International Journal of Breast Cancer The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Similarity of Fibroglandular Breast Tissue Content Measured from Magnetic Resonance and Mammographic Images and by a Mathematical Algorithm Tue, 15 Jul 2014 06:50:55 +0000 Women with high breast density (BD) have a 4- to 6-fold greater risk for breast cancer than women with low BD. We found that BD can be easily computed from a mathematical algorithm using routine mammographic imaging data or by a curve-fitting algorithm using fat and nonfat suppression magnetic resonance imaging (MRI) data. These BD measures in a strictly defined group of premenopausal women providing both mammographic and breast MRI images were predicted as well by the same set of strong predictor variables as were measures from a published laborious histogram segmentation method and a full field digital mammographic unit in multivariate regression models. We also found that the number of completed pregnancies, C-reactive protein, aspartate aminotransferase, and progesterone were more strongly associated with amounts of glandular tissue than adipose tissue, while fat body mass, alanine aminotransferase, and insulin like growth factor-II appear to be more associated with the amount of breast adipose tissue. Our results show that methods of breast imaging and modalities for estimating the amount of glandular tissue have no effects on the strength of these predictors of BD. Thus, the more convenient mathematical algorithm and the safer MRI protocols may facilitate prospective measurements of BD. Fatima Nayeem, Hyunsu Ju, Donald G. Brunder, Manubai Nagamani, Karl E. Anderson, Tuenchit Khamapirad, and Lee-Jane W. Lu Copyright © 2014 Fatima Nayeem et al. All rights reserved. Early Invasive Cancer and Partial Intraoperative Electron Radiation Therapy of the Breast: Experience of the Jules Bordet Institute Mon, 09 Jun 2014 05:56:06 +0000 Objectives. The aim of this prospective phase II study is to evaluate the treatment of early-stage breast cancer (T1 N0) with intraoperative electron radiation therapy (IOERT) in terms of local control, early complications, and cosmesis. Patients and Methods. From February 2010 to February 2012, 200 patients underwent partial IOERT of the breast. Inclusion criteria were unifocal invasive ductal carcinoma, age ≥40 years, histological tumour size ≤20 mm, and no lymph node involvement. A 21 Gy dose was prescribed over the 90% isodose line in the tumour bed. Median follow-up is 23.3 months (7–37). Results. Acute toxicity was not frequent (Grade 1: 4.5%, Grade 2: 1%). The cosmetic result was considered to be very good or good in 92.5%. One ipsi lateral out-quadrant recurrence at 18 months was observed. The crude and actuarial local recurrence rates after median follow-up were 0.5% and 0.9%, respectively. Conclusion. The preoperative diagnostic work-up must be comprehensive and the selection process must be rigorous for this therapeutic approach reserved for small ductal unifocal cancers. After a 23.3-month median follow-up time, the clinical results of IOERT for selected patients are encouraging for the locoregional recurrence and the toxicity rates. The satisfaction of our patients in terms of quality of life was extremely high. C. Philippson, S. Simon, C. Vandekerkhove, D. Hertens, I. Veys, D. Noterman, F. De Neubourg, D. Larsimont, P. Bourgeois, P. Van Houtte, and J. M. Nogaret Copyright © 2014 C. Philippson et al. All rights reserved. Methods of Cell Propulsion through the Local Stroma in Breast Cancer Mon, 07 Apr 2014 13:37:38 +0000 In the normal breast, cellular structures change cyclically in response to ovarian hormones. Cell proliferation, apoptosis, invasion, and differentiation are integral processes that are precisely regulated. Normal epithelial cells depend on the formation of intercellular adhesion contacts to form a continuous sheet of stratifying cell layers that are attached to one and other horizontally and vertically. Cells migrate by extending membrane protrusions to explore the extracellular space locating their targets in a chemotactic manner. The formation of cell protrusions is driven by the assembly of actin filaments at the leading edge. Reorganisation is regulated by a highly integrated signalling cascade that transduces extracellular stimuli to the actin filaments. This signalling cascade is governed by GTPases which act as molecular switches leading to actin polymerisation and the formation of filopodia and lamellipodia. This process is linked to downstream molecules known collectively as WASP proteins, which, in the presence of cortactin, form a complex leading to nucleation