bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety, efficacy and survival outcome of Ado-trastuzumab emtansine (T-DM1) in patients with metastatic HER2-positive breast cancer: An Indian experience.
Authors: Gogia Ajay , Gupta Anshul , Deo S.V.S. , Sharma Dayanand , Mathur Sandeep 
Published: June 2022

e13008 Background: Ado-trastuzumab emtansine (T-DM1) is the standard of care for patients with advanced HER2 positive breast cancer (BC) patients who progress on the first line anti-HER2 therapy or relapse within 6 months of adjuvant trastuzumab. There is a lack of data regarding the safety and efficacy of T-DM1 in the Indian population. Methods: This retrospective study aims to evaluate the efficacy and toxicity of T-DM1 in advanced HER2 positive female BC patients, registered at All India Institute of Medical Sciences, (AIIMS) New Delhi, India, between the years 2015-2021. The response was evaluated by Response evaluated Criteria in Solid Tumors(RECIST 1.1)guidelines. Progression-free survival (PFS) was calculated from the beginning of treatment with T-DM1 until disease progression or death from any cause. Overall survival (OS) was calculated from the beginning of treatment with T-DM1 until death from any cause. Results: This study included eighty patients with a median age of 49 years (27-73). Forty-four (55%) were premenopausal and hormone receptor positivity (either ER or PR) was found in 36 (45%) cases. The ECOG performance status was 0-1in 80% of patients. De- novo metastatic disease was found in 38(47.5%) cases whereas the remaining 42 (52.5%) patients were diagnosed with early or locally advanced disease and later become metastatic. The sites of metastasis were lungs in 26 (32.5%), brain in 23 (28.7%) liver in 23 (28.7%), bones in 18 patients (22.5%), lymph nodes in 15(18.7%), cutaneous and other rare sites in 8(10%) cases. All patients had received trastuzumab in the prior line of treatment and 18 (22.5%) patients had also received pertuzumab along with trastuzumab. The median number of T-DM1 cycles given was 9 (range 3-35). The overall response rate was 80%, 8(10%) achieved a complete response, 36 (45%) had a partial response, and 12 (15%) patients had stable disease. The Grade 3/4 toxicities were observed in 20(25%) cases and these were: thrombocytopenia 16 (20%), fatigue 10 (12.5%), transaminitis 10(12.5%), anemia 2 (2.5%), and peripheral neuropathy in 2 (2.5%) cases. Dose delay, interruption, and modification were observed in 25 (31.2%) cases. Within the median follow-up period of 18 months, the median PFS was 10 months and OS was 27 months. Hormone status (ER/PR) and prior pertuzumab therapy did not influence the outcome. Conclusions: This is the first study from the Indian subcontinent on T-DM1. It is safe and effective in our population and has shown comparable outcomes with the available literature however, higher rates of thrombocytopenia were observed.
Liquidscan mediated HER2 amplification detection in patient samples study.
Authors: Muller Rolf , Yeung Kay , Jones Stephenie , Brandt Christopher , Funari Vincent Anthony , Agersborg Sally , Muller-Cohn Judy , Dickerson Janet 
Published: June 2022

e13016 Background: Overexpression of HER2 serves as an oncogenic driver in breast cancer which can result in tumor progression and distant metastases. Amplification or overexpression of HER2 occurs in approximately 15–30% of breast cancers and serves as a therapeutic, prognostic and predictive biomarker. There have been tremendous advances in HER2+ breast cancer management and there is an need to identify patients with HER2+ early breast cancer who may benefit from de-escalation or escalation of treatment. In addition, selection of HER2 therapies beyond the 2nd line setting for HER2+ metastatic breast cancer is currently unclear. Therefore, rapid monitoring tests for treatment response are needed. Liquid biopsy may provide a cost effective, sensitive, and non-invasive approach to monitor response. Methods: Whole blood (8ml) from 20 consenting patients with confirmed stage 3 or 4 metastatic breast cancer with clinical Her2 status identified by solid tissue biopsy (10 HER2+ and 10 HER2-) were collected. Circulating tumor cells were isolated on the LiquidScan system, were probed by HER2 FISH, analyzed using automated and visual microscopy. Results: Protocols were optimized to obtain morphology and cellularity of the tumor cells allowing conclusive HER2 identification for all samples. All samples from patients identified as Her2+ by standard invasive solid tumor biopsies could be identified (100% concordance), whereas for one sample that was reported as HER2-, cells were identified with the liquid biopsy having HER2+ FISH morphology. Further molecular analysis on this patient is under way. Conclusions: We were able to demonstrate that non-invasive liquid biopsy with the LiquidScan identifies HER2 status. The method has high concordance with conventional solid biopsy approach and may be a promising for patient monitoring. We will expand to larger sample sets to explore the full capacity of liquid biopsy to monitor and diagnose HER2 related diseases.
Platelet-to-Lymphocyte ratio (PLR) as a predictive marker in HER2 positive metastatic breast cancer patients treated with first-line trastuzumab therapy.
Authors: Fang Zi-Ru , Shen Xia-Bo , Wu Jia-Yi , Chen Ke-Yu , Shao Xi-Ying , Wang Xiaojia 
Published: June 2022

