bluuebunny/crossref_metadata_2025_split huggingface dataset:
Highly prognostic signature for stage II colon cancer from the TOSCA trial: The PROSIT study.
Authors: Puccini Alberto , Ferrando Lorenzo , Mazzarella Luca , Frige Gianmaria , Pessino Anna Maria , Pastorino Alessandro , Martelli Valentino , Garuti Anna , Di Antonio Veronica , Ballestrero Alberto , Torri Valter , Labianca Roberto , Fassan Matteo , Lonardi Sara , Zoppoli Gabriele , Sobrero Alberto F. 
Published: June 2024

3524 Background: The predictive and prognostic value of current biomarkers for guiding the treatment of stage II colon cancer (CC) is very limited. Here, we aimed to develop a prognostic transcriptional signature for high-risk stage II CC patients undergoing adjuvant treatment with either 3 or 6 months of FOLFOX4/CAPOX within the framework of the phase III TOSCA Italian trial. Methods: We conducted an observational retrospective study based on the TOSCA trial database, matching 62 patients with high-risk stage II CC who relapsed with 62 who did not. The matching criteria included the center of recruitment, pT stage, adjuvant treatment type and duration (3 or 6 months). Transcriptome sequencing was performed on material from centrally assessed FFPE blocks on an Illumina Novaseq 6000 instrument. Generated data were processed using the nf-core/rnaseq (v 3.14.0) pipeline, aligned to the human genome GRCh37/hg19, and analyzed for differential gene expression, requiring a minimum absolute log fold change of 1 and false discovery rate below 0.1. Enrichment analysis was performed using GSVA package with the z-score method. Results: Out of the 124 stage II CC cases considered for the present analysis, 60% received 3 months and 40% 6 months of adjuvant chemotherapy. The median age was 64 years (IQR 55.2-71.1), with 40% of the cancers being right-sided. Fifty-seven percent of the patients received FOLFOX, while the remaining were treated with XELOX. Of the 124 matched samples, 72 were of sufficient quality for RNA-seq.We identified a signature among the top 17 differentially expressed genes (absolute log fold-change > 1, p-value < 0.001, FDR < 0.1, see Table). Patients exhibiting a lower prognostic signature (PROSIT-L) showed worse disease-free survival (DFS) compared to those with a high prognostic signature (PROSIT-H) (HR 3.5; 95% CI 1.53 – 7.9; p = 0.002), indicating its strong and independent prognostic value, regardless of the treatment received. Conclusions: The new transcriptomic signature may help in identifying stage II CC patients who are likely to relapse despite receiving adjuvant oxaliplatin-based treatment. [Table: see text]
Allele-specific KRAS mutations as prognostic biomarkers in mucinous adenocarcinoma of the appendix and colorectal cancer.
Authors: Khushman Moh'd M. , Abushukair Hassan Mohammed , Alhushki Sanad , Iglesia Michael , Lim Kian-Huat , Liu Xiuli , Trikalinos Nikolaos , Suresh Rama , Aranha Olivia , Grierson Patrick , Tan Benjamin R. , Pedersen Katrina Sophia 
Published: June 2024

