Increased Lymph Node Involvement Research Articles

Abstract PO5-20-08: A Case of Multifocal Ductal Breast Carcinoma with Extension into Lobules and Concurrent Primary Colon Adenocarcinoma

Abstract Background Multifocal (MF) multicentric breast cancer is a form of breast cancer that consists of disease independently developing at various locations due to a tumor clone spreading within the ductal complex. Multifocal breast cancer is associated with increased local recurrence. Our case highlights an example of multifocal breast cancer and addresses treatment challenges. Case presentation The patient is a 52-year-old African American female with a history of HCV cirrhosis, diabetes mellitus, and hypertension who presented with a palpable 4 cm right breast mass, without adenopathy, clinically Stage II, T2N0. Mammogram revealed a 2.5 cm right breast mass and three right level 1 axillary nodes with biopsy confirming invasive ductal carcinoma with extension into the lobules, ER positive (3%)/PR-/HER2-, Ki-67 95%. Neoadjuvant paclitaxel, carboplatin, and pembrolizumab was initiated but she incurred complications of decompensated liver cirrhosis after the second cycle and treatment was held. After 2 cycles her tumor was not palpable, and surgery was recommended, but due to COVID infection and concurrent decompensated liver failure surgery management was delayed. She underwent staged surgery with partial mastectomy without lymph node exploration. Histopathology showed DCIS grade 3 with extension into lobules and invasive ductal carcinoma with no lymphovascular invasion and all margins were negative, pathological stage ypT3NxM0. Immunohistochemistry demonstrated partial ER+ (50%)/PR-/HER2-, Ki-67 80%. She was given 4 cycles of adjuvant cyclophosphamide, adriamycin, pembrolizumab and continued on maintenance pembrolizumab. The patient was found with anemia out of proportion to chemotherapy and underwent colonoscopy that showed a colonic mass. Biopsy showed a primary moderately differentiated colonic adenocarcinoma. Her re-excision with new margins for partial mastectomy had negative margins, and 2 negative sentinel lymph nodes for ypN0. Genetic testing was negative. She continued on adjuvant immunotherapy with pembrolizumab for breast cancer. She is planned to start on adjuvant anastrozole. Patient has completed adjuvant radiation treatment and has no new complaints. She is pending curative intent completion colectomy for colon cancer. Discussion This case of MF breast cancer is significant, as one foci was ER negative, which responded to neoadjuvant chemoimmunotherapy and other ER positive that did not respond to treatment and was surgically excised. The pathology report from the surgical specimen revealed DCIS with extension into the lobules. Due to her tenuous clinical condition, she had staged surgeries for breast cancer, and now colon cancer. Genetic testing is negative. Currently, there is insufficient data to suggest which surgical approach is preferred in MF breast cancer. Based on the literature, breast conservation therapy (BCT) is a feasible option and is oncologically safe. Due to the patients’ medical condition and infections, it was felt a less invasive surgery could offer cure and minimize complications. Our patient underwent neoadjuvant chemoimmunotherapy, followed by partial mastectomy, adjuvant chemoimmunotherapy, second staged completion breast surgery, radiation therapy, and anti-estrogen therapy. MF breast cancer is associated with increased lymph node involvement. A 2022 meta-analysis found that multifocal and multicentric breast cancer has a slightly increased risk of death as compared to unifocal tumors. Lastly, our patient is African American, and multifocal tumors occur with a higher incidence in African Americans (43.4%) and Asian patients (37%) as compared to whites (28.9%). This case of breast cancer highlights treatment challenges in a case of multifocal multicentric breast cancer occurring concurrently with a secondary primary colonic cancer. Citation Format: Rabab Jafry, Hina Khan, Jessica Jones. A Case of Multifocal Ductal Breast Carcinoma with Extension into Lobules and Concurrent Primary Colon Adenocarcinoma [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-20-08.

Geriatric Importance of Histopathological Parameters Evaluated in Thyroidectomy Specimens: A Single Center Retrospective Analysis.

Nowadays, the aging human population exerts a notable influence on the treatment of thyroid diseases. The most appropriate approach for the treatment of benign and malignant thyroid diseases in older adults has not yet been determined. The aim of our study is to evaluate the effect of thyroidectomies in geriatric patients considering age, sex and histopathological parameters and to determine the importance of thyroidectomy as a treatment option in the geriatric population. A total of 910 cases from all age groups were included, for which thyroidectomies were examined and reported. In accordance with the College of American Pathologists Cancer Protocol for thyroid reporting, considering geriatric patients, the rate of Thyroid Follicular Nodular Disease was significantly higher among the tumor types in the benign tumor group (p = 0.033), while Anaplastic Thyroid Carcinoma rate was higher in the malignant tumor group. The diagnosis rate of malignant tumors was higher in males, reflecting a more advanced pT stage (p < 0.001), larger tumor size (p < 0.001) and increased lymph node involvement rate (p = 0.039). Given that increasing age is associated with a heightened incidence of thyroid disease, the safety of surgery for geriatric patients is an important issue. Thyroidectomy should be considered in the treatment of these patients, especially in males, as the rate of malignant diagnosis and worse histopathological parameters are seen with increasing age.

