bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term oncologic outcomes after omitting axillary surgery in older women with early stage, node-negative breast cancer: A systematic review and meta-analysis.
Authors: Rana Mariam , Lee Soyon , Lindsay Alistair , Silva Godinez Juan Carlos , Vakil Erik , Waugh Evelyn 
Published: June 2023

525 Background: In 2016, Choosing Wisely recommended the omission of routine sentinel lymph node biopsy (SLNB) in early stage, clinically node-negative, hormone receptor-positive, Her2-negative breast cancer in women ≥70 years old, although data supporting this was limited. Our study aimed to examine the long-term impact of omitting axillary staging in elderly women undergoing surgery for early stage, clinically node-negative breast cancer. Methods: A systematic review and meta-analysis was conducted. Medline (Ovid) and Embase were searched for published papers and abstracts using a systematic search strategy. Randomized and observational studies comparing women aged ≥70 years of age with early-stage, clinically node-negative breast cancer undergoing surgery for breast cancer with and without axillary staging, were included. Included studies reported at least one of the following outcomes: axillary recurrence (primary outcome), disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival. Risk ratios (RR) were calculated as summary estimates for all outcomes. A weighted pooled mean difference and 95% CI was calculated using a random-effects inverse variance meta-analysis for each outcome. Heterogeneity was calculated using I2 statistics, and explored using meta-regression. The Newcastle-Ottawa Scale was used to assess the methodological quality of eligible trials, based on the selection of patients, comparability of cohorts, and the methods of outcome assessment. Results: Nine studies were eligible for meta-analysis, including data for 48,523 patients. For the primary outcome of axillary recurrence, data for 3,591 patients was meta-analyzed. Axillary staging was found to reduce the risk of axillary recurrence compared to no axillary staging, although this was not statistically significant (RR 0.59, 95% CI: 0.26 to 1.35, I2= 46.6%, p = 0.21). For overall mortality, data for 14,981 patients was meta-analyzed, and a statistically significant protective effect of axillary staging on overall mortality was demonstrated (RR 0.55, 95% CI: 0.33 to 0.90, I2= 78.1%, p= 0.003). No significant differences were observed in DFS (RR 1.02, 95% CI: 0.51 to 2.07, I2 = 0.0%, p = 0.37) and BCSS (RR 0.96, 95% CI: 0.57 to 1.62, I2 = 0.0%, p = 0.78). Conclusions: Omission of axillary surgery to stage the axilla may be associated with a higher risk of overall mortality in older women with early-stage breast cancer compared to those who undergo axillary surgery. Omission of axillary surgery in this patient population should be carefully tailored to the individual patient, taking into consideration co-morbidity, life expectancy, and formal measures of frailty. Randomized trials are required to further explore the oncologic safety of omitting axillary staging in women aged 70 years or older undergoing breast cancer surgery.
Efficacy of ovarian function suppression of 3-monthly versus monthly GnRH agonist as endocrine therapy for premenopausal breast cancer patients.
Authors: Audi Blotta Daniella , Gomes Jessica Ribeiro , Moreira Shermann Brandão Rodrigues , Colosimo Danielle Fortes , Cavalcanti Gonçalves Ferreira Carolina , Forgiarini Elaine Aparecida , Gagliato Debora De Melo , Buzaid Antonio C. 