3628 Background: Kristen rat sarcoma virus ( KRAS) mutations (MT) are reported in 40-45% of colorectal cancer (CRC), and they are associated with poor prognosis. In mucinous adenocarcinoma of the appendix (MAAP), which is often treated as CRC due to its rarity, KRAS MT are reported in >50% of tumors, and they are associated with favorable prognosis. We explored whether allele-specific KRAS MT are associated with overall survival (OS) in stage IV MAAP and CRC. Methods: The cBioCancer Genomics Portal was used to obtain genomic data. The prevalence of KRAS MT and the OS associated with allele-specific KRAS MT were explored in stage IV CRC (MSK, Cancer Cell 2018 cohort) and MAAP (MSK, J Clin Oncol 2022 cohort) patients. Survival analysis was performed using the Kaplan-Meier method with log-rank test comparisons. Results: The prevalence of KRASMT in stage IV MAAP (N=149) and CRC (N=1099) was 79.8% and 44.2% respectively. The prevalence of allele-specific KRAS MT (G12D, G12V, G13D and G12C) in MAAP/CRC was 42.3% / 12.4%, 18.8% / 9%, 6.7% / 7.7% and 6% / 2.8% respectively. All other KRAS MT in MAAP/CRC were seen in 6% and 12.2% respectively. In MAAP, the median OS (mOS) in KRAS MT vs. KRAS wild-type (WT) was 147m vs. 50m (p=0.003). Compared to the mOS in KRAS WT, the mOS was 147m (p=0.004) in G12D, 74m (p=0.140) in G12V, not reached (NR) (p=0.049) in G13D and 34m (p=0.589) in G12C. In CRC, the mOS in KRAS MT vs. KRAS WT was 60m vs. 79m (p=0.012). Compared to the mOS in KRAS WT, the mOS was 58m (p=0.249) in G12D, 58m (p=0.015) in G12V, 49m (p=0.002) in G13D and 65m (p=0.437) in G12C. The mOS in MAAP vs. CRC was 50m vs. 79m (p=0.022) in KRAS WT, 147m vs. 58m (p=0.02) in G12D, 74m vs. 58m (p=0.34) in G12V, NR vs. 49m (p=0.044) in G13D and 34m vs. 65m (p=0.13) in G12C. The favorable mOS associated with G12D in MAAP remained significant after adjusting for age, grade and TP53 (p=0.028) Conclusions: KRAS MT are more common in MAAP (79.8%) than in CRC (44.2%). In contrast to CRC, KRAS MT in MAAP are associated with favorable prognosis. Allele-specific KRAS MT are associated with different mOS in MAAP and CRC. The mOS in MAAP with KRAS G12D was exceptionally favorable (147m). To our knowledge, this is the first study to explore allele-specific KRAS mutations as prognostic biomarkers in MAAP, and adds additional data to support the distinct differences between MAAP and CRC at the molecular level. [Table: see text]
Predictive biomarkers for pathological complete response in early-stage triple negative breast cancer following neoadjuvant chemotherapy.
Authors: Polho Gabriel Berlingieri , Testa Laura , BARROSO-SOUSA ROMUALDO , Bonadio Renata Colombo 
Published: June 2024

598 Background: Identifying predictive biomarkers for early-stage triple negative breast cancer (TNBC) is essential for tailoring neoadjuvant chemotherapy (NACT) strategies effectively. Methods: We investigated potential clinical and pathological biomarkers in early-stage TNBC patients who underwent NACT regimens with anthracyclines and taxanes at a single cancer center. Medical records were scrutinized for clinical and laboratory data, with categorical variables analyzed using Fisher’s exact test. Logistic regression assessed factors associated with pathological complete response (pCR). Sensitivity and specificity of the biomarkers were explored using receiver operating characteristics (ROC) curve analyses. Results: Among 110 TNBC patients receiving anthracycline- and taxane-based NACT with complete pathology data, the median age was 48 years, 60% had stage III tumors, and 30.9% achieved pCR. Stromal tumor infiltrating lymphocytes (TILs) > 10% were observed in 54.5%, 32.7% had TILs ≥30%, and 90.9% had Ki67 ≥ 50%. Univariate analysis showed no association between pCR and TILs >10% (p=0.5), Ki67 ≥ 50% (p=0.4), anatomic stage (p=0.06), eosinophil-to-lymphocyte ratio (p=0.3), platelet-to-lymphocyte ratio (p=0.08), age (p=0.5), grade (p=0.6), or HER2 status (p=0.6). Neutrophil-to-lymphocyte ratio (NLR) was significantly associated with pCR in both univariate (OR 3.92; 95% CI 1.67 - 9.57; p=0.002) and multivariable analyses (Table). No association was observed between NLR ≤ 1.76 and TILs, anatomic stage, or Ki67. The optimal NLR cutoff using ROC curve was 1.76, yielding 60.6% sensitivity and 71.8% specificity for pCR. NLR cutoffs of ≤ 1.43 had specificities higher than 85%. Although TILs value was not associated with pCR in the regression model, high TILs value (≥50%) yielded a specificity of 89.4% for pCR. Conclusions: NLR emerged as a significant and independent predictor of pCR in early-stage TNBC. Prospective studies should explore this readily available biomarker in assessing neoadjuvant strategy responses. Moreover, high specificities for pCR were observed with NLR ≤ 1.43 and TILs ≥ 50%, representing cutoff values that could be explored for treatment de-escalation. [Table: see text]
Predicting locoregional recurrence in triple-negative breast cancer using novel molecular subtyping.
Authors: Shao Shali , Shi Wei , Zhang Li , Zhang Qixian , Meng Jin , Yang Zhaozhi , Mei Xin , Chen Xingxing , Ma Jinli , Mo Miao , Shao Zhimin , Zhang Zhen , Guo Xiaomao , Yu XiaoLi 
Published: June 2024

