bluuebunny/crossref_metadata_2025_split huggingface dataset:
Demonstration of the value of liquid biopsy to identify metastatic breast cancer: Comparison and combination of cell and cell-free platforms.
Authors: Di Caro Giuseppe , Bourdon David , Byun Jiyun , Singer Tatjana , Anderson Amanda , Tubbs Alisa , Blankfard Martin , Wenstrup Rick 
Published: June 2022

e13004 Background: Liquid biopsy analysis detecting circulating tumor cells (CTC) or circulating tumor DNA (ctDNA) is a non-invasive approach that may provide clinically actionable information for patients’ (pts) treatment decisions when conventional biopsy is otherwise inaccessible or infeasible. Here we report a liquid biopsy analysis method including CTC characterization and ctDNA alterations in late-stage metastatic breast cancers (MBC). Methods: Blood samples were collected for cell and cell-free DNA analysis from 57 pts with MBC. 44 pts were progressing on treatment and 13 were responding to treatment. Blood was also collected from 25 blood donors (HD) with no known cancer history. After plasma isolation, nucleated cells were plated, and slides were bio-banked. Immunofluorescent staining and subsequent imaging were performed on replicate slides. CTCs were identified using Epic Sciences digital imaging and machine learning algorithms trained to identify breast cancer cells. Single-cell (sc) isolation for genomic quantification of large-scale transitions (scLST) was used to further characterize individual CTCs. cfDNA from bio-banked plasma was analyzed using a validated NGS panel to detect class 1A ctDNA alterations. Results: Within this cohort of 57 MBC pts, CTCs, scLST+CTCs and ctDNA alterations were detected in (77%, 49% and 33%, respectively). All MBC pts on active therapy (23%) had no CTC detected. No CTCs, scLST+CTCs or ctDNA were detected in the HD cohort, suggesting high specificity (100%, 100% and 100%, respectively). The presence of CTCs or of scLST+CTCs had low concordance with the presence of ctDNA+ alterations in MBC pts, suggesting that these platforms provide independent and complementary value when identifying MBC. To test this hypothesis, we designed combination models which added ctDNA to cell analysis methods ([CTC+][ctDNA+] and [scLST+CTC+][ctDNA+]). Adding ctDNA to either cell analysis method increased sensitivity by 5% and 12%, respectively, over the individual methods and retained 100% specificity. Conclusions: Here we demonstrate the value of comprehensive cell and cell-free liquid biopsy analysis for the detection of MBC pts. Our data suggest there may be clinical utility of adding cell-free to cell analysis for the identification of MBC. Analysis of the comparative and combined utility of these liquid biopsy methods in earlier settings is ongoing.
Whole genome sequencing of HER2+ metastatic breast cancer and CNA comparison between long term survivor and short-term survivor.
Authors: Andrieu Charlotte , Goldrick Caoimhe , Skrobo Darko , Eustace Alex , Ballot Jo , Quinn Cecily , Gullo Giuseppe , Walsh Naomi , Crown John 
Published: June 2022

e13019 Background: The introduction of anti-HER2 therapies such as trastuzumab for HER2+ metastatic breast cancer (MBC) has led to significant improvements to disease progression. We and others have reported long-term durable complete response to trastuzumab in patients with HER2+ MBC. We hypothesise that genomic copy number alteration (CNA) and tumour mutational burden (TMB) may act as a prognostic measure of predicting response to trastuzumab in long-term survivors (LTS) compared to short-term survivors (STS). Using whole-genome sequencing (WGS) to detect these alterations, we aim to identify the molecular characteristics of primary and metastatic lesions in patients with metastatic HER2+ breast cancer. Methods: WGS was performed on samples from two patients from a HER2+ MBC cohort; a of long-term survivor (PFS 27 months; OS > 60 months) and a short-term survivor (PFS 4 months; OS < 14 months). Primary tumours, adjacent normal tissue and metastases were sequenced at a mean depth of 60X. Reads were aligned on the hg38 reference genome using Burrows-Wheeler Aligner (bwa), CNA were detected using Control-FREEC to evaluate total CNA burden. Single nucleotide variants were detected using GATK Mutect2 to calculate TMB. Results: Analysis of DNA chromosome disruption (fraction of the genome amplified/deleted) revealed a higher overall fraction of disrupted genome in the LTS primary tumour and metastasis compared with the STS (0.061 and 0.064 vs 0.031 and 0.047, respectively). Further delineation of the distribution of CNA burden in all genomes identified chr1 as the most altered in the STS samples whereas chr17 was the most disrupted in the LTS samples. HER2 and CDK12 were amplified in both LTS and STS samples (4 copies in LTS primary tumour and metastasis, 18 and 14 copies in STS primary tumour and metastasis respectively). A high TMB was estimated in both samples but was higher in the STS primary tumour than in the LTS one (161 vs 142, respectively). TMB was increased in LTS metastatic lesions. NRAS mutation was found in LTS primary tumour but was lost in the metastasis. Conclusions: This pilot study highlights the potential for whole-genome sequencing to identify CNA and TMB in HER2+ MBC in patients who display long-term and short-term survival. Further samples from this cohort need to be studied to investigate the relationship between CNA burden and HER2+ MBC patient survival.
