bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sentinel lymph node biopsy in Merkel cell carcinoma: A multi-institutional study from the Pan-Canadian Merkel Cell Collaborative.
Authors: Delisle Megan E , Dingley Brittany , Apte Sameer , Mallick Ranjeeta , Hamilton Trevor D , Stuart Heather , Francescutti Valerie , McKinnon Greg , Jost Evan , Easson Alexandra , Merchant Shaila J. , Hebbard Pamela , Wright Frances Catriona , Berger Richardson David , Younan Rami , Meguerditchian Ari , Mathieson Alex , Hetu Jessika , Johnson Stephanie , Nessim Carolyn ,   Pan-Canadian Merkel Cell Collaborative
Published: June 2022

9583 Background: There is controversy regarding sentinel lymph node biopsy (SLNB) in clinically node-negative Merkel Cell Carcinoma (MCC). We compared MCC recurrence and survival between patients who did versus did not undergo a SLNB. Methods: Patients with MCC across 13 Canadian centers were reviewed, from 2000-2018. Of a total cohort of 750 patients, 485 had clinically node-negative disease at presentation. A propensity score was created. The association between SLNB and local, regional and distant recurrence, and cancer-specific and overall survival were evaluated using competing risks and Cox proportional hazards regression. Results: 195 patients (40.2%) underwent a SLNB. SLNB was performed more commonly in younger, healthier patients with MCC located in the extremities or torso (Table). The results of 177 SLNBs were available; 60 (33.9%) were positive. SLNB-positive patients underwent completion dissection (n=15, 25%), completion dissection and nodal radiation (n=22, 36.7%), nodal radiation alone (n=18, 30%) or observation (n=5, 8.3%). Patients who did not undergo a SLNB underwent nodal radiation alone (n=40, 13.8%) or observation (n=250, 86.2%). The median follow-up was 2.7 years (range 0.2-14.4). The regional recurrence rate was 14.5% (n=17) among SLNB-negative versus 15% (n=9) among SLNB-positive patients. Among patients who did not undergo a SLNB, the regional recurrence rate was 25.2% (n=63) among those who underwent observation and 15% (n=6) among those who received nodal radiation alone. After propensity score matching, SLNB patients had a lower risk of regional recurrence (sHR 0.54 95% CI 0.34-0.86 p=0.01) and improved overall survival (HR 0.32 95% CI 0.23-0.45 p<0.01), but there was no difference in local recurrence (sHR 0.92 95% CI 0.50-1.69 p=0.79), distant recurrence (sHR 0.88 95% CI 0.52-1.49 p=0.63), or cancer-specific survival (HR 0.67 95% CI 0.31-1.45 p=0.31). Conclusions: SLNB is associated with a reduced risk of regional recurrence and improved overall survival. The role of SLNB in selecting patients for emerging therapies, such as immunotherapy, needs to be evaluated. [Table: see text]
Fertility preservation decisions and outcomes of young women with breast cancer.
Authors: Isseroff Devora , Thom Bridgette , Chang Cassandra , Abdo Nadia , Semler Rosemary , Gemignani Mary , Kelvin Joanne Frankel , Goldfarb Shari Beth 
Published: June 2022

e12520 Background: As breast cancer (BC) survival improves, fertility preservation (FP) counselling prior to initiating gonadotoxic chemotherapy for women of child-bearing age becomes more important. This study explores the factors that influence the decisions to pursue FP before and after breast cancer treatment and the FP outcomes. Methods: An IRB approved web-based survey examining decisions about FP, factors influencing decisions, and post-decision regret was administered to English and Spanish speaking women (age 18-45) diagnosed with stage I-III BC. All women received education and counselling by a MSK Fertility Nurse Specialist prior to initiating cancer treatment at MSKCC in 2009-2017. Additional data was extracted from the medical record. Results: 211 women with BC (82% ER+, 19% HER-2+, 12% triple negative) with a mean age of 34 (age range 20-45) participated in this study. At the time of diagnosis 128 (61%) women were married/living with partner and 46 (22%) women had children. 151 (72%) wanted (additional) children, 48 (23%) were unsure if they wanted (additional) children and 12 (6%) did not want (additional) children. Of the 151 women who desired (additional) children, 94 underwent FP pre-treatment and 3 post-treatment. Of 48 unsure women, 14 underwent FP. A total of 115 women underwent FP before treatment: 73 froze eggs and 49 froze embryos. After treatment 28 (13%) women met with a reproductive endocrinologist and 13 underwent FP: 9 froze eggs and 4 froze embryo. The average number of eggs frozen was 14 pre-treatment and 18 post-treatment. The average number of embryos frozen was 7 both pre- and post-treatment. After completing primary breast cancer treatment, 61 women opted to try to build their family and 42 had children: 35 gave birth and 7 used a surrogate. In a multivariate analysis lower socioeconomic status and non-white race were predictive of discordance between desire for FP and completion of FP before treatment (p < 0.05). 65% of patients reported cost of freezing eggs/embryos was important in their decision. Insurance did not cover any FP treatment for 56/115 (49%) of women and 34% (39/115) of women paid $10,000 or more for their FP. Participants reported the ability to feel hopeful about their future (82%) and fear of regret (80%) were the most important factors when making their FP decision. 83% (176/211) of women believe they made the right FP decision and 80% would make the same decision again. Women had less regret if they underwent FP. Conclusions: Our study demonstrates the importance of discussing FP with women with BC of child-bearing age, regardless of race or economic status. Fertility preservation is often successful in women with BC. Regardless of pregnancy outcomes, women felt that having FP offered them a sense of control and hope for the future during a vulnerable time in their lives with low risk of regret.
Neuroendocrine differentiation in breast carcinoma-clinicopathological characteristics and prognostic significance.
Authors: Shafi Saba , Li Zaibo , Parwani Anil 
Published: June 2022

