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26.  Hormone Receptors and Age Distribution in Breast Cancer Patients at a University Hospital in Northern Egypt 
Introduction:
Breast cancer is the most common cancer among Egyptian women. The disease is often advanced at diagnosis. Since molecular profiling is not feasible in routine practice, we sought to examine the association of age distribution with hormone receptor profile, disease stage and outcome among Egyptian women.
Patients and methods:
We conducted a retrospective review of breast cancer patients treated at Mansoura University Cancer Center in the Nile Delta from 2006 through 2011. Age groups were examined in relation to hormone receptors status and tumor clinicopathological criteria. Additionally, the effect of receptor status on disease relapse and disease-free survival was examined with logistic regression and Kaplan–Meier analysis.
Results:
A total of 263 patients were included in the current analysis. About 66.9% (n = 176) of patients were hormone receptor positive, 14.1% (n = 37) were Her2/neu positive, and 19.0% (n = 50) were triple negative. Median age of the patients was 52 years and was equal across all receptor status types. Triple negative status correlated with increased risk of disease relapse (odds ratio = 1.8, P = 0.03) and with shortened disease-free survival (hazards ratio = 2.6, P < 0.01).
Conclusion:
The age distribution and receptor status pattern in the Nile Delta region does not explain the aggressive behavior of the disease. The age of the patients at diagnosis is older than patients in earlier studies from Egypt emphasizing the importance of implementing mammographic screening programs.
doi:10.4137/BCBCR.S12214
PMCID: PMC3694824  PMID: 23825439
breast cancer; hormone receptors; Egypt; prognosis
27.  Dose Distribution in the Heart and Cardiac Chambers Following 4-field Radiation Therapy of Breast Cancer: a Retrospective Study 
Purpose:
To evaluate cardiac doses in breast cancer patients with stage II/III treated with 4-field radiotherapy based on computed tomography (CT) dose planning.
Methods and Materials:
Based on archived CT images, whole heart and cardiac chamber radiation doses were analyzed in 216 (111 left-sided and 105 right-sided) mastectomized or lumpectomized breast cancer patients treated at a single institution, the Norwegian Radium Hospital, between 2000–2002. Individual dose volume histograms for the whole heart and for the four cardiac chambers were obtained, and mean, median and maximum doses to these structures were calculated. The dose (Gy) delivered to the 5% of the volume of each cardiac structure (D5%), and the volume percentage of each structure receiving ≥ 25 Gy (V25Gy) were reported. Normal tissue complication probability (NTCP) calculations were used to estimate the risk for ischemic heart disease (IHD).
Results:
Cohort-based medians of the whole heart mean dose (Dmean) for left- and right-sided tumors were 3.2 Gy and 1.3 Gy, respectively, with similar ventricular but lower atrial values. The atrial doses did not differ according to laterality of the breast tumor. In 13 patients with left-sided cancer, 5% of the heart volume was exposed to >25 Gy. The NTCP estimates were generelly low, with a maximum of 2.8%.
Conclusions:
During adjuvant CT-based locoregional radiotherapy of women with breast cancer, the cardiac radiation doses are, at the group level, below recommended threshold values (D5% < 25 Gy), though individual patients with left-sided disease may exceed these limits.
doi:10.4137/BCBCR.S11118
PMCID: PMC3615991  PMID: 23589693
heart; cardiac chambers; breast cancer and radiation therapy
28.  Axillary Ultrasound for Breast Cancer Staging: an Attempt to Identify Clinical/Histopathological Factors Impacting Diagnostic Performance 
Aim:
To assess the diagnostic value of pre-surgery axillary ultrasound for nodal staging in patients with primary breast cancer and to identify clinical/histopathological factors impacting diagnostic performance.
Study design:
Single-center, retrospective chart analysis. We assessed sensitivity, specificity, and positive and negative predictive value of clinical examination as well as axillary ultrasound vs. clinical examination alone. The histopathological results were the standard of truth. In addition, we analyzed clinical and histopathological factors regarding their potential to impact sensitivity and specificity.
Results:
We enrolled a total of 172 women in the study. Sensitivity of clinical examination plus ultrasound was significantly higher than for clinical examination alone (58% vs. 31.6%). Specificity and positive predictive value were similar while the negative predictive value increased from 63.4% to 73% when additionally applying ultrasound. Sensitivity and specificity of axillary ultrasound were impacted by tumor size (P = 0.2/0.04), suspicious axillary palpation (P < 0.01/<0.01), number of affected lymph nodes (P < 0.01/−) and distant metastases (P = 0.04/<0.01). All other factors had no impact.
