bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P3-09-04: The associations between body mass index and breast cancer intrinsic subtypes in Japanese women
Authors: Kimura K , Tanaka S , Iwamoto M , Uchiyama K 
Published: August 2014

Abstract
Purpose: The purpose of this study was to examine the associations between body mass index (BMI) and breast cancer intrinsic subtypes in Japanese women. A more complete understanding of the subtypes of breast cancer may help elucidate mechanisms affecting etiology and mortality associated with each subtype.
Methods: Tumor data on 531 invasive breast cancer cases subtyped by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (Her2) status were obtained (luminal A, luminal B, TN, and Her2-type). Demographics (age at diagnosis, menopausal status, and BMI) were collected from medical records. Case-only odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression, adjusting for age at diagnosis.
Results: In all cases, the patients were Japanese. Of the 531 cases with IHC marker data, 333 (62.7%) were classified as luminal A, 85 (16.0%) were luminal B, 43 (8.1%) were Her2-type, and the remaining 70 cases (13.2%) were TN. The distribution of patient demographics (age at diagnosis, menopausal status, and BMI) did not differ significantly by breast cancer tumor subtype. Case-only ORs comparing each subtype to luminal A were caluculated. Of the TN cases, postmenopausal TN cases were more likely to be underweight (OR = 3.14, 95% CI = 1.19 to 8.01). Although some epidemiological studies have reported that higher BMI was associated with premenopausal TN cases compared with luminal A cases, this association was not found among premenopausal TN cases analyzed using BMI 18.5 to 24.9 kg/m2 as the reference in this analysis. However, there were no underweight cases (BMI &lt; 18.5 kg/m2) among the premenopausal TN cases in the present study. Therefore, the association between BMI and the TN subtype was also analyzed using BMI &lt; 25 kg/m2 as the reference. Compared to luminal A cases, premenopausal TN cases were more likely to be obese (OR = 4.11, 95% CI = 1.10 to 14.40), similar to reports from Western countries. Compared to luminal A cases, premenopausal luminal B cases were likely to be underweight (OR = 3.27, 95% CI = 0.88 to 11.39) or obese (≥ 25 kg/m2) (OR = 3.32, 95% CI = 0.98 to 10.81), yet this association was of borderline significance. Compared to luminal A cases, luminal B and Her2-type cases were likely to be underweight (BMI &lt; 18.5 kg/m2), yet this association was of borderline significance (luminal B: OR = 2.12, 95% CI = 0.97 to 4.46; Her2-type: OR = 2.53, 95% CI = 0.92 to 6.36).
Conclusions: In the present study, significant heterogeneity of associations between BMI and tumor subtypes was observed. Breast cancer subtypes may have different etiologies associated with each subtype.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-09-04.
Abstract P3-10-04: Regulation of inflammatory breast cancer cell invasion through Akt1/PKBα phosphorylation of RhoC GTPase
Authors: Lehman HL , Van Laere SJ , van Golen CM , Vermeulen PB , Dirix LY , van Golen KL 
Published: August 2014

Abstract
With a 42% and 18% 5- and 10-year respective disease-free survival rate, inflammatory breast cancer (IBC) is arguably the deadliest form of breast cancer. IBC invades the dermal lymphatic vessels of the skin overlying the breast and as a consequence nearly all women have lymph node involvement and ∼1/3 have gross distant metastases at the time of diagnosis. One year after diagnosis ∼90% of patients have detectable metastases, making IBC a paradigm for lymphovascular invasion. Understanding the underlying mechanisms of the IBC metastatic phenotype is essential for new therapies. Work from our laboratory and others show distinct molecular differences between IBC and non-inflammatory breast cancers. Previously we demonstrated that RhoC GTPase is a metastatic switch responsible for the invasive phenotype of IBC. In the current study we integrate observations made in IBC patients with in vitro analysis. We demonstrate that the PI3K/Akt signaling pathway is crucial in IBC invasion. Key molecules involved in cytoskeletal control and cell motility are specifically upregulated in IBC patients compared with stage and cell-type-of-origin matched non-inflammatory breast cancer patients. Distinctively, RhoC GTPase is a substrate for Akt1 and its phosphorylation is absolutely essential for IBC cell invasion. Further our data show that Akt3, not Akt1 has a role in IBC cell survival. Together our data demonstrate a unique and targetable pathway for IBC invasion and survival.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-10-04.
Abstract P3-10-06: Patterns of failure in patients with inflammatory breast cancer: the case for aggressive local/regional treatment
Authors: Warren LE , Regan MM , Nakhlis F , Yeh ED , Jacene HA , Hirshfield-Bartek J , Overmoyer BA , Bellon JR 
Published: August 2014

