bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laparoscopic versus open-surgery in FIGO stage II endometrioid endometrium cancers: Is there a prognostic effect?
Authors: Reimer Daniel Uwe , Bargujar Tanu Priya , Leitner Katharina , Steger Katharina , Bartl Thomas , Marth Christian , Zeimet Alain G 
Published: June 2023

5605 Background: Based on two randomized trials (LACE and LAP2) minimal invasive surgery has turned into the surgical standard in early stage endometrial cancer including “high-risk” patients. However, these recommendations are predominately based on “low-risk” cancers, which are mainly represented in both trial collectives. We herein provide a retrospective study, which focuses on potential differences in clinical outcome in early stage endometrioid endometrial cancers with distinct risk constellations treated by laparoscopy or open surgery. Methods: 420 early stage endometrial cancers were retrospectively dichotomized according to the surgical approach and correlated to the recurrence rate and clinical outcome. In addition, subgroup analyses were performed according relevant clinical risk parameters, namely FIGO stage, grading and LVSI. Results: The analyzed collective consisted of 73.8% stage IA, 19.5% stage IB, and 6.7% stage II cases. Twenty-tree percent of patients exhibit G3 tumors and LVSI was detected in 12.4%. Minimal invasive surgery was performed in 54.5% of study patients. During a median follow-up of 5.0 years, recurrence or death were observed in 8.3% and 6.7%, respectively. Recurrences were predominately located in the vaginal cuff (n = 21; 60.0%), to a minor extent in loco-regional lymph nodes (n = 11; 31.4%), and in three patients (8.6%) in both sides. No distant metastases were detected at first recurrence. Also under consideration of the mentioned clinicopathologic parameters, the surgical approach in FIGO stage I did not influence the recurrence rate and patients’ survival. However, in a subgroup analysis of stage II disease, the laparoscopic approach was clearly associated with a significant higher recurrence rate (85.7% vs. 14.3%; p = 0.013). All of the recurrences were located in the vaginal cuff, and in one case, additional relapse was found in loco-regional lymph nodes. Moreover, laparoscopic surgery in stage II disease was associated with impaired progression-free and overall survival (HR 8.86 (1.008 – 20.85) and HR 6.36 (1.102 – 28.61), respectively). Conclusions: We herein demonstrate that a minimal invasive surgical approach in stage II endometrial cancer is associated with higher recurrence rates and impaired clinical outcome. These data could be interpreted to be in line with the results of the LACC trial in cervical cancer. Although, grounded on a retrospective analysis, these hypothesis-generating results warrants a confirmatory trial, which is ongoing in a much larger collective of stage II endometrial cancer patients.
Impact of surgical weight loss treatments on care burden among obese endometrial cancer survivors.
Authors: Noyes Katia , Myneni Ajay A , Boccardo Joseph , Zsiros Emese , Hoffman Aaron B 
Published: June 2023

5607 Background: Among obesity-related cancers globally, 40% of disability adjusted life years lost are attributed to endometrial cancer (EC). EC patients are more likely to die of obesity-related complications rather than the cancer itself. Metabolic and bariatric surgery (MBS) is an effective weight loss treatment that has been shown to reduce prevalence and severity of many obesity-related chronic conditions. However, there is limited evidence on MBS on EC survivors. We examined the burden of patient healthcare utilization among EC survivors who did and did not undergo MBS. Methods: We utilized the SEER-Medicare database to identify 31,437 patients diagnosed with endometrial cancer between 2015 and 2017. We selected 9,229 (29.4%) patients with documented obesity (ICD codes) among whom 75 (0.8%) patients underwent MBS after completing EC treatment (2017-2019). EC survivors with and without a history of MBS were matched on age at EC diagnosis. We examined annualized Medicare inpatient and provider claims payments among EC-MBS (starting 3 months after the surgery, n=66) and EC-no MBS patients (2017-2019) and used Wilcoxon Rank-Sum tests to examine differences in payments in a 1:5 matched sample. Results: EC-MBS patients were younger (59.9 years) at the time of cancer diagnosis compared to EC-no MBS patients (68.2 years, p<0.01). In an age-matched sample, annualized median inpatient and provider claim payments among EC-MBS patients ($1,824) were lower than that of EC-no MBS patients ($2,920, p<0.01). Conclusions: Surgical weight loss achieves rapid and effective weight loss and has the potential to lower healthcare utilization among EC survivors but less than 1% of eligible patients receive the surgery. Further research is needed to better understand patient, provider, and access barriers to surgical weigh loss in patients with obesity-related cancers. [Table: see text]
A multicenter, single-arm, phase 2 study of surufatinib plus toripalimab for patients with advanced endometrial cancer.