Histologic type predicts disparate outcomes in pediatric hepatocellular neoplasms: A Pediatric Surgical Oncology Research Collaborative study.

Hepatocellular carcinoma (HCC) is a rare cancer in children, with various histologic subtypes and a paucity of data to guide clinical management and predict prognosis. A multi-institutional review of children with hepatocellular neoplasms was performed, including demographic, staging, treatment, and outcomes data. Patients were categorized as having conventional HCC (cHCC) with or without underlying liver disease, fibrolamellar carcinoma (FLC), and hepatoblastoma with HCC features (HB-HCC). Univariate and multivariate analyses identified predictors of mortality and relapse. In total, 262 children were identified; and an institutional histologic review revealed 110 cHCCs (42%; 69 normal background liver, 34 inflammatory/cirrhotic, 7 unknown), 119 FLCs (45%), and 33 HB-HCCs (12%). The authors observed notable differences in presentation and behavior among tumor subtypes, including increased lymph node involvement in FLC and higher stage in cHCC. Factors associated with mortality included cHCC (hazard ratio [HR], 1.63; P = .038), elevated α-fetoprotein (HR, 3.1; P = .014), multifocality (HR, 2.4; P < .001), and PRETEXT (pretreatment extent of disease) stage IV (HR, 5.76; P < .001). Multivariate analysis identified increased mortality in cHCC versus FLC (HR, 2.2; P = .004) and in unresectable tumors (HR, 3.4; P < .001). Disease-free status at any point predicted survival. This multi-institutional, detailed data set allowed a comprehensive analysis of outcomes for children with these rare hepatocellular neoplasms. The current data demonstrated that pediatric HCC subtypes are not equivalent entities because FLC and cHCC have distinct anatomic patterns and outcomes in concert with their known molecular differences. This data set will be further used to elucidate the impact of histology on specific treatment responses, with the goal of designing risk-stratified algorithms for children with HCC. This is the largest reported granular data set on children with hepatocellular carcinoma. The study evaluates different subtypes of hepatocellular carcinoma and identifies key differences between subtypes. This information is pivotal in improving understanding of these rare cancers and may be used to improve clinical management and subsequent outcome in children with these rare malignancies.

Determining the relationship between cytokeratin expression and prognostic factors in human gastric cancer.

Determining the prognosis of gastric cancer is the most crucial step in the treatment process. Cytokeratins are intermediate filaments found in the intracellular structure of epithelial tissues. Recent researches have focused on determining the relationship between the expression of cytokeratins and the degree and prognosis of tumors. This study aimed to investigate the relationship between the incidence of cytokeratin-20 and cytokeratin-7 in patients with gastric carcinoma with factors influencing the prognosis. In this regard, the study was conducted cross-sectional. The expression of cytokeratin-20 and cytokeratin-7 was evaluated on 50 gastric adenocarcinoma specimens with different degrees of differentiation by the immunohistochemical method. We determined the relationship between the incidence of cytokeratin-20 and cytokeratin-7 with factors affecting the prognosis of patients, including the degree of differentiation of gastric cancer tissue, lymph node involvement, and the depth of tumor invasion. Data were statistically analyzed by Chi-square and Spearman tests. The results showed a statistically inverse relationship between the incidence of cytokeratin-20 and cytokeratin-7 with the degree of tissue differentiation and lymph node involvement in gastric cancer. Although there was a statistically significant relationship between the incidence of tissue invasion in gastric cancer and the incidence of cytokeratin-7, there was no association between the incidence of cytokeratin-20 and tissue invasion. In general, decreased cytokeratin-20 and cytokeratin-7 are associated with decreased tissue differentiation and increased lymph node involvement.

Evaluation of Vimentin Expression in Colorectal Cancer and Its Association With Prognostic Factors