Published: June 2023

527 Background: The combined analysis of the Suppression of Ovarian Function Trial (SOFT) and Tamoxifen and Exemestane Trial (TEXT) trials have shown significant survival benefit of adding ovarian function suppression (OFS) with GnRH agonists (GnRHa) to aromatase inhibitors (AI) versus tamoxifen in high-risk premenopausal patients (pts) with estrogen receptor (ER)-positive breast cancer (BC). In both studies, GnRHa was administered every 4 weeks. However, the efficacy of 3-monthly GnRHa plus AI has not been well studied. We conducted a retrospective study designed to assess the efficacy of OFS with 3-montlhy compared with monthly goserelin, associated with AI, in premenopausal pts with ER-positive BC. Methods: Medical records of premenopausal pts with ER-positive BC who received OFS with 10.8mg 3-montlhy goserelin plus AI or 3.6mg monthly goserelin plus AI, between June/2013 and January/2023 were reviewed. Patient characteristics, such as age, body mass index (BMI) and prior chemotherapy were analyzed. Estradiol (E2) levels were measured by gas chromatography tandem mass spectrometry. Pts with at least one E2 level above 2.72 pg/ml were considered to have ineffective OFS. Analysis of E2 measurements was divided into periods: < 3, 3 to 6, 6 to 9, 9 to 12, 12 to 18, 18 to 24 and > 24 months. E2 levels greater than 2.72 pg/ml were evaluated at each timepoint. Results: A total of 88 pts were included. 27 (30.7%) received monthly goserelin and 61 (69.3%) 3-monthly goserelin. Patient characteristics were well balanced between the groups. Relevant demographic data are shown in table. For E2 analysis, 20 (22.7%) pts had at least one measurement greater than 2.72 pg/ml, 11 (40.7%) in the monthly group and 9 (14.8%) in the 3-monthly group (p = 0.007). The percentages of E2 measurements ≥ 2.72 pg/ml, in each time period, were 0%, 40%, 12.5%, 16.7%, 33.3%, 50% and 50% in monthly group versus 8%, 4.2%, 10%, 14.3%, 4.8%, 8.3% and 5.6%, in 3-monthly group, respectively. Conclusions: Our study demonstrated that more pts who underwent 3-monthly goserelin had E2 levels below the defined threshold of 2.72 pg/ml compared with monthly goserelin, when associated with AI, with statistical significance. These findings suggest that 3-monthly goserelin may result in better efficacy in OFS when comparing with monthly and provide greater convenience for pts. [Table: see text]
Assessing the marginal costs of radiation therapy and antiestrogen therapy for post-lumpectomy, early-stage breast cancer across Medicaid and Medicare plans.
Authors: Wu Victoria , Khlopin Martha , Jagsi Reshma , McClelland Shearwood 
Published: June 2023

529 Background: With recent Level I evidence (FAST FORWARD) supporting radiation therapy (RT) duration as short as one week and Level I evidence (CALGB9343) supporting RT omission in favor of antiestrogen endocrine therapy (ET) alone in select patients, the necessity of both RT and ET, adjuvantly, in early-stage breast cancer (BC) has been questioned. Evidence providing granular details on the role of insurance in the aggregate cost of RT and ET is lacking. This project disaggregates costs by insurance plan to increase transparency of out-of-pocket (OOP) cost estimates. Methods: National Comprehensive Cancer Network guidelines were utilized to determine the proper treatments, with FAST FORWARD radiation dose/fractionation (26 Gy in 5 fractions) representing RT. Treatments were identified using Current Procedural Terminology and Healthcare Common Procedure Coding System codes. OOP costs, deductibles, and copay/coinsurance were calculated for Medicaid, Original Medicare, Medigap Plan G, and Medicare Part D Rx. The medicare.gov, medicaid.oh.gov, aarpmedicareplans.com, and cms.gov were used to determine pricing. Price estimates reflect actual costs per insurance plan rather than costs estimated from claims data. All procedures were considered to be performed in an Ohio hospital setting, insurance coverages were based on the zip code 44106, and total expenses were based on all treatments plus a 5-year follow-up (not adjusted for inflation). Results: Treatment charges for ET include medical oncology initial consultation, biannual medical oncology follow-up, baseline bone density study, and Anastrozole cost (5-years). Treatment charges for RT include initial consultation, treatment planning, dosimetry calculations, treatment device, simulation and verification, RT delivery, on-treatment visits, and medical physics consultation. Original Medicare beneficiaries face an OOP cost of 20% for Medicare Part B claims with no cost cap for approved procedures after the deductible. Medications are covered under Medicare Part D with copays. This results in a marginal OOP treatment charge (after 5-year follow-up) of $767.54 for ET alone and $1,416.78 for ET + RT. Medigap Plan G beneficiaries face a marginal OOP charge of $1,225 for both ET alone and ET + RT, assuming the $226 Medicare Plan B deductible is met by the cost of lumpectomy during the year of RT. For Medicaid beneficiaries (assuming all treatments are approved by Medicaid), all expenses are covered without limit, resulting in no OOP expense for either treatment plan. Conclusions: Discussions of adding RT to ET for post-lumpectomy early-stage BC often involves considerations of treatment costs. This model (based on actual cost estimates per insurance plan rather than claims data) can help to enhance cost transparency by comparing expenses between Medicare and Medicaid plans.
Association between patient-reported outcomes and therapeutic outcomes in patients with breast cancer: A pooled individual-participant data analysis.
