bluuebunny/crossref_metadata_2025_split huggingface dataset:
P4-14-05: Chemotherapy-Induced Alopecia, Body Image and Psychological Distress in Women with Breast Cancer: A Prospective Study.
Authors: Choi E-K , Kim I-R , Nam S-J , Lee J , Yang J , Lee S-K , Noh D-Y , Han W , Cho J 
Published: June 2012

Abstract
Purpose: While chemotherapy-induced alopecia (CIA) is known to be associated with lower quality of life, the longitudinal effect of alopecia on body image and distress in unknown. This study examined effect of CIA on body image and psychological distress during active breast cancer treatment.
Patients and Methods
Between July and Dec 2010, we recruited patients with non-metastatic breast cancer who were expected to receive adjuvant chemotherapy (N=411) from two cancer hospitals in Seoul, Korea. After excluding 15 patients with recurrence and 65 patients lost to follow-up, the present analysis is based on 331 patients (80.5%). Participants completed questionnaires on body image, quality of life, alopecia distress at enrollment (before surgery), before chemotherapy (2 weeks post surgery), during chemotherapy (3 months post surgery), and after chemotherapy (6 months post surgery). Body image and quality of life were assessed by the EORTC QoL Questionnaire BR23. Alopecia distress was assessed by the Alopecia Distress Scale, which evaluated distress in 4 domains: physical, emotional, daily activity, and relationship.
Results: The mean age of the participants was 46.4 (SD 7.91) year. 44.9% and 37.6% of them had stage I and II breast cancer, respectively. 83.0% of the patients had lumpectomy, and 70.6% and 85.9% had chemotherapy and radiotherapy, respectively. Patients who experienced alopecia had a significantly more negative body image and higher distress compared to those who did not experience alopecia. Body image rapidly decreased at 3 months post surgery coinciding with alopecia, and its effects lasted until 6 months post surgery. Moreover, there was a highly statistically significant association between more negative body image and higher alopecia distress after adjusting for other socio-demographic and clinical characteristics. The patterns and changes in body image and distress comparing patients with and without alopecia are reported in Table 1.

Discussion: Health professionals need to develop clinical pathways and education programs to help women with breast cancer manage alopecia distress and negative body image during active treatment.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-14-05.
P4-16-06: Expression Patterns of Receptor Activator of Nuclear Factor-kB (RANK) and Src in a Series of Primary Breast Tumors (BT) and Bone Metastases (BM) in Patients (pts) with Metastatic Breast Cancer (MBC).
Authors: Gucalp A , Comen E , Redana S , Evangelista L , Giri DD , Zhang XH , Patil S , Akram M , Norton L , Hudis CA , Fornier MN 
Published: June 2012

Abstract
Background
BM develops in 65–70% of pts with MBC. RANK and its ligand (RANK-L) can be critical in the development and progression of BM. Src overexpression and deregulation occurs in many solid tumors but it has not been fully characterized although an association between Src activity defined by a gene expression signature and BM particularly in ER+ pts has been described. (Zhang XH et al. Cancer Cell. 2009) Our goal was to elucidate the relationship between Src and RANK expression in BT and BM in relation to estrogen-/progesterone-receptor (ER/PR)/HER2 expression and tumor histology (invasive ductal carcinoma (IDC) vs invasive lobular carcinoma (ILC)).
Methods: Immunohistochemistry (IHC) for RANK (R&D Systems clone 80707) and Src (Cell Applications Inc. Phospho Tyr-416) protein expression was performed on archived paraffin embedded BT and BM. Scoring: 0=negative, 1+=weak, 2+=intermediate, 3+=strong and the percent of positive tumor cells; RANK+ = 2–3+, &gt; 1% of cells; Src+ = 1–3+; &gt; 1% of cells. Associations between RANK/Src expression and tumor characteristics were assessed using the chi-square test or McNemar's test for pairs, as appropriate.
Results: From the MSKCC database, using an IRB-approved waiver of consent, we identified 54 pts with MBC who underwent surgical biopsy of a metastatic bone lesion at our center between 2005–2010, and had tissue available for further testing. 17 corresponding BT samples were identified. At the time of diagnosis, 43 (79.5%) primary tumors were ER or PR (+); 6 (11%) were HER2+; 41 (76%) were invasive ductal carcinoma. 87% of BM expressed RANK and 44% expressed Src. (Table 1) No significant correlation between RANK or Src expression in BM and ER/PR/HER2 status of BT was observed. A significant correlation between RANK expression and BT histology was observed, (p=0.0016): 93% of IDC were RANK (+), in comparison to 50% of invasive lobular carcinomas. RANK expression was not significantly different between primary tumor and metastatic bone samples (p=0.99). There was a borderline significant difference in Src expression between primary and metastatic site (p=.06).