Vimentin is a cellular marker that has recently been considered in the prognosis of colorectal cancer (CRC), and its expression appears to indicate increased malignancy. The aim of this study was to investigate the expression of vimentin in CRC patients and its association with prognostic factors. This retrospective study was performed on CRC patients who had undergone colectomy at Imam Khomeini Hospital, Ahvaz, Iran, in 2019 and 2020. Data around the microscopic degree of the tumor differentiation and the status of lymph node involvement were extracted from the patients' pathology reports. Immunohistochemistry staining for vimentin was performed on biopsy specimens, and its expression was assessed and compared in both CRC specimens and normal colon tissues. Appropriate statistics were used with P&lt;0.05 considered as statistically significant. Out of 31 CRC patients, vimentin expression was moderate-positive in 20 (64.5%) and strong-positive in 11 patients (35.5%). Mean percentage of stained cells, the intensity of staining, and vimentin expression in the immunohistochemistry evaluations had no significant relationship with tumor grade and tumor invasion rate (P&gt;0.05), but they showed a significant relationship with lymph node involvement (P&lt;0.05) and mean percentage of stained cells, the intensity of staining, and expression of vimentin marker increased with increasing lymph node involvement. In the normal tissue samples, 5 out of 30 samples showed weak-to-moderate vimentin expression. Vimentin expression was significantly associated with lymph node involvement; however, further studies with larger sample sizes are required to determine its probable association with other prognostic variables.

MYBL2-Driven Transcriptional Programs Link Replication Stress and Error-prone DNA Repair With Genomic Instability in Lung Adenocarcinoma.

It has long been recognized that defects in cell cycle checkpoint and DNA repair pathways give rise to genomic instability, tumor heterogeneity, and metastasis. Despite this knowledge, the transcription factor-mediated gene expression programs that enable survival and proliferation in the face of enormous replication stress and DNA damage have remained elusive. Using robust omics data from two independent studies, we provide evidence that a large cohort of lung adenocarcinomas exhibit significant genome instability and overexpress the DNA damage responsive transcription factor MYB proto-oncogene like 2 (MYBL2). Across two studies, elevated MYBL2 expression was a robust marker of poor overall survival and disease-free survival outcomes, regardless of disease stage. Clinically, elevated MYBL2 expression identified patients with aggressive early onset disease, increased lymph node involvement, and increased incidence of distant metastases. Analysis of genomic sequencing data demonstrated that MYBL2 High lung adenocarcinomas had elevated somatic mutation burden, widespread chromosomal alterations, and alterations in single-strand DNA break repair pathways. In this study, we provide evidence that impaired single-strand break repair, combined with a loss of cell cycle regulators TP53 and RB1, give rise to MYBL2-mediated transcriptional programs. Omics data supports a model wherein tumors with significant genomic instability upregulate MYBL2 to drive genes that control replication stress responses, promote error-prone DNA repair, and antagonize faithful homologous recombination repair. Our study supports the use of checkpoint kinase 1 (CHK1) pharmacological inhibitors, in targeted MYBL2 High patient cohorts, as a future therapy to improve lung adenocarcinoma patient outcomes.

The association of lymph node involvement with lenfovascular invasion, perineural invasion and peritumoral lymphocytic reaction in surgically treated colon cancer patients

Aim: The American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) cancer staging system is the strongest prognostic parameter for colorectal cancer. However, additional markers are needed to improve clinical decision making. The aim of this study was to investigate the effects of lenfovascular invasion (LVI), perineural invasion (PNI) and peritumoral lymphocytic reaction (PLR) on lymph node involvement in surgically treated colon cancer patients.Materials and Methods: The historical records of patients having undergone colon cancer surgery in the Department of General Surgery were evaluated. In addition to demographic data and pathological TNM staging, parameters including tumor location, type, differentiation, LVI, PNI, PLR and tumor growth pattern were recorded and analyzed. p<0.05 was considered as statistically significant.Results: The study group of 71 patients consisted of 39 (54.9%) men and 32 (45.1%) women with a mean age of 65.1±12.3 (range: 39- 89) years. Tumors were located in the ascending colon in 18 (25.4%) patients, in the transverse colon in 3 (4.2%), in the descending colon in 8 (11.2%) and in the sigmoid colon in 42 (59.2%) patients. According to the postoperative histopathological examinations LVI was detected in 65 (91.6%) cases whereas PNI was found in 14 (19.7%) cases. PLR was detected in 69 (97.2%) cases that was mild in 53 (74.6%) and moderate in 16 (22.6%) cases. The incidence of PNI was significantly higher in stage N2 cases (p=0.001). On the other hand, no significant differences were found among N stage groups regarding LVI or PLR (p=0.409 and p=0.441, respectively). Although it was detected that LVI and PLR were present concomitantly in 63 (88.7%) cases, no significant differences were detected between mild, moderate or negative PLR with respect to LVI positivity (p=0.748).Conclusion: PNI was associated with increased lymph node involvement. Larger prospective randomized controlled studies are needed to be conducted in order to establish additional prognostic parameters in colon cancer surgery.

WNT/β-catenin pathway activation via Wnt1 overexpression and Axin1 downregulation correlates with cadherin-catenin complex disruption and increased lymph node involvement in micropapillary-predominant lung adenocarcinoma.