Authors: Modi Natansh , Abuhelwa Ahmad Y , Rowland Andrew , Menz Bradley D , McKinnon Ross Allan , Sorich Michael J , Hopkins Ashley Mark 
Published: June 2023

530 Background: Patient-reported outcomes (PROs) are captured in validated tools to provide the patients’ perspective and voice on their physical, social, emotional, functional, and cognitive abilities. Pre-treatment PROs have shown prognostic importance in other cancer types, however, the prognostic value of PROs in breast cancer has been minimally explored. Methods: In a pooled analysis of contemporary clinical trial IPD from patients with breast cancer, cox-proportional hazard analysis and binary logistic regression was used to assess the association between potential predictors with overall survival (OS) and adverse event (grade ≥ 3) outcomes, respectively. PROs were recorded using the EORTC QLQ-C30 version 3.0 questionnaire in the pooled cohort. Statistical significance was set at a threshold of P<0.05 and was determined via the likelihood ratio test. Model fit and linearity of variable associations were assessed via the Akaike information criterion (AIC). All analyses were stratified by age, performance status, treatment arm, and study. The primary assessed outcome was OS, with grade ≥ 3 adverse events assessed as a secondary outcome. A forward inclusion process (starting with the variable of lowest AIC, PRO domains were retained in the model if they decreased the AIC by 2 or more on addition, and remained statistically significant) was used to evaluate the value of multiple PRO domains on prognostic performances. Results: Within data available, the EORTC QLQ-C30 version 3.0 questionnaire was used in a pooled cohort of 8,544 patients across 8 clinicals trials. In the pooled cohort, the association between PROs and outcomes was best described by a linear association. Patient-reported physical functioning, appetite loss, and pain were significantly associated with OS. On forward-inclusion, only physical functioning remained within the OS prognostic model. Except for patient-reported financial difficulties, all PRO domains were significantly associated with grade ≥ 3 adverse events. On forward-inclusion, physical functioning, pain, and constipation all remained statistically significant. Conclusions: Within large high-quality IPD, pre-treatment PROs demonstrated significant prognostic relationships with therapeutic outcomes in patients with breast cancer initiating contemporary anticancer treatments. Patient-reported physical functioning was found to be the most prognostic PRO domain for OS, while patient-reported physical functioning, pain, and constipation were retained in a multivariable model prognostic of grade ≥ 3 adverse events.
Does RSClin provide additional information over classic clinico-pathologic scores (PREDICT 2.1, Influence, CTS-5)? A TEAM Pathology substudy.
Authors: Beltran-Bless Ana-Alicia , Pond Gregory Russell , Bayani Jane , Barker Sarah , Spears Melanie , Mallon Elizabeth , Taylor Karen J , Hasenburg Annette , Markopoulos Christos , Dirix Luc Yves , Seynaeve Caroline M. , Van De Velde Cornelis J.H. , Rea Daniel William , Vandermeer Lisa , Hilton John Frederick , Bartlett John , Clemons Mark J. 
Published: June 2023

533 Background: Gene-expression profiling tests (e.g. Oncotype, Mammaprint, Prosignia, Breast Cancer Index and EndoPredict) are widely used in the care of patients with early-stage hormone positive breast cancer (node negative or 1-3 lymph nodes). However, these tests are resource intensive, and few studies have compared their value with either free and widely available clinico-pathologic risk calculators (e.g. PREDICT 2.1, INFLUENCE 2.0, and CTS-5) or tools that combine genomic testing with clinico-pathologic data (e.g. RSClin). The TEAM pathology substudy population was used to compare these different predicted model scores with outcomes. Methods: The TEAM pathology study consists of 3284 postmenopausal hormone positive breast cancer patients treated with either exemestane or tamoxifen followed by exemestane. Accrual was from 2001 to 2006. Genes comprising the multi-parametric Oncotype Dx were used to train signatures to create true assay results. Patient data was then used to calculate recurrence scores through various tools. This included clinico-pathologic models and their respective endpoints PREDICT 2.1 (overall survival at 5 years), INFLUENCE 2.0 (distant metastasis at 5 years), CTS-5 (distant recurrence risk at year 5-10), the purely genomic Oncotype Dx trained results (distant recurrence risk at 9 years), as well as the new clinico-pathologic RSClin (distant recurrence risk at 10 years). We compared the level of association between these predictive model scores using Spearman correlation coefficients. The prognostic ability of each model was contrasted for each outcome using Harrell’s C-statistic. Results: Results were available for CTS-5 (3022 patients), INFLUENCE 2.0 (3485 patients), ODx-trained (3825 patients), and RSClin (3029 patients). Correlation coefficients showed low correlation between Influence ( r= 0.25) and CTS-5 ( r= 0.17) with Oncotype-Dx trained results, and high correlation between RSClin ( r = 0.84) and Oncotype-Dx trained results. The concordance index was similar (0.65 to 0.68) for all models with distant metastasis-free survival as the outcome. Analysis is ongoing and further results will be available at the time of presentation. Conclusions: Other clinico-pathologic tools such as Influence 2.0 and CTS-5 have good prognostic ability when compared to Oncotype Dx-trained results and RSClin. [Table: see text]
Image-only deep learning risk model performance in patients with known germline mutations.
