Aggressive Tumor Biology Research Articles

Triple-negative breast cancer: Pattern of recurrence and survival outcomes

Abstract Introduction: Triple-negative breast cancer (TNBC) is a subtype of breast cancer which is defined as the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 overexpression by immunohistochemistry. As the survival data on TNBC in the Indian population are scant, this study was done to analyze the clinicopathological features and clinical outcomes of TNBC patients. Materials and Methods: Data from medical records of patients with breast cancer between 2009 and 2014 were retrieved, and patients with TNBC were identified and analyzed for demographic and clinicopathological features. Survival analyses were performed using the Kaplan–Meier method for disease-free survival (DFS) and overall survival (OS). Results: A total of 1024 breast cancer patients were registered at our institute during the study period, of which 198 were TNBCs accounting for 19.3% of all breast cancers. Median age at the diagnosis was 50 years (range, 22–78 years). Lymph nodal positivity in TNBC was associated with larger tumor size (P = 0.003) and higher tumor grade (P = 0.01). At a median follow-up of 48 months (range, 12–88), 36 (19.1%) patients had recurrence of the disease, whereas 28 (14%) patients were lost to follow-up. Lung (52.7%) was the most common site of recurrence followed by bone (25%) and brain (11.1%). Three-year DFS and OS were 63.2% and 65.6%, respectively. On univariate analysis, nodal status, size of tumor, and lymphovascular invasion were found to have a significant impact on OS and DFS. On multivariate analysis, only nodal status was significant for DFS and OS (P < 0.001 and P = 0.001, respectively). Conclusions: TNBCs have a rapid clinical course, and early recurrences are common inspite of timely medical intervention which reflects the aggressive tumor biology. This warrants further studies on intensification of chemotherapy and identification and development of targeted therapy aimed at decreasing recurrences and improving survival in this patient population.

Selective Inhibition of the Lactate Transporter MCT4 Reduces Growth of Invasive Bladder Cancer

The significance of lactate transporters has been recognized in various cancer types, but their role in urothelial carcinoma remains mostly unknown. The aim of this study was to investigate the functional importance of the monocarboxylate transporter (MCT) 4 in preclinical models of urothelial carcinoma and to assess its relevance in patient tumors. The association of MCT4 expression with molecular subtypes and outcome was determined in The Cancer Genome Atlas (TCGA) cohort and two independent cohorts of patients with urothelial carcinoma. Silencing of MCT4 was performed using siRNAs in urothelial carcinoma cell lines. Effects of MCT4 inhibition on cell growth, apoptosis, and production of reactive oxygen species (ROS) were assessed. Moreover, effects on lactate efflux were determined. The in vivo effects of MCT4 silencing were assessed in an orthotopic xenograft model. MCT4 expression was higher in the basal subtype. Decreased MCT4 methylation and increased RNA and protein expression were associated with worse overall survival (OS). Inhibition of MCT4 led to a reduction in cell growth, induction of apoptosis, and an increased synthesis of ROS. MCT4 inhibition resulted in intracellular accumulation of lactate. In vivo, stable knockdown of MCT4 reduced tumor growth. The expression of MCT4 in urothelial carcinoma is associated with features of aggressive tumor biology and portends a poor prognosis. Inhibition of MCT4 results in decreased tumor growth in vitro and in vivo Targeting lactate metabolism via MCT4 therefore provides a promising therapeutic approach for invasive urothelial carcinoma, especially in the basal subtype.

Influences of adjuvant treatments in hormone receptor positive breast cancer on receptor conversion in recurrent breast cancer.