BackgroundMicropapillary-predominant adenocarcinoma (MPA) of the lung is associated with extensive lymph node involvement and rapid terminal metastasis. However, this subtype has been recognized for only a few years, and there have been few studies of the molecular mechanisms associated with its highly invasive behaviors.MethodsThe present study utilized immunohistochemical staining of surgically resected tissue blocks of MPA and lepidic-predominant lung adenocarcinoma to quantify the expression of specific biological markers in the WNT/β-catenin pathway and evaluate their influence on the lymph nodes invasion of these two types of lung adenocarcinomas.ResultsOur findings revealed that disruption of the cell membrane cadherin-catenin complex, which weakens the tumor cell adherence of MPA, was caused by the dissociation of β-catenin from the cadherin-catenin complex and the subsequent accumulation of β-catenin in the cytoplasm. This caused abnormal activation of the WNT/β-catenin pathway. We also found that Wnt-1-specific overexpression and Axin1 inhibition in MPA could explain the redistribution and cytoplasmic retention of β-catenin. Collectively, these findings suggest that an abnormality in the WNT/β-catenin pathway could enhance the invasiveness of MPA through the overexpression of Wnt-1 and downregulation of Axin1 molecules.ConclusionsOur data support the need for further research regarding the WNT/β-catenin pathway and the need to develop novel targeted therapies for restoration of tumor cell adherence and improvement of the prognosis of MPA.

CCAAT/Enhancer-Binding Protein Delta (C/EBPδ): A Previously Unrecognized Tumor Suppressor that Limits the Oncogenic Potential of Pancreatic Ductal Adenocarcinoma Cells.

Simple SummaryHere we show that a protein called C/EBPδ is present in healthy pancreas tissue but almost absent in pancreas tumors. Patients with less C/EBPδ in their tumors had the most metastases and the worst survival chances, showing that C/EBPδ has tumor-suppressive properties in pancreatic cancer. In this study, we reactivated C/EBPδ in pancreatic cancer cells in vitro and observed a reduction in cell proliferation in a 2-dimentional and 3-dimensional space. This implies that tumor cells grow slower when C/EBPδ is activated and they are likely also less capable to escape the primary tumor in order to form metastases. Conversely, when we deleted C/EBPδ in pancreatic cancer cells, we observed accelerated growth. We suggest that reactivating C/EBPδ can suppress tumor growth and formation of metastases, thereby improving patient survival.CCAAT/enhancer-binding protein δ (C/EBPδ) is a transcription factor involved in growth arrest and differentiation, which has consequently been suggested to harbor tumor suppressive activities. However, C/EBPδ over-expression correlates with poor prognosis in glioblastoma and promotes genomic instability in cervical cancer, hinting at an oncogenic role of C/EBPδ in these contexts. Here, we explore the role of C/EBPδ in pancreatic cancer. We determined C/EBPδ expression in biopsies from pancreatic cancer patients using public gene-expression datasets and in-house tissue microarrays. We found that C/EBPδ is highly expressed in healthy pancreatic ductal cells but lost in pancreatic ductal adenocarcinoma. Furthermore, loss of C/EBPδ correlated with increased lymph node involvement and shorter overall survival in pancreatic ductal adenocarcinoma patients. In accordance with this, in vitro experiments showed reduced clonogenic capacity and proliferation of pancreatic ductal adenocarcinoma cells following C/EBPδ re-expression, concurrent with decreased sphere formation capacity in soft agar assays. We thus report a previously unrecognized but important tumor suppressor role of C/EBPδ in pancreatic ductal adenocarcinoma. This is of particular interest since only few tumor suppressors have been identified in the context of pancreatic cancer. Moreover, our findings suggest that restoration of C/EBPδ activity could hold therapeutic value in pancreatic ductal adenocarcinoma, although the latter claim needs to be substantiated in future studies.

The association of serum vitamin D-binding protein and 25-hydroxyvitamin D in pre-operative and post-operative colorectal cancer.

BackgroundThe association between vitamin D–binding protein (VDBP) and 25‐hydroxyvitamin D (25 (OH)D) with colorectal cancer (CRC) is still ambiguous. This study was to further investigate the relationship between serum VDBP, 25 (OH)D levels and the clinical and pathological features of patients with CRC.MethodsEnzyme‐linked immunosorbent assay (ELISA) and chemiluminescence immunoassay were used to analyze the VDBP and 25(OH)D concentrations in serum. Pearson's correlation analysis was applied to evaluate the association between serum VDBP and 25(OH)D levels in CRC. Conditional logistic regression was performed to analyze the prediction value of serum VDBP or 25(OH)D as a risk factor for CRC.ResultsThe serological levels of 25(OH)D in patients were significantly lower than in healthy individuals, while VDBP levels were significantly higher than in healthy controls. The serum VDBP in pre‐operative was significantly lower than in post‐operative samples, while the serum 25(OH)D from pre‐operative patients was significantly higher than post‐operative patients. Patients with tumors with higher stage and increased lymph node involvement had lower serum post‐operative VDBP levels. In addition, our results showed that the pre‐operative VDBP level is a risk factor of CRC.ConclusionsThe levels of serum 25(OH)D and VDBP were both associated with CRC. Thus, serum 25(OH)D and VDBP levels might be of value in evaluating the pathogenesis and risk of CRC in the future. Moreover, serum VDBP or 25(OH)D levels were associated with patient's clinical and pathological features providing data for risk and prognostic prediction.

