bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical characteristics and real-world progression-free survival (rwPFS) of patients with HER2-positive and hormone receptor (HR)-positive metastatic breast cancer (MBC) initiating endocrine therapy (ET) in combination with the first line of treatment: An analysis of electronic health records in the United States.
Authors: Sanglier Thibaut , Shim Jinjoo , Eiger Daniel , Poppe Raf , Restuccia Eleonora 
Published: June 2022

e13028 Background: Dual HER2 blockade with pertuzumab (P) + trastuzumab (H), combined with taxane induction therapy, is the standard of care for the first-line treatment of patients with HER2-positive MBC. In clinical practice, after achieving clinical benefit with approximately 4–6 cycles of PH + taxane induction, maintenance therapy is continued with PH only until disease progression or unmanageable toxicity. Approximately 50–60% of patients with HER2-positive MBC also have concurrent HR expression and may receive ET in combination with PH. This study investigated the clinical characteristics and outcomes of patients initiating ET combined with PH as maintenance therapy after completion of PH + taxane induction. Methods: We conducted a retrospective cohort study using a nationwide US electronic health record-derived de-identified database (Flatiron Health). Patients with HER2-positive and HR-positive MBC who initiated an ET between Jan 1, 2012 and Feb 28, 2021 with concomitant PH after receiving at least four cycles of first-line PH + taxane induction were included. The index date was the date of ET initiation. Progression data were abstracted from the medical charts. Mortality data were abstracted and combined with patient-level structured data (obituaries and Social Security Death Index). rwPFS was defined as the time from index date until first progression event > 14 days after the index date, or date of death; otherwise, patients were censored on the date of last clinical note abstraction. Baseline characteristics were described using summary statistics, and rwPFS in the maintenance setting was described using a Kaplan–Meier estimator from the index date. Results: Of 24,690 patients diagnosed with MBC in the database, 252 (1%) met the eligibility criteria. All patients were female. The median age was 56.6 years; 149 patients (59%) were diagnosed with de novo MBC; 248 (98%), with estrogen receptor-positive disease; and 182 (72%), with progesterone receptor-positive disease. One hundred ninety-three patients (77%) received an aromatase inhibitor as ET. The median number of taxane cycles received prior to the index date was six. Median maintenance rwPFS was 21.4 months (95% confidence interval = 16.1, 25.3). Conclusions: Given the therapeutic opportunity presented by HER2/HR co-expression and the favorable maintenance rwPFS shown here with PH + ET following taxane induction, the investigation of more potent ETs combined with PH is justified in order to further improve outcomes in first-line HER2-positive/HR-positive MBC.
Quality of life in patients with de novo metastatic breast cancer undergoing locoregional surgery: A prospective observational study.
Authors: Chongxi Ren , Jianna Sun , Lingjun Kong , Kun Mu , Reize Ren 
Published: June 2022

e13044 Background: Breast cancer remains the most frequent type of cancer in women, with de novo metastatic breast cancer (dnMBC) accounting for approximately 10% of patients. Advances in diagnosis and treatment of breast cancer have led to an increase in cancer survival, resulting in quality of life (QoL) improvement. However, there are few reports on whether local treatment improves quality of life for de novo metastatic breast cancer (dnMBC). Aim: To evaluate QoL in dnMBC patients since randomization using scores from the FACT-B health survey. Settings and design: This study was designed as a prospective observational research project and was approved by the Ethics Committee of the Ethics Committee of Cangzhou Clinical College of Integrated Traditional Chinese and Western Medicine of Hebei Medical University (NO.20200212). Methods: Eighty-six patients with dnMBC were randomised to surgery of the primary tumor followed by systemic therapy (surgery group) or to primary systemic therapy without surgery (non-surgery group). QoL analyses covering the results at baseline, 6,12,18,24 and 30 months follow up of 81 (94%) patients, was assessed with the Functional Assessment of Chronic Illness Therapy General Questionnaire, including Breast Cancer Supplement (FACT-B) questionnaires. Inclusion criteria were: did not meet the diagnostic criteria of de novo metastatic breast cancer and patients could not cooperate QoL was assessed by FACT-BTOI variables evaluated at 6 time point. Average FACT-B TOI score was measured by the prorated aggregate score of 37 items from the FACT-B. The Wilcoxon rank sum test was used to compare the differences at each time point. The level for significance was set at p<0.05.All analyses were performed with STATA 16. Results: From 2019 to 2021,a total of 86 dnMBC patients were selected and recruited in Department of breast surgery of our hospitals. Among them, 81 completed FACT-B questionnaires and their data were analyzed. Forty-one (95%) patients in the surgery group and 40 (93%) in the non-surgery group were included in the QoL analyses. A total of 362 QoL questionnaires were analyzed, 81(100%) at baseline, and 73(90%), 64(79%), 58(72%), 47(58%), 39(48%) at 6,12,18,24, and 30 months, respectively. The average FACT-B TOI scores showed no statistically significant difference between the two groups at each time point, with a P value of 0.09 at baseline, and 0.47,0.67,0.36,0.45,0.34 at 6,12,18,24, and 30 months, respectively. No significant difference was found in QOL evaluation between the two groups. Conclusions: Our prospective randomized trial showed that compared with non-surgery counterparts, locoregional surgery does not improve QoL of patients with dnMBC. Clinical trial information: 20200212.
The modified glasgow prognostic score (MGPS) and the mortality prediction MODEL II (MPM II) CAN predict mortality in patients with breast cancer admitted to intensive care: A retrospective cohort study.
Authors: Olmez Omer Fatih , Tunay Burcu , Bilici Ahmet , Bayramgil Ayberk , Çavuşoğlu Güneş Dorukhan , Oz Huseyin 
Published: June 2022