To examine influences on the receptor status of a local cohort of patients with recurrent breast cancer after primary diagnosis of hormone receptor positive breast cancer. We retrospectively analyzed 2078 female patients with primary hormone receptor positive breast cancer treated at the university hospital of Wuerzburg between 2000 and 2013. Main focus was on discordance in receptor status in recurrent disease. 196 patients with the primary diagnosis of hormone receptor positive breast cancer developed recurrent disease. 29.1% of patients revealed discordance in estrogen receptor (ER), progesterone receptor (PgR) or HER2 receptor (ER+ to -: 33.3%; PgR+ to -: 59.6%; HER2+ to -: 8.8%; HER2- to +: 17.5%). Aggressive tumor biology such as low grading or involvement of axillary lymph nodes showed increased risk of receptor conversion in relapse. Premenopausal patients with adjuvant application of tamoxifen and the application of chemotherapy had a significantly lower risk for the development of ER negative recurrent disease. Receptor changes to ER and PgR negativity in recurrent disease showed a trend to worse overall survival (OS). Histological analysis of recurrent disease is indispensable, since one-third of patients with hormone receptor positive breast cancer develop change in the receptor status.

Racial disparities in breast cancer persist despite early detection: analysis of treatment of stage 1 breast cancer and effect of insurance status on disparities.

Prior research demonstrates racial disparities in breast cancer treatment. Disparities are commonly attributed to more advanced stage at presentation or aggressive tumor biology. We seek to evaluate if racial disparities persist in the treatment of stage 1 breast cancer patients who by definition are not delayed in presentation. We selected stage 1 breast cases in the National Cancer Data Base. Patients were divided into two cohorts based on race and included White and Black patients. We also performed a subgroup analysis of patients with private insurance for comparison to determine if private insurance diminished the racial disparities noted. We analyzed differences in time to treatments by race. Our analysis included 546,351 patients of which 494,784 (90.6%) were White non-Hispanic and 51,567 (9.4%) were Black non-Hispanic. Black women had significantly longer times to first treatment (35.5days vs 28.1days), surgery (36.6days vs 28.8days), chemotherapy (88.1days vs 75.4days), radiation (131.3days vs 99.1days), and endocrine therapy (152.1days vs 126.5days) than White women. When patients with private insurance were analyzed the difference in time to surgery decreased by 1.2days but racial differences remained statistically significant. Despite selecting for early-stage breast cancer, racial disparities between White and Black women in time to all forms of breast cancer treatment persist. These disparities while likely not oncologically significant do suggest institutional barriers for obtaining care faced by women of color which may not be addressed with improving access to mammography alone.

IFNL4-ΔG Allele Is Associated with an Interferon Signature in Tumors and Survival of African-American Men with Prostate Cancer.

Purpose: Men of African ancestry experience an excessive prostate cancer mortality that could be related to an aggressive tumor biology. We previously described an immune-inflammation signature in prostate tumors of African-American (AA) patients. Here, we further deconstructed this signature and investigated its relationships with tumor biology, survival, and a common germline variant in the IFNλ4 (IFNL4) gene.Experimental Design: We analyzed gene expression in prostate tissue datasets and performed genotype and survival analyses. We also overexpressed IFNL4 in human prostate cancer cells.Results: We found that a distinct interferon (IFN) signature that is analogous to the previously described "IFN-related DNA damage resistance signature" (IRDS) occurs in prostate tumors. Evaluation of two independent patient cohorts revealed that IRDS is detected about twice as often in prostate tumors of AA than European-American men. Furthermore, analysis in TCGA showed an association of increased IRDS in prostate tumors with decreased disease-free survival. To explain these observations, we assessed whether IRDS is associated with an IFNL4 germline variant (rs368234815-ΔG) that controls production of IFNλ4, a type III IFN, and is most common in individuals of African ancestry. We show that the IFNL4 rs368234815-ΔG allele was significantly associated with IRDS in prostate tumors and overall survival of AA patients. Moreover, IFNL4 overexpression induced IRDS in three human prostate cancer cell lines.Conclusions: Our study links a germline variant that controls production of IFNλ4 to the occurrence of a clinically relevant IFN signature in prostate tumors that may predominantly affect men of African ancestry. Clin Cancer Res; 24(21); 5471-81. ©2018 AACR.

Pediatric Solid Tumors in Resource-Constrained Settings: A Review of Available Evidence on Management, Outcomes, and Barriers to Care.