e13024 Background: The immune system reveals to play a pivotal role in HER2 positive breast cancer responsiveness to trastuzumab therapy. The platelet-lymphocyte ratio (PLR) is representative blood markers of systemic inflammatory responses. It is suggested as an immunity biomarker in gastric, lung cancer and other cancers, but is less well known in breast cancer. The aim of this study is to investigate the predictive role of PLR in HER2 positive metastatic breast cancer patients treated with first-line trastuzumab therapy. Methods: This study retrospectively includes 287 HER2 positive metastatic breast cancer patients with first-line trastuzumab therapy in Cancer Hospital of the University of Chinese Academy of Science from January 2010 to November 2021. The Peripheral blood cell count of these patients before trastuzumab treatment is evaluated to calculate PLR. All patients are separated into PLRhigh or PLRlow cohort according to cut-off value defined as median value. Median value of PLR is 154.5, more than 154.5 is defined by PLRhigh, otherwise defined as PLRlow. Kaplan–Meier curves is performed to assess progression-free survival (PFS). Univariate and multivariate analyses were performed using a logistic regression model. Results: Of 287 patients, 228 patients’ peripheral blood cell count were available. 114 patients are PLRhigh and 114 patients are PLRlow. Patients with PLRhigh achieved a significantly worse PFS compared to those with PLRlow (median PFS: 8.47 months vs.9.92 months, HR:1.475, 95% CI:1.068-2.038, P = 0.014). Besides, mean corpuscular volume (< 89.2fL), lymphocyte (< 1.3), mean hemoglobin (< 30PG) are also related to worse PFS ( P= 0.003,0.033,0.055,respectively). Importantly, PLRhigh, mean corpuscular volume, remain independent predictors in the multivariate COX analysis (HR 0.689,95%CI 0.493-0.962, P = 0.028;HR1.646,95%CI 1.177-2.302, P = 0.004). Conclusions: Patients with pre-treatment PLRhigh showed less sensitivity to trastuzumab therapy for metastatic breast cancer patients independent of other molecular characteristics. The pre-treatment PLR levels might serve as a predictive biomarker for HER2 positive breast cancer with trastuzumab therapy.
Treatment sequence for hormone receptor-positive HER2-negative advanced breast cancer: Results of a retrospective analysis of Russian patients diagnosed with aBC in 2014-2021.
Authors: Stenina Marina , Zhukova Lyudmila , Stroyakovskiy Daniil , Karaseva Vera V. , Tjulandin Sergei 
Published: June 2022

e13032 Background: CDK4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) have dramatically changed therapeutic landscape of hormone receptor-positive HER2-negative advanced breast cancer (HR+ HER2- aBC). There are three iCDK4/6 in Russia, which are available and included into the clinical guidelines as a preferred first line treatment option beginning since 2018. The aim of this study was to assess evolution of treatment approaches to HR+ HER2- aBC and identify demographic and disease characteristics in correlation with available groups of therapy (chemotherapy, endocrine therapy ±mTOR inhibitors/ CDK4/6i). Methods: Аdult patients diagnosed with de novo or recurrent HR+ HER2- aBC in 2014-2021 identified in outpatient departments of Moscow state oncology hospitals were included into our non-interventional, descriptive, retrospective cohort study. Primary objective of this real-world study was to describe the rate of CDK4/6i usage in the first line setting. As a secondary objective, we describe patient and disease characteristics in iCDK4/6 group, as well as in the endocrine monotherapy and chemotherapy groups. Results: From the cohort of 1000 patients (full-set analysis population) 874 cases were selected, who received treatment since 2018. 45.9% (95% CI 42.6, 49.2) patients were treated with CDK4/6i in combination with endocrine therapy in the first-line setting. From them in the subgroups of patients with or without visceral metastases 50.5% (95% CI 45.5, 55.5) and 42.1% (95% CI 37.7, 46.5) were treated with CDK4/6i in the first line setting, respectively. Among 874 cases 78.0% (95% CI 75.3, 80.7) patients received endocrine therapy ± targeted therapy; in the subgroups of patients with or without visceral metastases 69.5% (95% CI 64.9, 74.1) and 84.9% (95% CI 81.7, 88.1) were treated with endocrine therapy ± targeted therapy in the first line setting, respectively. Conclusions: Endocrine therapy is a predominant therapeutic option in the first line setting for HR+ HER2- aBC. Clinical trial information: NCT04852081. [Table: see text]
Factors associated with CDK 4/6 inhibitor use for patients with advanced, hormone positive, HER-2-negative breast cancer.
Authors: Weldon Christine B. , Trosman Julia R. , Li Xi , Gradishar William John 
Published: June 2022

