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26.  Integrative Analysis of Response to Tamoxifen Treatment in ER-Positive Breast Cancer Using GWAS Information and Transcription Profiling 
Variable response and resistance to tamoxifen treatment in breast cancer patients remains a major clinical problem. To determine whether genes and biological pathways containing SNPs associated with risk for breast cancer are dysregulated in response to tamoxifen treatment, we performed analysis combining information from 43 genome-wide association studies with gene expression data from 298 ER+ breast cancer patients treated with tamoxifen and 125 ER+ controls. We identified 95 genes which distinguished tamoxifen treated patients from controls. Additionally, we identified 54 genes which stratified tamoxifen treated patients into two distinct groups. We identified biological pathways containing SNPs associated with risk for breast cancer, which were dysregulated in response to tamoxifen treatment. Key pathways identified included the apoptosis, P53, NFkB, DNA repair and cell cycle pathways. Combining GWAS with transcription profiling provides a unified approach for associating GWAS findings with response to drug treatment and identification of potential drug targets.
doi:10.4137/BCBCR.S8652
PMCID: PMC3292850  PMID: 22399860
tamoxifen genome-wide association studies gene expression
27.  Bootcamp During Neoadjuvant Chemotherapy for Breast Cancer: A Randomized Pilot Trial 
Introduction
Exercise may improve cancer outcomes. Neoadjuvant chemotherapy (NC) for breast cancer provides a unique setting to evaluate intervention effects. Treatments leading to decreased post-neoadjuvant Ki-67 levels, smaller tumor size, and higher pathologic response are associated with improved survival and lower recurrence. This randomized, prospective pilot trial evaluates the feasibility of supervised exercise during NC for breast cancer.
Methods
Stage II-III, ER positive, cancer patients with BMI > 25 receiving NC were randomized to standard NC with supervised bootcamp (NC + BC) or NC alone. Ki-67, C-peptide, BMI, and tumor size were measured before chemotherapy and at time of surgery.
Results
There were no initial differences between groups in regards to tumor size, C-peptide, BMI, and Ki–67. The NC + BC (n = 5) group had a lower mean BMI at the conclusion of NC compared with those (n = 5) in the NC group (28.0 versus 35.8, P = 0.03). Final tumor size was 2.59 cm in the NC + BC group versus 3.16 cm for NC (P = 0.76) Mean Ki-67 for NC + BC was 7% versus 29% with NC (P = 0.14). C-peptide (ng/mL) was equivalent between the two groups (4.55 NC + BC versus 4.74 NC, P = 0.85).
Conclusions
Adding a supervised exercise program to NC is feasible, decreases BMI, and may lead to lower Ki-67 levels and improved survival.
doi:10.4137/BCBCR.S9221
PMCID: PMC3290117  PMID: 22399859
breast cancer; exercise; Ki-67; neoadjuvant chemotherapy
28.  Prediction of Non-Sentinel Lymph Node Status in Breast Cancer Patients with Sentinel Lymph Node Metastases: Evaluation of the Tenon Score 
Introduction
Current guidelines recommend completion axillary lymph node dissection (cALND) in case of a sentinel lymph node (SLN) metastasis larger than 0.2 mm. However, in 50%–65% of these patients, the non-SLNs contain no further metastases and cALND provides no benefit. Several nomograms and scoring systems have been suggested to predict the risk of metastases in non-SLNs. We have evaluated the Tenon score.
Patients and Methods
In a retrospective review of the Swedish Sentinel Node Multicentre Cohort Study, risk factors for additional metastases were analysed in 869 SLN-positive patients who underwent cALND, using uni- and multivariate logistic regression models. A receiver operating characteristic (ROC) curve was drawn on the basis of the sensitivity and specificity of the Tenon score, and the area under the curve (AUC) was calculated.
Results
Non-SLN metastases were identified in 270/869 (31.1%) patients. Tumour size and grade, SLN status and ratio between number of positive SLNs and total number of SLNs were significantly associated with non-SLN status in multivariate analyses. The area under the curve for the Tenon score was 0.65 (95% CI 0.61–0.69). In 102 patients with a primary tumour <2 cm, Elston grade 1–2 and SLN metastases ≤2 mm, the risk of non SLN metastasis was less than 10%.