and formation of branched filaments. In breast cancer, the cortactin is over expressed leading to increased cellular motility and invasiveness. This hugely complex and integrated signalling cascade transduces extracellular stimuli. There are multiple genes related to cell motility which are dysregulated in human breast cancers. Kerry J. Davies Copyright © 2014 Kerry J. Davies. All rights reserved. The Complex Interaction of Matrix Metalloproteinases in the Migration of Cancer Cells through Breast Tissue Stroma Thu, 27 Mar 2014 07:19:04 +0000 Breast cancer mortality is directly linked to metastatic spread. The metastatic cell must exhibit a complex phenotype that includes the capacity to escape from the primary tumour mass, invade the surrounding normal tissue, and penetrate into the circulation before proliferating in the parenchyma of distant organs to produce a metastasis. In the normal breast, cellular structures change cyclically in response to ovarian hormones leading to regulated cell proliferation and apoptosis. Matrix metalloproteinases (MMPs) are a family of zinc dependent endopeptidases. Their primary function is degradation of proteins in the extracellular matrix to allow ductal progression through the basement membrane. A complex balance between matrix metalloproteinases and their inhibitors regulate these changes. These proteinases interact with cytokines, growth factors, and tumour necrosis factors to stimulate branching morphologies in normal breast tissues. In breast cancer this process is disrupted facilitating tumour progression and metastasis and inhibiting apoptosis increasing the life of the metastatic cells. This paper highlights the role of matrix metalloproteinases in cell progression through the breast stroma and reviews the complex relationships between the different proteinases and their inhibitors in relation to breast cancer cells as they metastasise. Kerry J. Davies Copyright © 2014 Kerry J. Davies. All rights reserved. Smoking and Breast Cancer Recurrence after Breast Conservation Therapy Mon, 17 Feb 2014 11:07:57 +0000 Background. Prior studies have shown earlier recurrence and decreased survival in patients with head and neck cancer who smoked while undergoing radiation therapy. The purpose of the current study was to determine whether smoking status at the time of partial mastectomy and radiation therapy for breast cancer affected recurrence or survival. Method. A single institution retrospective chart review was performed to correlate smoking status with patient demographics, tumor characteristics, and outcomes for patients undergoing partial mastectomy and radiation therapy. Results. There were 624 patients who underwent breast conservation surgery between 2002 and 2010 for whom smoking history and follow-up data were available. Smoking status was associated with race, patient age, and tumor stage, but not with grade, histology, or receptor status. African American women were more likely to be current smokers (22% versus 7%, ). With a mean follow-up of 45 months, recurrence was significantly higher in current smokers compared to former or never smokers (). In a multivariate model adjusted for race and tumor stage, recurrence among current smokers was 6.7 times that of never smokers (CI 2.0–22.4). Conclusions. Although the numbers are small, this study suggests that smoking may negatively influence recurrence rates after partial mastectomy and radiation therapy. A larger study is needed to confirm these observations. Jennifer D. Bishop, Brigid K. Killelea, Anees B. Chagpar, Nina R. Horowitz, and Donald R. Lannin Copyright © 2014 Jennifer D. Bishop et al. All rights reserved. Impact of Undetected Comorbidity on Treatment and Outcomes of Breast Cancer Thu, 13 Feb 2014 09:46:39 +0000 Preexisting comorbidity adversely impacts breast cancer treatment and outcomes. We examined the incremental impact of comorbidity undetected until cancer. We followed breast cancer patients in SEER-Medicare from 12 months before to 84 months after diagnosis. Two comorbidity indices were constructed: the National Cancer Institute index, using 12 months of claims before cancer, and a second index for previously undetected conditions, using three months after cancer. Conditions present in the first were excluded from the second. Overall, 6,184 (10.1%) had undetected comorbidity. Chronic obstructive pulmonary disease (38%) was the most common undetected condition. In multivariable analyses that adjusted for comorbidity detected before cancer, older age, later stage, higher grade, and poor performance status all were associated with higher odds of undetected comorbidity. In