e13055 Background: We aimed to examine whether inflammatory markers and various risk scoring systems could be utilized to predict the prognosis of breast cancer patients hospitalized in the intensive care unit. Methods: In this retrospective cohort study, we evaluated 71 breast cancer patients followed and treated by the Medical Oncology Department of Medipol University Faculty of Medicine who were admitted to the intensive care unit at any stage of their treatment between 2014 and 2020. In addition to scoring systems developed to assess prognosis in the ICU, we recorded and calculated various inflammation-related markers. All data were compared between groups formed according to survival status. Results: The median age was 58 (range: 33-90) years. Thirty-seven (52.1%) patients had died and 34 (47.9%) patients had survived. Neutrophil lymphocyte ratio (p = 0.021), Modified Glasgow prognostic score (p < 0.001), APACHE II score (p < 0.001) and MPM II (admission) (p < 0.001) were significantly higher in the exitus group than in the survivors. Lymphocyte monocyte ratio (p = 0.030) and prognostic nutritional index (p = 0.004) were significantly higher in the discharged group than in the exitus group. When we evaluated performance of the prognostic scores to predict mortality, we found APACHE II score (AUC: 0.939, 95% CI: 0.888 - 0.990), MPM II-Admission (AUC: 0.936, 95% CI 0.880 - 0.992) and mGPS (AUC: 0.727, 95% CI: 0.600 - 0.854) had the highest area under curve values. Multivariable regression revealed that longer chemotherapy duration (≥2 weeks), having an mGPS score of 2 points, and high MPM-II (≥36 points) were independently associated with mortality. Conclusions: Among the inflammatory markers and scores examined, mGPS and MPM-II were found to be independently associated with mortality in breast cancer patients hospitalized in the intensive care unit. In addition, patients with longer chemotherapy duration had a higher risk of mortality, but this result was limited by various possible confounders.
Institutional review of African American (AA) patients with metastatic triple-negative breast cancer.
Authors: Vobugari Nikitha , Chitalia Ami 
Published: June 2022