Conclusion
The Tenon score performed inadequately in our material and we could, based on tumour and SLN characteristics, only define a very small group of patients in which negative non-sentinel nodes could be predicted.
doi:10.4137/BCBCR.S8642
PMCID: PMC3273320  PMID: 22346360
breast cancer; sentinel node; metastases
29.  Clinico-Pathological Characteristics of Triple Negative and Non Triple Negative High Grade Breast Carcinomas with and Without Basal Marker (CK5/6 and EGFR) Expression at a Rural Tertiary Hospital in India 
Aims of the study were to evaluate the expression Cytokeratin 5/6(CK5/6) and Epidermal Growth Factor Receptor (EGFR) among triple negative breast cancers and high grade infiltrating duct carcinomas. Further to probe if triple negative phenotype can be a surrogate marker for basal phenotype and to correlate the expression of basal markers with disease free survivals among triple negative phenotype and high grade infiltrating duct carcinomas.
Methods
Expression of CK5/6 and EGFR were studied by Immunohistochemistry (IHC) in 31 triple negative and 19 non-triple negative high grade breast carcinomas.
Results
21 of the 31 triple negative phenotype (67.7%) breast carcinomas and 7 out of 19 non-triple negative (36.8%) breast carcinomas showed expression of basal markers (CK5/6 and/or over-expression of EGFR). There were statistically significant associations of all the basal-like tumors with negative hormonal status. The basal markers positive phenotype subjects had a shorter disease free interval as compared to basal markers negative phenotype subjects.
Conclusion
Basal-like breast carcinomas constitute a unique clinical and pathological entity, characterized by high tumor grade and a propensity for lack of ER, PR and HER2 expression. Basal phenotypes have a more aggressive course than non-basal phenotype. “Triple negative” status cannot be used as a surrogate for “basal marker expression”.
doi:10.4137/BCBCR.S8611
PMCID: PMC3273309  PMID: 22346359
breast cancer; tumor grade; basal-like; triple-negative; CK5/6; EGFR
30.  Delivery of MicroRNA-10b with Polylysine Nanoparticles for Inhibition of Breast Cancer Cell Wound Healing 
Recent studies revealed that micro RNA-10b (mir-10b) is highly expressed in metastatic breast cancer cells and positively regulates breast cancer cell migration and invasion through inhibition of HOXD10 target synthesis. In this study we designed anti-mir-10b molecules and combined them with poly L-lysine (PLL) to test the delivery effectiveness. An RNA molecule sequence exactly matching the mature mir-10b minor antisense showed strong inhibition when mixed with PLL in a wound-healing assay with human breast cell line MDA-MB-231. The resulting PLL-RNA nanoparticles delivered the anti-microRNA molecules into cytoplasm of breast cancer cells in a concentration-dependent manner that displayed sustainable effectiveness.
doi:10.4137/BCBCR.S8513
PMCID: PMC3256732  PMID: 22259248
microRNA-10b; breast cancer metastasis; nanoparticles
31.  Expression of the Androgen Receptor and its Correlation with Molecular Subtypes in 980 Chinese Breast Cancer Patients 
Background
Recent studies have shown that androgen displays an inhibitory effect on breast cancer cell lines that express androgen receptor (AR) but not estrogen receptor (ER) and progesterone receptor (PR). We have previously reported that approximately 1/3 of ER negative high grade invasive ductal carcinomas express AR. Thus, AR can serve as a potential therapeutic target for this group of patients.
Aim
Here we investigated AR expression patterns in 980 consecutive breast carcinomas.
Results
We found that (1) AR was expressed more frequently (77%) than ER (61%) and PR (60%) in breast carcinomas; (2) AR expression was associated with ER and PR expression (P < 0.0001), small tumor size (P = 0.0324) and lower Ki-67 expression (P = 0.0013); (3) AR expression was found in 65% of ER negative tumors; (4) AR expression was associated with PR and Ki-67 in ER negative tumors, but not in ER positive tumors; (5) AR expression was higher in ER positive subtypes (Luminal A, Luminal B and Luminal HER2 subtypes, 80%–86%) and lower in ER negative subtypes [HER2, triple negative (TN), and TN EFGR positive subtypes; 52%–66%], with over 50% of TN tumors expressing AR.