Conclusions: In our cohort, no correlation between RANK or Src by IHC and ER/PR/HER2 was identified but RANK expression was more common in IDC than ILC. Fidelity was high for RANK between primary and metastatic lesions while Src expression may possibly vary.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-16-06.
P4-17-10: Insights into Mechanisms Involved in the Accumulation of Nanovectors within the Breast Cancer Brain Metastasis.
Authors: Yokoi K , Xuewu L , Alexander JF , Fidler IJ , Mauro F , Biana G 
Published: June 2012

Abstract
Systemic chemotherapy for brain metastasis of breast cancer (BMBC) is considered to be inefficient. It is widely accepted in the literature that blood-brain-barrier (BBB) is responsible for clinical failures with the conventional chemotherapy. We hypothesized that nanovectors, therapeutic carriers with submicron dimensions, can be delivered to the brain tissue through a different pathway than molecular therapeutics. The objective of this study was to examine the accumulation of various intravenously injected nanovectors into the brain metastasis of breast and other cancers loci and to explore possible mechanisms involved.
Both human (MDAMB231) and mouse (4T1) breast cancer brain metastasis were evaluated. We also tested lung (3LL) and colon (CT26) originated cancers. Orthotopic brain tumors were produced either by intracarotid injection or stereotactic brain injection of cancer cells. When the animals became moribund, they were injected intravenously with one of the following nanovectors including fluorescently labeled PEGylated (100nm) and non-PEGylated (100nm, 250nm, 500nm) liposomes, disc-shape silicon particles (600, 1000nm in diameter). The accumulation of the nanovectors was compared to an unencapsulated fluorescent molecule. The accumulation of the nanovectors in the brain tumor tissue was evaluated through live animal imaging (IVIS) and immunohistochemical analysis. Immunohistochemical staining of endothelial cells and basal membrane markers was performed to determine the integrity of the tumor associated vasculature and the co-localization of the fluorescent nanovectors/molecules with tumor associated vasculature.
Interestingly, we have found that brain metastasis of different tumors (originated form breast, lung and colon cancers) possess dissimilar accumulation profiles for intravenously administered nanovectors. For example when comparing various tumor origins, 4T1 breast cancer originated brain tumors enabled the highest accumulation of the nanovectors as compared to CT26 and 3LL. On the other hand, free molecule accumulated into the 4T1 brain metastasis model to a much lower extend than in nanovector. Finally, the observed brain distribution of nanovectors corresponded well with impairment in vascular endothelium and basal membrane integrity shown in immunohistochemical analysis.
The results of our study point toward a possibility to treat specific patients with impaired BBB function with nanovector encapsulated chemotherapeutics based on the fact that their transport, accumulation and retention in the brain tissue are governed by different biological mechanisms, such as Enhanced Permeation and Retention (EPR) effect. These studies indicate that it is possible to cross the blood brain barrier, thus giving hope to patients with brain metastasis.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-17-10.
P4-19-01: Male Breast Cancer According to Tumor Subtype and Race: A California Cancer Registry (CCR)-Population Based Study.
Authors: Chavez-MacGregor M , Clarke CA , Lichtensztajn DY , Hortobagyi GN , Giordano SH 
Published: June 2012