stage I–III cancer, undetected comorbidity was associated with lower adjusted odds of receiving adjuvant chemotherapy (Odds Ratio (OR) = 0.81, 95% Confidence Interval (CI) 0.73–0.90, ; , 95% CI 0.30–0.49, ; index score 1 or , respectively), and with increased mortality (Hazard Ratio (HR) = 1.45, 95% CI 1.38–1.53, ; , 95% CI 2.18–2.60, ; index score 1 or ). Undetected comorbidity is associated with less aggressive treatment and higher mortality in breast cancer. Robert I. Griffiths, Michelle L. Gleeson, José M. Valderas, and Mark D. Danese Copyright © 2014 Robert I. Griffiths et al. All rights reserved. Nodal Status Assessment in Breast Cancer: Strategies of Clinical Grounds and Quality of Life Implications Tue, 11 Feb 2014 12:53:28 +0000 Even in the era of gene-expression profiling, the nodal status still remains the primary prognostic discriminant in breast cancer patients. The exclusion of node involvement using noninvasive methods could reduce the rate of axillary surgery, thereby preventing from suffering complications. However, lymphatic mapping with sentinel node biopsy (SNB) is one of the most interesting recent developments in surgical oncology. Optimization of procedure could be implemented by dual mapping injection site skills, resection of all hot or blue nodes through tracer combination, and improvement in atypical drainage patterns mapping. This anatomical analysis suggests safety measures in patients with high probability of node metastasis through a renewed interest in surgical management. The perspective of a guided axillary sampling (GAS) could represent a potential development of recent anatomical and functional acquisitions, offering a dynamic technique shared according to clinical and anatomical disease parameters. Furthermore, the surgical staging procedures may adopt a conservative approach through the evaluation of upper arm lymphatics, thus defining a functional model aimed at the reduction of short- and long-term adverse events. Quality results in breast cancer surgery need to generate oncological safety devoid of complications through renewed clinical experience. Paolo Orsaria, Dimitrios Varvaras, Gianluca Vanni, Giampiero Pagnani, Jacopo Scaggiante, Federico Frusone, Alessandra Vittoria Granai, Giuseppe Petrella, and Oreste Claudio Buonomo Copyright © 2014 Paolo Orsaria et al. All rights reserved. Efficacy and Safety of the All-Oral Schedule of Metronomic Vinorelbine and Capecitabine in Locally Advanced or Metastatic Breast Cancer Patients: The Phase I-II VICTOR-1 Study Thu, 16 Jan 2014 12:16:20 +0000 Background. Vinorelbine (VRB) and capecitabine (CAPE) are demonstrated to be active in pretreated metastatic breast cancer patients. Different studies have demonstrated that the metronomic treatment is active with an acceptable toxicity profile. We designed a Phases I-II study to define the MTD of oral metronomic, VRB, and CAPE. Patients and Methods. Phase I: fixed dose of CAPE was 500 mg thrice a day, continuously. Level I of VRB was 20 mg/tot thrice a week for 3 weeks (1 cycle). Subsequent levels were 30 mg/tot and 40 mg/tot (Level III), respectively, if no Grades 3-4 toxicity were observed in the previous level. Phase II: further 32 patients received the MTD of VRB plus CAPE for a total of 187 cycles to confirm toxicity profile. Results. 12 patients were enrolled in Phase I and 22 in Phase II. Phase I: the MTD of VRB was 40 mg. Phase II: 187 cycles were delivered, observing 5.9% of Grades 3-4 toxicity. 31 patients are evaluable for efficacy, obtaining a clinical benefit rate of 58.1%. Conclusion. MTD of VRB with fixed dose of CAPE was 40 mg thrice a week and was the recommended dose for the ongoing Phase II multicenter study. M. E. Cazzaniga, V. Torri, F. Villa, N. Giuntini, F. Riva, A. Zeppellini, D. Cortinovis, and P. Bidoli Copyright © 2014 M. E. Cazzaniga et al. All rights reserved. Substituting Doxorubicin with Nonpegylated Liposomal Doxorubicin for the Treatment of Early Breast Cancer: Results of a Retrospective Study Sun, 12 Jan 2014 00:00:00 +0000 Introduction. Evidence from the metastatic setting suggests that replacing conventional doxorubicin with nonpegylated liposomal doxorubicin (NPLD) for early breast cancer may maintain efficacy whilst reducing long-term cardiotoxicity, an important consideration with many patients going on to receive multiple lines of treatment. Methods. Consecutive patients with early breast cancer treated with NPLD were assessed for disease progression and changes in cardiac function according to left ventricular ejection fraction (LVEF). Results. Ninety-seven patients (median age at diagnosis 51 (32–76) years) were studied. The majority received NPLD (60 mg/m2 plus cyclophosphamide 600 mg/m2) adjuvantly (79.4%) and in sequence with a taxane (79.4%; docetaxel 75 mg/m2). 