Conclusion
More breast carcinomas express AR than ER and PR, including significant numbers of ER negative and TN tumors, for which AR could serve as a potential therapeutic target.
doi:10.4137/BCBCR.S8323
PMCID: PMC3256731  PMID: 22259247
androgen receptor; breast cancer; estrogen receptor; HER2; Ki-67; molecular classification; progesterone receptor
32.  Efficacy of Bevacizumab-Capecitabine in Combination for the First-Line Treatment of Metastatic Breast Cancer 
There is an ongoing need for development of new chemotherapeutic regimens for metastatic breast cancer [mBC], especially when tumors lack therapeutic targets such as the estrogen or progesterone receptor [ER/PR], or the human epidermal growth factor receptor-2 [HER2]. Capecitabine is an orally bioavailable fluoropyrimidine approved for monotherapy in mBC, and bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor which has shown to be active in mBC and tolerable in combination with other chemotherapeutics. The combination of these two agents has been explored in multiple phase II and III clinical studies, with improvements in progression-free survival and overall response rates noted as compared to capecitabine monotherapy. However, the use of bevacizumab in combination with capecitabine and other chemotherapy agents for mBC remains beset with controversy due to safety concerns, cost issues, and pending regulatory decisions.
doi:10.4137/BCBCR.S7379
PMCID: PMC3235996  PMID: 22174585
metastatic breast cancer; capecitabine; bevacizumab
33.  The Possible Impact of Obesity on Androgen, Progesterone and Estrogen Receptors (ERα and ERβ) Gene Expression in Breast Cancer Patients 
Background
Obesity has been associated with increased mortality from hormone dependant cancers such as breast cancer which is the most prevalent cancer in women. The link between obesity and breast cancer can be attributed to excess estrogen produced through aromatization in adipose tissue. The role of steroid hormone receptors in breast cancer development is well studied but how obesity can affect the expression pattern of steroid hormones in patients with different grades of breast cancer was the aim of this study.
Methods
In this case-control study, 70 women with breast cancer participated with different grades of obesity (36 none obese, BMI < 25 kg/m2 and 34 obese, BMI ≥ 25 kg/m2). The mean age of participants was 44.53 ± 1.79 yr (21–70 yr). The serum level of estrogen, progesterone and androgen determined by ELISA. Following quantitative expression of steroid hormone receptors mRNA in tumor tissues evaluated by Real-time PCR. Patients with previous history of radiotherapy or chemotherapy were excluded. SPSS 16 was used for data analysis and P < 0.05 considered statistically significant.
Results
The difference in ERα, ERβ and PR mRNA level between normal and obese patients was significant (P < 0.001). In addition, the expression of AR mRNA was found to be higher than other steroid receptors. There was no significant relation between ERβ gene expression in two groups (P = 0.68). We observed a significant relationship between ERα and AR mRNA with tumor stage and tumor grade, respectively (P = 0.023, P = 0.015).
Conclusion
According to the obtained results, it is speculated that obesity could paly a significant role in estrogen receptors gene expression and also could affect progression and proliferation of breast cancer cells.
doi:10.4137/BCBCR.S7707
PMCID: PMC3235995  PMID: 22174584
obesity; breast cancer; steroid receptors; steroid hormones
34.  Exemestane in the Adjuvant Treatment of Breast Cancer in Postmenopausal Women 
Exemestane is an irreversible inhibitor of the aromatase enzyme, which is a key component in the production of estrogen. The majority of breast cancers are sensitive to the proliferative effects of estrogen. Exemestane is approved for the adjuvant treatment of postmenopausal women with breast cancer after 2 to 3 years of tamoxifen therapy, based on a 32% improvement in disease-free survival compared with 5 years of tamoxifen alone (P < 0.001). Exemestane has also shown clinical benefits as an upfront therapy. The safety profile of exemestane shares some side effects with tamoxifen (hot flashes and arthralgia), but is not associated with an increased risk of endometrial cancer or thromboembolic events. This review will discuss in detail the efficacy and safety of exemestane in early breast cancer.