e13059 Background: Atezolizumab+ Abraxane (Ate+Abx) was approved as 1st line treatment in metastatic TNBC based on IMPASSION (IM) 130 trial and was subsequently withdrawn per IM131 trial. Treatment of mTNBC remains challenging. Pembrolizumab with chemotherapy received accelerated approval based on Keynote-355. Poor outcomes among AA patients (pts) are linked to biological differences, BRCA1/2 mutations, obesity, and socioeconomic barriers. In TNBC clinical trials, AA pts continue to be underrepresented, e.g., 5.8% (26) in IM130 and 4.9% (21) in IM131. Our cancer center sees over 300 new BC pts a year, and at least 50% identify as AA. Here we examine our institutional experience. Methods: IRB-approved retrospective database search was conducted between 01/01/2019- 04/16/2021 to identify 11 pts treated with Ate+Abx for mTNBC at Medstar Washington Hospital Center, DC. Demographic variables manually extracted were age, BMI, insurance type and outcomes. Results: 10/11 (91%) pts were AA with lines of therapy ranging 1-6. 20% (2/10) showed partial response (PR) on 3-month (M) interval imaging per the RECIST 1.1 scoring. PD occurred in 6/10 (60%) of pts, although PD-L1 was positive in 90% (9/10) pts. Time to progression (TTP) was 1-7 M (median 3M) compared to TTP of 5.59 to 7.46M (median 7.16M) for all races in the IM130 study. Autoimmune colitis, peripheral neuropathy, and fatigue were notable adverse effects (AEs). 2/10 (20%) pts discontinued treatment due to AEs. Colitis and neuropathy in IM130 were <1%. Mean age at drug initiation was 52.2 vs. 55 years in IM130, indicating earlier onset of mTNBC in the AA population. Conclusions: Trends of higher PD and earlier TTP were noted in our AA pts. Young age at metastasis, high number of previous lines of therapy, high number of metastatic sites, and obesity were noted amongst our AA mTNBC pts. Positive PD-L1, BRCA mutations, metastatic sites, BMI, or insurance type did not correlate with outcomes. Pts with PR vs. PD were not different in terms of insurance, metastasis sites, and BMI. Differences in AEs are noted; however, the small pt population size and lack of a control group are limitations. While the FDA has withdrawn Ate from trials for mTNBC, this study suggests a need for more AA pts to be included in clinical trials for TNBC. Lack of health care access, insufficient education, inadequate recruitment, and distrust of the medical system are contributing factors that require continued efforts.[Table: see text]
Translational relevance of HER2-low expression in triple-negative breast cancer: A retrospective single-center study.
Authors: Mufti Suhail Sayeed , Sanghavi Niyati , Ramaswamy Veena , Naik Radheshyam , Ajaikumar Basavalinga Sadasivaiah 
Published: June 2022

e13061 Background: In current clinical practice, the decision of using anti-HER2 targeted agents for breast cancer is based primarily on HER2 protein overexpression, assessed using immunohistochemistry and/or HER2 gene amplification on FISH assay(2018 ASCO/CAP guidelines). It is increasingly being recognized that HER2-negative breast cancer is characterized by a wide spectrum of HER2 expression, particularly important for the triple-negative breast cancer (TNBC) group, the treatment options for which are far less compared to hormone receptor-positive tumors. HER2-low breast cancer (HER1+ or 2+, without gene amplification) is an emerging subtype with differing clinicopathologic and prognostic implications. There is accumulating evidence that HER2-negative tumors may switch to HER2-low status and vice versa at tumor recurrence. The development of newer drug classes like antibody-drug conjugates and immunotherapy have created a window of opportunity for this sub-category of breast cancer. Methods: We aimed to evaluate HER2 0/normal and HER2-low expression in TNBCs, their clinicopathological characteristics, and prognostic significance. Clinical and laboratory data for 207 TNBC cases (184 non-metastatic and 23 metastatic) diagnosed between February 2010 and December 2019 was available for analysis and cases were followed up until December 2021. Androgen receptor (AR) immunohistochemistry was performed on available FFPE blocks. Results: Non-metastatic TNBCs: Median age was 50 (SD 11.77; range 23 to 82) years. 91.9% of HER2-low cases were more than 40years old compared to 70.1% of HER2 0 cases, p = 0.006. 79.9% were HER2 0, 14.1% were HER2 1+, and 6% were HER2 2+. 30.7% (39/127) of cases were AR+. Compared with HER2 0, HER2-low cases exhibited a lower histological grade (Her2 0 - Grade 3: 72.7%, Grade 2: 27.3%; Her2-low- Grade 3: 57.1%, Grade 2: 40%, Grade 1: 2.9% p=0.048). Compared with HER2 0, more of HER2-low cases were AR+ (For Her2 0 26.5% were AR+; For Her2-low 48% were AR+, p=0.036). There was no significant difference in disease-free survival between the two groups. There was no significant difference in overall survival (OS) between the two groups (Her2 0- Mean: 102.0 months, Median: Not achieved; Her2-low - Mean: 69.60 months, Median: 77.4 months p=0.73). Within the Her2-low group, patients ≤40 years had a median OS of 44.3 months. Metastatic TNBCs: Median age was 47 (SD 10.38; range 30 to 74) years. There was no significant correlation between the clinicopathological characteristics. No significant difference in OS was seen (Her2 0- Median: 44.9 months; Her2-low- Median: 24.3 months, p=0.20). Conclusions: The non-significant trend towards a lower survival for Her2-low TNBCs, coupled with a surprisingly lower histologic grade and a higher AR positivity needs to be further evaluated in larger studies. Further translational research to optimize treatment for this subgroup is needed.
Phase I trial combining pembrolizumab and doxorubicin in patients with metastatic triple negative breast cancer.
Authors: Yuan Yuan , Ge Xuan , Yost Susan Elaine , Lee Jin Sun , Frankel Paul Henry , Ruel Christopher , Cui Yujie , Murga Mireya , Tang Aileen , Martinez Norma , Karimi Misagh , Somlo George , Mortimer Joanne E. , Waisman James Ross 
Published: June 2022