e12540 Background: Invasive breast carcinoma with neuroendocrine (NE) differentiation has been controversial in terms of its definition and clinical outcome. The recent 5th WHO edition classifies breast carcinoma with NE differentiation into two categories: 1) invasive breast carcinoma, NST (no specific type) with NE features (IBC-NE) (≤90% NE histologic features); 2) NE neoplasm (NEN) (>90% NE features), which is further separated into NE tumor (NET) or NE carcinoma (NEC). However, very little is known about the difference in outcomes, if any, in these three groups of breast carcinomas with NE differentiation. In this study, we examined the clinicopathological characteristics of these three groups of breast cancers and their prognostic significance. Methods: 56 breast cancer patients from 2006 to 2021 were included in this study (IBC-NE: n=41; NET: n=5 and NEC: n=10). Cohort annotation was done by retrospective review of electronic medical records. Results: NEC was significantly associated with higher grade (grade 3 vs. grade1/2) than IDC-NE (90% vs. 26.9%, p=0.0002). IEC-NE showed a significantly greater expression of ER/PR than NET/NEC (ER=100% vs. 64.3%, p<.0001; PR=80.5% vs. 50%, p=0.02). Notably, there was no significant difference in the HER2 status, T stage or survival outcomes between the three groups. NET/NEC had a significantly higher incidence of distant metastases than IDC-NE (46.6% vs. 19.5%, p=0.04). Conclusions: Our data suggest NE neoplasms harbored some different clinicopathologic features from IBC with NE features. In addition, NE neoplasms showed more distant metastasis than IBC with NE features, although no significant difference was observed in overall survival, which may be caused by the small size of current cohort and short follow-up period. [Table: see text]
Predicting breast cancer in women using liquid biopsy-derived glycoproteomic markers.
Authors: Mitchell Alan , Srinivasan Apoorva , Xu Gege , Rice Rachel , Castellanos Alyn , Bhadra Ranjan , Serie Danie , Cong Xin , Lindpaintner Klaus 
Published: June 2022