Abstract
Background: While the survival of patients with inflammatory breast cancer (IBC) is dictated by the status of their distant metastases, local/regional control remains an important component of quality of life. We have sought to determine patterns of local/regional recurrence (LRR) in patients presenting with inflammatory breast cancer.
Methods: The medical records of 92 patients (pts) diagnosed with IBC from 1997 until 2007 were reviewed. Pt cohorts were stratified by disease burden at presentation (metastatic or local/regional) and their tumor, treatment, and disease course were analyzed. Primary outcomes were time from diagnosis to LRR, time to distant recurrence, and overall survival (OS). Median follow-up (MFU) for the entire cohort was 6 years (yrs) (range 0.1 to 12.7 yrs); for those patients who presented with metastatic disease versus only local/regional disease, MFU is 2 yrs and 6 yrs, respectively. This study was approved by the hospital institutional review board.
Results: Median age at diagnosis was 49 yrs (range 24 to 72). 68 (74%) patients were without evidence of metastatic disease on presentation. With 6yr MFU, 40/68 (59%) had disease recurrence at either local or distant sites, and 15/68 (22%) had documented LRR, either as the first or subsequent site of recurrence. Estimated 5yr OS is 64%.
24 (26%) pts presented with metastatic disease (lung, liver, distant lymph nodes, pleura). All of the 24 pts presenting with metastatic disease developed systemic disease progression; 12/24 (50%) also developed LRR, and for 9/12 pts the LRR was first progression or concurrent with distant progression. Eleven of the 24 pts did not receive radiation or surgery; and within this cohort, 7 (64%) pts developed LLR at a median time of 9 months after diagnosis. Six pts received radiation therapy without surgery; 3/6 (50%) developed LRR. One pt had surgery alone; this patient was not known to have LRR, although had limited follow-up. Six pts received radiation therapy and surgery; 1 for palliation and 5 to prevent LRR. Of these 5 pts, 1/5 (20%) developed LRR that extended to the contralateral breast at 1.2y after diagnosis. Among the 24 patients, the cumulative incidence of LRR was 29%, 37%, and 43% at 1yr, 2yr, and 3yr (accounting for competing risk of death). The median OS was 2.9 yrs and estimated 5yr OS was 36%.
Conclusions: Pts with inflammatory breast carcinoma presenting with metastatic disease are at high risk for local/regional disease progression. Aggressive local therapy should be considered to prevent symptoms of uncontrolled local disease, despite an uncertain impact upon OS.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-10-06.
Abstract P3-10-08: A new in vitro method of growing and studying inflammatory breast cancer emboli
Authors: Lehman HL , Daasner EJ , Vermeulen PB , Dirix LY , Van Laere S , van Golen KL 
Published: August 2014

Abstract
Inflammatory breast cancer (IBC) is the deadliest form of breast cancer, presenting as intralymphatic emboli. Emboli within the dermal lymphatic vessels are thought to contribute to rapid metastasis. The lack of appropriate in vitro models has made it difficult to accurately study how IBC emboli metastasize. To date, attempts at creating IBC tumor emboli in vitro have used 3-dimensional culture on a solid layer of MatrigelTM, which does not resemble the physical properties of the lymphatic system. Dermal lymphatic fluid produces oscillatory fluid shear forces and is 1.5–1.7-fold more viscous than water with a pH range of 7.5–7.7. We have established a method for forming tumor emboli by culturing the IBC cell lines in suspension with either polyethylene glycol- or hyaluronic acid-containing medium and oscillatory fluid shear forces. Non-IBC cells do not form emboli under identical conditions. In vitro IBC emboli were analyzed for expression of markers associated with patient emboli and their ability to undergo amoeboid movement. In a direct comparison, the in vitro IBC emboli closely resemble IBC patient emboli with respect to size, composition and E-cadherin expression. Further, cells from the emboli are able to invade in clusters via RhoC GTPase-dependent amoeboid movement. Invasion by clusters of IBC cells is disrupted by exposure to TGFβ. This study provides a biologically relevant in vitro model to accurately grow and study inflammatory breast cancer biology and metastasis.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-10-08.
Abstract P3-12-07: Voyagers and their aids: The role of interactions between tumor and endothelial cells in brain metastasis
Authors: Shah KN , Faridi JS 
Published: August 2014