Conclusion:
Since pre-surgery axillary nodal staging is currently used to determine disease management, axillary ultrasound is a useful add-on tool in the diagnostic armamentarium for breast cancer patients. Tumor size, suspicious axillary palpation, number of affected lymph nodes and distant metastases increase diagnostic performance of this diagnostic modality.
doi:10.4137/BCBCR.S11215
PMCID: PMC3595984  PMID: 23515655
breast cancer; axillary ultrasound; staging
29.  Combining mTOR Inhibitors with Chemotherapy and Other Targeted Therapies in Advanced Breast Cancer: Rationale, Clinical Experience, and Future Directions 
Improvements in survival of patients with breast cancer have been attributed to the development of agents that target key components of dysregulated pathways involved in oncogenesis and progression of breast cancer. Aberrant mammalian target of rapamycin (mTOR) activation has been implicated in oncogenesis, angiogenesis, and the development of estrogen independence and resistance to chemotherapy in breast tumors. Several mTOR inhibitors (sirolimus, everolimus, temsirolimus, and ridaforolimus) have demonstrated antitumor activity in breast cancer cells. Combining mTOR inhibitors with endocrine therapies has demonstrated clinical antitumor activity in patients with metastatic breast cancer. In addition, mTOR inhibitor combinations with various targeted biologic agents or cytotoxic chemotherapeutic agents are being examined in more than 40 clinical trials with some early promising results. Combination therapies targeting multiple components of these central signaling pathways may be an optimal treatment strategy for patients with advanced breast cancer.
doi:10.4137/BCBCR.S10071
PMCID: PMC3579426  PMID: 23492649
mTOR; hormone receptor; HER2; advanced breast cancer
30.  ER, PR, HER2, Ki-67 and CK5 in Early and Late Relapsing Breast Cancer—Reduced CK5 Expression in Metastases 
Breast cancer can recur even decades after the primary therapy. Markers are needed to predict cancer progression and the risk of late recurrence. The estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), proliferation marker Ki-67, and cytokeratin CK5 were studied to find out whether their expression or occurrence in subgroups of breast cancers correlated with the time of recurrence. The expression of HER2, ER, PR, Ki-67, and CK5 was studied by IHC in 72 primary breast cancers and their corresponding recurrent/metastatic lesions. The patients were divided into three groups according to the time of the recurrence/metastasis: before two years, after 5 years, and after 10 years. Based on their IHC profiles, the tumors were divided into surrogates of the genetically defined subgroups of breast cancers and the subtype definitions were as follows: luminal A (ER or PR+HER2–), luminal B (ER or PR+HER2+), HER2 overexpressing (ER–PR–HER2+), triple-negative (ER–PR–HER2–), basal-like (ER–PR–HER2–CK5+), non-classified (ER–PR–HER2–CK5–) and luminobasal (ER or PR+CK5+). In multivariate analysis, tumor size and HER2 positivity were a significant risk of early cancer relapse. The metastases showed a significantly lower CK5 expression. CK5 positivity distinguished triple negative tumors into rapidly and slowly recurring cancers. The IHC subtype ER or PR+HER2– luminal A presented a significantly lower risk of early tumor recurrence. Ki-67 expression denoted early-relapsing tumors and correlated linearly with tumor progression, since Ki-67 positivity declined gradually from early-relapsing toward late-recurring cancers.
doi:10.4137/BCBCR.S10701
PMCID: PMC3579427  PMID: 23514931
early and late relapsing breast cancers; CK5; immunohistochemistry
31.  Adjuvant Chemotherapy for Breast Cancer in a Patient with Primary Autoimmune Neutropenia 
We report an extremely rare and complex case of a 44-year-old woman diagnosed with an early stage triple negative breast cancer in the setting of primary autoimmune neutropenia with a pre-existing severe neutropenia. This case-report demonstrates that adjuvant chemotherapy for breast cancer can be administered in a patient with severe neutropenia. The management is however complicated and requires careful monitoring of side-effects related to both chemotherapy and treatment of autoimmune neutropenia. The role of chemotherapy in the treatment of triple negative breast cancer, the approach to autoimmune neutropenia and potential interactions are reviewed. To our knowledge, this is the first case reporting on the use of chemotherapy in a patient with severe pre-existing primary autoimmune neutropenia.