doi:10.4137/BCBCR.S6234
PMCID: PMC3201097  PMID: 22084574
aromatase inhibitor; breast cancer; exemestane; disease-free survival; tamoxifen
35.  In Vitro Enhanced Sensitivity to Cisplatin in D67Y BRCA1 RING Domain Protein 
BRCA1 is a tumor suppressor protein involved in maintaining genomic integrity through multiple functions in DNA damage repair, transcriptional regulation, cell cycle checkpoint, and protein ubiquitination. The BRCA1-BARD1 RING complex has an E3 ubiquitin ligase function that plays essential roles in response to DNA damage repair. BRCA1-associated cancers have been shown to confer a hypersensitivity to chemotherapeutic agents. Here, we have studied the functional consequence of the in vitro E3 ubiquitin ligase activity and cisplatin sensitivity of the missense mutation D67Y BRCA1 RING domain. The D67Y BRCA1 RING domain protein exhibited the reduced ubiquitination function, and was more susceptible to the drug than the D67E or wild-type BRCA1 RING domain protein. This evidence emphasized the potential of using the BRCA1 dysfunction as an important determinant of chemotherapy responses in breast cancer.
doi:10.4137/BCBCR.S8184
PMCID: PMC3201098  PMID: 22084573
BRCA1; cisplatin; ubiquitination; cancer chemotherapy
36.  Management Options in Triple-Negative Breast Cancer 
Notorious for its poor prognosis and aggressive nature, triple-negative breast cancer (TNBC) is a heterogeneous disease entity. The nature of its biological specificity, which is similar to basal-like cancers, tumors arising in BRCA1 mutation carriers, and claudin-low cancers, is currently being explored in hopes of finding the targets for novel biologics and chemotherapeutic agents. In this review, we aim to give a broad overview of the disease’s nomenclature and epidemiology, as well as the basic mechanisms of emerging targeted therapies and their performance in clinical trials to date.
doi:10.4137/BCBCR.S6562
PMCID: PMC3153117  PMID: 21863131
triple-negative breast cancer; basal-like; targeted therapy
37.  Altered Endoplasmic Reticulum Calcium Pump Expression during Breast Tumorigenesis 
Endoplasmic reticulum calcium homeostasis is involved in several essential cell functions including cell proliferation, protein synthesis, stress responses or secretion. Calcium uptake into the endoplasmic reticulum is performed by Sarco/Endoplasmic Reticulum Calcium ATPases (SERCA enzymes). In order to study endoplasmic reticulum calcium homeostasis in situ in mammary tissue, in this work SERCA3 expression was investigated in normal breast and in its benign and malignant lesions in function of the cell type, degree of malignancy, and histological and molecular parameters of the tumors. Our data indicate, that although normal breast acinar epithelial cells express SERCA3 abundantly, its expression is strongly decreased already in very early non-malignant epithelial lesions such as adenosis, and remains low in lobular carcinomas. Whereas normal duct epithelium expresses significant amounts of SERCA3, its expression is decreased in several benign ductal lesions, as well as in ductal adenocarcinoma. The loss of SERCA3 expression is correlated with Elston-Ellis grade, negative hormone receptor expression or triple negative status in ductal carcinomas. The concordance between decreased SERCA3 expression and several histological, as well as molecular markers of ductal carcinogenesis indicates that endoplasmic reticulum calcium homeostasis is remodeled during tumorigenesis in the breast epithelium.