Abstract
Background
Breast cancer in men is a rare disease and accounts for 0.6% of all breast cancer cases. Prior reports suggest that male breast cancer typically has a ductal histology and is more likely than cancers of the female breast to express estrogen and progesterone receptors (ER and PR). To our knowledge, there are no population-based estimates of the rates of Her-2 positive breast cancer or of the distribution of breast cancer subtypes in male patients. The categorization of breast cancers according to tumor subtype has important implications in the prognosis and in the management of breast cancer patients. We explored the tumor subtype distribution by race/ethnicity in the large, ethnically diverse population of California.
Methods: Retrospective study using the CCR. Participants included all male breast cancer patients diagnosed with invasive breast cancer between 2005–2009 with known ER, PR and Her2neu status. Among the patients with hormone receptor positive (HR+) tumors, survival analysis using Kaplan-Meier method was used. Differences in probability of survival between groups were compared using logrank test.
Results: Six-hundred and seven patients were included. Median age at diagnosis was 68 years. Ductal histology was present in 84.7% (n=514) of the cases, 51.6% (n=313) of all the tumors were classified as grade II. Four hundred and ninety four (81.4%) patients had HR+ tumors, defined as ER+ and/or PR+ and Her2neu negative. Ninety (14.8%) had Her2neu positive, and 23 (3.8%) had triple receptor negative tumors (TN). The majority of patients were white (71%), 11% were Hispanic, 7.6% black and 10.4% were Asian/Pacific Islander/other. The breast cancer tumor subtype varied significantly across races/ethnicities (p&lt;.0001). Among non-Hispanic Whites, 82.6% had HR+, 14.6% had Her-2+, and 2.8% had TN breast cancer. For Blacks and Hispanics the distributions were 73.9% HR+, 17.4% Her-2+, 8.7% TN and 77.6%, 16.4%, 6.0% respectively. Among HR+ patients, blacks and Hispanics were less likely to have PR+ tumors compared to whites. The rate of ER+PR- was 6.3% among whites, 19.6% among blacks and 16.4% among Hispanics (p&lt;0.001). A survival analysis among HR+ patients showed significant differences according to race (p=0.018) and stage (p&lt;0.001), with Black patients and patients with higher stage disease having poorer outcomes.
Conclusions: In this large cohort of male breast cancer patients, the distribution of tumor subtype was different than what has been reported in females. Among males, differences in tumor subtype exist among different racial/ethnic groups. Blacks were more likely to have triple receptor negative tumors and more likely to have ER+/PR- tumors than white patients. Among HR+ patients, blacks experience the worse survival.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-19-01.
P4-19-03: Physical and Psychological Sequelae of Breast Cancer in Men.
Authors: Ruddy KJ , Giobbie-Hurder A , Giordano SH , Goldfarb S , Kereakoglow S , Winer EP , Partridge AH 
Published: June 2012

Abstract
Introduction: Little is known about the physical and emotional health of men with breast cancer. Information is also lacking regarding whether their informational and supportive care needs are being met regarding fertility and genetic concerns.
Methods: In an online pilot study recruiting participants through three websites focused on male breast cancer, www.outoftheshadowofpink.com, www.malebreastcancer.org, and www.malebreastcancer.ca, we surveyed men with breast cancer about their attitudes, symptoms, experiences, and health perceptions. We measured anxiety and depression using the Hospitalized Anxiety and Depression Scale (HADS), health-related quality of life (QOL) using Functional Assessment of Cancer Therapy-Breast (FACT-B), and hormonal and sexual symptoms using the Expanded Prostate Cancer Index Composite (EPIC) Hormonal and Sexual Scales. We assessed select toxicities from therapy and history of genetic and fertility counseling.
Results: Forty-two men responded to this online survey at least in part.

Conclusions: Men with breast cancer experience substantial symptoms in follow-up. Sexual functioning, in particular, may be impaired (in men without cancer, mean EPIC Sexual Score is 61.4 with SD 23.6). Hormonal symptoms are also prevalent (in men without cancer, mean EPIC Hormonal Score is 91.7 with SD 9.7). We plan to use data from this pilot study to inform a larger study and develop targeted interventions to improve sexual functioning and reduce symptoms in male breast cancer survivors.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-19-03.
P5-02-01: ErbB4 Ectodomain as a Biomarker and a Potential Therapeutic Target for Breast Cancer.
Authors: Hollmen M , Liu P , Wildiers H , Reinvall I , Vandorpe T , Smeets A , Deraedt K , Vahlberg T , Joensuu H , Leahy D , Schoffski P , Elenius K 
Published: June 2012