e12545 Background: Breast cancer is the most common cancer among women worldwide.Traditional methods of cancer detection such as tissue biopsy are invasive, costly, time consuming and not amenable for repetition. As a result, minimally invasive liquid biopsies, especially blood-based biomarkers show potential value for breast cancer risk prediction and early detection. In this study, we investigated the use of serum glycoproteins circulating in blood to identify a panel of potential prognostic markers that may aid in predicting breast cancer in women. Methods: We applied a novel platform for characterizing blood glycoproteomic biomarkers, combining liquid-chromatography/mass spectrometry (LC-MS) with artificial intelligence/neural networks (AI-NN) to analyze serum samples from 279 breast cancer patients (median age 56 years, with stage 0-4 N’s: 1 / 83 / 114 / 56 / 25) and 102 healthy control samples (median age 52 years). A panel of 596 serum glycosylated and non-glycosylated peptides, representing 71 serum proteins, were analyzed. Age-adjusted differential expression analysis for 596 normalized biomarkers were performed to evaluate statistically significant differential abundances using an FDR q-value of 0.05 as a cutoff. Using the top differentially expressed markers as input, a LASSO penalized logistic regression model with 5-fold repeated cross validation was applied to identify the top biomarkers contributing to the separation between healthy controls and breast cancer patients. Results: We identified 243 out of 596 markers that were differentially expressed (FDR <<0.05) between breast cancer samples and healthy controls. Out of those, 11 markers were obtained as the top predictors in classifying breast cancer patients and healthy controls. The classification algorithm yielded an accuracy of 94% (95.9% sensitivity, 88.7% specificity) and an AUC of 0.983 on the training set. This classifier was validated on an independent test set with 30% of the subjects, yielding an accuracy of 93% (96.4% sensitivity, 83.9% specificity) and an AUC of 0.974. Test sensitivity was high across stages, at 96% / 90% / 95% / 90% in stages 1-4, respectively. Conclusions: Based on the results, we conclude that circulating glycoproteins in serum may be useful in screening applications in breast cancer, and strongly demonstrates the utility of glycoprotein profiles as a powerful non-invasive diagnostic tool.
Circulating levels of PCSK9, ANGPTL3 and Lp(a) in stage III breast cancers.
Authors: Wong Chong Emilie , Joncas France-Hélène , Seidah Nabil Georges , Calon Frédéric , Diorio Caroline , Gangloff Anne 
Published: June 2022

e12547 Background: Cholesterol plays an important role in sustaining tumor growth and metastasis in a large variety of cancers. New and powerful cholesterol-lowering drugs are being used in combination to treat cardiovascular diseases. As drugs directed against PCSK9 (evolocumab, alirocumab, inclisiran), ANGPTL3 (evinacumab) and Lp(a) (pelacarsen) are available, it becomes of interest to assess the circulating levels of these drug targets and their role in cancers. Our purpose here is to compare circulating levels of PCSK9, ANGPTL3, and Lp(a) in women with stage III breast cancer versus women with a premalignant or benign breast lesion. Methods: Twenty-three plasma samples from women diagnosed with a stage III breast cancer (ductal, lobular or mixed) were matched for age with twenty-three plasma samples from women bearing premalignant (stage 0, n=9) or benign (n= 14) breast lesions. Lipid profile (Apo B, total cholesterol, HDL and triglyceride levels) and Lp(a) were measured on a Roche Modular analytical platform. LDL levels were calculated with the Friedewald formula. ANGPTL3 and PCSK9 plasma levels were quantitated by ELISA. Difference between breast disease groups was deemed significant when group-comparison generated p-values < 0.05. Results: PCSK9 levels were significantly higher in women with stage III breast cancer compared to age-matched counterparts presenting a benign lesion (95.9 +/- 27.1 ng/mL vs. 78.5 +/- 19.3 ng/mL, p<0.05, n=14). Moreover, PCKS9 levels positively correlated with breast disease severity (benign, stage 0, stage III) (Rho=0.34, p<0.05, n=46). In contrast, ANGPTL3, Lp(a) or lipid plasma levels did not display any correlation with breast disease severity. Conclusions: In this cohort of 46 women, PCSK9 levels increased along with the severity of breast disease. Given that PCSK9 plays an important role in maintaining cholesterolemia and has been shown to degrade MHC-I on tumor cells, impeding immune T-cells response to tumors, confirmation of PCSK9 elevation in a larger cohort would pave the way for trials studying lipid-lowering drugs as adjuvant treatments in breast cancer.
Circulating tumor cells and vitamin D in primary breast cancer.
Authors: Mego Michal , Vlkova Barbora , Karaba Marian , Minarik Gabriel , Benca Juraj , Sedlackova Tatiana , Kalavska Katarina , Pindak Daniel , Mardiak Jozef , Celec Peter 
Published: June 2022