doi:10.4137/BCBCR.S7481
PMCID: PMC3153116  PMID: 21863130
breast cancer; calcium signaling; endoplasmic reticulum; SERCA; calcium pump; ion transport
38.  Delphinidin Inhibits HER2 and Erk1/2 Signaling and Suppresses Growth of HER2-Overexpressing and Triple Negative Breast Cancer Cell Lines 
Delphinidin is a polyphenolic compound found in many brightly colored fruits and vegetables. Delphinidin is also the major bioactive component found in many dietary supplements that are currently consumed as complementary cancer medicine including pomegranate extract. The purpose of the current study was to determine the in vitro biological effects of delphinidin on established breast cancer cell lines of varying molecular subtypes in comparison to non-transformed breast epithelial cells. We examined cell proliferation, apoptosis, and growth inhibition in response to delphinidin using a tetrazolium salt-based assay, DNA fragmentation assay, and anchorage-independent growth assay. In comparison to vehicle control, delphinidin inhibited proliferation (P < 0.05), blocked anchorage-independent growth (P < 0.05), and induced apoptosis (P < 0.05) of ER-positive, triple negative, and HER2-overexpressing breast cancer cell lines with limited toxicity to non-transformed breast epithelial cells. MAPK signaling was partially reduced in triple negative cells and ER-negative chemically transformed MCF10A cells after treatment with delphinidin. In addition, delphinidin induced a significant level of apoptosis in HER2-overexpressing cells in association with reduced HER2 and MAPK signaling. Since delphinidin is often consumed as a complementary cancer medicine, the effect of delphinidin on response to specific HER2-targeted breast cancer therapies was examined by proliferation assay. Results of these drug combination studies suggested potential antagonism between delphinidin and HER2-directed treatments. In summary, the data presented here suggest that single agent delphinidin exhibits growth inhibitory activity in breast cancer cells of various molecular subtypes, but raise concerns regarding potential drug antagonism when used in combination with existing targeted therapies in HER2-overexpressing breast cancer.
doi:10.4137/BCBCR.S7156
PMCID: PMC3140266  PMID: 21792311
breast cancer; delphinidin; HER2; erbB2; triple negative
39.  Increased Circulating Level of the Survival Factor GP88 (Progranulin) in the Serum of Breast Cancer Patients When Compared to Healthy Subjects 
Introduction:
GP88 (PC-Cell Derived Growth Factor, progranulin) is a glycoprotein overexpressed in breast tumors and involved in their proliferation and survival. Since GP88 is secreted, an exploratory study was established to compare serum GP88 level between breast cancer patients (BC) and healthy volunteers (HV).
Methods:
An IRB approved prospective study enrolled 189 stage 1–4 BC patients and 18 HV. GP88 serum concentration was determined by immunoassay.
Results:
Serum GP88 level was 28.7 + 5.8 ng/ml in HV and increased to 40.7 + 16.0 ng/ml (P = 0.007) for stage 1–3 and 45.3 + 23.3 ng/ml (P = 0.0007) for stage 4 BC patients. There was no correlation between the GP88 level and BC characteristics such as age, race, tumor grade, ER, PR and HER-2 expression.
Conclusion:
These data suggest that serial testing of serum GP88 levels may have value as a circulating biomarker for detection, monitoring and follow up of BC.
doi:10.4137/BCBCR.S7224
PMCID: PMC3140268  PMID: 21792312
progranulin; GP88; breast cancer; biomarker
40.  3D Symmetry Measure Invariant to Subject Pose During Image Acquisition 
In this study we evaluate the influence of subject pose during image acquisition on quantitative analysis of breast morphology. Three (3D) and two-dimensional (2D) images of the torso of 12 female subjects in two different poses; (1) hands-on-hip (HH) and (2) hands-down (HD) were obtained. In order to quantify the effect of pose, we introduce a new measure; the 3D pBRA (Percentage Breast Retraction Assessment) index, and validate its use against the 2D pBRA index. Our data suggests that the 3D pBRA index is linearly correlated with the 2D counterpart for both of the poses, and is independent of the localization of fiducial points within a tolerance limit of 7 mm. The quantitative assessment of 3D asymmetry was found to be invariant of subject pose. This study further corroborates the advantages of 3D stereophotogrammetry over 2D photography. Problems with pose that are inherent in 2D photographs are avoided and fiducial point identification is made easier by being able to panoramically rotate the 3D surface enabling views from any desired angle.
doi:10.4137/BCBCR.S7140
PMCID: PMC3140267  PMID: 21792310
three-dimensional; stereophotogrammetry; subject pose; validation; breast; symmetry; surgical planning; pBRA
41.  The Relationship between Visuospatial Memory and Coping Strategies in Breast Cancer Survivors 
Background:
In the US there are over 2.5 million breast cancer survivors (BCSs), most of whom have required some type of intensive treatment. How individuals cope with the treatment process may relate to why neurocognitive problems arise.