80.4% had radiotherapy and 15.5% received trastuzumab. Mean time to disease recurrence was 87.0 months (80.7–93.2 [95% confidence interval]) and 5-year disease-free survival was 86.0%. Mean LVEF values remained within the normal range of ≥55% during treatment and throughout the cardiac follow-up period (median 7 months, range 1–21 months). Use of trastuzumab and age at diagnosis did not appear to influence LVEF. Conclusion. NPLD appeared to be a well-tolerated substitute for conventional doxorubicin in patients with early breast cancer. Neville Davidson, Teresa Camburn, Ian Keary, and David Houghton Copyright © 2014 Neville Davidson et al. All rights reserved. A Comparison of Tumor Biology in Primary Ductal Carcinoma In Situ Recurring as Invasive Carcinoma versus a New In Situ Sun, 29 Dec 2013 17:27:14 +0000 Introduction. About half of all new ipsilateral events after a primary ductal carcinoma in situ (DCIS) are invasive carcinoma. We studied tumor markers in the primary DCIS in relation to type of event (invasive versus in situ). Methods. Two hundred and sixty-six women with a primary DCIS from two source populations, all with a known ipsilateral event, were included. All new events were regarded as recurrences. Patient and primary tumor characteristics (estrogen receptor (ER), progesterone receptor (PR), HER2, EGFR, and Ki67) were evaluated. Logistic regression was used to calculate odd ratios and 95% confidence intervals in univariate and multivariate analyses. Results. One hundred and thirty-six of the recurrences were invasive carcinoma and 130 were in situ. The recurrence was more often invasive if the primary DCIS was ER+ (OR 2.5, 95% CI 1.2–5.1). Primary DCIS being HER2+ (OR 0.5, 95% CI 0.3–0.9), EGFR+ (OR 0.4, 95% CI 0.2–0.9), and ER95−/HER2+ (OR 0.2, 95% CI 0.1–0.6) had a lower risk of a recurrence being invasive. Conclusions. In this study, comparing type of recurrence after a DCIS showed that the ER−/HER2+ tumors were related to a recurrence being a new DCIS. And surprisingly, tumors being ER+, HER2−, and EGFR− were related to a recurrence being invasive cancer. Wenjing Zhou, Christine Johansson, Karin Jirström, Anita Ringberg, Carl Blomqvist, Rose-Marie Amini, Marie-Louise Fjallskog, and Fredrik Wärnberg Copyright © 2013 Wenjing Zhou et al. All rights reserved. Accuracy of Individual Descriptors and Grading of Nodal Involvement by Axillary Ultrasound in Patients of Breast Cancer Thu, 19 Dec 2013 15:29:20 +0000 Background. Four-node sampling is a useful substitute for sentinel node biopsy in low resource settings. USG is being increasingly used as a preoperative tool to evaluate axilla. We conducted this study to assess the accuracy of different descriptors of axillary ultrasound and to formulate a model on grading of axillary involvement. Material and Methods. Thirty-four patients with clinically negative axilla underwent preoperative axillary ultrasound. The suspicious nodes were marked and details of various descriptors were noted. These nodes were sampled during axillary dissection and correlation of ultrasonographic findings with histopathological report was done to calculate accuracy of different descriptors. Based on this, a grading system of axillary lymph nodes involvement was formulated. Results. Based on the presence of various descriptors, five grades of nodal involvement could be defined. The most accurate descriptors to indicate nodal involvement were loss of hilar fat and hypoechoic internal echoes with specificity of 83% and positive predictive value of 92% each. The combination of descriptors of round shape with loss of hilar fat and hypoechoic internal echos had 100% specificity and positive predictive value. Conclusions. Grading of nodal involvement on axillary USG can be useful for selecting the most suspicious nodes for sampling during axillary dissection. Navneet Kaur, Pradeep Sharma, Akhil Garg, and Anupama Tandon Copyright © 2013 Navneet Kaur et al. All rights reserved. Utilization of Oncotype DX in an Inner City Population: Race or Place? Wed, 18 Dec 2013 15:22:35 +0000 Oncotype DX, a 21-gene-array analysis, can guide chemotherapy treatment decisions for women with ER+ tumors. Of 225 ER+ women participating in a patient assistance trial, 23% underwent Oncotype DX testing: 31% of whites, 21% of blacks, and 14% of Hispanics () were tested. Only 3 white women were treated at municipal hospitals and none was tested. 