Authors: Sodagari Faezeh , Lehman Constance Dobbins , Mercaldo Sarah , Carney Andrew , Lamb Leslie 
Published: June 2023

536 Background: Mammograms contain highly predictive biomarkers of future breast cancer risk, which can be identified by deep learning (DL) risk stratification models. DL model performance in discerning risk in patients with known germline mutations has yet to be established. The aim of this study is to assess image-only DL model risk score performance in patients with and without a germline mutation undergoing screening breast MRI. Methods: This retrospective, multisite study included the first screening MRI of consecutive females ≥30 years from 3/1/2011 to 11/30/2021 at four facilities, with a prior bilateral screening mammogram containing a DL risk score and at least one year of follow-up. A mammography-based DL five-year model was used to assess risk, with an increased-risk threshold of ≥2.2 and high-risk of ≥5.8. Patient demographics, germline mutation status, and traditional risk factors were extracted from electronic medical records. Standard screening performance metrics including cancer detection rate (CDR) within one year of MRI were determined. Cancer outcomes were determined via linkage to a regional tumor registry. DL model performance was compared using Pearson’s chi-squared tests. Results: 4025 patients who underwent screening breast MRI met inclusion criteria. 381(9.5%) had a known germline mutation. There was no significant difference in age of those with or without a germline mutation (54.9y ± 10.5 vs 54.8y ± 8.8, p = 0.284) or family history of breast cancer (68.5% vs 65.3%, p = 0.205). Patients with a germline mutation were more likely to be White (95.0 vs 91.4%, p < 0.05), have non-dense breasts (52.8% vs 35.3%, p < 0.001) and less likely to have a personal history of breast cancer (25.7% vs 36.3%, p < 0.001). The CDR in those with a germline mutation was higher than those without a mutation (39.4 vs 20.3, p < 0.05). The median DL risk score in those with a germline mutation was lower than those without a mutation: 1.9 (IQR: 1.4-2.5) vs 2.3 (IQR: 1.7-3.8), p < 0.001. In patients with a germline mutation, the CDR in those with elevated DL scores was higher than those with low DL scores (47.6 vs 34.2, p = 0.512: increased-risk threshold; 60.6 vs 37.4, p = 0.512: high-risk threshold). A similar trend was seen in those without a germline mutation (26.4 vs 12.8, p < 0.01: increased-risk threshold; 27.1 vs 19.0, p = 0.203: high-risk threshold). Trends were demonstrated across all comparisons, but significance was only reached in the largest group. Conclusions: Compared to patients without germline mutations, those with mutations had higher CDRs on MRI but lower DL risk scores. Patients with higher DL risk scores had higher CDRs in those identified as increased or high-risk by DL model, regardless of germline mutation status. Further study to elucidate mechanisms to explain differential performance of DL models in patients with germline mutations is ongoing.
Effect of astragalus polysaccharides (PG2) treatment of adjuvant chemotherapy-induced fatigue in premenopausal patients with breast cancer.
