBTR occurred post-SF-IORT an average of 141.7 months, range 88.3 to 195.8 months. 2/6 IBTR occurred near the biopsy cavity. Subsequent surgery included mastectomy (3), re-excision lumpectomy/RT (2), or axillary LN dissection/RT (1) showing 4 IDC, 1 IDC/DCIS, and 1 IDC /ILC (6/6 ER +; 3/6 PR positive; 2 PR weakly positive; and 5 HER2 negative, 1 HER2 equivocal). Ki-67 ranged from 1-70%. Conclusions: 6/90 (6.6%) patients had an IBTR an average of 141.7 months post SF-IORT with 2/6 near the biopsy cavity. Breast MRI reliably screens patients for SF-IORT. Co-registration of imaging can help distinguish true recurrences from new primary tumors.
Is BMD (Bone Mineral Density) a prognostic factor for luminal A breast cancer in postmenopausal women?
Authors: Lee Seungju , Kim Hyun Yul 
Published: June 2022

e12542 Background: There are some studies concerned about the relationship of BMD (Bone Mineral Density) and breast cancer risks in menopausal women. However, most studies have limitations in that they did not distinguish the subtypes of breast cancer. Therefore, we assessed the BMD as a risk factor of recurrences, metastases, or occurrences of contralateral breast cancer in the luminal A breast cancer patients with menopause. Methods: In this retrospective study, the data of 348 luminal A type breast cancer patients, who underwent treatment at the Pusan National University Yangsan Hospital from 2012 to 2016, were analyzed. BMD of the lumbar spine, total femur, and femoral neck was measured by Dual Energy X-ray Absorptiometry (DXA). According to the measured BMD and WHO criteria, the group with T scores ≥ -1.0 was defined as normal, the group with T scores < -1.0 and > -2.5 was defined as osteopenia, and the group with T scores < -2.5 was defined as osteoporosis. The patients were divided into two groups: those with normal BMD and those with low BMD including osteopenia or osteoporosis in preoperative examination. We also divided patients as three groups: one group with no change of BMD, the other group with improvement of BMD and the other with deterioration of BMD during treatment. We used Chi-squared tests, Kaplan-Meier method and Cox-regression model to analyze the relationship between BMD and breast cancer risk. Results: Among the 348 patients, normal BMD was confirmed by preoperative examination in 129 patients and low BMD was identified in 219 patients. There was no change in BMD during the treatment in 243 patients. The improvement in BMD was identified in 37 patients, and the deterioration of BMD was confirmed in 68 patients. Younger patients were distributed in normal BMD compared to low BMD (55.7±6.9 vs 61.8±8.0, p<0.05). There were only 14 patients (4.0%) with recurrences, distant metastases or occurrences of contralateral breast cancer during a median follow-up period of 78 months. Among the 219 patients with low BMD, disease-free survival at 5 years was 98.2% compared to 95.0% for 129 patients with normal BMD ( p=0.326). In addition, disease-free survival at 5-years was 97.0% in no change of BMD during treatment, 94.6% in improvement of BMD, and 98.4% in deterioration of BMD ( p=0.785). Conclusions: In this study, BMD did not have statistically significance in the recurrences, metastases, or occurrences of contralateral breast cancer in luminal A breast cancer patients with menopause. In addition, there was no statistically importance in relationship between BMD change during treatment and recurrences, metastases, or occurrences of contralateral breast cancer. Therefore, we should perform treatments to breast cancer patients preventing decreased BMD.
Correlation of the oncotype DX breast recurrence score and the ki-67 IHC MIB-1 pharmDX score in HR+, HER2-, node-positive early breast cancer.
Authors: Crager Michael , Wijayawardana Sameera R. , Gruver Aaron M. , Blacklock Andrea , Baehner Frederick L , Russell Christy , Sapunar Francisco J. 
Published: June 2022

e12556 Background: In monarchE, abemaciclib, an oral CDK4/6 inhibitor, when combined with endocrine therapy (ET, tamoxifen or aromatase inhibitor) significantly improved invasive disease-free survival in patients with HR+, HER2-, node positive early breast cancer (EBC) at high risk of early recurrence and Ki-67 score ≥20%. The US FDA subsequently approved the Ki-67 IHC MIB-1 pharmDx assay (Dako Omnis) as a companion diagnostic. The Oncotype DX Breast Recurrence Score assay has similarly been validated in HR+, HER2- invasive breast cancers (IBC) to predict chemotherapy benefit and risk of distant recurrence at 10 years regardless of node status. While several studies have previously shown a relationship between Ki-67 IHC assays and RS, this relationship has not yet been evaluated using the standardized Ki-67 assay established for monarchE. The primary objective was to estimate the correlation between the Recurrence Score (RS) result and the monarchE Ki-67 IHC score using prospectively collected node positive, HR+, HER2- IBC specimens. A secondary objective assessed the proportion of node positive, HR+ patients with RS 26-100 that have Ki-67 IHC score >20%. Methods: IBC samples were acquired from Exact Sciences following an IRB-approved protocol. Samples from US patients with HR+, HER2- IBC, 1-3 positive lymph nodes (N1) with available RS result and sufficient tumor content were eligible. After collection of 275 samples with all RS results eligible (“All- RS pool”), 36 more samples with RS 26-100 were collected with high RS (HI RS only”). Unstained tissue sections were subsequently sent to Agilent Technologies for Ki-67 IHC using the monarchE assay. The consensus diagnostic category (positive/negative) and an average of the two closest % positivity scores were used for the final dataset. Spearman rank correlation and cross tabulations of RS result with % Ki-67 were performed according to the predetermined statistical analysis plan. Results: 311 samples were collected, 1 with a null Ki-67 result. Twelve samples had a pathology report with node negative assessment, leaving 298 samples and 262 in the All-RS pool. The rank correlation between % Ki-67 and RS result in the all-RS pool in the node positive population was 0.396 (95% CI 0.288 – 0.493). Cross-tabulations of the Ki-67 diagnostic category (< 20% vs ≥ 20%) against the RS were made using all available data (All-RS pool+HI RS only). Among 218 samples with RS 0-25, 164 (75%) had Ki-67 <20% and 54 (25%) had Ki-67 ≥20%. Among 80 samples with RS 26-100, 57 (71%) had Ki-67 ≥20% and 23 (29%) had Ki-67 <20%. Conclusions: A moderately positive correlation between the Oncotype DX Breast Recurrence Score result and the Ki-67 IHC MIB-1 pharmDx Score in HR+, HER2- node positive EBC was observed in the All-RS pool. These findings are consistent with prior studies.
Assessing the interrelation between oestrogen receptor status, heart rate variability and serum nitric oxide in breast cancer patients: Understanding their prognostic relevance.
Authors: Taranikanti Madhuri , Mudunuru Aswin Kumar , Dronamraju Akhila , Guntuka Rohith Kumar , Yerra Aruna Kumari , Maddur Srinivas , Manchikanti Lasya , Taranikanti Sai Shriya 
Published: June 2022