doi:10.4137/BCBCR.S10767
PMCID: PMC3572877  PMID: 23440399
breast cancer; autoimmune neutropenia; chemotherapy
32.  Why, After Chemotherapy, is it Necessary to Assess Memory Using Translational Testing? 
As the number of cancer survivors rises, so does the importance of understanding what happens post-chemotherapy. The evidence is clear that chemotherapy affects not only cancer cells, but also healthy cells including neurons, leading to long-term cognitive dysfunction in a large portion of survivors. In order to understand the mechanism of action and in the hope of reducing the potential neurocognitive side effects of chemotherapy, pre-clinical testing should be used more effectively. However, the field is lacking translation from clinical studies to animal models. Spatial learning and memory paradigms based on the water maze, the most commonly used rodent model, are available for translational testing in humans and could overcome this weakness. There is an overwhelming need in the field to understand whether the water maze is an adequate model for post-chemotherapy impairments or whether other paradigms should be used. This is of great importance for the understanding of the mechanisms, side effects of new drugs, appropriate pharmacotherapy, and confounding factors related to chemotherapy treatment regiments. This review is very important to both basic scientists and clinicians determining how translational paradigms are critical to future cancer research, as well as what type of paradigms are appropriate in our technically advancing society.
doi:10.4137/BCBCR.S10293
PMCID: PMC3512448  PMID: 23226022
water maze; cancer; memory; spatial; translation
33.  Is the Improved Efficacy of Trastuzumab and Lapatinib Combination Worth the Added Toxicity? A Discussion of Current Evidence, Recommendations, and Ethical Issues Regarding Dual HER2-Targeted Therapy 
Following FDA approval of trastuzumab in 1998 and lapatinib in 2007, several clinical studies have addressed the question of whether trastuzumab and lapatinib combination therapy is better than trastuzumab alone in the metastatic breast cancer and neoadjuvant setting. In this review, updated to September 2012, we focus on the relevant clinical trials that address this question and, based on the available data, reach conclusions regarding a rational and reasonably individualized approach to the management of HER2+ breast cancer. With the FDA approval of pertuzumab in June 2012 and the likely approval of T-DM1 approaching, several ethical issues overshadow the excitement oncologists have for these new treatment options. We discuss the potential evolution of highly active anti-HER2 therapy (HAAHT) as an optimal treatment paradigm for HER2+ breast cancer. Additionally, we review lessons learned from the evolution of HAART for HIV treatment.
doi:10.4137/BCBCR.S9301
PMCID: PMC3512454  PMID: 23226023
HER2; breast cancer; lapatinib; trastuzumab; dual; T-DM1; pertuzumab
34.  Five-Year Follow-Up of Patients with Early Stage Breast Cancer After a Randomized Study Comparing Additional Treatment with Viscum Album (L.) Extract to Chemotherapy Alone 
Additional therapy with extracts of Viscum album [L.] (VaL) increases the quality of life of patients suffering from early stage breast cancer during chemotherapy. In the current study patients received chemotherapy, consisting of six cycles of cyclophosphamide, anthracycline, and 5-Fluoro-Uracil (CAF). Two groups also received one of two VaL extracts differing in their preparation as subcutaneous injection three times per week. A control group received CAF with no additional therapy. Six of 28 patients in one of the VaL groups and eight of 29 patients in the control group developed relapse or metastasis within 5 years. Subgroup analysis for hormone- and radiotherapy also showed no difference between groups. Additional VaL therapy during chemotherapy of early stage breast cancer patients appears not to influence the frequency of relapse or metastasis within 5 years.
doi:10.4137/BCBCR.S10558
PMCID: PMC3493140  PMID: 23150723
mistletoe therapy; chemotherapy; breast cancer; randomized clinical trial; disease-free survival rate; 5-year follow-up
35.  Taxanes for the Treatment of Metastatic Breast Cancer 
Taxanes have remained a cornerstone of breast cancer treatment over the past three decades, improving the lives of patients with both early- and late-stage disease. The purpose of this review is to summarize the current role of taxanes, including an albumin-bound formulation that enhances delivery of paclitaxel to tumors, in the management of metastatic breast cancer (MBC). Since the introduction of Cremophor EL-paclitaxel to the clinic in the mid-1990s, a substantial amount of investigation has gone into subjects such as formulation, dose, schedule, and taxane resistance, allowing physicians greater flexibility in treating patients with MBC. This review will also examine how the shrinking pool of taxane-naive patients, a result of the expansion of taxanes into the neoadjuvant and adjuvant settings, will respond to taxane retreatment for metastatic disease. Taxane treatment seems likely to continue to play an important role in the treatment of MBC.
