bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors impacting survival after diagnosis of breast cancer (BC) brain metastases (BM).
Authors: Aicardi J. , Moore D. H. , Rugo H. S. , Chien A. J. , Park J. W. , Moasser M. M. , Munster P. N. , Melisko M. E. 
Published: February 2017

31 Background: With improvements in control of systemic disease, subsets of breast cancer patients (pts) including those with HER2+ and triple negative (TN) BC appear to have an increased risk of BM. We sought to evaluate factors influencing outcomes after diagnosis of BM. Methods: We collected treatment information and outcomes for pts diagnosed with BM who received ongoing care at our center from 1997 to 2011. We correlated clinical, treatment, and pathologic characteristics including age, hormone receptor (HR) and HER2 status, Karnofsky Performance Score (KPS) and number of BM (#BM) at diagnosis with outcomes. Patients were characterized as one of three subtypes: HR+/HER2+, HER2+, or TN. Results: 184 patients are included in this analysis. Median time to BM diagnosis (TTBM) was 38.8 months (mo) (range, 0–274); median survival (OS) after diagnosis of BM was 14.9 mo. Both varied by tumor subtype. Multivariate analysis revealed that TN disease, age >50 and KPS <90 were associated with decreased OS after diagnosis of BM. Progression of systemic disease and >3 BM at diagnosis were univariate predictors of decreased OS (P=0.0005 and P=0.02 respectively) but were not significant in multivariate analysis. Pts treated with gamma knife (GK) as initial therapy followed by whole brain radiation therapy (WBRT) as salvage had similar OS to patients who received WBRT first then had GK as salvage (31.8 vs. 28 mo). Patients who received WBRT or GK only had worse OS (7.7 and 16.3 mo respectively). Since the year 2000, OS after diagnosis of BM remained relatively constant. Conclusions: Underlying tumor biology appears to drive outcomes, and patients with TN BC continue to have a poor prognosis after BM diagnosis. Despite the reported improvement in OS following BM diagnosis compared to previous decades, we did not observe a reduction in risk of death based on calendar year of diagnosis of BM. [Table: see text]
Male breast carcinoma in United States: Survival rate and determinants of prognosis.
Authors: Talluri S. , Kakarala R. , Karedan T. , Kakarala M. 
Published: February 2017

32 Background: Male breast cancer (MBC) is rare and accounts for less than 1% of all cancers in men. It causes significant morbidity and mortality due to late diagnosis. The primary objective of our study is to update information about the receptor status, pathology, survival rates, and prognostic factors for MBC. Our secondary objective is to determine racial differences in survival of MBC and compare tumor characteristics with female breast cancer (FBC) patients. Methods: We analyzed a retrospective cohort of breast cancer patients included in National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) from 1990 to 2007. Differences between patient and disease characteristics at the time of diagnosis among MBC and FBC patients were compared using chi-square test. Overall survival was estimated using Kaplan-Meier method. Cox proportional hazards regression model was used to determine the independent variables that affect survival. Results: We included 2,475 men and 393,259 women with breast cancer in our analysis. Median age at diagnosis was higher in men compared to women (67 vs 61years). Men had more frequent lymph node involvement (32% vs. 22%), ER positivity (66% vs. 57%) and PR positivity (57% vs. 49%) breast cancer than women (P<0.001). Overall median survival in MBC was 9 years, 5-year survival was 63% and 10-year survival was 43%. Increased age, larger tumor size, higher grade, lymph node involvement, ER and PR negative status were significantly associated with decreased survival in univariate analysis (P <0.05). In multivariate analysis, age > 65 years at the time of diagnosis, larger tumor size, positive lymph node status, ER negative status and poorly differentiated grade were associated with decreased survival (P <0.02). However PR status was not a significant predictor of survival. The median survival in African American males was lower as compared to Caucasians (7.08 vs. 9.2 yrs.) (P=0.02). Conclusions: Male breast cancer differs from female breast cancer in important biological characteristics with a higher age at diagnosis and frequent lymph node involvement. Age greater than 65 years, tumor size, grade, lymph node involvement and ER status of the tumor are independent predictors of survival in MBC.
Immunologic markers associated with favorable prognosis in breast cancer patients: Role of innate immune system.
Authors: Ascierto M. L. , Kmieciak M. , Idowu M. O. , Bedognetti D. , De Maria A. , Bear H. D. , Wang E. , Marincola F. , Manjili M. 
Published: February 2017

43 Background: Recognition of tumor cells by NK cells is mediated by the interaction of activating and inhibitory NK cell receptors with ligands expressed on the interacting cell. In addition to inhibitory and activating receptors, NK cells express adhesion molecules that allow conjugate formation between NK cells and their tumor targets. We have recently identified by transcriptional analysis of breast tumor specimens a signature of 5 genes, which included B cell response and interferon signaling, found to predict with > 85% accuracy relapse-free survival. In the current study we analyzed by gene expression profile, whether a differential expression of activatory and inhibitory receptors and gene involved in NK cell-target interactions could be identified in relapse and relapse free patients.Methods: RNA extraction and gene expression analysis was performed on tumor specimens with at least 10% of infiltrating cells deriving from 9 from breast cancer patients who had either 3-7 years relapse-free survival (n=9) or developed tumor relapse within 1-3 years after the initial treatment (n=8). Data were analyzed by BRB tools and Partek software.Results: Our results showed that patients with a favorable prognosis showed increased expression of genes involved in NK interaction with tumor cells and NK activating signaling. In particular an up-regulation of leukocyte function-associated antigen 1 (LFA-1) gene, typically involved in NK cells adhesion to target cells and DNAM 1, usually associated with activation of NK cells and considered one of the major protagonist of NK- Dendritic cells crosstalk, was observed to occur in relapse free patients. In addition, an up regulation of CD96 and CRTAM which, like DNAM 1, promote NK cell-target cell adhesion by interacting with the Necl2 and poliovirus receptor (PVR), was observed in relapse free patients. Conclusions: Our observation suggests that the NK signatures are associated with favorable outcome in breast cancer and allow us to generate new hypothesis on the role of innate immunity in this contest.
Evaluation of ER/PR and HER2 status by RNA sequencing in tissue core biopsies from preoperative clinical trial specimens.
Authors: Kamalakaran S. , Lezon-Geyda K. , Varadan V. , Banerjee N. , Lannin D. R. , Rizack T. , Sikov W. M. , Abu-Khalaf M. M. , Janevski A. , Harris L. ,   Brown University Oncology Group
Published: February 2017

46 Background: Next-generation sequencing for measuring RNA (RNASeq) offer increased sensitivity, dynamic range and provide unbiased detection of all transcripts. To evaluate the clinical utility of such methods, we sequenced entire transcriptomes from fresh-frozen biopsies in a cohort of 120 patients enrolled on a preoperative therapy trial receiving carboplatin, nab paclitaxel and either bevacizumab (HER2-) or trastuzumab (HER2+). Methods: Total RNA was extracted and amplified from frozen breast core biopsies and libraries constructed using TruSeq (Illumina). Sequencing was performed on the Illumina GAII platform. 75bp reads were mapped using Tophat and transcript abundance in FPKM units (Fragments per kilo-base of mRNA per million reads) calculated using Cufflinks. CLIA approved assays were performed for ER, PR, HER2 (IHC+/- FISH) on patient tumors. Four tumors from each subtype (ER +ve/HER2 -ve; HER2 +ve; ER/HER2 -ve) were analyzed for correlation with clinical status. PAM50 classification will be provided for verification of molecular subtypes. Results: RNA-Seq library construction/sequencing were successful in 12/12 samples with 50-90% reads mapped. ER +ve tumors ranged in FPKM values from 1.76-22.67 and ER -ve tumors ranged from 0.00-0.79. i.e. ER RNASeq measurements can separate clinical ER status. HER2 +ve tumors ranged in FPKM values from 2.62-21.71 and HER2 -ve tumors from 0.21-1.79. Of note, 7/8 HER2 -ve tumors ranged from 0.21-0.87 with one ‘outlier’ at 1.79±0.3. This outlier was HER2 IHC 2+, FISH ratio 1.1 with 45% of tumor cells with polysomy chromosome 17. Correspondence of ER/PR and HER2 status with molecular subtyping by PAM50 analysis will be presented. Conclusions: RNASeq has potential to provide in depth analysis of the breast cancer transcriptome and a single analysis test for standard markers. In addition, RNASeq may uncover unexpected expression patterns in conventionally-defined HER2 -ve tumors. If reproducible in larger datasets, this technology may provide both standard and novel information previously unavailable to oncologists and their patients.
Intermethod comparison of breast receptor studies by immunohistochemistry and quantitative RT-PCR (21 gene assay).
Authors: Fulton R. S. , Baehner F. L. 
Published: February 2017

48 Background: The ASCO/CAP Guidelines mandate that laboratories performing HER2 and hormone receptor analyses monitor and correlate their results with results obtained from outside testing. Herein, we evaluate the concordance between results obtained by the 21 gene assay (ODx) with those performed by immunohistochemistry (IHC) at the Kaiser Permanente Northern California Regional IHC Laboratory (KP-NCAL). Methods: Sequential specimens from KP-NCAL were evaluated by IHC for ER (SP1), PR (PgR636) using 5% staining for positivity and HER2 (4B5) using >30% with 3+ positivity. Standardized quantitative RT-PCR analysis for ER, PR and HER2 was performed using pre-defined cutoffs of 6.5, 5.5, 11.5 units. Reference normalized expression measurements ranged from 0 to 15, where each 1-unit increase reflects about a 2-fold increase in RNA. The percent positive agreement (PPA) and percent negative agreement (PNA) was calculated for each of the three markers. For the purposes of this inter-method comparison we define ODx as the reference test; in this comparison, a “true positive” is IHC+ and ODx+. A “false positive” would be IHC+ and ODx-. Results: Evaluable data was obtained from 216 sequential patients from 11/2009 to 5/2010 with both IHC (KP-NCAL) and the 21 gene assay (ODx) results. The HER2 PPA was 100%, PNA 99.4%. The ER PPA was 99.1%, PNA 100%. The PR PPA was 92%, PNA 52%. Conclusions: There is a high degree of agreement between KP-NCAL IHC and ODx results for ER and HER2. This level of agreement is particularly striking given that in >90% of cases, IHC was performed on an initial biopsy, while the RT-PCR assay was performed on a subsequent excision specimen. The negative agreement for PR was moderate and suggests a possible lack of sensitivity in the IHC assay that needs to be studied further. [Table: see text]
Risk factors of brain metastasis in a series of Egyptian breast cancer patients: A single-institution experience.
Authors: Azim H. A. , Malek R. A. , Abdelmonem D. , Amin S. , Abdelsalam M. 
Published: February 2017

50 Background: Incidence of cerebral metastasis is increasing among breast cancer patients. Many factors have been reported associated with increased risk of brain metastasis. The aim of this retrospective analysis is to investigate the predictive factors for the development of brain metastasis in breast cancer patients. Methods: We retrospectively analyzed histologically proven breast cancer patients who presented to Cairo Oncology Center (COC) in the period from 1999 till 2008, with follow up period of 6 months at least for those in adjuvant setting. The following factors were analyzed: age, tumor size and grade, nodal status, ER, PgR and HER2 over-expression status. Results: Our study included 2,338 patients. 96 patients (4.1%) experienced brain metastasis during the course of their disease. 3 patients had brain metastasis among other sites of distant spread at first presentation to COC. 30 out of 96 patients (31.25%) with localized breast cancer had brain metastasis at first relapse with 13 (13.5%) of them had isolated brain metastasis. In a median follow-up of 37.1 months (6-277) the median time to develop brain metastasis was 26.5 months (0-144). Based on univariate analysis, the following variables were associated with shorter time to develop brain metastasis: tumor size more than 5 cm (HR = 2.1, 95% CI 1.14-3.87), lymph node involvement at diagnosis (HR = 1.57, 95%CI 1.17-2.10), ER negativity (HR = 1.58, 95%CI 1.33-1.73), PgR negativity (HR = 1.55, 95%CI 1.29-1.72) and HER2-neu over-expression (HR = 2.68, 95%CI 1.51-4.75). On multivariate analysis, only patients with lymph node involvement at diagnosis and those with HER2-neu positive breast cancer were associated with shorter time to develop brain metastasis. Conclusions: We concluded that HER2 over-expression as well as lymph node involvement are the 2 main factors associated with shorter time to develop brain metastasis. These patients could be good candidates for trials investigating the role of any prophylactic intervention to decrease their risk to develop brain metastases.
Predicting possibility of positive non-sentinel nodes in sentinel node–positive breast cancer patients: A Singapore series.
Authors: Yong W. S. , Chang M. H. , Chen W. J. J. 
Published: February 2017