e13071 Background: Pembrolizumab (pembro) in combination with chemotherapy (chemo) has recently become standard of care in patients with programmed death-ligand 1 (PD-L1) positive metastatic triple negative breast cancer (mTNBC). Optimal chemo partner with pembro remains debatable. The current phase I study evaluated the safety and efficacy of doxorubicin (dox) + pembro in anthracycline-naïve mTNBC patients (NCT02648477). Methods: Patients with mTNBC, no prior anthracycline, and ≤2 lines of prior chemo for metastatic disease were enrolled. Patients received pembro 200mg IV and 50-60 mg/m2 dox IV every 3 weeks x6, followed by pembro maintenance until progression or unacceptable toxicity. The primary objectives were safety and objective response rate (ORR per RECIST 1.1). For the safety lead-in, we employed a 3-at-risk rolling design. Results: Ten patients were accrued between March 2016 and November 2019. The trial stopped early due to poor accrual. The first 3 patients received dox at 50mg/m2 without dose limiting toxicities and dose was escalated to 60mg/m2 for the remaining patients. Median age was 62 years (range 41-87). Grade ≥ 3 AEs were: 4 neutropenia, 2 dyspnea, 2 fatigue, 1 oral mucositis, 1 hyponatremia, 1 acidosis, 1 alkalosis, 1 hypotension and 1 respiratory failure. One patient (age 87) received 1 dose of therapy, developed neutropenia and respiratory failure which led to death, and was not eligible for response assessment. 1 patient did not have RECIST measurable disease. Two patients had dose delay (1 G3 neutropenia and 1 G2 upper airway infection). 1 patient had dose reduction due to G3 fatigue. Immune toxicity was consistent with known pembro toxicity. Of 9 evaluable patients, responses were : 1 CR, 3 PR, 2 UPR, 2 SD and 1 PD, which translated to a best ORR of 67% (95% CI, 13.7%, 78.8%). CBR at 6 mo was 56% (95% CI 21.2%, 86.3%). Median follow-up time was 34.6 mo (range 14.5 - 45.4 mo). Median PFS was 5.2 mo (95% CI 4.7, NA); and median OS was 15.6 mo (95% CI 13.3, NA). Eight patients had PD-L1 (22C3) testing: 4 positive and 4 negative. No association between the PD-L1 status and response was observed. Conclusions: The combination of pembro+dox was well tolerated and had modest activity in anthracycline-naïve patients with mTNBC. The finding needs to be further confirmed with future study. Clinical trial information: NCT02648477.
Characteristics of disease course in patients with locally advanced primarily inoperable HER2-negative breast cancer.
Authors: Samaneva Natalia Yu. , Vladimirova Liubov Yu , Storozhakova Anna E. , Kalabanova Elena A. , Kabanov Sergey N. , Tishina Anna V. , Gaysultanova Yakha S. , Teplyakova Maria A. , Lyanova Aza A. , Abramova Natalia A. , Ryadinskaya Ludmila A. , Udalenkova Irina A. , Tikhanovskaya Natalia M. , Popova Irina L. , Sergeeva Marina M. , Vashchenko Larisa N. 
Published: June 2022

e13072 Background: Breast cancer (BC) is the most common cancer in women worldwide. The purpose of the study was to analyze immediate and long-term results of treatment in patients with locally advanced primarily inoperable HER2-negative breast cancer depending on the time of progression. Methods: The study included 104 women with locally advanced primarily inoperable HER2-negative breast cancer who developed an early disease progression within 6 to 12 months after standard combination treatment. The blood levels of circulating tumor cells (CTCs) were measured in all patients during the progression stage. Results: An analysis of the overall (OS) and event-free (EFS) survival showed that median EFS in patients with luminal B subtype was 9 months, in patients with triple-negative (TNBC) subtype 8 months. EFS at 6 months was 87.5% in luminal B subtype and 79.4% in TNBC, p = 0.37985. Median OS in patients with luminal B subtype was 25 months, in patients with TNBC 26 months. One-year OS was 100% in luminal B subtype and 93.9% in TNBC, p = 0.138. 2-year OS was 54.2% in luminal B subtype and 55.9% in TNBC, p = 0.697. 3-year OS was 37.5% in luminal B subtype and 41.2% in TNBC, p = 0.639. CTCs were detected in all patients, with higher levels in patients with luminal B subtype than in TNBC patients. HER+ CTCs were found in 30% of patients with luminal B subtype but not registered in patients with TNBC. Such results were obtained for the first time. Conclusions: The absence of significant differences demonstrated the aggressive disease course in patients with luminal BC with identified primary hormone resistance, similar to the TNBC course. The results should be taken into account when predicting the course of the disease and developing further treatment tactics.
The effects of bone targeted therapy in patients with greater than two years survival with metastatic breast cancer and bone metastasis.
Authors: Jayan Athira , Raghavendra Akshara Singareeka , Bassett Roland L. , Barcenas Carlos Hernando 
Published: June 2022