3% of women treated in municipal hospital as compared to 30% treated at tertiary referral centers were tested (). Within tertiary referral centers, there was no racial difference in testing: 32% of whites, 29% of blacks, and 19% of Hispanics (). Multivariate analysis (model c-statistic = 0.76; ) revealed that women who underwent testing were more likely to have stage 1B (; 95% CI: 1.45–1.85) and to be treated after 2007 (; 95% CI: 1.01–1.65) and less likely to be treated at a municipal hospital (; 95% CI: 0.04–0.94). Women treated at municipal hospitals were less likely to undergo testing resulting in a misleading racial disparity that is driven by site of care. As Oncotype DX can reduce overuse of chemotherapy, it is imperative to expand testing to those who could benefit from yet experience underuse of this test, namely, women treated at safety net hospitals. This trial is registered with NCT00233077. Amber A. Guth, Susan Fineberg, Kezhen Fei, Rebeca Franco, and Nina A. Bickell Copyright © 2013 Amber A. Guth et al. All rights reserved. Evaluation of Diabetic Patients with Breast Cancer Treated with Metformin during Adjuvant Radiotherapy Thu, 12 Dec 2013 11:46:45 +0000 Purpose. The purpose of this study was to evaluate acute locoregional toxicity in patients with breast cancer receiving concurrent metformin plus radiation therapy. Methods and Materials. Diabetic breast cancer patients receiving concurrent metformin and radiation therapy were matched with nondiabetic patients and diabetic patients using an alternative diabetes medication. Primary endpoints included the presence of a treatment break and development of dry or moist desquamation. Results. There was a statistically significant increase in treatment breaks for diabetic patients receiving concurrent metformin when compared to the nondiabetic patients ( value = 0.02) and a trend toward significance when compared to diabetic patients receiving an alternate diabetes medication ( value = 0.08). Multiple logistic regression analysis demonstrated concurrent metformin use as being associated with a trend toward the predictive value of determining the incidence of developing desquamation in diabetic patients receiving radiation therapy compared to diabetic patients receiving an alternate diabetes medication ( value = 0.06). Conclusions. Diabetic patients treated with concurrent metformin and radiation therapy developed increased acute locoregional toxicity in comparison with diabetic patients receiving an alternate diabetes medication and nondiabetic patients. Further clinical investigation should be conducted to determine the therapeutic ratio of metformin in combination with radiation therapy. Adam Ferro, Sharad Goyal, Sinae Kim, Hao Wu, Neil K. Taunk, Devora Schiff, Aneesh Pirlamarla, and Bruce G. Haffty Copyright © 2013 Adam Ferro et al. All rights reserved. Vascular Endothelial Growth Factor Receptor-1 Expression in Breast Cancer and Its Correlation to Vascular Endothelial Growth Factor A Thu, 12 Dec 2013 11:00:54 +0000 VEGF-A is the most potent angiogenic factor in tumour angiogenesis. Its effects are mediated via two receptors VEGFR-1 and VEGFR-2. Primary aim of our study was to examine the expression of VEGFR-1 in breast cancer and its correlation to VEGF expression, lymph node status, tumour size, histological grade, and hormone receptor status. To examine the VEGFR-1 and VEGF expressions in tumour and surrounding tissue of 51 breast cancer patients, and in healthy breast tissue of 30 benign breast diseases patients, we used three-step immunohistochemical staining. VEGFR-1 and VEGF expressions were significantly increased in breast cancer tumour in relation to surrounding tissue (), and the VEGF expression was significantly increased in lymph node positive breast cancer patients (). VEGFR-1 and VEGF expressions were significantly higher in breast cancer tumour compared with healthy breast tissue (). Significant correlation between VEGF and VEGFR-1 expressions was found (). No significant correlations between VEGF and VEGFR-1 expressions and tumour size, histological grade, and hormone receptor status were found. Increased expression of VEGFR-1 and VEGF in breast cancer tumour and significant correlation between these proteins suggest the possible role of VEGF/VEGFR-1 signalization in breast cancer development, although VEGFR-1 potential prognostic value was not confirmed. Nahida Srabovic, Zlata Mujagic, Jasminka Mujanovic-Mustedanagic, Adaleta Softic, Zdeno Muminovic, Adi Rifatbegovic, and Lejla Begic Copyright © 2013 Nahida Srabovic et al. All rights reserved. Comparison of Fluorescence In Situ Hybridization and Chromogenic In Situ Hybridization for Low and High Throughput HER2 Genetic Testing Thu, 05 Dec 2013 