e12549 Background: Triple-negative breast cancer (TNBC) presents a poorer prognosis compared to other breast cancer subtypes, characterized by a higher likelihood of early recurrence and increased incidence of visceral metastases. Evidence from numerous randomized clinical trials indicates that postmastectomy radiotherapy (PMRT) reduces locoregional recurrence (LRR) and improves breast cancer survival in TNBC. Previous reports creatively divided TNBC into four molecular subtypes for personalized treatment. The present study aims to elucidate patterns of LRR in different subtypes of TNBC after PMRT. Methods: From 2019 to 2022, data from 349 AJCC 7th edition stage II-III breast cancer patients treated with mastectomy and PMRT were retrospectively analyzed. These patients were classified into the basal-like immune-suppressed (BLIS) and non-BLIS groups based on the immunohistochemistry biomarkers. The cumulative incidence function was applied to estimated LRR rates, with death as a competing risk, using Gray's test for comparisons. Results: According to the IHC results, a total of 255 patients belonged to the non-BLIS group and 94 to the BLIS group. The 3-year LRR for the entire cohort was 5.16%. There were 9 cases each in the non-BLIS subtype (3.5%) and BLIS subtype (9.6%). The cumulative incidence of LRR between the two groups was significantly different, with a rate of 4.0% in the non-BLIS group and 9.0% in the BLIS group ( P = 0.02). Among the 18 patients with LRR in the whole population, 11 had isolated LRR and 7 were diagnosed with LRR with concurrent distant metastases. The most common area of recurrence in both subtypes was the supraclavicular region. The majority of recurrences occurred within the RT field (in-field), and no isolated out-of-field relapse was observed. In multivariate analysis, independent factors predicting higher LRR were the BLIS subtype (HR = 3.06, P = 0.02). Conclusions: Study results suggest that TNBC of the BLIS subtype is at higher risk for LRR. Immunohistochemistry-based molecular typing may serve as a prognostic biomarker to guide postmastectomy radiotherapy in patients with TNBC. New strategies are needed to improve local control rates in patients with BLIS subtype.
LC3AB protein-based gene (PbG) signatures as an indicator of relapse even after achieving pathological complete response.
Authors: Singhal Sandeep K. , Gardner Kevin 
Published: June 2024

e12552 Background: The application of tissue-based quantitative protein and morphological profiling of breast cancer tissues combined with RNA sequencing provides a flexible and generally applicable and scalable method to develop Protein-based Gene (PbG) signatures with significant prognostic value. Methods: A racially and subtype diverse breast cancer cohort (N=555) with available subset of RNA-seq data was used to develop gene expression-based signatures by stratifying patients according to protein expression (IHC) based on survival information and tumor lymphocyte infiltration (TILs) using survival-derived cutoff values. The predictive value of these signatures was then compared with other popular biomarkers scoring systems such as ROR.score, and OncotypeDx (Gene 21). Here we describe the predictive value of these signatures is evaluated by logistic regression modeling of publicly available gene expression data (N=996) from patients receiving neoadjuvant chemotherapy (anthracycline +/- taxane) with a final validation in an independent cohort (N=443) receiving similar therapy. Results: A model of PbG-derived signature from Kaiso, LC3A/B IHC and quantitative TIL-measurements together with ROR score, MAPK, PTEN, Immune and Gene21 signatures show significant prediction of distant metastasis-free survival in all patients: (DMFS, AUC= 0.737, 95% CI: 0.665- 0.819); and in non-pCR patients DMSF (AUC= 0.71, 95% CI: 0.633-0.773). When examining the role of all those markers among the patients who achieved the pCR and had relapse, the LC3A/B PbG-derived score was found to be highly predictive of those patients who would not achieve pCR and ultimately have recurrent disease. Conclusions: PbG-based signatures utilizing on LC3A/B protein values offer a novel and clinically relevant predictive biomarker of response to therapy and relapse in breast cancer patients.
Clinicopathological features and prognosis for pregnancy-associated breast cancer: A matched case-control study.
Authors: Al-Awadhi Aydah , Al-Shamsi Saif , Hourani Mohammad , Hussein Mawada , AlKindi Fatima , Wahba Lina , Alagha Abla , Shoqeir Alaa , Younis Tallal 
Published: June 2024