Authors: Yuan Guangwen , Li Zhiping , Ye Feng , Zhang Bingzhong , Shen Lin , Zhang Yan-qiao , Yu Xianjun , Cheng Ying , Liu Baorui , Wang Jianliu , Chen Xiaojun , Zhou Jinghong , Shi Haiyan , Tan Panfeng , Fan Songhua , Shi Michael , Su Weiguo , Wu Lingying 
Published: June 2023

5609 Background: Several immunotherapy monotherapies, or combined with antiangiogenic inhibitors, have shown antitumor efficacy in endometrial cancer (EMC) and been approved by FDA. However, therapeutic options for EMC after failure of first-line treatment remain scarce in China. The open-label, multi-cohort, single-arm phase 2 study was performed to evaluate the efficacy and safety of the combination of surufatinib (a small-molecule inhibitor of VEGFR 1-3, FGFR1 and CSF-1R) with toripalimab (an anti-PD-1 antibody) for Chinese patients (pts) with EMC after failure of one or more prior lines of systemic treatment. Methods: Pts with EMC who progressed or were intolerable after at least one prior line of systemic antitumor therapy were eligible and enrolled. They received 21-day cycles of surufatinib 250 mg orally, QD, plus toripalimab 240 mg IV, Q3W, until disease progression or reaching the maximum treatment duration with toripalimab of 24 months, or other protocol-specified criteria. The primary endpoint was objective response rate (ORR) per RECIST 1.1. Results: From August 2020 to March 2022, 28 pts were enrolled and received the combination treatment (median duration: 4.6 months). Median age was 58 years (range: 50-71), and 22 (78.6%) pts were endometrioid adenocarcinoma at diagnosis. 9 (32.1%) pts had received ≥2 prior lines of therapy. As of 28 Dec 2022, the median follow-up duration was 16.8 months. Microsatellite status was available in 25 pts. 20 with mismatch repair-proficient (pMMR) and 5 with mismatch repair-deficient (dMMR) were determined. All 28 pts were evaluable with at least one post-baseline tumor assessment. Efficacy results were: confirmed ORR, 28.6% (8 partial response [PRs]); DCR, 82.1%; mDoR, 5.7 months; mPFS (95%CI), 5.4 months (2.7, 8.3); 12-month OS rate, 71.0%. Among pts with pMMR, the confirmed ORR was 25.0%; DCR was 85.0%; mDoR was 4.2 months; mPFS (95%CI) was 4.0 months (2.7, 8.3); 12-month OS rate was 75.4%. All pts experienced at least one treatment-emergent adverse event (TEAE), and 19 (67.9%) of them reported grade ≥3 TEAEs. The most common (≥5% pts) grade ≥3 TEAEs were hypertension (28.6%), aspartate aminotransferase increased (14.3%), alanine aminotransferase increased (10.7%), proteinuria (7.1%), Gamma-glutamyltransferase increased (7.1%) and malignant neoplasm progression (7.1%). No new safety signals were observed. Conclusions: Surufatinib plus toripalimab had a promising antitumor activity and a manageable safety profile in pts with EMC after failure of one or more prior lines of systemic therapy. Clinical trial information: NCT04169672 .
Prognosis of squamous cell carcinoma of the breast by biological subtypes and the efficacy of radiotherapy: The Japanese Breast Cancer Registry analysis.