Survival of stage 4 primary breast cancer cases after surgery by intrinsic subtype: HER2-positive subtype potentially curable.
Authors: Kamada Yoshihiko , Takigami Naoko , Uehara Kanou , Tamaki Kentaro , Tamaki Nobumitsu 
Published: June 2022

e13026 Background: With the incorporation of anti-HER2 agents in the treatment of HER2 positive primary breast cancer, stage 4 disease of this subtype has become potentially curable. However, the duration of clinical CR that is needed be certain that the patient is cured, and therefore the necessary duration of anti-HER2 treatment is uncertain. We address this issue in this presentation. Methods: We present cases of stage 4 primary breast cancer who underwent breast surgery after their distant metastases were controlled, with continued post-operative systemic therapy. There were 52 cases of which the intrinsic subtype as of immunohistochemical analysis was as follows; Luminal A - 7 cases, Luminal B, - 14 cases, Luminal-HER2 - 9 cases, HER2-enriched - 7 cases, and Triple negative -15 cases. The patients were followed up for duration of treatment and overall survival. Results: The average post-operative observation period for all 52 cases was 32.6 months. The five year overall survival rate for HER2-enriched cases was 100%, for Luminal-HER2 cases 80%, for Luminal A cases 80%, for Luminal B cases 55%, and for Triple-negative cases 0%. Of the 16 HER2 positive cases (Luminal-HER2 and HER2 enriched), there was only one death at 48.4 months post-operation. The survival of 5 of 15 surviving HER2 positive cases exceed 60 months (5 years). Of the five, only one at 72.0 months has clinically observable disease (cSD). The remaining 4 cases all are clinically disease free (cCR). Of the 4 cCR cases, only 1 case which originally had multiple lung metastases is continuing anti-HER2 therapy at 90.3 months post-operation. The remaining three discontinued anti-HER2 therapy at 18.1 months (lung metastases CR, observation period 71.7 months), 72.3 months (liver and lymph node metastases CR, observation period 90.3 months), and 101.9 months (liver and bone metastases CR, observation period 102.3 months), respectively. The last case terminated anti-HER2 therapy after testing negative for ERBB2 related genes on liquid biopsy. Conclusions: With the proper incorporation of anti-HER2 therapy, Stage 4 HER2 positive primary breast cancer disease seems to be a potentially curable disease, and anti-HER2 therapy probably can be discontinued in cCR patients after 5 years. Liquid biopsy for tumor related genes (e.g. ctDNA, miRNA) might facilitate decision making.
Diagnosis of asymptomatic bone metastases from breast cancer.
Authors: Krokhmal Julia N. , Rozenko Lyudmila Ya , Frantsiyants Elena M. , Guskova Nailya K. , Gusareva Marina A. , Vereskunova Marina I. , Guskova Ekaterina A. , Udalenkova Irina A. , Donskaya Aliya K. , Selyutina Olesya N. , Solntseva Anna A. , Vasilieva Ekaterina O. , Tolmacheva Ekaterina A. , Karnaukhova Elena A. , Rodionova Olga G. , Shatova Iuliana S. , Vashchenko Larisa N. , Ausheva Tatiana V. , Voshedskiy Vitaliy I. , Sakun Pavel G. 