Abstract
Clinically, brain metastases are most commonly observed in breast, lung, and melanoma cancers. When a tumor cell leaves its site of origin, it enters a nearby blood vessel on a voyage to find a new tissue to invade. These circulating tumor cells will act as voyagers and they interact with a endothelial cell. For example, in the case of brain metastasis, tumor cells need to adhere to brain endothelial cells before they can invade into the surrounding brain tissue. Thus, investigating the mechanisms of tumor and endothelial cell interactions can serve as a very powerful tool to inhibit the voyage of these tumor cells and prevent the formation of metastases. In this study, we performed trans-endothelial migration assay using HBMVEC cells to study tumor-endothelial interactions. In general, HBMVEC cells were seeded to BD-Falcon cell culture inserts at a density of 2 × 105 cells and allowed to grow for 24 hours to form a confluent monolayer and GFP expressing tumor cells (MCF-7, Akt3 overexpressing MCF7, MDA-MB-231 and MDA-MB-231-BR) were incubated at suitable interval at 37°C. At the end of incubation period, cells were fixed and number of tumor cells that will penetrate the monolayer of HBMEC were counted using Phase-contrast microscope in 12 different visual fields. Transmigrating tumor cells are thought to be able to overcome the endothelial barrier by inducing changes within endothelial cells. We identified the molecular changes responsible for such adhesion and invasion by cell sorting for gene expression analysis. After co-culturing the HBMEC (after transfecting with Mcherry protein) with GFP expressing tumor cells and Mcherry labeled HBMEC, we used cell sorting to separate tumor and HBMEC cells. After sorting the tumor cells and endothelial cells from co-culture, (MCF-7 monolayer vs MCF-7 co-cultured, MDA-MB-231 monolayer vs MDA-MB-231 co-cultured, HBMEC monolayer vs HBMEC co-cultured) gene expression analysis was performed using SABiosciences cell adhesion assay kit to accurately capture the genetic changes that occured in the tumor and endothelial cells upon co-culture.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-12-07.
Abstract P3-12-08: Incidence, predictive factors and outcome of brain metastases (BM) in a single institution cohort of breast cancer patients.
Authors: Perelló A , Alarcon J , Garcias C , Duran J , Colom B , Clemente G , Avella A , Canet R , Torrecabota J , Rifa J 
Published: August 2014

Abstract
Background: The aim of the study was to determine the cumulative incidence of BM, predictive factors of BM, and survival from diagnosis of BM in a cohort of breast cancer patients in a single institution.
Patients and Methods: We collected data from a cohort of 793 breast cancer patients between January 2000 and December 2005 in our institution. Variables recorded include age at diagnosis, hormonal receptor status (HRS), human epidermal growth factor receptor 2 status (HER2), histological grade, T stage and N stage. We analyzed the 5 and 10-year cumulative incidence of BM. Time to detection of BM and survival from BM were estimated using Kaplan-Meier method. Cox regression model was used to analyze the variables associated with time to BM
Results: With a median follow-up of 100 months, 49 patients went on to develop BM. The overall 5 and 10 year cumulative incidence of BM were 4.9% and 8.2% respectively. The table shows the 5 and 10 year cumulative incidence and hazard ratio (HR) of the predictive factors for the development of BM in the univariable analysis.