e12558 Background: Circulating tumor cells (CTCs) contributing to the metastatic cascade and represent an independent survival predictor in breast cancer (BC) patients. Vitamin D has pleiotropic effects and its low concentrations are associated with infections, cancer, but also other pathologic conditions. The aim of this study was to assess plasma vitamin D level in primary BC patients in relation to CTCs. Methods: This study included 91 non-metastatic breast cancer patients (stage I-III) with plasma samples available in the biobank of the National Cancer Institute in Slovakia. Blood samples for the analyses were drawn at the time of surgery. Peripheral blood mononuclear cells (PBMCs) were depleted of hematopoetic cells using RossetteSepTM negative selection kit. RNA extracted from CD45-depleted PBMCs was analyzed for the expression of transcription factors (TWIST1, SNAIL1, SLUG, ZEB1) that induce epithelial-to-mesenchymal transcription (EMT-TF) and epithelial ( CK19) gene transcripts using qRT-PCR. Patient samples with higher epithelial and/or mesenchymal gene transcripts than those of healthy donors (n = 60) were considered CTCs positive. Total 25-OH vitamin D was measured in plasma using ELISA. Results: CTCs were detected in 30 (33%) patients, 14 (15.4%) patients had detectable CTCs with epithelial characteristics, 13 (14.3%) patients had CTCs with an EMT phenotype, while peripheral blood of 3 (3.3%) patients exhibit both CTCs subtypes. Patients with detectable CTCs in peripheral blood had significantly lower vitamin D concentrations in comparison to patients without detectable CTCs (mean ± SD) 8.50 ± 3.89 µg/L for CTCs positive vs. 9.69 ± 3.49 µg/L for CTCs negative patients respectively, P = 0.03). There was no association between plasma vitamin D and other patient/tumor characteristics. At a median follow-up of 96.5 months (range: 8.4 - 109.4 months), 28 patients (30.8%) had experienced a progression and 24 patients (26.4%) had died. Patients with vitamin D above median had better overall survival (HR = 0.36, 95%CI 0.16 – 0.80, P = 0.017) compared to patients below median vitamin D. Conclusions: According to our knowledge, this is the first report of an association between plasma vitamin D concentrations and CTCs in primary breast cancer patients. We suggest that vitamin D could play a direct role in tumor dissemination and its supplementation might affect metastatic cascade. Alternatively, decreased vitamin D could be a consequence and hence a biomarker of a more invasive disease. Animal experiments and interventional studies are needed to prove the causality of the observed association.
Serial genomic analysis of circulating tumor cells and circulating tumor DNA in triple-negative and HER2-positive advanced, metastatic breast cancer.
Authors: Lee Ji Eun , Shin Kabsoo , Joe Seung Yeon , Lee Hayoon , Park Junghoon , Jeon Byung Hee , Lee Ahwon 
Published: June 2022

e12561 Background: Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) have a promising role for detecting early response and progression in breast cancer. We performed serial genomic analysis of CTC and ctDNA in advanced, metastatic triple negative breast cancer (TNBC) and HER2 positive breast cancer (BC). Methods: Serial CTCs, ctDNA were prospectively collected in 9 early or advanced, and 10 metastatic BC patients periodically during systemic chemotherapy. CTC was isolated from whole blood through EpCAM positive bead selection, and ctDNA was isolated from plasma. For genomic profiling of CTC and ctDNA, Oncomine™ Comprehensive Assay Plus and Oncomine™ Pan-Cancer cfDNA assay (included BRCA1, BRCA2 and MYCN customized panel) was performed and analyzed, respectively. Results: TP63 was most commonly detected mutation (13 patients, 68.4%) at serial CTC analysis with median variant of allele frequency (VAF) of 18.6% (range 11.5̃25.2%), irrespective of tumor subtype and stage. In ctDNA analysis, 11 patients showed TP53 mutation with low VAF (median 1.4%, range 0.3̃12.3%). FGFR4 was equally detected, with median variant of allele frequency (VAF) of 57.2% (range 46.6-99.8) and there was no change of FGFR4 VAF irrespective of tumor response in CTC analysis. In three gBRCA1 mutated patients, BRCA1 was identically detected in 3 patients based on CTC analysis and in 2 patients based on ctDNA analysis with VAF of approximately 50%. There were no significant changes of VAF in target mutations of CTC irrespective of tumor response and subtype. In TNBC patients who received neoadjuvant chemotherapy, tumor mutation burden (TMB) showed gradual decrease during treatment. However, there were initial surge of TMB in HER2 positive BC patients who received neoadjuvant chemotherapy, irrespective of presence of pathologic complete response. Conclusions: Our study suggest that serial follow up CTC and ctDNA is feasible and reflect the general characteristics of baseline characteristics and dynamic molecular alteration of breast cancer. Further analysis with larger patient sample and correlation with tumor tissue is warranted in the future.
The relationship of oncotype Dx Recurrence Score (RS) with Ki 67 in early stage breast cancer patients in a community based cancer center in rural central Nebraska.
Authors: Copur Mehmet Sitki , Peterson Tonya , Tun Soe Min , Horn Adam , Wedel Whitney , Duckert Randall , Lintel Nicholas , Springer Carlene R. , Muske Chandra , Robbins Leslie , Arbogast Jessica , Fakkema Emily , Marshall Alison , Brunt Kathryn , Kelly Jacqueline 
Published: June 2022