Method:
We explored the impact of treatment for breast cancer (BC) on performance of the Memory Island task, both on working memory and on the general index of cognitive performance in relation to coping strategies of BCSs compared to age-matched controls.
Results:
The evidence obtained suggests a reduced performance in visuospatial memory in BCSs. Those who used emotional coping strategies displayed reduced performance in visuospatial learning and immediate memory. Those women who used problem-focused coping strategies performed better in those tasks measuring psychomotor speed, general intelligence, and delayed visuospatial memory.
Conclusions:
It is concluded that further investigation of the relationship between coping strategies and performance on visuospatial tasks may provide useful information on residual levels of neurocognitive deficits and psychosocial adaptation in BCSs.
doi:10.4137/BCBCR.S6957
PMCID: PMC3117625  PMID: 21695096
breast cancer survivors; Puerto Rican; emotion-focused; problem-focused; visuospatial memory; Memory Island
42.  Social Support and Hope Among Egyptian Women with Breast Cancer after Mastectomy 
Introduction:
Breast cancer is the most common cancer among Egyptian women. We report the unique assessment of hope and social support outcomes of women with breast cancer after mastectomy in Egyptian community.
Patients and methods:
Between July 2009 and June 2010, three hundred and one women with newly diagnosed breast cancer joined this study. Socio-demographic data including patient’s age, level of education, occupation, social status, and residence were collected by means of structured interviews based on special questionnaires. These questionnaires were designed to measure hope and social support.
Results:
Age ranged from 21 to 88 years (median = 45.8 years and SD ± 13.3). A low degree of hope was reported in 103 patients (34.2%), a moderate degree in 109 patients (36.2%), and a high degree in 89 patients (29.6%). A low degree of social support was reported in 119 patients (39.5%), a moderate degree in 101 patients (33.6%), and a high degree in 81 patients (26.9%).
Conclusions:
Social support is related to many psychological factors, which can be quantitatively analyzed and it can predict hope. However, there were no significant differences between the socio-demographic variables (age, educational levels, residence and martial status) and social support, hope, and their sub-components among Egyptian women with breast cancer.
doi:10.4137/BCBCR.S6655
PMCID: PMC3117623  PMID: 21695094
breast cancer; social support; hope; mastectomy
43.  Intratumoral Immune Responses Can Distinguish New Primary and True Recurrence Types of Ipsilateral Breast Tumor Recurrences (IBTR) 
Ipsilateral breast tumor recurrence (IBTR) is an increasingly common clinical challenge. IBTRs include True Recurrences (TR; persistent disease) and New Primaries (NP; de novo tumors), but discrimination between these is difficult. We assessed tumor infiltrating leukocytes (TIL) as biomarkers for distinguishing these types of IBTR using primary tumors and matched IBTRs from 24 breast cancer patients, half of which were identified as putative TRs and half as NPs using a previously reported clinical algorithm. Intratumoral lymphocyte populations (CD3, CD8, CD4, CD25, FOXP3, TIA1, CD20) and macrophages (CD68) were quantified by immunohistochemistry in each tumor. Compared to matched primaries, TRs showed significant trends towards increased CD3+ and CD8+ TIL, while these populations were often diminished in NPs. Comparison of IBTRs showed that TRs had significantly higher levels of CD3+ (P = 0.0136), CD8+ (P = 0.0092), and CD25+ (P = 0.0159) TIL than NPs. We conclude that TIL may be a novel diagnostic biomarker to distinguish NP from TR IBTRs.
doi:10.4137/BCBCR.S7344
PMCID: PMC3117626  PMID: 21695097
breast cancer; ipsilateral breast tumor recurrence; true recurrence; new primary; immune response; tumor infiltrating leukocytes
44.  Hormone Receptor Status in Breast Cancer and its Relation to Age and Other Prognostic Factors 
Background:
Increasing evidence shows the importance of young age, estrogen receptor (ER), progesterone receptor (PR) status, and HER-2 expression in patients with breast cancers.