Authors: Ogita Mami , Kubo Makoto , Kumamaru Hiraku 
Published: June 2023

561 Background: Primary squamous cell carcinoma (SCC) of the breast is a rare disease, accounting for about 0.1% of all breast cancers. We aimed to determine the clinical features and prognosis of breast SCC, and the effect of radiotherapy by biological subtypes using the Japanese Breast Cancer Registry. Methods: We conducted a matched-pair analysis of 350,977 breast cancer patients with SCC or invasive ductal cancer (IDC) in the Japanese Breast Cancer Registry between 2004 and 2014. Inclusion criteria were female breast cancer patients who underwent surgery with stage I–III diseases, SCC or IDC, and age ≥ 18. Patients who received preoperative radiotherapy were excluded. We performed 1:1 SCC-IDC exact matching analysis by predominant subtypes in SCC: ER(-) and PgR(-)/HER2(-) or ER(+) and/or PgR(+)/HER2(-). Overall survival (OS), breast cancer-specific survival (BCSS), recurrence-free survival (RFS), and first locoregional or distant metastasis recurrence incidence were compared between IDC and SCC by Kaplan-Meier methods and log-rank test. In-field area recurrence was compared between those who received radiotherapy and those who did not. Results: We included 452 SCC and 182,707 IDC patients for the analysis. SCC patients were more likely to present with advanced stage disease compared to those with IDC. Among SCC patients, 59% was ER(-)/PgR(-)/HER2(-), 19% was ER(+)/PgR(+)/HER2(-), 8% was ER(-)/PgR(-)/HER2(+), 2% was ER(+)/PgR(+)/HER2(+), and 12% was data missing. Ten-year OS, BCS, and RFS rates were 70%, 80%, and 66% in SCC, and 88%, 93%, and 81% in IDC, respectively, and SCC carried a significantly worse prognosis than IDC (all P < 0.001). For exact-matched analysis, 10-year BCS of ER(-)/PgR(-)/HER2(-) SCC patients was significantly worse than IDC (P = 0.02), whereas there were no significant differences between SCC and IDC of ER(+)/PgR(+)/HER2(-) patients in OS, BCS, and RFS. Among patients who received radiotherapy, no difference was found in in-field area recurrence between SCC and IDC in either ER(-)/PgR(-)/HER2(-) or ER(+)/PgR(+)/HER2(-) subtype. Conclusions: SCC of the breast was often diagnosed in an advanced stage and had a worse prognosis than IDC. More than half of them were triple-negative subtype. In the triple-negative subtype, SCC was an independent poor prognostic factor. No significant differences in in-field area recurrence after radiotherapy between SCC and IDC suggested that the effect of radiotherapy on local control for SCC was similar to IDC.
Lipidomic signature from plasma to detect localised breast cancer.
Authors: Lamoury Gillian , Batarseh Amani M. , Kehelpannala Cheka , Pascovici Dana , Li Desmond , Heffernan Kerry 
Published: June 2023

565 Background: An effective and accurate blood test to detect localised breast cancer may increase the screening detection rate and improve patient outcomes. We have previously reported a series of lipidomic studies and derived a lipid signature from plasma enriched extracellular vesicles (EVs) that effectively distinguished people with localised breast cancer from cancer-free controls. here we report on a significant refinement to the test methodology allowing the assessment of the lipid signature directly from plasma samples and its performance, with the aim of advancing the commercial viability of the test as we move towards clinical application. Methods: Lipids were extracted from enriched EVs from plasma samples donated by fasted people with localised breast cancer and control samples (n=793) and analysed by high resolution accurate mass liquid chromatography-mass spectrometry (LC-MS). Over 400 manually curated lipids were quantified. Following variable selection, a lipid signature capable of distinguishing breast cancer samples from controls was derived. The lipid signature was modelled on each of the cohorts using leave-one-out internal cross-validation. Next, we analysed the lipids in cancer and control (n=256) plasma samples corresponding to patients from Cohorts 3 and 4 previously used for EV preparations, and applied the signature derived using EVs on plasma lipidomic data. Results: EV samples of people with breast cancer were distinguished from controls with an area under the curve (AUC) of 0.77-0.89 across 4 cohorts. When the lipid signature was assessed directly from plasma the test achieved a comparable AUC of 0.84. Assessing the markers directly from plasma samples would make the test more scalable, higher throughput and easier to perform. Conclusions: Our study demonstrated the high performance of a lipid biomarker signature derived from plasma enriched EVs for early detection of localised breast cancer. Our results suggest that that the lipidomic signature could potentially be assessed directly from plasma samples instead of EVs reducing the test complexity. Ongoing studies will optimise the plasma lipidomic signature and prospectively compare the test against mammographic and pathological diagnoses. [Table: see text]
Association of anthracyclines induced cardiotoxicity (AIC) in patients with early breast cancer (eBC) with germline BRCA1/2 (gBRCA1/2) mutation: BRCAN study.