International disparities in outcomes from pediatric solid tumors remain striking. Herein, we review the current literature regarding management, outcomes, and barriers to care for pediatric solid tumors in low- and middle-income countries (LMICs). In sub-Saharan Africa, Wilms Tumor represents the most commonly encountered solid tumor of childhood and has been the primary target of recent efforts to improve outcomes in low-resource settings. Aggressive and treatment-resistant tumor biology may play a role in poor outcomes within certain populations, but socioeconomic barriers remain the principal drivers of preventable mortality. Management protocols that include measures to address socioeconomic barriers have demonstrated early success in reducing abandonment of therapy. Further work is required to improve infrastructure and general pediatric care to address disparities.

Impact of tumor size on survival of patients with resected pancreatic ductal adenocarcinoma: a systematic review and meta-analysis

BackgroundThe impact of tumor size on prognosis for surgically treated patients with pancreatic ductal adenocarcinoma (PDAC) remains controversial. A systematic review and meta-analysis was performed to evaluate this issue.MethodsRelevant studies published from January 2000 to June 2017 were identified through EMBASE and PUBMED. Data were pooled for meta-analysis using Review Manager 5.3.ResultsTwenty eight observational studies involving a total of 23,945 patients were included. Tumors > 2 cm was associated with poor prognosis: the pooled hazard ratio (HR) estimate for overall survival was 1.52 (95% confidence interval [CI]: 1.41–1.64; P < 0.0001) by univariate analysis and 1.61 (95% CI: 1.35–1.91; P < 0.0001) by multivariate analysis; the pooled HR estimate for disease-free survival was 1.74 (95% CI: 1.46–2.07; P < 0.0001) by univariate analysis and 1.38 (95% CI: 1.12–1.68; P = 0.002) by multivariate analysis. When compared with patients with tumors ≤2 cm, those with the tumors > 2 cm had higher incidences of lymph node metastasis, poor tumor differentiation, lymph vessel invasion, vascular invasion, perineural invasion, and positive intraoperative peritoneal cytology.ConclusionThese data demonstrate that PDAC size > 2 cm is an independent predictive factor for poor prognosis after surgical resection and associated with more aggressive tumor biology.

Main Symptom that Led to Medical Evaluation and Diagnosis of Vestibular Schwannoma and Patient-Reported Tumor Size: Cross-sectional Study in 1,304 Patients.

Objectives Although vestibular schwannomas (VS) are known to cause cranial nerve deficits, cerebellar symptoms, and hydrocephalus, the role of these symptoms as the key driver of presentation from the patient's perspective has not been described. Our objective was to survey a large, retrospective VS cohort to document the patient-reported principal initial symptom, and self-reported tumor size, and to study trends in VS patient presentation. Methods Patients diagnosed with VS at our tertiary referral center and belonging to the Acoustic Neuroma Association (ANA) answered a questionnaire between 2015 and 2017. Demographic data, self-reported tumor size, and symptomatology were analyzed. Results 1,304 patients completed the questionnaire. Tumors were diagnosed from 1966 to 2017 at a mean 51.8 years (range: 8-86 years); 66% were female, and 1.1% had confirmed neurofibromatosis type 2 (NF2). Tumor size was reported using a 6-point scale: 0 to 1 cm (22.9%), 1 to 2 cm (28.7%), 2 to 3 cm (20.5%), 3 to 4 cm (10%), greater than 4 cm (7.2%), and unknown (10.6%). Hearing loss was the most common symptom that led to diagnosis (51.5%), followed by dizziness (17%), tinnitus (11.2%), and incidental diagnosis (10.2%); a fraction that has increased significantly in the last decade ( p = 0.022). Larger tumors and NF2 were significantly associated with young age ( p < 0.001). Conclusion Our large-scale questionnaire-driven review of 1,304 patients confirms that VS presentations are stereotypical, with most individuals recalling hearing loss, dizziness, or tinnitus as their chief complaint. Many tumors were incidentally diagnosed; an expanding population, attributable to increased access to magnetic resonance imaging (MRI). Large tumors were significantly more prevalent among younger patients at diagnosis, excluding NF2 patients, suggesting a more aggressive tumor biology that remains incompletely understood.

Percutaneous Cement Injection for the Palliative Treatment of Osseous Metastases: A Technical Review.