e13038 Background: “CDK4/6 inhibitors have emerged as a standard of care for patients with HR-positive, HER2-negative advanced breast cancer.” Wayne Kuznar ASCO Reading Room 10.29.2019. Within an academic institution there were concerns that CDK 4/6 inhibitors were not utilized as indicated. We conducted an analysis of CDK 4/6 inhibitor use for patients with advanced, hormone positive, HER2 negative breast cancer to assess factors associated with CDK 4/6 inhibitor use. Methods: We conducted a retrospective medical records review of patients treated at an academic medical center from 01/1/2015 to 9/30/2020 with stage IV, hormone positive and HER2 negative breast cancer. We compared characteristics for patients that received one or more CDK 4/6 inhibitors to those who did not receive any CDK 4/6 inhibitors. Statistical analysis used Fishers exact 2-sided test via GraphPad QuickCalcs website. Results: 162 patient records met inclusion criteria, 73% (119/162) received one or more CDK 4/6 inhibitors as part of their care. The average age of patients who received CDK 4/6 inhibitors was 59.9, as compared to 66.9 average age in patients who did not receive CDK 4/6 inhibitors. Patients who received CDK 4/6 inhibitors were more likely to have received chemotherapy (Table, p < 0.0001), have a family history of cancer (p < 0.0001) and have a Charlson comorbidity index of 5 or more (p = 0.0005). Patients receiving CDK 4/6 inhibitors trended more likely to have used tobacco at some point (p = 0.09). Patients who did not receive CDK 4/6 were more likely to have refused, moved or be in hospice (p = 0.003). There were no statistically significant differences based on patient status, timing of diagnosis or timing of first hormone receptor positive dose. Further analysis of the 27% (43/162) of patients not receiving CDK 4/6 inhibitors identified that 40% (17/43) died, 28% (12/43) had Charlson comorbidity score of 7 or more, 19% (8/43) refused treatment. The remaining 14% (6/43), 4% (6/162) of entire population, did not have a clear reason for not getting CDK 4/6 inhibitors, of those 4 received hormone therapy, 1 received chemotherapy and 1 received both. Conclusions: In a retrospective analysis of patient records, we found consistent use of CDK 4/6 inhibitors for indicated patients. Patients who did not receive CDK 4/6 inhibitors died, had a high co-morbidity index, or refused treatment. Only 4% of the population analyzed did not have a visible reason to not receive CDK 4/6 inhibitors.[Table: see text]
Comparison of DNA sequencing, immunohistochemistry, and in-situ hybridization techniques to determine HER2 status in metastatic breast cancer patients.
Authors: Lal Lincy S. , Milne Dana , Walker Mark S. , Kovach Marina 
Published: June 2022