Patients and methods:
We organized an analytic cross-sectional study of 105 women diagnosed with breast cancer who have been operated on between 2008 to 2010. We evaluated age, size, hormone receptor status, HER-2 and P53 expression as possible indicator of lymph node involvement.
Results:
There is a direct correlation between positive progesterone receptor status and being younger than 40 (P < 0.05). Also, compared with older women, young women had tumors that were more likely to be large in size and have higher stages (P < 0.05). Furthermore patients with negative progesterone receptor status were more likely to have HER-2 overexpression (P < 0.05). The differences in propensity to lymph node metastasis between hormone receptor statuses were not statically significant.
Conclusions:
Although negative progesterone receptor tumors were more likely to have HER-2 overexpression, it is possible that higher stage and larger size breast cancer in younger women is related to positive progesterone receptor status.
doi:10.4137/BCBCR.S7199
PMCID: PMC3117624  PMID: 21695095
breast cancer; estrogen receptor; progesterone receptor; lymph node metastasis; age
45.  ODAM Expression Inhibits Human Breast Cancer Tumorigenesis 
We have posited that Odontogenic Ameloblast Associated Protein (ODAM) serves as a novel prognostic biomarker in breast cancer and now have investigated its potential role in regulating tumor growth and metastasis. Human breast cancer MDA-MB-231 cells were transfected with a recombinant ODAM plasmid construct (or, as a control, the plasmid vector alone). ODAM expression increased adhesion and apoptosis of the transfected MDA-MB-231 cells and suppressed their growth rate, migratory activity, and capability to invade extracellular matrix-coated membranes. Implantation of such cells into mouse mammary fat pads resulted in significantly smaller tumors than occurred in animals that received control cells; furthermore, ODAM-expressing cells, when injected intravenously into mice, failed to metastasize, whereas the control-transfected counterparts produced extensive lung lesions. Our finding that induction of ODAM expression in human breast cancer cells markedly inhibited their neoplastic properties provides further evidence for the regulatory role of this molecule in tumorigenesis and, consequently, is of potential clinical import.
doi:10.4137/BCBCR.S6859
PMCID: PMC3091406  PMID: 21603257
invasion; cell adhesion; cell aggregation; breast tumor cell inhibition; tumor imaging
46.  The Characterization of Cell Line Crl-2335 as a Basal-Like Breast Carcinoma Model 
Basal-like breast cancer has been reported to be the most aggressive and deadly carcinoma sub-type. Patients diagnosed with this subtype have a less than 50% five-year survival. In addition, many studies have reported that this sub-type is more prevalent in specific ethnic groups and is believed to be a key factor that drives certain ethnic disparities in mortality. In order to effectively study this sub-type and determine unique gene expression and biochemical pathways which sustain this cancer’s growth, we sought to identify human breast cancer cell lines that represent a model for the basal-like subtype. Here, we report our findings which indicate the African American cell line CRL-2335 is a true representative of basal-like breast carcinoma.
doi:10.4137/BCBCR.S7087
PMCID: PMC3091405  PMID: 21603256
basal-like breast cancer; cell line model; triple negative breast cancer
47.  Safety and Efficacy of nab-Paclitaxel in the Treatment of Patients with Breast Cancer 
Taxanes are highly active chemotherapeutic agents in the treatment of early-stage and metastatic breast cancer. Novel formulations have been developed to improve efficacy and decrease toxicity associated with these cytotoxic agents. nab-paclitaxel is a solvent free, albumin-bound 130-nanometer particle formulation of paclitaxel (Abraxane®, Abraxis Bioscience), which was developed to avoid toxicities of the Cremophor vehicle used in solvent-based paclitaxel. In a phase III clinical trial, nab-paclitaxel demonstrated higher response rates, better safety and side-effect profile compared to conventional paclitaxel, and improved survival in patients receiving it as second line therapy. Higher doses can be administered over a shorter infusion time without the need for special infusion sets or pre-medications. It is now approved in the US for treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant therapy, where prior therapy included an anthracycline. Recently, several phase II studies have suggested a role for nab-paclitaxel as a single agent and in combination with other agents for first-line treatment of metastatic breast cancer.
doi:10.4137/BCBCR.S5857
PMCID: PMC3091407  PMID: 21603258
nab-paclitaxel; nab-technology; paclitaxel; metastatic breast cancer; taxanes
48.  Five Methods of Breast Volume Measurement: A Comparative Study of Measurements of Specimen Volume in 30 Mastectomy Cases 
Background:
To compare breast volume measurement techniques in terms of accuracy, convenience, and cost.