Published: June 2022

e13042 Background: The purpose of this study was to analyze the prognostic value of blood levels of fibrinogen (F) in bone metastases from breast cancer (BC). Methods: The study included 160 patients with nodular BC pT2-3N0-1M0-1, including 48 patients in a prospective group (PG) and 112 patients in a retrospective group (RG). All patients underwent initial clinical and laboratory examinations, including determination of alkaline phosphatase (AP) activity (Cobas Integra 4000 plus, Switzerland) and parameters of coagulation hemostasis (STA Compact, France). Bone scintigraphy was performed for complaints of bone pain and/or in cases of elevated AP activity, regardless of SXCT data. Results were considered statistically significant at p < 0.05. Results: Patients in PG were divided into two subgroups depending on F levels: in 31 (64.6%) patients F = 3.67±0.5 g/L, insignificantly exceeding the norm (2.8±0.3 g/L); in 17 (35.4%) patients F = 6.9±0.3 g/L, being 1.9 and 2.5 times (p < 0.05) higher than in subgroup 1 and the norm, respectively. AP activity exceeded the norm by 26% and 40%, respectively (p < 0.1). Bone metastases were detected before treatment in 24 (21.4%) women of RG with pain syndrome; all these patients showed increased blood levels of F, on average up to 7.86±0.8 g/L, similarly to patients in subgroup 2 of PG. F levels in other 88 (78.6%) patients in RG were 3.4±0.6 g/L. The nature and severity of AP changes in RG patients and in both PG subgroups were similar. Initially elevated F levels in 17 PG patients remained unchanged after antitumor treatment (6.2±0.6 g/L). AP activity values were stable after treatment being only 36% and 28% (p < 0.1) higher than the norm, respectively. None of the patients with high F levels complained about bone pain. Unscheduled bone scintigraphy was appointed to 17 patients of PG without clinical symptoms or x-ray (SXCT) signs of pathology but with initially high F which did not decline after treatment. Bone scintigraphy showed metastases to the spine and pelvic bones in 12 of 17 (70.5%) patients 1 month after treatment, subsequently confirmed by MRI results. Conclusions: Initial levels of F within 6.9±0.6 g/L which do not decline after the special treatment allow predicting unfavorable BC course and the presence of metastases to the spine and/or pelvic bones without clinical signs of progression. The proposed method allows diagnosis of advanced tumor process in the absence of clinical signs of the disease with an accuracy of 87.8%, and allows timely corrections to the treatment plan.
Prevalence and survival of TNBC patients vs non-TNBC patients in India: A multi-centric real-world experience based study.
Authors: Ajaikumar Basavalinga Sadasivaiah , Gupta Roshini Das , Raju Anisha , Verma Girdhar , Gupta Anuj 
Published: June 2022

e13064 Background: Triple-Negative Breast cancer (TNBC) is a highly aggressive form of breast cancer, characterized by the lack of expression of Estrogen Receptor (ER), Progesterone Receptor (PR), and Human Epidermal Growth Factor-2 (HER-2). Patients with TNBC do not benefit from hormonal or Trastuzumab therapy due to the lack of appropriate targets for these drugs. The current retrospective multicentric hospital-based study at HCG, India, aims to analyze the available treatment paradigms in TNBC patients in real-world evidence. Methods: Data from 3180 female breast cancer patients was collected and compiled from various medical records department (MRD) and hospital database from three HCG centers. The data comprised demographic and clinicopathological details, treatment details and survival information. In addition, the clinical and pathological parameters and survival outcomes were compared between TNBC and non-TNBC patients. Results: About 22.92% (729/3180) patients had TNBC, and 77.08% (2451/3180) patients had designated as non-TNBC. In the TNBC subgroup, 22.36% (163/729) patients belonged to the younger age group (< 40 years), 65.98% (481/729) patients were in the 41-65 age group, while 11.66% (85/729) patients were > 65 years old. Whereas the age-wise distribution in the non-TNBC group was as follows: < 40 years- 15.46% (379/2451) patients, 41-65 years- 70.34% (1724/2451) patients, and > 65 years- 14.2% (348/2451) patients. In the present cohort, TNBC and non-TNBC groups' mean age was 51.06 ± 12.15 years and 