The technical art to percutaneous injection of polymethyl methacrylate (PMMA) cement for the palliative treatment of osseous metastases is not without pitfalls. Pathologic fracture, cortical bone erosion, large lytic tumor, aggressive tumor biology, and tumor vascularity may increase the risk of cement leakage or limit complete consolidation. A calculated and determined approach is often necessary to achieve satisfactory patient-tailored results. This article reviews the challenges and potential complications during the consolidation of osseous metastases. Case examples are presented to facilitate early detection of impending cement leakage, minimize procedural risks, and provide management suggestions for complications. Technical pearls are provided to refine consolidative techniques and improve the comprehensive treatment of painful osseous metastases.

The Prognostic Impact of KRAS Mutation in Patients Having Curative Resection of Synchronous Colorectal Liver Metastases

Backgroundm-KRAS has been recently reported to be a significant prognostic factor in patients undergoing resection of colorectal liver metastases. This is due to the lack of response to monoclonal epithelial growth factor receptor antibodies, and potentially as a result of a more aggressive tumor biology. MethodsThe National Cancer Database was queried to identify patients with known KRAS status presenting with colorectal cancer and liver metastases who underwent resection of the primary tumor and metastatic disease between 2010 and 2015. ResultsA total of 2655 patients were identified of which 1116 (42%) had m-KRAS. Tumor size, lymph node involvement rates, and margin status of the primary tumor were similar between patients with m-KRAS and wild-type KRAS (wt-KRAS). In the multivariable analysis, African-American race and right-sided colon cancers were independently associated with m-KRAS (both p < 0.001). m-KRAS patients had a significantly lower overall survival (OS) than those with wt-KRAS, with a 3- and 5-year OS of 51 vs. 64% and 31 vs. 42%, respectively (p < 0.001). After adjustment for available prognostic confounders, factors independently associated with worse OS were increasing age, receipt of monoagent chemotherapy, tumor size, positive lymph node, and resection margin status of the primary tumor, right-sided cancers, and m-KRAS. Conclusionsm-KRAS is associated with worse OS in patients presenting with colorectal cancer and liver metastases undergoing resection of the primary tumor and metastatic disease. Right-sided lesions and African-American race were associated with m-KRAS. However, while right-sided remained an independent prognostic factor for OS, race did not.

Integrated CT-Fluoroscopy Equipment: Improving the Interventional Radiology Approach and Patient Experience for Treatment of Musculoskeletal Malignancies.

Integrated CT-fluoroscopy equipment augments the comprehensive approach to the treatment of musculoskeletal (MSK) malignancy by interventional radiology techniques. As the role of minimally invasive treatment expands to meet the highly variable presentation of MSK malignancy, creative solutions to treatment challenges are required to improve locoregional tumor control and durability of pain palliation. Challenges to effective treatment can often be attributed to a combination of aggressive tumor biology, large size, forbidding location, and adverse vascularity. In these cases, a tailored treatment approach may necessitate the application of multiple interventional radiology (IR) techniques that require different image guidance capabilities. Integrated CT-fluoroscopy equipment provides the means to leverage both imaging modalities within the same procedural setting to facilitate the simultaneous application of multiple synergistic treatments and protective measures. This article examines the potential role of hybrid units in the IR treatment of challenging MSK malignancies as a means to empower a paradigm transition for a more comprehensive and patient-tailored approach.