Including all significant variables in the model, HER2 positive and node positive patients had an increase risk of BM, HR 2.46 (95% CI: 1.22–4.95) and 2.51 (95% CI: 1.19–5.29) respectively. HRS positive patients had a decreased risk of developing BM, HR 0.44 (95% CI: 0.21–0.89).
Median survival from BM of HER2 positive and HER2 negative patients was 9 and 3 months respectively (p = 0.015), and 6 and 1 month for HRS positive and negative respectively (p = 0.02)
Conclusion: Predictive factors independently associated with a high risk of BM in our cohort are HER2 positivity and positive nodes. Patients with positive HRS have a decreased risk of BM. Survival time following BM is poor. HER2 positive and HRS positive patients have a better survival than HER2 negative and HRS negative patients.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-12-08.
Abstract P3-12-09: The risk of brain metastases according to expression of selected immunohistochemical markers in primary breast cancers
Authors: Sosinska-Mielcarek K , Winczura P , Duchnowska R , Badzio A , Majewska H , Lakomy J , Peksa R , Pieczynska B , Radecka B , Debska S , Zok J , Rogowski W , Strzelecka M , Kulma-Kreft M , Blaszczyk P , Litwiniuk M , Jesien-Lewandowicz E , Rutkowski T , Jaworska-Jankowska M , Adamowicz K , Foszczynska-Kloda M , Biernat W , Jassem J 
Published: August 2014

Abstract
Background: About 10–30% of breast cancer patients will develop brain metastases.
In untreated patients with brain metastases the median survival is 1–2 months, and in those undergoing palliative radiotherapy — 3–6 months. The mechanism of brain metastases remains largely unknown. The identification of molecular markers might help in selecting high risk patients, and enable active surveillance, prevention and early treatment. The aim of this study was to analyze predictive value of expression of selected tumor proteins for the risk of brain metastases in breast cancer patients.
Material and methods: This study included 198 advanced breast cancer patients treated between 2001 and 2007 in 11 oncology centers in Poland, including 96 woman with and 102 without overt brain metastases, respectively. The median age at diagnosis in these two groups was 52 and 60 years, respectively, with 52% and 32% of patients being premenopausal. Stage at diagnosis was similar in both groups and ductal carcinoma was a dominant histological type (76% and 86% of cases, respectively). Immunohistochemistry was performed on formalin-fixed paraffin embedded microarray cores derived from the primary tumor. Expression analysis included ER, PR, HER2, Ki67, CK5/6, EGFR, HER3, CXCR4, RAD51, E-cadherin, and claudin 3 and 4. Cox regression model was used to estimate the relative risk of brain metastases.
Results: Expression of HER2, CK5/6, EGFR, RAD51 (both cytoplasmatic and nuclear staining), CXCR4 (cytoplasmatic staining) and Ki67 ≥14%, as well as ER or PR negativity was associated with increased risk of brain metastases in the univariate analysis (Table 1). Of those, Ki67 ≥14% (HR 2.76 [95%CI 1.70–4.48]; p &lt; 0.001), cytoplasmatic expression of double strand DNA repair gene RAD51 (HR 1.87 [95%CI 1.14–3.08]; p = 0.014) and ER negativity (HR 1.72 [95%CI 0.36–0.94]; p = 0.029) were found to be significantly related to the risk of brain relapse in the multivariate analysis. Four molecular profiles composed of the latter three markers were created, of which a profile including ER, Ki67 and RAD51 was associated with the highest risk of brain metastases (HR 4.43 [95%CI 2.69–7.27]; p &lt; 0.001). Molecular subtype analysis showed the highest risk of BM in the ER/PR/ HER2-negative (triple negative) subset (HR 1.21 [95%CI 1.11–1.32]; p &lt; 0.001).
Conclusion: Expression of proteins related to high tumor proliferation, DNA repair and ER negativity is associated with increased risk of brain metastases in breast cancer patients.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-12-09.
Abstract P3-12-10: Age, breast cancer subtype approximation and the risk of the development of brain metastasis in breast cancer patients
Authors: Hung M-H , Liu C-Y , Chao T-C , Wang Y-L , Tsai Y-F , King K-L , Chiu J-H , Shiau C-Y , Shyr Y-M , Tzeng C-H , Tseng L-M 
Published: August 2014