Authors: Serrano Domingo Juan José , Cordero David , Menacho Miriam , del Rey Jose Manuel , Chamorro Jesús , Rosero Diana I. , Sotoca Pilar , del Campo Laura , Alonso Gonzalo , Saavedra Serrano Cristina , Fernández-Abad María , Gion Cortes Maria , Guerra Eva M. , Martinez-Jañez Noelia , Lopez-Miranda Elena , Vida Navas Elena Maria , Fuentes Mateos Raquel , GUILLEN PONCE CARMEN , Salazar Maria Teresa , Cortés Salgado Alfonso 
Published: June 2023

567 Background: BRCA1/2 genes play a critical role in genome stability and DNA repair in human cells, including cardiomyocytes. In animal models, loss of cardiomyocyte-specific BRCA1/2 is associated with DNA damage, apoptosis, cardiac dysfunction, and cardiac mortality following anthracyclines (A) exposure. However, whether these preclinical findings translate to humans still remains unclear. We conducted the BRCAN study to assess the impact of gBRCA1/2 status on AIC in a cohort of patients with eBC. Methods: This is a single center retrospective/prospective study including patients diagnosed with HER2-negative eBC treated with A based chemotherapy in the neo/adjuvant setting, known gBRCA1/2 status, left ventricular ejection fraction (LVEF) ≥ 50% at baseline and no previous significant cardiovascular events. During follow-up, we performed myocardial dysfunction blood biomarkers (MDBB), cardiac ultrasound and quality of life questionnaires (QoL). Primary objective was to assess the absolute LVEF change from baseline in BRCA1/2 mutation carriers (gBRCA1/2mut) versus non-carriers (gBRCA1/2wt). Secondary objectives were comparing MDBB and QoL in these groups. Results: 137 patients with eBC were included in the study (103 gBRCA1/2wt and 34 gBRCA1/2mut). Patients’ characteristics were similar between both groups in terms of age, baseline LVEF, radiotherapy (RT) on left side, total A accumulative dose, time from A exposure, antihypertensive or hypolipidemic agents use and smoking habit. Compared to baseline, LVEF % reduction was -4.7 [-12.0, 0.0] versus -9.5 [-18.0, -5.0] in gBRCA1/2wt and gBRCA1/2mut, respectively (p=0.027). To correct for confounding, we fit a regression model for the variables smoking habit, antihypertensive and hypolipidemic agents use. On average, LVEF % reduction in gBRCA1/2mut group was -4.5 [CI 95% -8.6, -0.4, p=0.032] compared to gBRCA1/2wt. No differences between MDBB (protein C-reactive, hsTn, NT-ProBNP, D-Dimer, ST-2 or Galectine-3) and QoL (MLHFQ and EQ5-D index) were detected between groups. Conclusions: Our data suggest that gBRCA1/2mut patients could represent a high risk population for AIC. A baseline comprehensive cardiovascular risk assessment and a closer follow-up should be recommended in these patients. Further research is needed on order to identify early predictive biomarkers for AIC. [Table: see text]
ERBB2 mRNA expression to distinguish HER2-low/neg breast cancer prognosis.