doi:10.4137/BCBCR.S8205
PMCID: PMC3486789  PMID: 23133315
taxanes; metastatic breast cancer; paclitaxel; docetaxel; nab-paclitaxel
36.  NGlycolylGM3/VSSP Vaccine in Metastatic Breast Cancer Patients: Results of Phase I/IIa Clinical Trial 
Patients treated with vaccines based on NGlycolil gangliosides have showed benefit in progression free survival and overall survival. These molecules, which have been observed in breast cancer cells, are minimally or not expressed in normal human tissue and have been considered as antigen tumor-specific. For this reason they are very attractive to immunotherapy. A phase I/II clinical trial was carried out in metastatic breast cancer patients with the NGlycolylGM3/VSSP vaccine administered by subcutaneous route. Selecting the optimal biological doses of the vaccine in these patients was the principal objective based on the immunogenicity, efficacy and safety results. Six levels of doses of vaccine were studied. Treatment schedule consisted of five doses every two weeks and then monthly until reaching a fifteenth doses. Doses levels studied were 150, 300, 600, 900, 1200 and 1500 μg. Five patients in each level were included except at the 900 μg dose, in which ten patients were included. Immunogenicity was determined by levels of antibodies generated in patients after vaccination. The response criteria of evaluation in solid tumors (RECIST) was used to evaluate antitumoral effect. Safety was evaluated by Common Toxicity Criteria of Adverse Event (CTCAE). The vaccine administration was safe and immunogenic in all does levels. Most frequent adverse events related to vaccination were mild or moderate and were related to injection site reactions and “flu-like” symptoms. Vaccination induced specific anti-NeuGcGM3 IgM and IgG antibodies responses in all patients. Disease control (objective response or stable disease) was obtained in 72.7% of evaluated patients. Median overall survival was 15.9 months. Two patients of two different dose levels achieved overall survival values of about six years. The dose of 900 μg was selected as biological optimal dose in which overall survival was 28.5 months.
doi:10.4137/BCBCR.S8488
PMCID: PMC3465086  PMID: 23055739
metastatic breast cancer; clinical trial; therapeutic vaccine; ganglioside; NGcGM3
37.  Oscillation of Clock and Clock Controlled Genes Induced by Serum Shock in Human Breast Epithelial and Breast Cancer Cells: Regulation by Melatonin 
This study investigates differences in expression of clock and clock-controlled genes (CCGs) between human breast epithelial and breast cancer cells and breast tumor xenografts in circadian intact rats and examines if the pineal hormone melatonin influences clock gene and CCG expression. Oscillation of clock gene expression was not observed under standard growth conditions in vitro, however, serum shock (50% horse serum for 2 h) induced oscillation of clock gene and CCG expression in MCF-10A cells, which was repressed or disrupted in MCF-7 cells. Melatonin administration following serum shock differentially suppressed or induced clock gene (Bmal1 and Per2) and CCG expression in MCF10A and MCF-7 cells. These studies demonstrate the lack of rhythmic expression of clock genes and CCGs of cells in vitro and that transplantation of breast cancer cells as xenografts into circadian competent hosts re-establishes a circadian rhythm in the peripheral clock genes of tumor cells.
doi:10.4137/BCBCR.S9673
PMCID: PMC3448497  PMID: 23012497
melatonin; clock genes; circadian; serum shock; breast cancer
38.  Early Contralateral Shoulder-Arm Morbidity in Breast Cancer Patients Enrolled in a Randomized Trial of Post-Surgery Radiation Therapy 
Introduction
Shoulder/arm morbidity is a common complication of breast cancer surgery and radiotherapy (RT), but little is known about acute contralateral morbidity.
Methods
Patients were 118 women enrolled in a RT trial. Arm volume and shoulder mobility were assessed before and 1–3 months after RT. Correlations and linear regression were used to analyze changes affecting ipsilateral and contralateral arms, and changes affecting relative interlimb differences (RID).
Results
Changes affecting one limb correlated with changes affecting the other limb. Arm volume between the two limbs correlated (R = 0.57). Risk factors were weight increase and axillary dissection. Contralateral and ipsilateral loss of abduction strongly correlated (R = 0.78). Changes of combined RID exceeding 10% affected the ipsilateral limb in 25% of patients, and the contralateral limb in 18%. Aromatase inhibitor therapy was significantly associated with contralateral loss of abduction.