e13076 Background: Administration of bone targeted therapy such as zoledronic acid (ZA) or of denosumab (D) decrease the risk of skeletal related events (SRE) such as radiation to the bone, pathological bone fractures, and spinal cord compression in patients with a diagnosis of metastatic breast cancer (MBC) and bone metastasis. As these patients continue to live longer it is unknown what are the impacts from long-term administration of ZA or D among those who live longer than 2 years. Methods: This was a retrospective analysis of patients with MBC and bone metastasis who lived for more than 2 years since diagnosis and received treatment at MD Anderson Cancer Center for MBC in addition to ZA and/or D between 2015 and 2021. Patient demographics, date of diagnosis, tumor characteristics, bone targeted agent treatment plans and SRE were extracted from the institutional database and electronic health records. We defined 3 patterns of receipt of bone targeted therapy: Pattern A: ZA every 3-4 weeks; Pattern B: D every 4-6 weeks; Pattern C; D every 4-6 weeks for a period followed by every 3 months. The association between these patterns and SRE was assessed using Fisher’s exact test. Results: We included 178 patients: Pattern A with 49 patients, Pattern B with 85 patients, and Pattern C with 44 patients. The proportion of patients who suffered a SRE in Patterns A, B, and C were 22.4% (11/49), 20% (17/85), and 21.4% (10/44). There was no statistical difference in the proportion of SRE between these three groups (p = 0.92). Conclusions: We did not observe a difference in the rate of SRE between the three different patterns of bone targeted therapy administration in patients with MBC and bone metastasis. Other treatment patterns will be considered in future analysis.[Table: see text]
Evaluating efficacy on tumor biopsy tissue ex vivo before treatment for equitable cancer care.
Authors: Patel Heli K. , Punjani Zeenia , Charania Areesha A. , Patel Zeelu H. , Papachristou Georgios , Contreras Carlo M. , Tsung Allan , Budhwani Karim I. 
Published: June 2022

e13502 Background: Nearly half the world will be diagnosed with cancer. Each year, > 1.7 million new cancers are diagnosed in the US. Worse, systemic therapy turns out to be ineffective in 70% of patients because those drugs do not match the patient’s tumor, imposing a substantial physical, emotional, and financial burden. Each tumor’s distinct composition and heterogeneity can result in diverse responses to the same treatment. There is a critical and urgent need to develop ex vivo personalized cancer models that match patients with the right treatment – before treatment. Here we present a low-cost ex vivo personalized cancer model to rapidly evaluate effectiveness of various therapeutics on intact core biopsy tissue obtained from a patient’s tumor. Objective: The goal of this study is to deliver multiple isolated fluid streams to spatially distinct regions (SDRs) of intact core biopsy specimens for evaluating efficacy of multiple anticancer agents simultaneously. Methods: Core biopsies were generated from xenograft and resected human tumor tissue using 18-gauge and 20-gauge spring-loaded biopsy systems. Xenografts were established using cell lines with known sensitivity and resistance profiles. Fluid streams with anticancer agents, nucleic acid stains, and mock drugs were delivered to spatially distinct regions (SDRs) on intact core biopsy specimens in our patented Personalized Oncology Efficacy Test (POET) lab-chip bioreactors. High content imaging and custom image processing algorithms were used to measure differential activity. Results: No lateral fluid surface conduction, and only minimal lateral diffusion, was observed up to 200 μm deep in tissue. Extent of observed lateral diffusion was within operational parameters of the bioreactor. Integrity of spatially distinct regions on intact core tissue was maintained. Differential activity from anticancer agents compared to mock drugs was observed and quantitatively measured using custom image processing algorithms. Conclusions: The NCI warns that “current methods to assess potential cancer treatments are cumbersome, expensive, and often inaccurate.” A personalized medicine approach, based on efficacy observed on tissue directly from the patient’s own tumor, is fundamentally better than the current approach. Low-cost next generation ex vivo cancer models that can rapidly match treatments to tumors, such as POET, could transform cancer treatment and make a significant impact on the lives of patients.