e13045 Background: Limited studies exist comparing methods for HER2 status determination using real-world data (RWD). Results of metastatic breast cancer (MBC) patients with Next Generation Sequencing (NGS) within the ConcertAI Genome360 dataset with DNA sequencing were compared to the standard immunohistochemistry (IHC) or in-situ hybridization (ISH) or both IHC and ISH for HER2 status. Methods: Patients diagnosed with MBC, with HER2 status determined with NGS DNA sequencing, IHC, or any of the ISH tests, by various laboratories within 2 months of each other, from August 19, 2011 to March 9, 2021, were analyzed. Patients were classified as positive, negative, or equivocal based on each of the testing methods. Comparisons were made between DNA sequencing and IHC results, DNA and ISH results, and DNA and IHC and subsequent ISH results. Results: The study sample included 252 patients (99% female, mean age [SD] of 62 [11.93]) with 382 test combinations as follows: 220 (58%) with DNA sequencing and IHC results, 127 (33%) with DNA sequencing and ISH results, and 35 (9%) with DNA sequencing and IHC and ISH results. Of the 220 combinations with DNA sequencing and IHC results, 15 were uniformly considered HER2+, 160 HER2-, and 1 equivocal, while 44 differed in the results, resulting in 80% match rate. Of the 127 combinations with DNA sequencing and ISH results, 14 were HER2+ and 96 HER2-, while 17 differed, resulting in 87% match rate. Of the 35 combinations with DNA sequencing and IHC and ISH, 3 were HER2+ and 26 were HER2-, while 6 differed, resulting in 83% match rate. Match rate was significantly higher for patients with negative results, than positive results. Specimen type, site, and type of expression had no impact on match rates. Conclusions: RWD indicate relatively high level of match rate among DNA sequencing, IHC, and ISH results in MBC patients. However, 13-20% of the combinations did not match. For these patients, mechanisms to reach consensus need to be explored to determine optimal treatments.
Clinical outcome and characteristics of Turkish breast cancer patients during SARS-Cov-2 pandemic: Single center experience.
Authors: Isıklar Aysun , Soyder Aykut , Gumusay Ozge , Basaran Gul 
Published: June 2022

e13049 Background: COVID-19 pandemic has placed an unprecedented burden on health care system. Patients with cancer are reported to have a higher risk of infection and a more complicated COVID-19 course. Breast cancer (BC) is the most common cancer in women in Turkey. We aimed to evaluate the clinical outcome of breast cancer patients who had a diagnosis of COVID-19. Methods: Medical records of breast cancer patients who had COVID-19 between July 2020-2021 at our center were retrospectively rewieved. We recorded pathological, clinical, treatment characteristics, and the clinical outcome of COVID-19 infection. Results: A total 82 breast cancer (BC) patients had COVID-19 between July 2020-2021. All patients were female, with a median age of 49 (43-64 years). Eighty-five % of all patients had early and 14.6% had advanced stage BC. COVID-19 had a mild clinical course in 73%, hospitalization was required in 27% of patients. Twenty-five patients who required hospitalization were discharged. Three (3,6%) patients who had heavily pretreated metastatic breast cancer, required ICU and died due to COVID-19. Metastatic disease (p 0.002) and chemotherapy within 7 days of COVID-19 diagnosis (p = 0.024) have been associated with increased mortality. Conclusions: In our breast cancer cohort, most patients had a mild COVID-19 course. Advanced disease and chemotherapy within 7 days of diagnosis were the two risk factors for increased mortality.
Risk of seizures in a population of women with BRCA-positive metastatic breast cancer in the United States.
Authors: Sebby Wendy , Kilpatrick Ryan , Mazumder Debasish , Ghosh Anirban , Papademetriou Eros , Potluri Ravi , Liede Alexander 
Published: June 2022

e13056 Background: Real-world evidence on the risk of seizures in subgroups of women with advanced breast cancer (BC) across treatment-related or clinical subtypes is limited. A large electronic health record (EHR) dataset was used in this study to measure incidence and risk factors for seizures among women diagnosed with BRCA-associated metastatic BC (mBC). Methods: We used the Optum EHR database, which includes natural language processing (NLP) abstracted details from physicians’ notes, to identify a cohort of females with mBC (based on secondary malignancy ICD-9/-10 codes or NLP) diagnosed between 2008-2018 with 12 months of pre-index history, evidence of BRCA mutation positive (BRCA+) status, and no history of prior cancers. Analyses were stratified by the overall BRCA+ cohort and 4 molecular phenotypes: HER2+/HR-, HER2-/HR+, HER2+/HR+, and triple negative BC (TNBC). Incidence of seizures was measured using diagnosis codes and NLP, and incidence rates were calculated as the number of women with a seizure over the period from metastasis to first seizure or the end of follow up. Incidence rates were also measured across the following risk factors: PARP inhibitor use, diagnosed brain metastases, history of seizures, and anticonvulsant use before BC diagnosis, while controlling for age at metastasis, number of prior lines, and metastasis location. Results: Of the 7,941 BRCA+ patients identified, 27.8% had ≥1 seizure during mean follow-up of 2.35 years, with an incidence rate of 11.83 (95% CI: 11.35-12.33) per 100 person-years. The HER2-/HR+ and TNBC subgroups had the lowest and highest seizure incidence rates, respectively (10.94 [95% CI: 10.23-11.71] and 16.83 [95% CI: 15.34-18.46]). Kaplan-Meier analysis of time to seizure showed that HR- phenotype was associated with a longer time to first seizure. Patients with diagnosed brain metastases or a history of seizures had higher seizure incidence rates compared to patients without the respective risk factors (42.55 [95% CI: 28.59-63.30] vs 5.26 [4.20-6.59] and 34.76 [23.24-52.01] vs 6.35 [5.11-7.88]). Incidence trended higher with PARP inhibitor use, but patient numbers were low. Conclusions: Using both diagnosis codes and NLP, this study shows that seizures occur frequently in women with BRCA+ mBC, even those without diagnosed brain metastases. The seizure incidence rates by phenotype underscore their relevance when assessing seizure risk. These findings may have implications for clinical practice and for assessing benefit-risk ratios of novel agents.[Table: see text]
A preliminary review of adoption of new HCPCS codes for NGS in CMS claims.
Authors: Smart Dave , Moore Wendy , Fosvig Susanne Munksted , Bloom Kenneth Joel 
Published: June 2022