e12573 Background: Pregnancy-Associated Breast Cancer (PABC) is defined as breast cancer diagnosed during pregnancy or within 1 year postpartum. Studies indicate that PABC tends to have poorer prognostic characteristics and often worse outcomes compared to non-PABC. The primary goal of this study is to examine disease characteristics associated with PABC versus non-PABC in the United Arab Emirates (UAE), where breast cancer is characterized by a younger age and more advanced stage compared to North America and Europe. Additionally, the UAE has a younger mean age for first-time mothers and a similar age for all mothers compared to North America and Europe. Methods: Patients with PABC were selected from BC cases of women ≤40 years treated at Tawam Hospital, the largest tertiary cancer center in the UAE between January 2003 – December 2020. Each PABC patient was matched to two non-PABC patients (controls) according to cancer stage, age, and year of diagnosis. The Fisher's exact and Kruskal-Wallis tests were used to compare both study groups. Results: 66 women with PABC were identified, with a median age at diagnosis of 33.0 (interquartile range [IQR]: 30.0-37.0) years. Most presented with stage II (45.5%) or stage III (39.4%) disease and underwent mastectomy and axillary lymph node dissection. Invasive ductal carcinoma was the most frequent histological type in both groups (86.4% for PABC and 85.6% for non-PABC). PABC was associated with higher grade 3 disease compared with non- PABC (53% vs 51.5% p= 0.009). More women with PABC received neoadjuvant chemotherapy (NACT) and radiation therapy (RT) compared with non-PABC (48.5% vs 3%, p <0.001 and 80.3% vs 65.9%, p= 0.046, respectively). There were no statistically significant differences with regards to tumor size, nodal involvement, underlying histologic subtype, ER/PR expression or HER-2 status, rates of breast-conserving surgery and adjuvant chemotherapy receipt between the two groups. The median progression-free survival (PFS) was 3.2 years (IQR: 1.9-7.1) in PABC and 3.4 years (IQR: 1.2-6.2) in non-PABC group (P=0.306). The median overall survival (OS) was 4.5 years in the PABC (IQR: 2.4-7.9) versus 4.5 years (IQR: 1.9-7.9) in the non-PABC group (P = 0.786). Conclusions: PABC in women ≤40 years appears to be associated with grade III tumors and NACT and RT receipt compared to non-PABC. However, there were no significant difference in PSF and OS between PABC and non-PABC. Further analysis is underway to evaluate the prognostic factors and their effect on survival.
Is there a correlation between estrogen receptor expression level and early breast cancer survival? A retrospective study.
Authors: Rasmy Ayman , Zeeneldin Ahmed , Abozeed Walid , Elsamany Shereef 
Published: June 2024

e12574 Background: The optimal cut-off of estrogen receptor (ER) positivity is still debatable; however, adjuvant hormonal therapy is usually given if ER expression is ≥ 1%. The present study aims to assess the clinicopathological features and survival outcomes of patients with low compared to high ER expression levels. Methods: In this retrospective, we checked non-metastatic hormonal receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients who presented to three hospitals in Egypt and Saudi Arabia between 2016 and 2019. Different clinicopathological factors and data on relapse were checked in patients’ medical records. These data were compared in patients with ER-Low (1–10%) vs. ER-High (>10%) expression levels. Results: We included 419 patients who met the eligibility criteria for the study. Only 3.3% of patients had ER-Low. Compared to the ER-high group, the ER-low expression group was more likely to have grade 3 tumours (64.3% vs. 21.0%, p = <0.0001) and PR-negative tumors (64.3% vs. 16.3%, p = <0.0001). Furthermore, younger age (≤ 50 years) was more frequent in the ER-Low group compared to ER-High patients (71.4% vs. 42.5%, respectively, p = 0.032). Likewise, ER-high patients were more likely to have high ER-staining intensity (74.1% vs. 0.0%, p<0.0001). Disease-free survival (DFS) was numerically improved in patients with ER-high, but without statistical significance. After adjustment of different clinicopathological prognostic factors, the DFS benefit in the ER-high group was more definite (hazard ratio (HR) = 3.59, 95%, confidence interval (CI) = 1.11–11.55, and p value = 0.032). Conclusions: A lower estrogen receptor expression level (varying from 1 to 10%) in hormone-positive early breast cancer patients is an uncommon pattern associated with more aggressive disease features at diagnosis. This group of patients had a lower DFS than those with a higher degree of estrogen receptor expression, although there was no statistically significant difference in OS.
Can patients with biopsy-diagnosed DCIS safely spare sentinel lymph node biopsy (SLNB)?
Authors: Li Xinyu , Li Yudong , Liu Qiang 
Published: June 2024