Stromal PD-1/PD-L1 Expression Predicts Outcome in Colon Cancer Patients

IntroductionThe programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) axis plays an important role in controlling immune suppression by down-regulating T effector cell activities, enabling tumor cells to escape from the host’s antitumor immunsurveillance. While only a small part of colon cancer cells express PD-L1, we sought to evaluate the differential impact of stromal and epithelial PD-L1 expression of primary tumors and liver metastasis on overall survival (OS) in colon cancer patients. Patients and MethodsUsing a next-generation tissue microarray approach, we assessed both epithelial and stromal PD-L1 expression levels in primary tumors (n = 279) and corresponding liver metastases (n = 14) of colon cancer patients. PD-L1 positivity was graded according to the percentage (0.1%-1%, > 1%, > 5%, > 50%) of tumor cells with membranous PD-L1 expression or as the percentage of positive stroma cells and associated inflammatory infiltrates. We also assessed the interplay between stromal PD-1/PD-L1 and both intratumoral and stromal CD8 count and their impact on outcome. The primary end point was OS. ResultsStromal PD-L1 and PD-1 expression were both associated with less aggressive tumor behavior in colon cancer patients, which translated into better OS and disease-free survival, respectively. Conversely, PD-L1 staining in the tumor cells was less frequent than stromal staining and was associated with features of aggressive tumor biology, although without impact on outcome. Interestingly, the PD-L1 staining pattern remained similar between primary tumors and corresponding liver metastases. Stromal PD-1 expression correlated significantly with stromal PD-L1 staining and both intratumoral and stromal CD8 expression. ConclusionStromal PD-1/PD-L1 expression might serve as a prognostic marker in colon cancer patients.

P01.161 Neurocognitive evaluation in elderly Glioma patients

Glioblastoma (GBM) is the most common primary brain tumor in adults, with an increasing incidence in patients aged 75 through 85. Prognosis in these patients is particularly dismal due to more aggressive tumor biology, lower functional reserve and high prevalence of comorbidities. Many studies report cognitive impairment in GBM patients, ranging from 29 to 90%. This study was aimed at evaluating neurocognitive status and comorbidities of an elderly population with high grade glioma and the correlation with clinical and demographical variables. patients underwent an extended neuropsychological evaluation with a battery of standardized tests on 8 cognitive domains: global function (GF); verbal learning (VL); short and long-term memory (STM); executive functions (EF); abstract reasoning (AR); attention (ATT) and visuo-constructional abilities (CA). Moreover, the Cumulative Illness Rating Scale was administered to each patient for comorbidities evaluation. We assessed 69 patients with median age at diagnosis of 74 years (range 65–85). 43 patients (62%) presented multi-domain cognitive impairment, and only 8 (12%) showed no cognitive impairment. Neuropsychological deficit mainly affected executive functions (n=42), short term memory (n=28), long term memory and attention (n=22). Patients with AR deficit had a poorer PFS and OS (p<0. 001%). At the follow up, 7 out of 12 patients showed cognitive improvement, 4 resulted furtherly deteriorated and 1 patient was stable. Attention was the most affected function at follow up, while verbal learning was the most improved one. Our results highlight the high prevalence of cognitive deficits in patients with Glioma. Moreover, this study underlines the need to include cognitive functioning and comorbidities evaluation in the assessment of elderly neuro-oncological patients.

Adverse Oncologic Impact of New-Onset Diabetes Mellitus on Recurrence in Resected Pancreatic Ductal Adenocarcinoma

Diabetes mellitus (DM) is prevalent with pancreatic ductal adenocarcinoma (PDAC). Importantly, new-onset DM is characteristic of the disease and could be an early sign of PDAC. The clinical outcome of PDAC with new-onset DM may differ from that in patients without DM or long-standing DM. We retrospectively reviewed medical records of PDAC patients who underwent curative resection between 2006 and 2014. New-onset DM was defined as a diagnosis of DM within 24 months before the diagnosis of PDAC. Survival analysis and Cox regression were performed to evaluate oncologic outcomes. No significant differences in clinical characteristics were found in 3 groups. Overall survival of patients with new-onset DM was worse than non-DM (22 vs 33 months, P = 0.039). New-onset DM was highly associated with early recurrence (hazard ratio, 1.451; 95% confidence interval, 1.054-1.999; P = 0.022). Poor oncologic outcome of new-onset DM was more pronounced in low T stage patients (overall survival in low vs high T stage, 33 vs 18 months; P = 0.129). Pancreatic ductal adenocarcinoma with new-onset DM has worse oncologic outcomes than non-DM or long-standing DM. These results suggest that new-onset DM represents aggressive tumor biology, especially in the early stage of PDAC.