e13522 Background: Adequate reimbursement is considered a prerequisite for adoption of new diagnostic technologies that facilitate patient access to better treatments. Detailed longitudinal investigation of the adoption of new HCPCS codes and the factors influencing it are scarce, although the availability of large-scale claims databases should facilitate such studies. We examined claims for three CPT codes used for next generation sequencing (NGS): 81445, 81450 and 81455 in a large database of claims data from CMS and attempted to correlate presumptive drivers of test adoption such as coverage decisions and payments with test volume. Methods: CMS claims data were accessed using CMS’ Virtual Research Data Center (VRDC) under data use agreement 50486. Any claim with a CPT code of 81445, 81450 or 81455 was extracted from the data and analysed using SAS Enterprise Guide with results summarised in Microsoft Excel. Data relating to national/local coverage determinations were located by internet searches. Results: Test volumes for all 3 codes showed significant variability, including a large decrease around Q1-2 of 2020, likely due to the COVID-19 pandemic. Utilization of the 3 CPT codes varied by patient diagnosis. Details of the top 5 diagnoses for each CPT are given in the Table. The top 30 diagnoses for each CPT code accounted for 80.33%-88.45% of patients. Conclusions: Utilisation of NGS testing from 2016-2021 was highly variable, confounding attempts to match potential drivers to changes in monthly test volumes. A relatively small number of conditions accounted for >80% test use. Increased use of 81445 and 81450 from 2019 onwards may be related to CMS LCD issued in March 2018, suggesting that it can take 8-9 months or more for a LCD to filter through to testing practice. Decreases in test volume around March 2020 coincide with decreased patient presentation and testing for cancer because of the COVID-19 pandemic indicating that factors beyond reimbursement can significantly affect test use. Changes in reimbursement or adoption of proprietary lab analysis (PLA) codes covering specific NGS tests may have caused the drop in test volumes in the latter half of 2021. This study demonstrates that determination of factors affecting adoption of a test technology can be problematic due to wide variation in claims over a relatively short space of time. However, determination of these factors is important as they ultimately affect patient access to testing and potentially to therapy. [Table: see text]
Preoperative anemia in gynecologic oncology surgery: Analysis of the National Surgical Quality Improvement Program Database.
Authors: Cain Abigail , Galvan-Turner Valerie Bianca 
Published: June 2022

e13528 Background: Preoperative anemia has been identified as risk factor for adverse postoperative outcomes following hysterectomy for benign indications. However, studies have not yet been performed looking at the effect of preoperative anemia on women undergoing surgery for a gynecologic malignancy. Methods: We used the National Surgical Quality Improvement Program data from 2014 to 2019 to conduct a retrospective, population-based cohort study. Our exposure of interest was preoperative anemia, defined as a hemoglobin value <12 g/dL and stratified using the National Cancer Institute grading system. We preformed a logistic regression was used to calculate the adjusted odds ratio evaluate the effect of anemia on the outcomes. Results: Of the 54,569 women in the cohort, 13,232 (24.2%) had anemia. Conclusions: Preoperative anemia, at any grade, is associate with an increase in postoperative morbidity and that the effect is increased with worsening grade of anemia.[Table: see text]