Abstract
ErbB4 function is controversial in breast cancer and influenced by alternative splicing of the ERBB4 gene. Here we evaluated the cleavable ErbB4 JM-a isoform as a potential drug target and biomarker. To address ErbB4 cleavage in breast cancer tissues in vivo, extracellular and intracellular cleavage products of ErbB4 were assessed by ELISA and immunohistochemistry using matched serum and tissue samples from a series of 243 breast cancer patients. Elevated serum ectodomain level (≥40 ng/mL) and nuclear immunoreactivity were present in 21% and 52% of the patients, respectively. An elevated serum ErbB4 ectodomain concentration was not associated with tumor nuclear immunoreactivity, but was significantly associated with the premenopausal status at diagnosis (P = 0.04). Estradiol also enhanced ErbB4 cleavage and ErbB4 cleaving enzyme activity in vitro, supporting a role for estrogen signaling in regulation of ErbB4 cleavage. Selective targeting of the cleavable ErbB4 JM-a in human breast cancer cells with an ErbB4 isoform-specific mAb 1479 inhibited ErbB4 cleavage and reduced tumor formation in a mouse xenograft model. Consistent with blocking of ErbB4 cleavage, mutagenesis studies and the 3.4 Å X-ray crystal structure of a complex of the ErbB4 extracellular region and the 1479 Fab localized the binding site of mAb 1479 on ErbB4 to a region on subdomain IV encompassing JM-a-specific residues. These data demonstrate that ErbB4 is cleaved in a subset of breast cancer patients, and suggest that the mechanisms by which mAb 1479 suppresses breast cancer cell growth involves inhibition of ErbB4 cleavage. Serum ErbB4 ectodomain concentration could be used as a biomarker to monitor the activity of compounds, such as mAb 1479, that target ErbB4 cleavage.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-02-01.
P5-02-05: Real-Time Subcellular Imaging of Breast Cancer Cell Attachment in Blood Vessels Using GFP-Labeled Paxillin in Live Mice.
Authors: Suetsugu A , Digman M , Gratton E , Moriwaki H , Saji S , Bouvet M , Hoffman RM 
Published: June 2012

Abstract
Background: Paxillin is involved in the assembly of focal adhesions. We wish to visualize paxillin behavior in breast cancer cells in vivo, as well as in vitro.
Materials and Methods: Dual-photon confocal microscopy was used to image paxillin behavior by linking it to GFP. MDA-MB-231 human breast cancer cells expressing paxillin-GFP were imaged in vitro and in vivo adhering and trafficking in blood vessels in mice. 106 paxillin-GFP expressing breast cancer cells were injected in the epigastric cranialis vein.
Results: In vitro, round breast cancer cells had greater paxillin movement than stretched cancer cells as seen by fluorescence imaging. Paxillin-GFP breast cancer cells in the epigastric cranialis vein were initially rounded and had GFP-expressing protrusions. At later timepoints, many paxillin-GFP-expressing breast cancer cells stretched. The breast cancer cells then extravasated and subsequently grew around the outer surface of the blood vessel after one week. Two weeks after injection, paxillin-GFP expressing breast cancer cells were imaged migrating along the vessel wall. Most of the paxillin-GFP expressing breast cancer cells were stretched and were not mobile. With anti-VEGF treatment, paxillin was observed in round structures within the cells rather than stretched structures and paxillin movement within the cell was arrested.
Discussion: These results demonstrate that breast cancer cells brightly expressing paxillin-GFP and two-photon confocal microscopy can allow the visualization of the behavior of paxillin within breast cancer cells during adhesion and migration along the walls of blood vessels, as well as during anti-angiogenesis therapy.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-02-05.
P5-03-02: Aurora A Is Closely Linked to an Aggressive Phenotype of Breast Cancer.
Authors: Yamamoto Y , Ibusuki M , Murakami K , Iwase H 
Published: June 2012