The Effect of Insurance and Race on Breast Cancer Tumor Biology and Short-Term Outcomes

To determine whether low-income status as demonstrated by insurance type has any association with aggressive tumor biology and breast cancer outcomes. Retrospective review of 535 women with new diagnosis of breast cancer from January 2009 to March 2013 was performed. There was no significant association between race and stage at diagnosis. Women with Medicaid/Charity coverage were diagnosed at more advanced stages, more likely to have triple-negative breast cancer (TNBC), and had longer time to treatment. Rate of TNBC was higher in black women and younger patients. There was no significant difference in breast cancer recurrence or survival by race, insurance type, age, or tumor biology. In multivariable analysis, only black race (P = 0.003) and Medicaid/Charity Insurance (P = 0.0008) were the most significant predictors of TNBC. Presentation of aggressive tumor biology and advanced stage is strongly associated with socioeconomic factors as reflected by Medicaid funding and lack of insurance.

Abstract 1916: Targeting adhesion signaling network blocks tumor growth in gallbladder cancer

Abstract 96 Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:Calibri; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin;} Gallbladder cancer (GBC) is a highly fatal malignancy with a 5-year survival rate of 17.6%. The prognosis of GBC is poor due to the aggressive tumor biology, late presentation, complicated anatomic position, and advanced stage at diagnosis. Characterized by a poor response to chemotherapy and radiotherapy, locally advanced and metastatic disease in patients with GBC is often treated with chemotherapy with palliative purpose. Therefore, development of new effective therapies is urgently needed for the treatment of GBC. The aim of the current study is to evaluate whether triptolide and its water soluble analog Minnelide is effective against GBC cells. We have previously shown that triptolide/Minnelide reduces tumor growth in various cancer models via regulating epithelial -mesenchymal transition (EMT), an important mechanism underlying metastasis. In our preliminary findings using two GBC cell lines, GB-d1 and NOZ, we demonstrate that triptolide inhibits the proliferation of GBC cells. Mice harboring subcutaneous gallbladder tumors, treated with Minnelide, exhibited a significant reduction in tumor weights and volume. In order to elucidate the mechanism underlying triptolide/Minnelide mediated inhibition of cellular proliferation in GBC cells and reduction in tumor growth, we identified Aurora Kinase A (AURKA) and FAK as two new targets for triptolide action in GBC cells. Triptolide regulates the activity of AURKA and FAK via an adhesion signaling protein NEDD9 which regulates the activation of several oncogenic proteins including FAK and SRC. By targeting both FAK and AURKA, triptolide disrupts the integrity of focal adhesion structures via deregulating adhesion signaling network. In addition, by targeting AURKA in GBC cells triptolide inhibits the cap-dependent translation machinery via eukaryotic translation initiation factor 4E (eIF4E). Our preliminary findings regarding potential use of Minnelide in GBC are promising. &amp;lt;!–EndFragment–&amp;gt; Citation Format: Mahendra K. Singh, Kaustav Majumder, Bhuwan Giri, Nivedita Arora, Shrey Modi, Vrishketan Sethi, Claudia P. Garcia, Juan C. Roa, Vikas Dudeja, Sulagna Banerjee, Ashok K. Saluja. Targeting adhesion signaling network blocks tumor growth in gallbladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1916.

PAM50 and Risk of Recurrence Scores for Interval Breast Cancers

Breast cancers detected after a negative breast screening examination and prior to the next screening are referred to as interval cancers. These cancers generally have poor clinical characteristics compared with screen-detected cancers, but associations between interval cancer and genomic cancer characteristics are not well understood. Mammographically screened women diagnosed with primary invasive breast cancer from 1993 to 2013 (n = 370) were identified by linking the Carolina Breast Cancer Study and the Carolina Mammography Registry. Among women with a registry-identified screening mammogram 0 to 24 months before diagnosis, cancers were classified as screen-detected (N = 165) or interval-detected (N = 205). Using logistic regression, we examined the association of mode of detection with cancer characteristics (clinical, IHC, and genomic), overall, and in analyses stratified on mammographic density and race. Interval cancer was associated with large tumors [>2 cm; OR, 2.3; 95% confidence interval (CI), 1.5-3.7], positive nodal status (OR, 1.8; 95% CI, 1.1-2.8), and triple-negative subtype (OR, 2.5; 95% CI, 1.1-5.5). Interval cancers were more likely to have non-Luminal A subtype (OR, 2.9; 95% CI, 1.5-5.7), whereas screen-detected cancers tended to be more indolent (96% had low risk of recurrence genomic scores; 71% were PAM50 Luminal A). When stratifying by mammographic density and race, associations between interval detection and poor prognostic features were similar by race and density status. Strong associations between interval cancers and poor-prognosis genomic features (non-Luminal A subtype and high risk of recurrence score) suggest that aggressive tumor biology is an important contributor to interval cancer rates. Cancer Prev Res; 11(6); 327-36. ©2018 AACR.