Abstract
Purpose: Biological subtypes and age were well-known risk factors associated with the development of brain metastasis in breast cancer patients. However the impact of each biological subtype in different age group was less discussed.
Patient and methods: Patients with invasive ductal carcinoma of breast diagnosed from January 2000 to December 2009 were divided by age of diagnosis into three groups: age below 35, age from 36–59 and age above 60. Four biological subtypes of breast cancer subtype were approximated as luminal A, luminal B, HER2 enriched and triple negative breast cancer by intergrading status of estrogen receptor, progesterone receptor and HER2 and grade.
Result: With a median follow-up time of 54.2 months, there were 164 patients (7.3%) among the 2248 enrolled patients developed brain metastasis. Patients with HER2 enriched [hazard ratio (HR) 2.53; 95% confidence interval (CI): 1.57–4.07, p &lt; 0.0001)], triple negative breast cancer (HR 4.42; 95% CI: 2.86–6.85, p &lt; 0.0001) and diagnosed age younger than 35 years-old (HR 2.09; 95% CI: 1.15–3.81, p = 0.016) were strongly associated with higher incidence of brain metastasis. Table 1 showed the important characteritics according to different age group.

Furthermore the influence of each biological subtype amoung different age group were investigated. For patient younger than 35 years-old, risk of the developement of brain metastasis was independent to biological subtype (p = 0.507); while the risk of brain metastasis was influenced by biological subtype in older age groups. For patients older than 35, patients with triple negative and HER2 enriched disease had significantly increased risk for brain metastasis compared to luminal A; but for patients with luminal B disease, such incremental risk for the development brain metastasis was only observed in patients older than 60 years-old.
Conclusion: Our study found that each biological subtypes of breast cancer had distinct impact on the development of brain metastasis among different age group. Further studies were needed to disclose the biology underneath. Also the findings should be taken into consideration when developing strategy for brain metastasis prevention.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-12-10.
Abstract P3-13-02: Safety and Efficacy of Zoledronic Acid Beyond 24 Months in Breast Cancer Patients
Authors: Suzuki Y , Saito Y , Ogiya R , Oshitanai R , Terao M , Terada M , Morioka T , Tsuda B , Niikura N , Okamura T , Tokuda Y 
Published: August 2014

Abstract
Background: Bisphosphonate therapy has decreased the risk of skeletal complications associated with osteolytic bone lesions in patients with breast cancer and multiple myeloma. The large prospective studies have used 21 to 24 months of treatment. We studied the safety and efficacy of Zoledronic acid in a subset of patients who received therapy for more than 24 months.
Patients and Methods: Patients who received Zoledronic acid were identified. Data on skeletal events and laboratory parameters were gathered by chart review. The treatment regimen is 4 mg of Zolendronic acid at 3- to 4-week intervals, and concurrent chemotherapy, hormonal therapy, and radiation therapy was included. Before approval of Zoledronic acid, we were using Pamidronate and Incadronate.
Results: We used the Zoledronic acid in 221 patients from June 2006 until December 2011 (range, 1–69 times of administration). We analyzed 71 cases in which the treatment could be continued for more than 24 months (range, 24–69 times of administration). No significant calcium, phosphorus, electrolyte abnormalities were encountered. There were no significant differences between the long-term treatment patients with Zoledronic acid and all the other patients in the range of pain felt at the time of the bone metastasis diagnosis, or the bone metastases sites. In addition, by March 2012, more than 50% patients of long-term usage of Zoledronic acid had continued receiving treatment. And in all of the patients, as well, the most cited reason for discontinuing treatment was a disease progression, adverse effect was few. In long-term treatment patients, 4 cases of fractures and 2 cases of spinal compression were encountered. The median time until an SRE occurred was 37 months. There were fewer occurrences of SREs in our investigation than in the 12 months of a clinical trial conducted in Japan with Zoledronic acid and a placebo. As for adverse effects, BRONJ appeared in 4 (1.8%) out of a total of 221 cases, and in 3 (4.2%) at prolonged treatment patients. The other adverse effects were fever in 4 cases and fatigue in 2 cases.
Conclusion: Prolonged treatment with Zoledronic acid seems to be well tolerated and should be studied in prospective, randomized studies to document prolonged skeletal efficacy and survival.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-13-02.