e12564 Background: Heart Rate Variability (HRV) is a non-invasive procedure to assess cardiac functions and provides an index of autonomic function that intricately controls vascular tone. Studying the alteration in HRV with agents producing oxidative stress will provide useful information about disease progression. Lower HRV indicates low level of Parasympathetic Nervous System activation and dysregulation of cardiac functions. Elements of tumour microenvironment like prostaglandin E2, oestrogen and hypoxia stimulate nitric oxide (NO) production which reacts with free radicals released by tumour tissue forming oxidising agents. NO enhances oxidative stress causing vascular dysfunction. Very few studies have reported an interrelationship between NO and HRV parameters in breast cancer. The aim of the study is to verify the relation between HRV and serum NO levels in ER+ and ER- breast cancer groups. Methods: Study design: Analytical, Cross sectional. Sample Size: 135 women above 20 years of age with and without breast cancer. 69 women with histologically proven breast cancer in different stages and 66 women who were healthy age matched controls were included. Oestrogen Receptor (ER) status was obtained from clinical records. Out of 69 women with breast cancer, 31 were ER- with 15 in stage 1 and 16 in stage 2. 38 women were ER+ with 5 in stage 2 and 33 in stage 3. Serum NO was measured using colorimetry. Heart Rate Variability was measured from lead II ECG using Power Lab 15T and lab chart software. Serum NO levels and HRV parameters were compared between ER groups. Results: ER+ women had higher HRV with parasympathetic predominance compared to ER- with p<0.001. ER+ women also had higher serum NO levels compared to ER- group with p<0.001. Though no direct correlation was noticed between NO and HRV, multiple analysis of variance showed significant (p<0.001) difference of all values across the groups. irrespective of menopausal status. Conclusions: A significant difference was observed in HRV of ER+ and ER- women with breast cancer. Most ER+ women were in stage 3 with significantly higher NO levels. Serum NO is expected to be the factor most responsible for HRV changes particularly in stage 3/ER+. Parasympathetic predominance seen in ER+ women possibly is due to high NO levels.[Table: see text]
Single cell profile of tumor and immune cells in primary triple-negative breast cancer and different sites in the axillary lymph nodes.
Authors: Liao Ning , Li Cheukfai , Cao Li , Chen Yanhua , Ren Chongyang , Chen Xiaoqing , Mok Hsiaopei , Wen Ling-Zhu , Li Kai , Wang Yulei , Zhang Yuchen , Li Yingzi , Lv Jiaoyi , Cao Fangrong , Luo Yuting , Li Hongrui , Wu Wendy , Balch Charles M. , Giuliano Armando E. 
Published: June 2022

e12570 Background: Little is known about the host-tumor interaction in the lymph node basin at a single cell level. This study examines single cell sequences in breast cancer nodal metastasis of a patient with triple negative breast cancer. Methods: The primary breast tumor, sentinel lymph node, an adjacent lymph node with metastatic involvement and a clinically normal-appearing lymph node were collected during operation. Single-cell sequencing was performed on all specimens. Results: 14,016 cells were clustered as 6 cell populations. Cancer cells demonstrated the molecular characteristics of TNBC basal B subtype and highly expressed genes in the MAPK signaling cascade. Tumor associated macrophages regulated antigen processing and presentation and other immune-related pathways to promote tumor invasion. CD8+ and CD4+ T lymphocytes concentrated more in sentinel lymph node and mainly stratified as two transcriptional states. Conclusions: The first single cell report investigates the host-tumor interaction in the lymph node basin of triple-negative breast cancer. Single-cell sequencing analysis suggested that the sentinel lymph node was the initial meeting site of tumor infiltration and immune response, where partial T lymphocytes perform anti-tumor activity while other T cells exhibit an exhaustion state. We proposed a molecular explanation to the well-established clinical principle that the 5-year and 10-year survival outcomes were noninferior between sentinel lymph node dissection (SLND) and axillary lymph node dissection (ALND).