10:08:58 +0000 The purpose was to evaluate and compare 5 different HER2 genetic assays with different characteristics that could affect the performance to analyze the human epidermal growth factor 2 (HER2) gene copy number under low and high throughput conditions. The study included 108 tissue samples from breast cancer patients with HER2 immunohistochemistry (IHC) results scored as 0/1+, 2+, and 3+. HER2 genetic status was analysed using chromogenic in situ hybridization (CISH) and fluorescence in situ hybridization (FISH). Scoring results were documented through digital image analysis. The cancer region of interest was identified from a serial H&E stained slide following tissue cores were transferred to a tissue microarrays (TMA). When using TMA in a routine flow, all patients will be tested for HER2 status with IHC followed by CISH or FISH, thereby providing individual HER2 results. In conclusion, our results show that the differences between the HER2 genetic assays do not have an effect on the analytic performance and the CISH technology is superior to high throughput HER2 genetic testing due to scanning speed, while the IQ-FISH may still be a choice for fast low throughput HER2 genetic testing. Tim S. Poulsen, Maiken L. M. Espersen, Vibeke Kofoed, Tanja Dabetic, Estrid Høgdall, and Eva Balslev Copyright © 2013 Tim S. Poulsen et al. All rights reserved. Use of Cox’s Cure Model to Establish Clinical Determinants of Long-Term Disease-Free Survival in Neoadjuvant-Chemotherapy-Treated Breast Cancer Patients without Pathologic Complete Response Thu, 05 Dec 2013 10:04:35 +0000 In prognostic studies for breast cancer patients treated with neoadjuvant chemotherapy (NAC), the ordinary Cox proportional-hazards (PH) model has been often used to identify prognostic factors for disease-free survival (DFS). This model assumes that all patients eventually experience relapse or death. However, a subset of NAC-treated breast cancer patients never experience these events during long-term follow-up (>10 years) and may be considered clinically “cured.” Clinical factors associated with cure have not been studied adequately. Because the ordinary Cox PH model cannot be used to identify such clinical factors, we used the Cox PH cure model, a recently developed statistical method. This model includes both a logistic regression component for the cure rate and a Cox regression component for the hazard for uncured patients. The purpose of this study was to identify the clinical factors associated with cure and the variables associated with the time to recurrence or death in NAC-treated breast cancer patients without a pathologic complete response, by using the Cox PH cure model. We found that hormone receptor status, clinical response, human epidermal growth factor receptor 2 status, histological grade, and the number of lymph node metastases were associated with cure. Junichi Asano, Akihiro Hirakawa, Chikuma Hamada, Kan Yonemori, Taizo Hirata, Chikako Shimizu, Kenji Tamura, and Yasuhiro Fujiwara Copyright © 2013 Junichi Asano et al. All rights reserved. Expression of the Classical and Nonclassical HLA Molecules in Breast Cancer Mon, 02 Dec 2013 10:44:28 +0000 Considering that downregulation of HLA expression could represent a potential mechanism for breast carcinogenesis and metastasis, the aim of the present study was to use immunohistochemical methods to analyze the expression of HLA-Ia, HLA-DR, HLA-DQ, HLA-E, and HLA-G in invasive ductal carcinoma (IDC) of the breast and to relate this HLA profile to anatomopathological parameters. Fifty-two IDC from breast biopsies were stratified according to histological differentiation (well, moderately, and poorly differentiated) and to the presence of metastases in axillary lymph nodes. The expression of HLA molecules was assessed by immunohistochemistry, using a computer-assisted system. Overall, 31 (59.6%) out of the 52 IDC breast biopsies exhibited high expression of HLA-G, but only 14 (26.9%) showed high expression of HLA-E. A large number (41, 78.8%) of the biopsies showed low expression of HLA-Ia, while 45 (86.5%) showed high expression of HLA-DQ and 36 (69.2%) underexpressed HLA-DR. Moreover, 24 (41.2%) of 52 biopsies had both low HLA-Ia expression and high HLA-G expression, while 11 (21.2%) had low HLA-Ia expression and high HLA-E expression. These results suggest that, by different mechanisms, the downregulation of HLA-Ia, HLA-E, and HLA-DR and the upregulation of HLA-G and HLA-DQ are associated with immune response evasion and breast cancer aggressiveness. Gisela Bevilacqua Rolfsen Ferreira da Silva, Tarsia Giabardo Alves Silva, Roberta Aparecida Duarte, