bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P6-07-37: Impact of body mass index on recurrence risk in patients with ductal carcinoma in situ.
Authors: Klepczyk LC , Meredith RF , De Los Santos JF , Li Y , Keene KS 
Published: August 2014

Abstract
Background: Body mass index (BMI) has been correlated with risk of recurrence in invasive breast cancer, but the association between BMI and recurrence in ductal carcinoma in situ (DCIS) is less clear. Recent retrospective data indicates that local recurrence is not related to BMI at initial diagnosis. Here we examine the relationship between initial BMI and recurrence in a separate cohort of patients with DCIS.
Methods: One hundred eighty-nine patients with DCIS treated between the years of 1999 and 2005 at the University of Alabama at Birmingham were analyzed. BMI was divided into 4 categories as follows: underweight (BMI &lt;18.5 kg/m (2)), normal weight (BMI 18.5–24.9 kg/m (2)), overweight (BMI 25–29.9 kg/m (2)), and obese (BMI ≥30 kg/m (2)). Fisher's exact test was used to evaluate the association between likelihood of recurrence based on initial BMI and the log rank test was used to evaluate recurrence-free survival. Risk of both overall recurrence and specifically local recurrence were analyzed.
Results: There were 199 cases of DCIS identified in our cohort of 189 patients (10 patients had bilateral disease). Of these 189 patients, 1.1% (2/189) were underweight, 31.2% (59/189) were normal weight, 22.7% (43/189) were overweight, and 21.7% (41/189) were obese. BMI could not be obtained for 23.3% (44/189) of patients. With a median follow-up of 87.2 months, there were 28 total recurrences identified in the 199 cases (14.1%) with 85.7% of these including a local recurrence. No significant associations were found between the likelihood of overall or local recurrence and any of the four BMI categories. Further, analysis of recurrence-free survival did not show any significant associations between BMI and recurrence.
Conclusions: Our data supports recently reported evidence that BMI at diagnosis does not affect the risk of overall or local recurrence in patients with DCIS.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-07-37.
Abstract P6-07-38: The Value of Progesterone Receptor in Predicting the Recurrence Score for Hormone-Receptor–Positive Invasive Breast Cancer Patients
Authors: Onoda T , Yamauchi H , Yagata H , Hayashi N , Yoshida A , Nakamura S 
Published: August 2014

Abstract
Background: Molecular genomic profiling currently plays a major role in treatment decisions for breast cancer patients. The 21-gene signature (Oncotype DX® [ODX]) is one of the most well-validated assays. Herein we evaluated the associations between high Recurrence Score (RS) measured by the ODX and pathological factors.
Methods: From October 2007 to October 2010, the ODX assay was performed for 139 hormone-receptor–positive invasive breast cancer patients at single institution. Correlations between the RS and the following pathological factors were analyzed: tumor size (T), lymph node metastasis (N), nuclear atypia (NA), mitotic counts (MC), nuclear grade (NG), lymphatic and vascular invasion (LI and VI), estrogen receptor (ER), progesterone receptor (PgR), HER2, and Ki-67. Expression of ER, PgR, HER2, and Ki-67 was examined by immunohistochemistry. The Ki-67 labeling index was automatically counted with an Ariol-SL50 instrument (APPLIED IMAGING). The other pathological factors were estimated under the supervision of one experienced pathologist. Spearman rank correlation coefficients were calculated for the analyses. When the r was &gt;0.4 or &lt;–0.4 for two factors, they were determined to be well correlated.
Results: Of 139 patients, the ODX assay revealed 68 (49%) low RS cases, 52 (37%) intermediate RS cases, and 19 (14%) high RS cases. Moderate positive or negative correlations were noted between the RS and PgR (r = −0.53), the RS and Ki-67 (r = 0.42), and the RS and NG (r = 0.41). No patients had high RS with PgR (3+) or NG1. The rate of high RS with Ki-67 (&lt;20%) was one patient (2%). The number of cases who did not show PgR (3+) or NG1 or Ki-67 (&lt;20%) was only 34 (25%). Among high RS cases, the correlation between PgR (0) and NG3 was 83%, the correlation between PgR (0) and NG2 was 75%, and the correlation between PgR (1+) and NG3 was 75%.

The rate of high RS with PgR (0) and Ki-67 (≥20%) was 70%, that of PgR (1+) and Ki-67 (≥20%) was 58%, and that of PgR (2+) and Ki-67 (≥20%) was 21%.

Correlations with T, N, NA, MC, LI, VI, ER, and HER2 were smaller (r ranging from −0.33 to 0.38).
Conclusion: This study demonstrated that PgR, NG, and Ki-67 tend to be strongly correlated with the RS. Judging from PgR (3+), NG1, and Ki-67 (≥20%), we could select the patients who were proposed to perform the ODX. Among these factors, the correlation with PgR was particularly robust. PgR expression is a known marker of a functional ER and represents ER activity. In addition, the absence of PgR may reflect hyperactive cross-talk between ER and growth factor signaling pathways. We consider that these mechanisms could enhance the value of PgR in predicting the RS.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-07-38.
Abstract P6-07-40: Initial Neutrophil-to-Lymphocyte ratio in primary breast cancer patients: a simple and useful biomarker as prognostic factor
Authors: Han A , Noh H , Lee J 
Published: August 2014

Abstract
Background: Increasing neutrophil/lymphocyte ratios (NLR) on preoperative blood tests have been associated with worse survival of patients with colorectal, gastric, hepatocellular, pancreatic and lung cancer. However the utility of NLR to predict mortality in breast cancer patients has not been studied. The aim of our study was to determine whether the NLR is predictive of disease specific mortality in breast cancer and subtype-adjusted prognostic effect in breast cancer patients.
Methods: We retrospectively identified all the patients with primary breast cancer diagnosed at Yonsei University Wonju Medical School between January 2000 and June 2011 who underwent primary surgery and completed all phase of their treatment. Breast cancer with infiltrating ductal histology was included and divided into 4 subtypes: Luminal A, Luminal B, Her2-enriched, and basal type. Each immunohistochemical characteristics are as followings: Luminal A: ER and/or PgR positive and negative Her2, Luminal B: ER and/or PgR positive with positive HER2, Her2-enriched: negative ER and PR with positive Her2, and triple negative as basal.
Results: Patients with NLR≥2.5 showed significantly lower 5-year, 10-year breast cancer specific survival than patients with NLR&lt;2.5. (5-year survival; 88.6% vs. 96.4%, p = 0.009, 10-year survival; 84.3% vs. 92.2%, p = 0.006). Cox proportional multivariate hazard model for cancer-specific mortality showed that patients with NLR≥2.5 has hazard ratio 4.71 with 95% confidence interval 1.77–12.53. Further analysis was done according to stratified patients' subgroup with intrinsic subtype. In Luminal A subtype, patients with NLR≥2.5 showed higher mortality rate(p = 0.014), while NLR≥2.5 failed to show statistical significance in the other subtype such as Luminal B, Her2 enriched, and triple negative subtype.
Conclusion: Increased preoperative NLR is a significant prognostic factor in breast cancer specific survival and relevant in Luminal A subtype. This study shows that NLR could be a useful prognostic factor for breast cancer specific survival. And this study suggests that different factors could contribute as prognostic factor to each subtype, such as NLR was significant prognostic factor in Luminal A, while we couldn't find increased NLR is significant in other subtypes.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-07-40.
Abstract P6-07-41: Sub classification of early stage hormone positive (HP) Her-2 negative breast cancer (BC) by immunohistochemistry (IHC) into intrinsic subtypes (IS) and their correlation with Oncotype Recurrence Score (RS)
Authors: Mahesh S , Lane J , Ravichandran P 
Published: August 2014

Abstract
Background: Early stage HPBC is a heterogenous disease and various models of prognostication are available. Molecular profiling by IS i.e. Luminal A (LA) and Luminal B (LB) is one such attempt but is complex and expensive. Literature suggests a Ki-67 index of ≥14% as a cutoff between LA and LB tumors. LB subtype is associated with worse breast cancer outcomes. Oncotype RS is one of the most robust tools to assess prognosis and predict benefit from chemotherapy in HP Her-2 negative early BC. We sought to investigate the correlation between IHC classification of IS and RS. In addition, we also evaluated incidence of basal immunophenotype in this population.
Methods: Early Stage Her-2 negative HPBC cases that had RS testing from 2007–2011 were found through our database. IHC for Ki-67, CK 5/6 and EGFR was performed if adequate tissue blocks were present. IHC classification of IS was as follows: Ki-67 ≥ 14%: LB; Ki-67 &lt; 14%: LA; CK 5/6 and/or EGFR expression: Basal. An exploratory analysis using Ki-67 cutoff of 19% i.e. LA (&lt;19%); LB (≥19%) was performed to evaluate its effect on correlation with RS.
Results: We found 115 patients. Median age: 62 years. Stage 1: 79/115 (69%) Stage 2: 36/115 (31%). Using Ki-67 cutoff of 14%, LA: 42/115 (36.5%); LB: 72/115 (62.6%); Using Ki-67 cutoff of 19%, LA: 66/115 (57.4%); LB: 48/115 (41.7%); Basal: 1/115(0.9%). Characteristics of LA and LB and their comparison with Oncotype Dx are shown in the Table 1. Compared to LA, LB patients were younger (p = 0.004) and had higher oncotype scores (p = 0.007). However, range of RS in both subtypes was large. Among LB patients, 43% fell in low risk category and only 15% fell into high risk category. Among LA, results seemed to correlate more with expectations; 69% were in low risk category while 5% were in high risk category. When a cutoff of Ki-67 &lt;/≥19% was used to classify LA/LB, 42% of LB were still in low risk category of Oncotype Dx. Only 1 patient had basal immunophenotype (Ki-67 25%, RS 42).

Conclusion: Majority (85%) of LB patients were in Low or Intermediate category of RS. This did not change when a higher KI-67 cutoff was used. Thus, relying solely on Ki-67 to classify LA/LB and using it as a surrogate marker for obtaining benefit from chemotherapy would be inappropriate.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-07-41.
Abstract P6-08-09: Overcoming Breast Cancer: The Importance of Connecting with Fellow Survivors
Authors: Geoghegan C , Whitman B 
Published: August 2014

Abstract
Y-ME National Breast Cancer's Organization, founded in 1978, is not-for-profit organization with a mission to “To assure through information, empowerment, and peer support, that no one faces breast cancer alone.” Each year, Y-ME's 24×7×365 Breast Cancer Hotline receives approximately 40,000 contacts. Callers to Y-ME's toll-free Hotline are referred by clinicians, community groups and global cancer organizations that recognize the importance of providing emotional relief to patients and their loved ones. Trained and certified peer counselors, all breast cancer survivors, staff the hotline. Callers can speak to a Spanish or English speaking peer counselor or have an interpreter in any of over 150 languages added to the line.
An online survey conducted by Whitman Insight Strategies on behalf of the Y-ME National Breast Cancer Organization was conducted to better understand the psychosocial needs of breast cancer patients and survivors. Surveys were conducted on April 3–5, 2012, among 400 breast cancer patients and survivors 18 years of age and older across the United States. The margin of error for total sample is ±4.9% at the 95% confidence interval. Respondents received an email invite to participate in a short online survey; their emails were selected at random among online market research panelists who had previously indicated that they have or had breast cancer.
The results indicate that talking to a breast cancer survivor can be instrumental in overcoming breast cancer: 84% of breast cancer patients and survivors say this is one of the most important ways of coping with breast cancer and 68% wish that they could have been connected to other survivors. Access to a 24×7×365 hotline, where breast cancer survivors provide emotional support and practical advice, is considered important by virtually all women surveyed (95%)–73% think this is “extremely” or “very” important. Unfortunately, although Y-ME provides such a hotline; however, awareness of it is extremely low (14%). We encourage all healthcare providers to encourage patients to reach our to Y-ME by calling 800–221-2141 and time of the day or night.
Those who had another survivor to talk were asked to select among a number of relevant responses to the question: What did talking to another breast cancer patient/survivor provide you with? The following table provides the proportion that selected each response.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-08-09.
Abstract P6-09-03: Fatigue after breast cancer may be related to conditions other than the cancer. The impact of comorbidity is essential.
Authors: Reidunsdatter RJ , Hjermstad M , Oldervoll L , Lundgren S 
Published: August 2014