53.29 ± 11.55 years, with no statistical significance. About 11.8% (86/729) of patients in the TNBC group and 10.4% (255/2451) of patients in the non-TNBC group opted for neo-adjuvant chemotherapy. About 32.37% of patients in TNBC and 37.45% of patients in the non-TNBC group underwent surgery. The 5-year OS was 68.58% and 83.41% for TNBC and non-TNBC patients, respectively, with a median 5-year survival of 2.13 years (95% CI 2.528-3.204) for TNBC patients whereas 5-year median survival of 2.096 (95% CI 1.36-4.368). The mean survival in TNBC patients < 40 years was 10.14 years, which was significantly lower when compared to patients in the 41-65 years (14.12 years) and > 65 years (19.45 years). Also, patients in the TNBC group who underwent surgery had a higher mean survival of 16.72 years than those who did not opt for surgery (14.49 years). Further, chemotherapy and radiotherapy also increased the life expectancy in patients in both the TNBC and non-TNBC groups. Conclusions: In the present study cohort, TNBC distribution in the at the HCG center in the Indian subcontinent is similar to that of the western population (23% in the US and the UK). Adjuvant chemotherapy and radiotherapy were significantly higher among TNBC cases than non-TNBC cases. Lack of patient consent or proper patient follow-up further reduces survival
Real-life data of antiandrogens (AA) use in metastatic androgen receptor positive triple negative breast cancer (AR+ TNBC): The ATOVAT retrospective French cohort.
Authors: Rhanine Yasmine , Bonnefoi Herve R. , Goncalves Anthony , Debled Marc , Le Moulec Sylvestre , Bonichon-Lamichhane Nathalie , Dubroca-Dehez Benedicte , Grellety Thomas 
Published: June 2022

e13074 Background: AR+ TNBC account for around 25% of all TNBC. Identification of those patients is difficult since AR expression (IHC) testing is not routinely recommended. Published data of 3 trials using different antiandrogens (AA) found clinical benefit rates (CBR) at 6 months ranging from 19 to 29% with excellent toxicity profiles. The aim of this retrospective trial was to assess the clinical benefit of AA in real life. Methods: Patients with metastatic AR+ (IHC staining > 10% assessed by local laboratories) TNBC treated with an antiandrogen in metastatic setting were eligible. Patients should have received at least one dose of the following AA: abiraterone acetate, enzalutamide or bicalutamide. Antiandrogens had to be given after documented progression and must not be carried out as part of a clinical trial. Patients could be chemotherapy naïve for their metastatic disease or have received any number of previous line. 30 oncology centers involved in clinical research in France were screened by questionnaire and data were collected in each patient files. The aim was to describe the 6-months CBR and safety in real-life patients. Assessable patients received at least 4 weeks of AA and present at least one disease assessment. Results: 26 patients from 5 French sites were deemed eligible and 24 patients were assessable. Treatment were conducted between January 2002 and January 2021. Median age at initiation of AA was 70 years (range 50-90). 50 % (N = 13) presented liver and/or lung mets and 27% (N = 7) non progressing and non-symptomatic cerebral mets. Median number of previous line of chemotherapy was 3 (range 0-10). AA used were: abiraterone acetate (62%), enzalutamide (8%) and bicalutamide (30%). Median time from mets diagnosis to AA treatment initiation was 18 months (range 0-168). 6-months CBR were 29% (N = 7) with 5 objective responses (2 CR, 3 PR) and 2 SD. 4-months CBR were 33% (N = 8). PFS and OS were 3.2 months (0.8- 36.1) and 9.5 (1.3-63.8) months, respectively. 2 pts further received second line AA with 1 with SD as a best response. 57% (4/7) of patients presenting 6-months clinical benefit received AA in first line versus 18% (3/17).There were no grade 3 or more side effects reported. Conclusions: Real-life data of antiandrogens use in metastatic AR+ TNBC are in line with data from published clinical trials using the same drugs. There were no new safety signal in this retrospective cohort supporting the use of antiandrogens in AR+ (> 10%) TNBC in the absence of other therapeutic opportunity or available clinical trials.
Use of systemic cancer treatments based on a validated survival prediction model in metastatic cancer.