Authors: Liu Yueping , Lv Hong , Shen Mengjia , Shui Ruohong , Ye Feng , Meng Yue , Jia Ying , Liu Chao , An Shun , Yuan Xiaoying , Li Xingmin , Yang Wentao , Bu Hong 
Published: June 2023

569 Background: Antibody-drug conjugates such as Trastuzumab deruxtecan significantly improved progression-free and overall survival for the HER2 low expression (HER2-low) breast cancer (BC) patients, pushing the research field of HER2-low to a new climax. In fact, the traditional immunohistochemistry (IHC) to identify the HER2-low or HER2-negative expression (HER2-neg) has been challenged, and it cannot predict the prognosis of HER2-low/neg patients well. Methods: Three pathologists evaluated the HER2 expression status of the subjects via IHC. More than two pathologists judged HER2 0-2 and FISH negative samples were included in this trial. ERBB2 mRNA level of formalin-fixed, paraffin-embedded BC post-surgery specimens were detected by MammaTyper quantitative real-time polymerase chain reaction (qRT-PCR) kit. The consistency of HER2 immunohistochemistry (IHC) and MammaTyper results were analyzed by interclass correlation coefficients (ICC). Differences in disease-free survival (DFS) were assessed by Kaplan Meier analysis. Results: 793 cases were included. The ICC value between IHC and MammaTyper, assessed for HER2-neg vs HER2-low is 0.28. With a median follow up of 2.5 years, there were 36 events in the whole subjects. In the whole subjects, MammaTyper successfully showed that the prognosis of HER2-low was significantly better than HER2-neg (P < 0.001, HR = 3.497, 95%CI,1.807-6.77), but IHC could not distinguished them (P = 0.1071, HR = 1.776, 95%CI, 0.9194-3.43). Although the follow-up time is short, HER2-low subjects also showed better prognosis than HER2-neg in TNBC subjects distinguished by MammaTyper (P = 0.0271, HR = 2.912, 95%CI,1.129-7.511), not by IHC (P = 0.1032, HR = 2.213, 95%CI, 0.8512-5.756). However, in 291 cases of IHC and MammaTyper detection discordancy group, IHC results showed that the prognosis of HER2-low was worse, which was contrary to the MammaTyper results and the results of the above overall test results, suggesting that IHC could not verily reflect the amount of HER2 expression in some samples, and the prognosis of HER2-low population might be more related to the mRNA expression of HER2. Conclusions: Compared with IHC/FISH, MammaTyper qRT-PCR assay may actually reflect the prognosis of HER2-neg/low, which is expected to become a diagnostic beacon for HER2-low target drugs.
Outcomes in premenopausal patients with HR+/HER2- breast cancer and lymph node micro-metastasis based on the 21-gene recurrence score.
Authors: Bilani Nadeem , Patel Rima , Tiersten Amy 
Published: June 2023

571 Background: Postmenopausal patients with hormone receptor positive, HER2-negative (HR+/HER2-) early breast cancer (EBC) and 21-gene OncotypeDX (ODX) recurrence scores (RS) <26 do not benefit from chemoendocrine therapy (‘CET’) compared to endocrine monotherapy (‘E’). The TAILORx and RxPONDER trials demonstrated this was consistent in node-negative and node-positive disease, respectively. In premenopausal patients, however, guidelines for those with low RS diverge between disease involving 0 (pN0) vs. 1-3 (pN1a-c) lymph nodes. Additionally, treatment decisions are less clear for patients with micro-metastasis (pN1mi), who comprised only about 10% of patients in RxPONDER. This study used the National Cancer Database (NCDB) to assess treatment patterns and survival outcomes in premenopausal patients with EBC and lymph node micro-metastasis. Methods: A cohort of patients aged <50, diagnosed between 2004-2019 with HR+/HER2- EBC and who underwent ODX testing, was recruited from the NCDB. (A) Firstly, we described demographic and clinical characteristics of a sub-cohort with micro-metastasis using univariate statistics. (B) We confirmed the prognostic value of ODX in this sub-cohort with multivariate Cox regression analysis of overall survival (OS). (C) We explored patterns of practice amongst the total cohort with ODX <26 with chi-squared testing for differences in CET use by nodal status. (D) To elucidate the predictive value of this assay, we performed Kaplan-Meier models comparing OS for those with RS <26 receiving E vs. CET, controlling granularly for nodal status: (i) pN1a-c, (ii) pN1mi, and (iii) pN0. Results: Of n=72,068 patients aged <50 with HR+/HER2- EBC and ODX data, 6.1% (n=4,402) had micro-metastasis. (A) The median age of this subgroup was 45 (IQR 41-47) years. Most tumors were grade II (n=2,472, 57.7%) with ductal histology (n=3,500, 80.3%). 