Abstract
Purpose: Fatigue after treatment for breast cancer is common, but is also prevalent in people with chronic diseases such as heart failure, diabetes, and depression etc. The primary objective was to compare the level of fatigue between BC patients one year after end of treatment with data from a representative survey of the Norwegian population (GenPop). Secondary aim was to explore the association between chronic conditions and fatigue and in both samples.
Design and Method: 245 patients treated with chemo –and/or radiotherapy after surgery, were assessed one year after treatment. Comorbidity was recorded by clinical examinations in patients and by self-report in the GenPop (N = 652). Fatigue was measured by the 3-item subscale of the EORTC QLQ-C30, with higher scores on the 0–100 scale implying more fatigue. Analysis of covariance was applied to compare age-adjusted mean scores between groups.
Results: Mean age was 58 (9) years in patients and 52 (14) years in GenPop. 23% of patients and 32% of GenPop had one or more of the following conditions; cardiovascular- or pulmonary disease, diabetes or depression. No significant differences were found in fatigue between BC patients and GenPop (mean score 26.7 vs. 29.7). Comorbidity was the greatest determinant of increased fatigue, regardless of BC treatment. Patients with comorbidity were significantly more fatigued than those without comorbidity (mean difference 10.4), as found in the GenPop (mean difference 13.3).
Conclusion: Similar fatigue levels in BC patients and GenPop one year after treatment is promising, but longer follow-up is needed. Comorbidity conditions should always be assessed when evaluating fatigue and other patient related outcomes. Prevention or treatment of common chronic conditions might be considered in rehabilitation programs to reduce fatigue in cancer survivors.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-09-03.
Abstract P6-10-06: Rational combination therapy against triple-negative breast cancer
Authors: Al-Ejeh F , Miranda M , Simpson PT , Chenevix-Trench G , Lakhani SR , Khanna KK 
Published: August 2014

Abstract
Background: Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer with higher incidence of recurrence, more distant metastasis, and poorer survival. This subtype is also characterized by complex genomes where little of their genomes remain at normal copy number but without high, focal copy number amplifications. At the transciptome level, the majority of TNBC (∼75%) are classified as basal-like breast cancer (BLBC) according to the five intrinsic subtypes. Despite considerable genomic and gene expression characterization of TNBC, proteomic and phospho-proteomic investigations of this disease are limited with no available targeted therapies in clinical use.
Methods & Results: We used the Kinex™ antibody array (http://www.kinexus.ca/) to interrogate protein/phosphoproteins levels in 43 primary breast cancer biopsies (16 TNBC, 16 ER/PR positive and 11 HER2-positive) and 16 breast cancer cell lines. Unsupervised hierarchical clustering of protein/phosphoprotein levels revealed two subgroups of TNBC in comparison to other subtypes. Western blotting and Proteome Profiler™ Arrays (R&D Systems) were used to validate deregulated proteins/phosphoproteins in TNBC. Pathway analysis revealed that one subgroup of TNBC exploits overlapping and cross-talking networks for survival. These signaling networks are downstream from elevated activation of EGFR, integrins and Insulin-like growth factor 1 receptor (IGF1R).
Targeted molecular inhibitors of activated kinases in these pathways showed specificity against basal-like/TNBC cell lines compared to other subtypes in vitro. These activated kinases/networks represent druggable targets for the treatment of TNBC but may be limited by compensatory effect of the complex cross-talking signaling networks.
To overcome compensatory downstream signaling that would limit the inhibition of a given pathway; we developed EGFR-targeted radioimmunotherapy (RIT) strategy to systemically deliver cytotoxic loads of beta particles (177Lu) that would kill targeted cells and surrounding cells by crossfire effect. The combination of EGFR-directed RIT with chemotherapy and PARP inhibition successfully treated orthotopic and metastatic TNBC models established from cell lines and patient-derived xenografts. The superior efficacy of this triple-agent combination therapy is explained by enhanced DNA damage and reduced DNA repair response, higher apoptotic cell death and the elimination of putative breast cancer stem cells.
Conclusion: Proteomic analysis of TNBC provides a powerful tool to elucidate druggable signaling networks with therapeutic potential. TNBC utilizes complex interacting signaling networks and rational combination therapies are required for effective therapy.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-10-06.
Abstract P6-11-09: FAK Inhibitor VS-4718 Attenuates Breast Cancer Stem Cell Function In Vitro and In Vivo
Authors: Kolev VN , Vidal CM , Shapiro IM , Pavdal M , Keegan M , Xu Q , Pachter JA 
Published: August 2014