Aggressiveness and increased lymph node involvement in younger patients (

Introduction: Breast cancer is 4th leading cause of death in many parts of world. Unexplained increase in aggressiveness and more number of lymph node involvements in young females with breast cancer is of interest. Objective: This study is designed to assess the lymph node involvement in younger patients (<40 years) suffering from breast cancer Method: This study has been done on MRM specimen of 90 females of breast cancer from (Jan 2014-jan 2015) in pathology department of Shri. M. P. Shah. Govt. Medical College, Jamnagar. This study includes the age, lymph node status, grading and staging. Results: After analyzing, only 2(2.22%) females 40 years has been diagnosed as invasive breast cancer. 63% females 3 lymph node positive while only 34% females >40 years showing >3 lymph node positivity. Out of this statistics younger patients showing most of lymph nodes out of total to be positive as compared to older age group as it affects TNM staging and treatment protocol. Conclusion: Increase in risk of lymph node involvement in younger patients (25-40). All the young women in their 20s and 30s should examine herself and every 3 years by her health care professionals.

Nomogram for predicting preoperative lymph node involvement in patients with invasive micropapillary carcinoma of breast: a SEER population-based study

BackgroundInvasive micropapillary carcinoma (IMPC) is an unusual and distinct subtype of invasive breast tumor with high propensity for regional lymph node metastases. This study was to identify risk factors accounting for IMPC of the breast and to develop a nomogram to preoperatively predict the probability of lymph node involvement.MethodsA retrospective review of the clinical and pathology records was performed in patients diagnosed with IMPC between 2003 and 2014 from Surveillance, Epidemiology, and End Results (SEER) database. The cohort was divided into training and validation sets. Training set comprised patients diagnosed between 2003 and 2009, while validation set included patients diagnosed thereafter. A logistic regression model was used to construct the nomogram in the training set and then varified in the validation set. Nomogram performance was quantified with respect to discrimination and calibration using R 3.4.1 software.ResultsOverall, 1407 patients diagnosed with IMPC were enrolled, of which 527 in training set and 880 in validation set. Logistic regression analysis indicated larger lesions, younger age at diagnosis, black ethnic and lack of hormone receptor expression were significantly related to regional nodes involvement. The AUC of the nomogram was 0.735 (95% confidential interval (CI) 0.692 to 0.777), demonstrating a good prediction performance. Calibration curve for the nomogram was plotted and the slope was close to 1, which demonstrated excellent calibration of the nomogram. The performance of the nomogram was further validated in the validation set, with AUC of 0.748 (95% CI 0.701 to 0.767).ConclusionsThe striking difference between IMPC and IDC remains the increased lymph node involvement in IMPC and therefore merits aggressive treatment. The nomogram based on the clinicalpathologic parameters was established, which could accurately preoperatively predict regional lymph node status. This nomogram would facilitate evaluating lymph node state preoperatively and thus treatment decision-making of individual patients.

Abstract P4-09-10: Nomogram for predicting lymph node involvement in patients with invasive micropapillary carcinoma of breast: A SEER population-based study

Abstract Background: Invasive micropapillary carcinoma (IMPC) is an unusual and distinct subtype of invasive breast tumor with high propensity for regional lymph node metastases. Because of its lymphotropic nature at initial presentation, IMPC is considered to have an unfavorable prognosis when compared with invasive ductal carcinoma (IDC). The aim of this study was to identify risk factors accounting for its lymphotropic features and to develop a nomogram to predict the probability of lymph node involvement in IMPC. Patients and Methods: A retrospective review of the clinical and pathology records was performed in patients diagnosed with IMPC between 2003 and 2014 from Surveillance, Epidemiology, and End Results (SEER) database. Training set comprised patients diagnosed between 2003 and 2009, while validation set included patients diagnosed thereafter. Ethical approval of the study was granted by the Institutional Review Board of Fudan University Shanghai Cancer Center. Multiple logistic regression analysis was conducted. A logistic regression model was used to construct the nomogram in the training set and then validated in the validation set. Nomogram performance was quantified with respect to discrimination and calibration. Results: Overall, 1407 patients diagnosed with IMPC were enrolled, of which 527 in training set and 880 in validation set. The demographic characteristics were comparable within sets. Larger lesion, younger age at diagnosis, black ethnic and lack of hormone receptor expression were significantly related to regional nodes involvement. The AUC of the nomogram was 0.735 (95 percent confidence interval 0.692 to 0.777), demonstrating a good prediction performance. A calibration curve for the nomogram was plotted to evaluate the agreement between actual (observed) outcomes and expected probabilities. The slope of the calibration curve was close to 1, which indicated excellent calibration of the nomogram. The performance of the nomogram was further validated in the validation set, in which AUC was 0.734 (95 percent confidence interval 0.701 to 0.767). Conclusions: The striking difference between IMPC and IDC remains the increased lymph node involvement in IMPC and therefore merits aggressive treatment. The nomogram based on the clinical parameters was established, which could accurately predict regional lymph node status. This nomogram would facilitate evaluating lymph node state preoperatively and thus treatment decision-making of individual patients, especially in neoadjuvant settings. Citation Format: Ye F, Hu X, Shao Z. Nomogram for predicting lymph node involvement in patients with invasive micropapillary carcinoma of breast: A SEER population-based study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-09-10.