e12566 Background: Oncotype Dx recurrence score (RS), is a prognostic and predictive test utilized for decision making in adjuvant therapy of 0-3 node/hormone receptor positive(HR+)/ HER-2-negative early breast cancer. Ki-67 is a marker of proliferating cells and is associated with prognosis and response. Immunohistological (IHC) assessment of Ki 67 expression is less expensive and with the approval of CDK inhibitors in the high risk adjuvant setting, it is increasingly being utilized in clinical decision making. A moderate to strong correlation between Ki67 and Oncotype Dx RS has been reported in the literature. We sought to examine the relationship of Ki 67 to Oncotype Dx RS in a community-based cancer center in rural central Nebraska. Methods: Forty-three consecutive postmenopausal breast cancer patients(pts) diagnosed and treated at our community based cancer center between 2020-2021 with T1–2 N0-1 M0, HR+, HER-2-negative disease were evaluated for histological type, tumor size, Nottingham grade, HR levels, Ki 67 expression (low < 10%, intermediate 10 ≥ Ki67 < 25 high ≥ 25), and Oncotype Dx RS(low <16,intermediate 16⩽RS<26), high ⩾26). Ki 67 and Oncotype Dx RS were treated as continuous variables to calculate a Pearson correlation coefficient. Results: Mean age at diagnosis was 59.4 years (range 48-89). Mean tumor diameter was 15.6 mm. 78.9% were intermediate histologic grade and 9.7% patients had lymph node involvement. Median expression of ER and PR were 90% (5-100) and 70% (0-100), respectively. The mean Ki 67 value was 17.5 (range 5-60 %), and mean Oncotype RS was 14.4 (range 4-34). There was a positive linear correlation between Ki 67 expression and Oncotype Dx RS (Pearson Correlation Coefficient=0.49, P-value <0.001). The vast majority of high Ki 67 pts (80%) had high/intermediate Oncotype RS. All pts with low Ki 67 (100%) had low/intermediate RS. Conclusions: Our community based rural cancer center data support a linear, statistically significant, positive correlation between Ki 67 and Oncotype Dx RS in early stage 0-3 node/HR+ positive breast cancer pts. Increasing use of Ki 67 testing in different clinical settings will generate more data to better define this correlation.[Table: see text]
A prospective decision impact study to evaluate the utility of the Oncotype DX Breast DCIS score assay in selecting patients with ductal carcinoma in situ (DCIS) following breast conservation surgery (BCS) for radiotherapy.
Authors: Barry Mitchel , Walsh Siun , Kelly Sinead , Stokes Maurice , Gribbin Anne , Maher Michael A. , Kell Malcolm R. 
Published: June 2022

e12571 Background: There is increasing reliance on data provided by genomic risk assessment assays to guide therapeutic decisions. The objective of this prospective study was to assess the impact of the Oncotype DX Breast DCIS Score assay on radiation treatment recommendations in patients with DCIS undergoing BCS. Methods: This decision impact study is a prospectively enrolled observational study of newly diagnosed patients (n = 135) following BCS for removal of DCIS of all grades 30mm or less with clear margins (i.e. 2 mm or normal re-excised margins). Only patients who were candidates to receive radiation therapy were considered. Fifteen patients withdrew from the study or had insufficient volume of DCIS for assay analysis. Radiation Oncologists were blinded to the Oncotype DX Breast DCIS Score assay prior to recording their recommendation for radiotherapy or not. IRB approval was granted following review of study protocol and informed consent was obtained from all patients. Results: Among 120 patients tested, the Oncotype DX Breast DCIS Score assay determined that 58/120 (48.3%) of patients had a low score (LS) (0-38), 30/120 (25%) had an intermediate score (IS) (39-54) and 32/120 (26.7%) had a high score (HS) (>55). The Oncotype DX Breast DCIS Score assay concurred with the Radiation Oncologists recommendation to proceed with radiation treatment in 96.7% of patients (i.e. 60/62 patients with an IS or HS). The Oncotype DX Breast DCIS Score assay altered treatment decisions in 12.5% (4/32) of patients with a HS and in 7.1% (2/28) patient with an IS. In patients where the Oncotype DX Breast DCIS Score assay altered treatment recommendation all had a low volume (i.e. less than 10mm) of high/intermediate grade DCIS with an IS or HS. Conclusions: This study demonstrates that Oncotype DX Breast DCIS Score assay accurately supports the selection of patients with DCIS for radiation treatment and equally can be helpful in selecting a subgroup of patients with small volumes of intermediate/high grade DCIS who can potentially avoid radiotherapy.