Abstract
(Purpose) Aurora A, a mitotic serine/threonine kinase, is involved in important process of mitotic progression. The aim of this study is to clarify characteristics of breast cancer with Aurora A expression. (Methods) We examined, by immunohistochemical analysis, the expression of Aurora A in primary invasive breast cancer. We also investigated the correlation between expression of Aurora A and clinicopathological and biological factors. In addition, we studied the prognostic value of Aurora A in breast cancer.
(Results) In 215 cases of invasive cancer examined, Aurora A was mainly identified in tumor nuclei. Aurora A expression was detected in 67 (31.2%) cases. Expression of Aurora A was correlated with tumor size (p=0.002), lymph node metastasis (p=0.002), tumor stage (p=0.04) and histological grade (p=0.0031). Aurora A expression was also associated with hormone receptor negativity (p=0.0001), and increased levels of HER2 (p&lt;0.0028), Ki67 (p&lt;0.0001), HIF-1alpha (p&lt;0.0001), VEGF (p=0.007), COX-2 (p=0.002) and p53 (p&lt;0.0001). Patients who had increased Aurora A levels in their tumor showed shorter disease-free survival (DFS) (p&lt;0.0001) and overall survival (OS) (p=0.0002) than those lacking Aurora A in univariate analysis. However, in multivariate analysis of DFS and OS, Aurora A was not identified an independent prognostic factor.
(Conclusion) Aurora A expression was significantly correlated with tumor burden, poorly differentiation, negativity of hormone receptors, tumor cell proliferation, and tumor angiogenesis. These findings suggest that Aurora A was closely related with an aggressive phenotype in breast cancer.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-03-02.
P5-05-03: The Effect of Breastfeeding on Molecular Characteristics of Invasive Breast Cancer.
Authors: Ellsworth RE , Valente AL , Kane JL , Shriver CD 
Published: June 2012

Abstract
INTRODUCTION: Breastfeeding has been associated with an overall decreased risk of developing breast cancer and the protective effect of breastfeeding has been associated with decreased risk of triple negative and estrogen-responsive breast cancer. Although the mechanism by which breastfeeding provides a protective effect is not well-defined, physical changes in the mammary epithelium reflecting maximal differentiation, may be involved.
METHODS: The database of the Clinical Breast Care Project was queried to identify all patients born between 1946 and 1964 (“baby boomers”) with invasive breast cancer who had given birth to at least one living child. Clinicopathologic characteristics were compared between patients who breastfed for at least six cumulative months and those who never breastfed using chi-square and Fisher's exact tests. RNA was isolated after laser-microdissection of 24 pairs of breastfeeding and non-breastfeeding tumors matched by stage, subtype and grade. Gene expression data was generated using HG U133A 2.0 microarrays and analyzed using the Partek Genomics Suite using a FDR&lt;0.05, 2-fold expression difference to define significance.
RESULTS: Of the 1,008 parous women with invasive breast cancer in the database, 325 (33%) breastfed at least 6 months, 165 (16%) breastfeed less than 6 months, and 518 (51%) never breastfed. Women who breastfed &lt;6 months were not included in additional analyses. Age at menarche and first birth and number of children did not differ between groups; age at diagnosis was significantly (P&lt;0.0001) lower (54.5 years) in women who breastfed compared to those who did not (61.0 years). No differences were detected between patients who breastfed and those who did not for ethnicity or for any tumor characteristics, including tumor stage, grade or size, hormone, HER2 or lymph node status, or subtype. At the molecular level, however, 21 probes representing 19 genes were differentially expressed between women who breastfed and those who did not. Eleven genes, including HAPLN1, had significantly higher and 8 genes, including LGALS7, had significantly lower expression in tumors from women who did not breastfeed.
CONCLUSIONS: Despite the matching of tumor samples, and lack of differences in pathological characteristics between women who breastfed ≥6 months and those who did not breastfeed, differentially expressed genes were identified between tumors from the two groups. Many of the differentially expressed genes have been associated with prognosis, especially in ER negative breast tumors. These data suggest that breastfeeding does alter the underlying molecular characteristics of invasive breast tumors, and may reflect alterations in exposure to estrogen levels during breastfeeding.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-05-03.