Clinicopathological characteristics and survival outcomes in pleomorphic lobular breast carcinoma of the breast: a SEER population‐based study

The purpose of this study was to explore the clinicopathological features and survival outcome of pleomorphic lobular carcinoma (PLC) of breast, we identified 131 PLC patients and 460,109 invasive ductal carcinoma (IDC) patients in the Surveillance, Epidemiology, and End Result (SEER) database. PLCs presented with increased lymph node involvement, older age, higher AJCC stage and grade, and lower median survival months (PLC 84 ± 51.03 vs. IDC 105.2 ± 64.39 P < 0.01). Compared to IDC patients, PLC patients were more inclined to be treated with mastectomy. In univariate analysis, PLC patients showed a worse disease‐specific survival (DSS) than that of IDC patients (hazard ratio = 0.691, 95% confidence interval 0.534–0.893, P < 0.01). In multivariate analysis, we took into account other prognostic factors and found that the histology types were no longer an independent prognostic factor (P = 0.120). DSS have no difference between matched IDC and PLC groups (P = 0.615). This result may be due to PLCs presenting higher tumor stage, higher tumor grade, and higher rate of LN metastasis than IDCs. Our conclusion is that PLC and IDC have many different characteristics, but there is not enough difference on the DSS.

Breast cancer-specific survival in patients with lymph node-positive hormone receptor-positive invasive breast cancer and Oncotype DX Recurrence Score results in the SEER database.

The Oncotype DX® Breast Recurrence Score™ (RS) assay is validated to predict breast cancer (BC) recurrence and adjuvant chemotherapy benefit in select patients with lymph node-positive (LN+), hormone receptor-positive (HR+), HER2-negative BC. We assessed 5-year BC-specific survival (BCSS) in LN+ patients with RS results in SEER databases. In this population-based study, BC cases in SEER registries (diagnosed 2004-2013) were linked to RS results from assays performed by Genomic Health (2004-2014). The primary analysis included only patients (diagnosed 2004-2012) with LN+ (including micrometastases), HR+ (per SEER), and HER2-negative (per RT-PCR) primary invasive BC (N=6768). BCSS, assessed by RS category and number of positive lymph nodes, was calculated using the actuarial method. The proportion of patients with RS results and LN+ disease (N=8782) increased over time between 2004 and 2013, and decreased with increasing lymph node involvement from micrometastases to ≥4 lymph nodes. Five-year BCSS outcomes for those with RS<18 ranged from 98.9% (95% CI 97.4-99.6) for those with micrometastases to 92.8% (95% CI 73.4-98.2) for those with ≥4 lymph nodes. Similar patterns were found for patients with RS 18-30 and RS≥31. RS group was strongly predictive of BCSS among patients with micrometastases or up to three positive lymph nodes (p<0.001). Overall, 5-year BCSS is excellent for patients with RS<18 and micrometastases, one or two positive lymph nodes, and worsens with additionally involved lymph nodes. Further analyses should account for treatment variables, and longitudinal updates will be important to better characterize utilization of Oncotype DX testing and long-term survival outcomes.