Conclusions
High incidence of early contralateral arm morbidity warrants further investigations.
doi:10.4137/BCBCR.S9362
PMCID: PMC3418149  PMID: 22904635
early breast cancer; short-course radiation therapy; image-guided radiation therapy; shoulder/arm morbidity; breast cancer-related lymphedema
39.  Identification of Breast Cancer-Associated Lipids in Scalp Hair 
A correlation between the presence of breast cancer and a change in the synchrotron-generated X-ray diffraction (XRD) pattern of hair has been reported in several publications by different groups, and on average XRD-based assays detect around 75% of breast cancer patients in blinded studies. To date, the molecular mechanisms leading to this alteration are largely unknown. We have determined that the alteration is likely to be due to the presence of one or more breast cancer-associated phospholipids. Further characterization of these lipids could be used to develop a novel, sensitive and specific screening test for breast cancer, based on hair initially, and potentially extendable to other biological samples.
doi:10.4137/BCBCR.S9607
PMCID: PMC3411328  PMID: 22872787
hair; breast cancer; lipids; phospholipids; hair
40.  Radiation-Triggered NF-κB Activation is Responsible for the Angiogenic Signaling Pathway and Neovascularization for Breast Cancer Cell Proliferation and Growth 
Tumors require blood supply to survive, grow, and metastasize. This involves the process of angiogenesis signaling for new blood vessel growth into a growing tumor mass. Understanding the mechanism of the angiogenic signaling pathway and neovascularization for breast cancer cell proliferation and growth would help to develop molecular interventions and achieve disease free survival. Our hypothesis is that the surviving cancer cell(s) after radiotherapy can initiate angiogenic signaling pathway in the neighboring endothelial cells resulting in neovascularization for breast cancer cell growth. The angiogenic signaling pathway is initiated by angiogenic factors, VEGF and FGF-2, through activation of a transcriptional regulator NF-κB, which in turn is triggered by therapeutic doses of radiation exposure Human breast adenocarcinoma cells (MCF-7 cells) were exposed to Cesium-137 (137Cs) γ rays to a total dose of 2 Gy at a dose rate of 1.03 Gy/min. The results of mobility shift assay showed that radiation at clinical doses (2 Gy) could induce NF-κB DNA-binding activity. Then, we examined the communication of angiogenic signals from irradiated MCF-7 cells to vascular endothelial cells. At the protein level, the western blot showed induction of angiogenic factors VEGF and FGF-2 in MCF-7 cells irradiated with 2 Gy. Inhibition of NF-κB activation attenuated VEGF and FGF-2 levels. These factors are secreted into the medium. The levels of VEGF and FGF-2 in the extra cellular medium were both increased, after 2 Gy exposures. We also observed corresponding expression of VEGFR2 and FGFR1 in non-irradiated endothelial cells that were co-cultured with irradiated MCF-7 cells. In support of this, in vitro tube formation assays provided evidence that irradiated MCF-7 cells transmit signals to potentiate cultured non-irradiated endothelial cells to form tube networks, which is the hallmark of neovascularization. Inhibition of NF-κB activation attenuated irradiated MCF-7-induced tube network formation. The data provide evidence that the radiation exposure is responsible for tumor growth and maintenance by inducing an angiogenic signaling pathway through activation of NF-κB.
doi:10.4137/BCBCR.S9592
PMCID: PMC3411495  PMID: 22872788
breast cancer; angiogenic factors; NF-κB activation; neovascularization
42.  Unusual Presentation of Multiple Fibroadenomas in Bilateral Breasts and Axillary Accessory Breast 
We report an extremely rare case with a total of 50 fibroadenomas simultaneously presented in bilateral breasts and left axillary accessory breast, up to 8 cm in size, in a 20 year-old Chinese woman. The histopathologic and immunophenotypic features of the fibroadenomas are described and possible underlying pathogenesis is discussed. To our knowledge, this is the first case with such a large number of bilateral multiple breast fibroadenomas in a young female reported in the literature.
doi:10.4137/BCBCR.S9512
PMCID: PMC3337783  PMID: 22553423
multiple fibroadenoma; bilateral breasts; axillary accessory breast
43.  Efficacy and Tolerability of Lapatinib in the Management of Breast Cancer 
Approximately 20%–25% of all breast cancers over express a key cell surface growth factor receptor known as HER2. HER2 plays a key role in cell growth and proliferation and is linked to worse clinical outcomes, making it a logical therapeutic target. The first HER2 targeted drug to be approved by the FDA, was the humanized monoclonal antibody trastuzumab, after it showed improvements in survival in the adjuvant setting, and delayed time to progression in the metastatic setting. Although highly effective, for reasons that are not clear, some patients display resistance to trastuzumab. Lapatinib is an oral, small molecule tyrosine kinase inhibitor, that inhibits both the HER1 ahd HER2 receptors and may be able to overcome trastuzumab resistance. Lapatinib is approved in the second line setting for use in combination with capecitabine or with letrozole. In this review, we will discuss the indications, concerns or any issues with regards to the drug.
doi:10.4137/BCBCR.S6374
PMCID: PMC3306225  PMID: 22438669
breast cancer; lapatinib; efficacy; tolerability
44.  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
45.  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
46.  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
47.  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
48.  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
49.  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
50.  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

Results 26-50 (110)