Epithelial‑mesenchymal transition was identified as a potential marker for breast cancer aggressiveness using reverse transcription‑quantitative polymerase chain reaction.

The primary cause of breast cancer‑associated mortality is the formation of distant metastasis. During the metastatic process, single tumor cells dissolve from the primary tumor site and undergo various changes in cell adhesion and motility properties. The tumor cells invade the blood stream and travel to different sites of the body, where they may initiate outgrowth. These cells are referred to as circulating tumor cells (CTCs). The process of changing cellular properties is known as epithelial to mesenchymal transition (EMT). As a different set of genes is upregulated during EMT, such genes may serve as marker genes for the detection of CTCs based on reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). Therefore, EMT‑ and breast cancer‑related genes were selected as RT‑qPCR markers. These genes were tested for performance in a model system of blood samples from healthy donors, to which a number of various breast cancer cell lines were added. The genes with optimal performance were subsequently used in RT‑qPCR with 35breast cancer patient samples. The genes which showed the highest and most consistent increase in gene expression with the increase in the number of cancer cell line cells added were CK19, Snail, FoxC2 and Twist. Following RT‑qPCR for all patient samples, two subgroups were arranged: One group in which all genes were downregulated and the second group with at least one gene indicated an upregulation of gene expression. Comparisons were made between the tumour characteristics from these two groups. Results suggested that carcinomas of the first group exhibited a less aggressive tumor biology compared with those in the second group. The present study indicated a novel RT‑qPCR based test for tumor malignancy.

Local recurrence of soft-tissue sarcoma: issues in imaging surveillance strategy.

Soft-tissue sarcomas pose diagnostic and therapeutic challenges to physicians, owing to the large number of subtypes, aggressive tumor biology, lack of consensus on management, and controversy surrounding interval and duration of surveillance scans. Advances in multidisciplinary management have improved the care of sarcoma patients, but controversy remains regarding strategies for surveillance following definitive local control. This review provides an updated, comprehensive overview of the current understanding of the risk of local recurrence of soft-tissue sarcoma, by examining the literature based on features such as histological type and grade, tumor size, and resection margin status, with the aim of helping clinicians, surgeons, and radiologists to develop a tailored approach to local imaging surveillance.

Revision of Surgical Margin under Frozen Section to Achieve R0 Status on Survival in Patients with Pancreatic Cancer

ObjectiveThe aim is to investigate whether additional resection based on intraoperative frozen section (FS) to a secondary R0(s) status are associated with different long-term survivals in pancreatic cancer patients, comparing to those with R1 or primary R0(p) status. MethodsA systematic literature search (PubMed, Embase, Science Citation Index, Springer-Link, and Cochrane Central Register of Controlled Trials) was performed to identify all studies published up to June 2017. Survivals of patients undergoing pancreatic surgery according to the results of FS and re-resection were pooled for analysis. ResultsFive cohort studies were qualified for inclusion in this review with a total of 2980 patients. Long-term survival outcomes favored R0(p) resection as compared to R0(s) resection (HR = 1.58, 95%CI 1.24–2.01, P = 0.0002, I2 = 58%). No significant difference was observed for patients with or without additional resection at the time of surgery when positive FS was detected (HR = 0.98, 95CI% 0.65–1.47, P = 0.91, I2 = 81%). ConclusionsThe present study did not support the concept of achieving an R0 resection by intraoperative re-resection would benefit the patient’s survival. R1 margin at the time of surgery is more like a marker of aggressive tumor biology. Future well-designed randomized controlled trials are needed to confirm the conclusion.