Abstract P4-12-04: Breast cancer subtype, age and lymph node status as predictors of local recurrence following breast-conserving therapy

Abstract Purpose/Objectives: Advances in breast-conserving therapy (BCT) have yielded local control rates comparable or superior to those of mastectomy. Here, we sought to identify risk factors associated with isolated local recurrence (LR) following BCT. Materials/Methods: This study included a multi-institutional cohort of 2,233 consecutive breast cancer patients who underwent BCT between 1998 and 2007. Patient characteristics and disease parameters were stratified by age, subtype and nodal status. Biologic subtype was approximated by receptor status and tumor grade. No patients received HER2/neu-directed therapy. The association of clinicopathologic features with LR was evaluated using Cox proportional hazards regression models. Results: At a median follow-up of 106 months, 69 LR events (3.1%) were observed. Among the overall cohort, 10-year freedom from LR was 95.9%. On univariate Cox regression analysis, risk factors associated with LR included subtype other than luminal A (hazard ratio [HR] for luminal B = 3.01, HER2 = 6.29, triple negative [TNBC] = 4.72; p&amp;lt;0.001 for each), younger age (HR of oldest versus youngest quartile = 0.43; p=0.005), regional lymph node involvement (HR for 4-9 involved nodes = 3.04; &amp;gt;9 nodes = 5.82; p&amp;lt;0.01 for each), positive resection margins (HR = 2.43; p=0.005), and high-grade disease (HR = 5.37; p &amp;lt;0.001). Presence of LVI (HR = 1.56; p=0.06) or 1-3 involved nodes (HR = 1.55; p=0.07) approached significance. Multivariate Cox regression demonstrated an association with LR among those with non-luminal A subtypes (HR for luminal B = 2.64, HER2 = 5.42, TNBC = 4.32; p&amp;lt;0.001 for each), younger age (HR for age &amp;gt;50 = 0.56; p=0.01), and any nodal disease (HR=1.06 per involved node; p&amp;lt;0.004). Conclusions: BCT yields favorable outcomes for the large majority of patients, although increased LR was observed among those with non-luminal A subtypes, younger age, and increasing lymph node involvement. Risk factors for LR following BCT appear to be converging with those following mastectomy in the current era. Citation Format: Braunstein LZ, Taghian AG, Niemierko A, Salama L, Capuco A, Wong JS, Punglia RS, Bellon JR, MacDonald SM, Harris JR. Breast cancer subtype, age and lymph node status as predictors of local recurrence following breast-conserving therapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-12-04.

Breast-cancer subtype, age, and lymph node status as predictors of local recurrence following breast-conserving therapy.

Advances in breast-conserving therapy (BCT) have yielded local control rates comparable or superior to those of mastectomy. In this study, we sought to identify contemporary risk factors associated with local recurrence (LR) following BCT. We analyzed a multi-institutional cohort of 2233 consecutive breast-cancer patients who underwent BCT between 1998 and 2007. Patients were stratified by age, biologic subtype (as approximated by receptor status and tumor grade), and nodal status. Patients who received HER2/neu-directed therapy were excluded due to variations in practice over the study period. The association of clinicopathologic features with LR was evaluated using Cox proportional hazards regression models. With a median follow-up of 106months, 69 LRs (3%) were observed. On univariate analysis, LR was associated with non-luminal-A subtype (hazard ratio [HR] for luminal-B=3.01, HER2=6.29, triple-negative [TNBC]=4.72; p<0.001 each), younger age (HR of oldest vs. youngest quartile=0.43; p=0.005), regional nodal involvement (HR for 4-9 involved nodes=3.04;>9 nodes=5.82; p<0.01 for each), positive margins (HR2.43; p=0.005), and high grade (HR5.37; p<0.001). Multivariate Cox regression demonstrated that non-luminal-A subtypes (HR for luminal-B=2.64, HER2=5.42, TNBC=4.32; p<0.001 for each), younger age (HR for age>50=0.56; p=0.01), and nodal disease (HR1.06 per involved node; p<0.004) were associated with LR. The 8-year risk of LR was 2.8% for node-negative patients and 5.2% for node-positive patients. BCT yields favorable outcomes for the large majority of patients, although increased LR was observed among those with non-luminal-A subtypes, younger age, and increasing lymph node involvement. Risk factors for LR after BCT appear to be converging with those after mastectomy in the current era.

OC-055 Blood-Based Biomarkers in the Oesophageal Cancer Model – Results from the PigA Mutant Phenotype Study