e12583 Background: While the guidelines generally recommend that most patients with biopsy-diagnosed breast ductal carcinoma in situ (DCIS) can be spared from axillary staging if receiving breast conserving surgery, the percentage of such patients received SLNB is still as high as 50-70%. SOUND trial recently provides some low risk invasive breast cancer patients with the option of omitting SLNB, further highlighting the necessity of omitting SLNB in DCIS patients. This study aimed to retrospectively analyze the chance of turning into invasive cancer and lymph node metastasis in the patients who are diagnosed as DCIS by biopsy. Methods: Preoperative biopsy-diagnosed breast pure DCIS patients between 2011-2023 were retrospectively reviewed in Sun Yat-sen Memorial Hospital. Patients with axilla staging were grouped by pathology status (LN- versus LN+). Differences were compared using either t test or chi-squared test. Multi-variate logistic regression model was conducted to stratify the risk for LN metastasis. Results: 1193 patients were eligible for analysis, of whom 51.8% turned invasive breast cancer (IBC) in post-surgery pathology. 42% and 81% of IBCs were only T1mi and less than 1cm foci (T1a,b) respectively. 1161 (97.3%) patients had available axilla LN information and their axillary metastasis rate was 7.1% (0.9% and 12.5% in DCIS and IBC). Only 22 (1.9%) or 15 (1.3%) patients had ≥ 3 or 4 positive LN involved. Multi-variate analysis identified four risk factors associated with LN metastasis: ultrasound suspicious lymph node (OR=2.22, 95%CI: 1.21-4.07), tumor size (>2cm vs ≤2cm: OR=2.85, 95%CI:1.10-7.42), biopsy method (core biopsy vs excision: OR=7.04, 95%CI:1.60-31.25) and necrosis (OR=2.20, 95%CI: 1.23-3.94). Among 440 patients with excision biopsy, only 1.4% had LN involved. In the other 721 patients diagnosed by core biopsy, the LN metastasis rate of patients who had 0,1,2 and 3 risk factors were 3.6%, 6%, 21% and 29.5%, respectively. Based on the number of risk factors patients were stratified to low risk (having 0-1 risk factor) and high risk (having ≥2 risk factors), with low risk patients having only 5.4% LN metastasis. Conclusions: Although the patients diagnosed with preoperative pure DCIS had a high chance of upgrading to invasive cancer, only 7.1% of them had lymph node metastasis. 98% of them are Z0011-eligible and 40% of them are SOUND-eligible if they receive breast conserving surgery, indicating the futility of axillary staging in these patients. We identified four independent risk factors for LN metastasis (suspicious lymph node on US, tumor size, biopsy method and necrosis). Even in the patients who received mastectomy, if they have only 0-1 risk factors, SLNB can still be safely omitted.
Interpectoral nodal dissection for invasive breast cancer: A retrospective single institution study from India.
Authors: Vijayakumar Varadharajan , Venkitaraman Balasubramanian , Kajamohideen Suhaildeen 
Published: June 2024

e12585 Background: Interpectoral lymph nodes are one of the axillary lymphatic drainage sites in breast carcinoma. Usually dissection of Interpectoral nodes (IPN) avoided during axillary dissection as they are not the primary lymphatic drainage site. Our study aims to identify the rate of positivity of Interpectoral nodes in invasive breast cancer, predictors of IPN positivity in relation to tumour location, size, grade and hormone receptor status and to evaluate the need for IPN clearance during axillary dissection. Methods: A retrospective analysis of histopathology reports of 367 patients who underwent Axillary dissection in a single centre from Jan 2017-Dec 2022 for breast cancer was analysed. Inclusion criteria: Female Patients with operable Invasive Breast cancer with node positive axilla who underwent axillary dissection (upfront and post chemotherapy). Exclusion criteria: metastatic breast cancer, node-negative patients/sentinel lymph node biopsy, inadequate nodal dissection, and incomplete clinicopathological information. Data was analysed looking for presence of nodes in interpectoral tissue in Axillary dissection and to identify the positivity of interpectoral lymph nodes in specimens. Results: Interpectoral nodal dissection was done in n=216 of the 367 patients. The clinicopathological characters are described in Table. IPN were identified in 35% (n=77) of the 216 Axillary dissection specimens. IPN were positive in 7.8% (17 of 216) of patients who had interpectoral nodal dissection. 22% of the interpectoral lymph nodes removed were positive. As regards tumour size, Rotter's nodes were identified commonly in T3 and T4 tumours and positive in people with N2 and N3 disease. By multivariate analysis, T stage and N stage were the most important determinants of IPN yield and positivity. Site of tumour, neoadjuvant therapy, molecular subtype or Ki 67 were not found to be associated with either presence or positivity of interpectoral nodes. In 5 cases IPN positivity upstaged the nodal stage and in 1 patient it was the only positive node. Conclusions: As IPN is positive in most LABC, whenever axillary dissection is done in such cases Interpectoral nodes can be safely removed while dissecting level III nodes. Nodal recurrence is the most common site of recurrence post mastectomy and hence Interpectoral nodes need to be routinely removed in patients undergoing Axillary dissection for operable breast cancer to enable accurate staging and to prevent local or systemic failure. [Table: see text]