51 Background: Sentinel lymph node (SLN) biopsy is an accepted method for determining the axillary status in early breast cancer patients. If positive, a standard axillary clearance is performed. However, recent studies have shown that many of these patients may not have additional positive non sentinel nodes, and the removal of these additional nodes may not be necessary or confer any benefit. We set out to identify factors that determine non sentinel node positivity and whether this could be predicted from our series of early breast cancer patients. Methods: We retrospectively reviewed 337 of our early breast cancer patients from 2005 to 2008 who had atleast one positive sentinel node and had undergone a full axillary clearance. Tumour factors and sentinel node variables were collected and compared between those patients with additional positive non sentinel nodes and those with no positive nodes in the axillary clearance. Results: Five factors were found on univariate analysis to be associated with non sentinel node positivity. They are ratio of positive SLN to total number of SLN, number of positive SLNs, size of metastasis in the SLN, tumour size and lymphovascular invasion. The first 3 factors were used to model a logistic-regression model which has good prediction ability to predict positivity of non SLNs (value under ROC curve 0.726 [95% CI 0.666-0.786]). Conclusions: Tumor factors and SLN variables are able to help us predict the possibilty of additional positive non SLN once at least a SLN is positive. This can help the surgeon and patient in the decision making process on the need for a full axillary clearance.
Is modified Bloom-Richardson grade a reliable predictor of breast cancer recurrence?
Authors: Yap K. K. L. , Efiom-Ekaha D. N. 
Published: February 2017

52 Background: Modified Bloom-Richardson (MBR) grade is a pathologic grading system for breast cancer that has been shown to have prognostic significance in patients with node-negative disease. Oncotype DX Score is a 21-gene expression analysis that has been clinically validated as a reliable predictor of recurrence risk for node-negative estrogen receptor-positive breast cancer. A score of less than 18 signifies a low risk of recurrence, a score of 18 to 31 signifies an intermediate risk and a score greater than 31 signifies a high risk. Several reports have questioned the concordance between the Oncotype score and MBR grade. The objective of this study is to evaluate the concordance between Oncotype score and MBR grade, thereby ascertaining if MBR is a reliable predictor of breast cancer recurrence. Methods: An IRB-exempted restrospective chart review of female patients at Wellspan Group who had Oncotype DX analysis in 2008 and 2009 was carried out. Data collected included Oncotype DX score, MBR grade, BMI and menopausal status. Data were analyzed to determine the association between Oncotype DX score and MBR grade. Results: A total of 125 patients were identified. Of these, 107 had MBR grades available. The remaining patients did not have MBR grade as it was not applicable to their breast cancer type. The mean Oncotype scores were 15.11 (95% CI 13.33-16.89) for patients with MBR grade 1 carcinoma, 20.31 (95% CI 17.90-22.72) for MBR grade 2 carcinoma, and 39.93 (95% CI 30.05-49.80) for MBR grade 3 carcinoma. The mean Oncotype score differences were 5.201 (P = .007, 95% CI 1.46-8.94) between MBR grades 1 and 2, and 19.616 (P < 0.001, 95% CI 14.14-25.09) for MBR grades 2 and 3. The ranges of Oncotype scores for MBR grade 1, grade 2 and grade 3 were 3 to 36, 9 to 56 and 20 to 70 respectively. Conclusions: MBR grade may predict breast cancer recurrence risk reliably as there is acceptable concordance between MBR grade and Oncotype Dx recurrence risk.
Functional metabolic tomographic optical breast imaging (TOBI) to monitor response to neoadjuvant therapy in breast cancer.
Authors: Carp S. A. , Wanyo C. , Specht M. C. , Schapira L. , Moy B. , Finkelstein D. M. , Boas D. , Isakoff S. J. 
Published: February 2017