Introduction Improving our mechanisms of risk stratification of patients with Barrett’s oesophagus (BO) requires easily analysable, cheap and reproducable biomarkers. The PigA phenotype assay is a novel flow cytometric analysis, which can be undertaken using a fingerprick test. The PigA gene codes for GPI-anchors, which tether proteins to the surface of circulating blood cells. Silencing mutations, induced by acid or bile, will therefore result in absence of surface GPI-anchors and negative fluorescence on flow cytometry analysis. Our laboratory has already demonstrated the effects of bile in inducing such mutant events in blood based cell lines. Methods Here, we investigate the baseline background PigA phenotype frequency in patients with GORD, BO, and those with oesophageal adenocarcinoma (OAC). We recruited 120 patients for analysis of baseline frequency in circulating red blood cells. We correlated these findings with symptoms, diet, lifestyle, endoscopic features and radiological stage. We also undertook Western Blotting analysis of endoscopic biopsies to assess GPI-anchor status in retrieved tissue. Results A clear correlation was seen with increased PigA frequency with histological status from healthy patients with GORD to those with OAC, p Older age, smoking status and unhealthy lifestyle (diet measured using the DQS score) all resulted in higher frequencies. Length of Barrett’s and degree of inflammation (LA classification) had no effect, but aspirin use appeared to be protective and resulted in lower frequencies (p Evaluation of patients with cancer (n = 15) found that PigA frequency increased with increasing lymph node involvement and metastasic spread (both p Finally western blotting of crude protein extracted from oesophageal biopsies revealed a reduction in GPI-anchor levels from normal squamous tissue, through to cancer, thus corroborating our results above. Conclusion We have developed a blood-based biomarker assay, which can potentially stratify patients’ underlying genomic instability by indirectly measuring GPI-anchor status on circulating blood cells. We have also demonstrated the potential onco-protective effects of aspirin in these patients. The mechanisms behind these observations remain unclear, but western blot analysis suggests mutation may occur in the distal oesophagus where circulating blood cells are exposured to mutagenic chemicals such as bile and acid. Further evaluation in other cancer models as well as a wider cohort of non-cancer patients (to evaluate lifetyle) will establish how useful the assay may be outside of the Barrett’s model. Disclosure of Interest None Declared

Pooled Analysis of the Prognostic Relevance of Circulating Tumor Cells in Primary Breast Cancer.

Although unequivocal evidence has shown the prognostic relevance of circulating tumor cells (CTC) in the peripheral blood of patients with metastatic breast cancer, less evidence is available for the prognostic relevance of CTCs at the time of primary diagnosis. We conducted a pooled analysis of individual data from 3,173 patients with nonmetastatic (stage I-III) breast cancer from five breast cancer institutions. The prevalence and numbers of CTCs were assessed at the time of primary diagnosis with the FDA-cleared CellSearch System (Janssen Diagnostics, LLC). Patient outcomes were analyzed using meta-analytic procedures, univariate log-rank tests, and multivariate Cox proportional hazard regression analyses. The median follow-up duration was 62.8 months. One or more CTCs were detected in 20.2% of the patients. CTC-positive patients had larger tumors, increased lymph node involvement, and a higher histologic tumor grade than did CTC-negative patients (all P < 0.002). Multivariate Cox regressions, which included tumor size, nodal status, histologic tumor grade, and hormone receptor and HER2 status, confirmed that the presence of CTCs was an independent prognostic factor for disease-free survival [HR, 1.82; 95% confidence interval (CI), 1.47-2.26], distant disease-free survival (HR, 1.89; 95% CI, 1.49-2.40), breast cancer-specific survival (HR, 2.04; 95% CI, 1.52-2.75), and overall survival (HR, 1.97; 95% CI, 1.51-2.59). In patients with primary breast cancer, the presence of CTCs was an independent predictor of poor disease-free, overall, breast cancer-specific, and distant disease-free survival. Clin Cancer Res; 22(10); 2583-93. ©2016 AACR.

The rs11515 Polymorphism Is More Frequent and Associated With Aggressive Breast Tumors with Increased ANRIL and Decreased p16 (INK4a) Expression.

Chromosome position 9p21 encodes three-tumor suppressors p16INK4a, p14ARF, and p15INK4b and the long non-coding RNA ANRIL (antisense non-coding RNA in the INK4 locus). The rs11515 single-nucleotide polymorphism in the p16INK4a/p14ARF 3′-untranslated region is associated with glioblastoma, melanoma, and other cancers. This study investigated the frequency and effect of rs11515 genotypes in breast cancer. Genomic DNA samples from 400 women (200 with and 200 without a diagnosis of breast cancer) were genotyped for the rs11515 major (C) and minor (G) alleles. The rs11515 polymorphism was also investigated in 108 heart tissues to test for tissue-specific effects. Four 9p21 transcripts, p16INK4a, p14ARF, p15INK4b, and ANRIL were measured in breast tumors and myocardium using quantitative PCR. Heterozygotes (CG genotype) were more frequent in women with breast cancer compared to the control population (P = 0.0039). In those with breast cancer, the CG genotype was associated with an older age (P = 0.016) and increased lymph node involvement (P = 0.007) compared to homozygotes for the major allele (CC genotype). In breast tumors, the CG genotype had higher ANRIL (P = 0.031) and lower p16INK4a (P = 0.006) expression compared to the CC genotype. The CG genotype was not associated with altered 9p21 transcripts in heart tissue. In breast cancer, the rs11515 CG genotype is more frequent and associated with a more aggressive tumor that could be due to increased ANRIL and reduced p16INK4a expression. The absence of association between rs11515 genotypes and 9p21 transcripts in heart tissue suggests this polymorphism has tissue- or disease-specific functions.