Abstract
Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that mediates signal transduction by integrins as well as growth factor receptors. FAK has been implicated in multiple steps of carcinogenesis including tumor initiation, growth and metastasis. Amplification and overexpression of FAK have been observed in aggressive human cancers including breast cancer. We have now observed that VS-4718, a selective FAK kinase inhibitor, exhibits preferential inhibitory effects on breast cancer stem cells.
VS-4718 is a potent and selective FAK kinase inhibitor that blocks fibronectin-stimulated FAK autophosphorylation at Tyr397 at low nanomolar concentrations. To determine if FAK plays a role in the biology of breast cancer stem cells, VS-4718 was evaluated in a multitude of cancer stem cell assays both in vitro and in vivo. In parallel, treatment of SUM159 triple negative breast cancer cells in vitro with FAK shRNA inhibits tumorsphere formation. These data taken together indicate a role of FAK in breast cancer stem cell renewal. Similarly, pre-treatment of SUM159 cells with VS-4718 in matrigel attenuated secondary tumorsphere formation. Furthermore, VS-4718 reduced the side population (SP) and the percentage of ALDEFLUOR+ cancer stem cells in SUM159 breast cancer cells in vitro. In direct contrast, standard-of-care agent paclitaxel increased the percentage of ALDEFLUOR+ cancer stem cells in all three assays.
The in vivo effect of VS-4718 on cancer stem cells was evaluated in SUM159 and MDA-MB-231 human triple negative breast cancer xenograft models. Following systemic administration, VS-4718 induced significant reduction of cancer stem cells in tumors as assessed by a decrease in ALDEFLUOR+ cells and tumorsphere-forming efficiency relative to vehicle-treated tumors.
In summary, our results indicate the importance of FAK in the self-renewal of breast cancer stem cells in vitro and in vivo, and support the clinical development of the selective FAK inhibitor VS-4718 to target cancer stem cells for the treatment of triple negative breast cancer.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-11-09.
Abstract P6-11-12: Nanoparticle-enhanced chemotherapeutics delivery in drug-resistant triple-negative breast cancer
Authors: van de Ven AL , Landis MD , Paskett LA , Meyn A , Frieboes HB , Chang JC , Ferrari M 
Published: August 2014

Abstract
Chemotherapeutics delivery is generally poor in tumors characterized by rapid perfusion and low blood volume fraction. Systemically administered nanoparticles can be engineered to overcome abnormal flow conditions to act as intravascular drug depots for the localized delivery of high concentrations of chemotherapeutics. The feasibility of this approach was first demonstrated using melanoma, and is now being further investigated using well-characterized human triple-negative breast cancer biopsies implanted into mice. Intravital microscopy studies of human cancer-in-mice selected for differing vascular morphologies have yielded intriguing preliminary data regarding the role of tumor vascularity in drug and particle delivery. The first-pass perfusion of a 40kDa dextran tracer revealed that BCM-2665 tumors are perfused ∼6x more rapidly than BCM-4195 tumors (11.3 ± 2.3s vs. 67.6 ± 11.0) and contain ∼30% lower volume fraction of blood (0.046 ± 0.011 vs. 0.062 ± 0.015). Interestingly, flow parameters that adversely impact drug accumulation appear to favor plateloid particle accumulation. BCM-2665 xenografts receiving an i.v. injection of 1000×400 nm particles show ∼10x more particle accumulation than BCM-4195 tumors (24.8 ± 3.2 × 103/mm3 vs. 3.5 ± 0.4 × 103/mm3). The ability of these therapeutic particles to reach tumors appears to be primarily driven by flow-related parameters, which we characterize using a combination of intravital microscopy, computed tomography, and mathematical modeling. The total number of particles accumulated within a given tumor appears to be largely driven by the number of particles entering the tumor, since ∼65–70% of entering plateloid particles are retained by the tumor vasculature. This suggests that cytotoxic intravascular drug depots may be a promising strategy for increasing the efficiency of chemotherapeutics delivery to drug-resistant tumors and is the premise of ongoing therapeutic response studies. Clearly if more drugs can be delivered to the tumors, better outcomes can be expected for the patients.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-11-12.