73.4% of pN1mi cases had RS <26, while 26.6% had RS ≥26. (B) Multivariate Cox regression – adjusting for comorbidity, race and chemotherapy use – confirmed significance in this pN1mi cohort of RS ≥26 prognosticating poorer OS compared to RS 0-15 (HR 4.42, 95% CI 2.35-8.31, p<0.001). (C) 29.0% (n=1,033) of patients with pN1mi and ODX <26 underwent CET, greater than 15.2% (n=6,568) with pN0 and less than 47.3% (n=2,884) with pN1a-c staging (p<0.001). (D) A benefit in OS (p=0.017) was observed in cases with RS<26 and pN1a-c using CET (5-year OS: 99%) vs. E (5-year OS: 97.5%), but not in pN1mi (p=0.49) or pN0 (p=0.57) disease. Conclusions: The management of premenopausal patients with HR+/HER2- EBC, isolated micro-metastasis, and ODX <26 is unclear. Our large registry study found the addition of chemotherapy to endocrine therapy was associated with improved survival in cases with ODX<26 involving 1-3 lymph nodes, but not in node-negative or micro-metastatic disease. Prospective trials are needed to confirm these findings.
Somatic mutations in tumor-adjacent normal breast tissue in young women with high risk family history.
Authors: Rozenblit Mariya , Suwalska Aleksandra , Hofstatter Erin Wysong , Reisenbichler Emily , Harigopal Malini , Marczyk Michal , Pusztai Lajos 
Published: June 2023

576 Background: It’s incompletely understood why some women without germline breast cancer predisposing mutations develop early onset breast cancer. Breast cancer in young women is often more aggressive, with high histologic grade, worse prognosis, and higher risk of recurrence. We hypothesize that these women have somatic mutations in the normal breast tissue that contribute to breast cancer tumorigenesis. Methods: Whole exome sequencing (WES) data was analyzed from normal tissue adjacent to breast tumor and compared to matched peripheral blood (n=28). All patients were <50yo, had high risk family history as per NCCN guidelines, and had negative Ambry Genetics panel testing. FFPE sections were reviewed by two pathologists to identify normal breast tissue furthest away from tumor. WES was performed on Illumina HS4000 using 100-base pair paired-end reads. Samples were mapped to the human reference genome (vGRCh38). PCR duplicates were marked (Picard), and indel regions were adjusted (GATK). High-quality germline variants (HaplotypeCaller), somatic mutations (Mutect), and indels (IndelGenotyper) were called. Low-quality variants were filtered out. The classification and number of mutations per gene per sample were extracted and analyzed. Results: Majority of patients were white (86%), median age 45, with invasive ductal carcinoma (86%), ER+/PR+/HER2- (100%). Median somatic variants per sample were 97 (range: 45-285), all single nucleotide variants, mostly missense mutations, C>T conversions were seen in 45% of mutations. This suggests cytidine deaminase (APOBEC) involvement. All samples had alterations in at least one of the top ten affected genes which include transcription factors in zinc finger family (listed below). Zinc finger proteins play a key role in tumorigenesis, cancer progression and metastasis in a variety of cancers. Upregulation of zinc finger proteins has been associated with worse prognosis in breast cancer. Conclusions: We describe novel somatic mutations in zinc finger proteins in normal breast tissue adjacent to tumor that may contribute to early onset breast cancer in patients with high risk family history. [Table: see text]