Authors: Rau Kun Ming , Shen Wen-Chi , Chen Shin-Cheh , Wang Cheng-Hsu , Hsieh Ruey Kuen , Hung Chao-Ming , Peng Mengting , Liu Chien-Ting , Chang Yuehshih , Kuo Wen-Ling , Chou Hsu-Huan , Yeh Kun-Yun , Wu Tsung-Han , Wu Chun-Feng , Pei-Hung Chang , Huang Yen-Min , Yu Chi-Chang , Lee Chun-Hui 
Published: June 2023

537 Background: Fatigue is one of the most common symptoms of breast cancer (BC) patients who are receiving adjuvant chemotherapy. Astragalus Polysaccharides (PG2) had been proved to relieve cancer-related fatigue in advanced BC patients. The aim of this study is to evaluate the efficacy of PG2 as a complementary treatment among stage II/III BC patients with adjuvant chemotherapy of epirubicin-cyclophosphamide(EC) regimen in reduction of chemotherapy-induced toxicity and encouraging compliance with chemotherapy. Methods: This double blind, multicenter, phase II trial randomized stage II/III BC patients who would receive adjuvant EC at least 4 cycles to either PG2 500 mg or placebo on day1, 3, 8 every 21 days as the combination. Changes in chemotherapy-related fatigue score (CRFS) was evaluated by the Brief Fatigue Inventory-Taiwanese Form and incidence of Grade 3/4 neutropenia were the primary endpoints. Results: A total of 66 eligible patients were enrolled and equally randomized to PG2 and placebo groups, 30 cases in each group completed this trial. In general, there was no significant difference in the mean change of CRFS and fatigue intensity between the groups. But the CRFS and fatigue intensity in premenopausal-PG2 group were less aggravated after 4 cycles of EC than that of postmenopausal-placebo group. Persisted significance difference in CRFSs from cycle 1 day 5 (PG2: 0.6; Placebo: 1.9, P = 0.023) to cycle 4 day 15 (PG2: -0.3; Placebo: 0.7, P = 0.002). In all population, a lower proportion of patients suffered from grade 3/4 neutropenia from cycle 1 to cycle 4 were observed in the PG2 group compared to the placebo group (78.8% vs. 87.9% in intent-to-treat population). Conclusions: PG2 combined with adjuvant EC significantly improved adjuvant EC-induced fatigue in premenopausal BC patients. PG2 assists these patients with maintaining normal daily life and job activities, also less need of family support during chemotherapy. Furthermore, patients treated with PG2 might have better compliance to complete the whole course of adjuvant chemotherapy. Clinical trial information: NCT03314805 .
Prognostic impact of adjuvant endocrine therapy for estrogen receptor-positive and HER2-negative T1a/bN0M0 breast cancer.
Authors: Takahashi Yuko , Sasada Shinsuke , Kondo Naoto , Hashimoto Hiroya , Terata Kaori , Sagara Yasuaki , Naito Yoichi , Kida Kumiko , Ueno Takayuki , Anan Keisei , Suto Akihiko , Kanbayashi Chizuko , Takahashi Mina , Nakamura Rikiya , Ishiba Toshiyuki , Tsuneizumi Michiko , Nishimura Seiichiro , Hara Fumikata , Shien Tadahiko , Iwata Hiroji 
Published: June 2023

538 Background: Adjuvant endocrine therapy (ET) is the standard of care for Estrogen Receptor (ER)-positive early-stage breast cancer. However, many patients suffer from adverse events associated with ET. The prognosis of patients with T1a/bN0 breast cancer with ER-positive and human epidermal growth factor 2 (HER2)-negative is excellent, and it is not clear whether adjuvant ET should be recommended. Here we evaluate the effect of adjuvant ET for ER-positive and HER2-negative T1a/bN0M0 breast cancer. Methods: This study was a multicenter, retrospective cohort study that evaluated adjuvant ET for patients with ER-positive and HER2-negative T1a/bN0M0 breast cancer. Patients who underwent surgery between 2008 and 2012 in 47 institutions of the Japan Clinical Oncology Group (JCOG) breast cancer group were eligible. We analyzed the cumulative incidence of distant metastasis as primary endpoint using the Gray test model and time to event endpoints (distant disease free survival and overall survival) using log-rank test between patients treated with and without adjuvant ET. We also used Gray test model for the analysis of the cumulative incidence of ipsilateral and contralateral breast cancer. Predictive factors were assessed using the Fine-Gray model and the Cox proportional hazards model. Results: The median follow-up period was 9.2 years. Of 4758 eligible patients (1202 T1a [25.3%] and 3556 T1b [74.7%] diseases), 3991 (83.9%) received adjuvant ET. The 9-year cumulative incidence of distant metastasis was 1.5% with ET and 2.6% without ET (adjusted subdistribution hazard ratio [sHR], 0.54; 95% CI, 0.32-0.93). In the multivariate analysis, the independent risk factors of distant metastasis were no ET, mastectomy, high grade, and lymphatic invasion. The 9-year overall survival was 97.0% and 94.4% (HR, 0.54; 95% CI, 0.38-0.77). Adjuvant ET reduced the incidence of ipsilateral and contralateral breast cancer (9-year rates; 1.1% vs 6.9%; sHR, 0.17; 95% CI 0.11-0.28, and 1.9% vs 5.2%; sHR, 0.33; 95% CI, 0.22-0.49). Conclusions: Adjuvant endocrine therapy significantly reduces distant metastases, however the absolute difference is small for ER-positive and HER2-negative T1a/bN0M0 breast cancer. Furthermore, it reduced ipsilateral and contralateral breast cancer as well. Shared decision making regarding the omission of adjuvant endocrine therapy is crucial, especially in patients with low risk of distant metastasis.