60 Background: Recent studies using near-infrared optical measurements in breast tumors have demonstrated the promise of early monitoring of neoadjuvant chemotherapy (NAC) to predict outcome. Technologies to date have focused primarily on static measurements. Dynamic optical imaging, in conjunction with fractional mammographic compression, offers access to multiple functional and metabolic tissue biomarkers that may be used to predict treatment response. We have developed a novel tomographic optical breast imaging (TOBI) device to evaluate the early (day 7) prediction performance of this advanced technology. Methods: We are conducting a pilot feasibility study in female patients with unilateral locally advanced breast cancer undergoing standard-of-care NAC. Pre-treatment and day 7 post-treatment TOBI scans are obtained, with additional scans on day 1 of each subsequent chemotherapy cycle. The affected and contralateral normal breasts are compressed to 6-8 lbs of force and optical images are acquired once every 2 seconds for two minutes. Time-resolved oxy-(HbO), deoxy-(HbR), and total-(HbT) hemoglobin concentration and hemoglobin oxygen saturation (SO2) are calculated. The compression-induced rate of change of HbT correlates with changes in tissue blood volume indicative of biomechanical properties and the evolution of tissue SO2 estimates tissue metabolism. Results: We report initial data from two patients. One patient had a near-pathologic complete response (responder) and showed 21% and 23% decreases in HbT and HbR, respectively. The second patient had no significant response (non-responder) and had 2% and 1% decreases in HbT and HbR, respectively. Interestingly, the responder showed a dynamic decrease in HbT during compression in the tumor region at day 0 that disappeared at day 7, while the non-responder had similar rates of HbT change at both scans. Conclusions: We demonstrate for the first time the feasibility of dynamic optical breast tomography and show that optically derived parameters may be sensitive to therapyinduced changes in breast cancer. These dynamic measurements may provide novel insight into the physiologic changes in breast tumors during treatment.
Correlation of efficacy between rash and lapatinib/capecitabine therapy in Japanese HER2-positive metastatic breast cancer patients.
Authors: Nagai S. E. , Inoue K. , Kaneko S. , Uchida S. , Higuchi T. , Hayashi Y. , Yoshida T. , Takei H. , Kurosumi M. , Tabei T. 
Published: February 2017

62 Background: Lapatinib (L) is an oral dual-tyrosine kinase inhibitor with specificity for both EGFR and HER2. A phase III randomized trial (EGF100151) demonstrated that L+ capecitabine (C) is superior to C alone in patients with HER2-positive advanced breast cancer that progressed following prior therapy including trastuzumab. Although, Japanese phase I/II trial (EGF109749) demonstrated better response rate and higher rate of rash over a previous phase III trial. Recent reports demonstrated the correlation of efficacy between EGFR targeted therapy and rash in colon cancer. In lung cancer EGFR mutation, which are predominantly found in patients of East Asia origin are highly sensitive to EGFR-TKI. Analyzing correlation of efficacy between rash and EGFR targeted therapy is important in breast cancer. Methods: From June 2009 to February 2010, we treated 28 HER2-positive MBC patients who developed progression after anthracyclines, taxanes and trastuzumab based regimens with L 1,250 mg p.o. daily plus C 2,000 mg/m2 p.o. days 1-14 q 21 in Saitama Cancer Center. EGFR status was evaluated by immunohistochemistry. We analyzed the correlation among rash, clinical outcome and EGFR status. Results: Fourteen (50%) patients experienced rash, which were two grade 3, four grade 2 and eight grade 1. Rash experienced group showed superior response rate (77% : 24%, p<0.05) and median survival time (N/A: 259 days, p<0.05) over non-rash group. EGFR status has no correlation between rash and clinical outcome. Conclusions: According to our single institute experience, rash might be predictive factor in Japanese HER2 positive breast cancer patients treated with L+C therapy.