Methods:
Breast volumes of 30 patients who were scheduled to undergo total mastectomy surgery were measured preoperatively by using five different methods (mammography, anatomic [anthropometric], thermoplastic casting, the Archimedes procedure, and the Grossman-Roudner device). Specimen volume after total mastectomy was measured in each patient with the water displacement method (Archimedes). The results were compared statistically with the values obtained by the five different methods.
Results:
The mean mastectomy specimen volume was 623.5 (range 150–1490) mL. The breast volume values were established to be 615.7 mL (r = 0.997) with the mammographic method, 645.4 mL (r = 0.975) with the anthropometric method, 565.8 mL (r = 0.934) with the Grossman-Roudner device, 583.2 mL (r = 0.989) with the Archimedes procedure, and 544.7 mL (r = 0.94) with the casting technique. Examination of r values revealed that the most accurate method was mammography for all volume ranges, followed by the Archimedes method.
Conclusion:
The present study demonstrated that the most accurate method of breast volume measurement is mammography, followed by the Archimedes method. However, when patient comfort, ease of application, and cost were taken into consideration, the Grossman-Roudner device and anatomic measurement were relatively less expensive, and easier methods with an acceptable degree of accuracy.
doi:10.4137/BCBCR.S6128
PMCID: PMC3076010  PMID: 21494401
breast density; mammography-negativity; macromastia; oncoplastic surgery; reduction mammaplasty
49.  Optimized Protocol for Protein Extraction from the Breast Tissue that is Compatible with Two-Dimensional Gel Electrophoresis 
Proteomics is a highly informative approach to analyze cancer-associated transformation in tissues. The main challenge to use a tissue for proteomics studies is the small sample size and difficulties to extract and preserve proteins. The choice of a buffer compatible with proteomics applications is also a challenge. Here we describe a protocol optimized for the most efficient extraction of proteins from the human breast tissue in a buffer compatible with two-dimensional gel electrophoresis (2D-GE). This protocol is based on mechanically assisted disintegration of tissues directly in the 2D-GE buffer. Our method is simple, robust and easy to apply in clinical practice. We demonstrate high quality of separation of proteins prepared according to the reported here protocol.
doi:10.4137/BCBCR.S6263
PMCID: PMC3076014  PMID: 21494400
2D-GE; breast tissue; sample preparation; SBO4 buffer
50.  Plasma Leptin, hTERT Gene Expression, and Anthropometric Measures in Obese and Non-Obese Women with Breast Cancer 
Introduction:
Expression of human telomerase reverse transcriptase (hTERT) occurs in most cancers but its relation with obesity is unclear. This study explores the association between leptin levels and anthropometric indices with hTERT mRNA levels in breast cancer patients of different obesity grades.
Materials and methods:
In this case-control study, 65 breast cancer patients participated. Expression of tissues hTERT mRNA was carried out by real-time reverse transcription polymerase chain reaction. Leptin concentrations were measured by enzyme-linked immunoassay.
Results:
Twelve patients (18.46%) were hTERT negative and 53(81.54%) were positive. hTERT mRNA levels were associated with BMI but not with waist circumference (WC) (r = 0.219, P = 0.22) and waist to hip ratio (WHR) (r = 0.212, P = 0.237). Leptin level and hTERT mRNA levels (r = 0.484, P = 0.008) were correlated as well as BMI and hTERT expression.
Conclusions:
This study has shown a correlation between leptin levels and hTERT expression. These findings may clarify the role of leptin in breast carcinogenesis, and hence obesity could be responsible for increased incidences in breast cancer as well as its progression via enhanced production of leptin.
doi:10.4137/BCBCR.S6734
PMCID: PMC3076011  PMID: 21494399
breast cancer; obesity; adipokienes

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