Authors: Roy Mohana , Gensheimer Michael F. , Chang Daniel Tandel , Singhal Surbhi , Khaki Ali Raza 
Published: June 2022

e13515 Background: Use of systemic anti-cancer treatment near the end of life (EOL) is recognized as a low value practice with limited benefit to patients. Machine learning (ML) models that identify patients in close proximity to death can help prospectively assess oncology practice of systemic therapy use. We hypothesized that systemic therapy use would be higher based on predicted survival compared with actual survival. Methods: We calculated prevalence of systemic therapy use based on predicted and actual survival among patients with metastatic cancer at Stanford Healthcare from 2008-2019. Patients were included if they were in the test set of the ML model, had an eligible outpatient oncology clinic visit for which a predicted survival was calculated and were deceased . Median predicted survival was calculated from the ML model at each outpatient oncology visit and treatment was linked to a visit date if within 14 days of each other. Prevalence of systemic therapy was calculated for patients with a predicted or actual survival of < 6 months, 6-12 months, 12-18 months and 18-24 months. The five categories of treatment were: chemotherapy, targeted/antibody, hormone, immunotherapy, and other. Results: A total of 951 deceased patients who received anticancer treatment are included and a total of 21,283 doses of treatment were administered with a mean of 22 doses per patient. The median age at metastatic cancer diagnosis was 58 years, 53% of patients were female and most patients identified as White (55%) or Asian (23%). The most common disease groups were gastrointestinal (21.6%), thoracic (18.6%) and breast (14.9%). Overall, the use of different treatment types did not differ based on either predicted or actual survival (Table). In all the survival groupings, chemotherapy remained the predominant medication type, however with a trend of decreasing use with longer predicted and actual survival. Conclusions: The use of cancer medications and the type of medication given did not change based on predicted or actual survival in a large group of patients with metastatic cancer. There was a trend of decreasing chemotherapy use with longer prognosis. Further investigation into use in time intervals closer to (predicted or actual) death and inclusion of those who did not receive any systemic therapy are underway.[Table: see text]
Characteristics and information needs of patients with cancer contacting My Cancer Navigator (MCN): A personalized information service of the Anticancer Fund (ACF).
Authors: Kuijten Gabry A.M. , Battisti Nicolo Matteo Luca , Vandeborne Liese , Buyens Guy , Crispino Sergio 
Published: June 2022

e13521 Background: The ACF is an independent private research foundation, based in Belgium and active internationally. Since its inception in 2013, patients and their relatives spontaneously contact the Fund to request information on treatment options including clinical trials. MCN consists of a dedicated team of physicians and scientists, which provides patients and healthcare professionals with free, evidence-based, unbiased, and personalised information to support shared decision-making. All patients receive a summary report, which is discussed in a (video)call with one of our physicians. The objective of the current study was to analyse the characteristics and information requests of people contacting us in 2020-2021 in order to better understand their needs. Methods: For every information request through MCN, the patient agreed to the collection of anonymised data such as sex, age, geographic location and tumor type. We tracked questions asked in 8 categories, tracking a category only once per patient and including only those requiring a literature search. Only descriptive statistics were applied. Results: In 2020-2021, we received information requests for 511 unique patients: 483 adults (95%) and 28 children (5%). In 46% of the cases the patient established contact; for 51% it was a relative or friend, and in 3% the physician. 377 patients (73%) were from Europe, of whom 222 (43%) from Belgium, 56 (11%) from the UK and 23 (5%) from the Netherlands. 109 patients (21%) came from all other continents – of those, 60 (12%) were from the USA. Tumor diagnoses included: gastro-intestinal (114, 22%), breast (110, 22%), central nervous system (77, 15%), gynecological (36, 7%), hematologic (35, 7%), genito-urinary (29, 6%), with sarcomas, lung, head and neck, skin and unknown cancers making up the remainder. Most patients had more than 1 question requiring research, resulting in a total of 880 questions. The Table shows the number and percentage for each category. Conclusions: Within this population, evidence-based information on treatment options, clinical trials, complementary treatments and repurposed drugs were key information needs. Healthcare institutions may lack resources to address all information needs, and My Cancer Navigator may contribute to closing that gap and support patients and healthcare providers. Although the service seems to be well perceived, we are now developing a method to formally assess satisfaction with and impact of our service.[Table: see text]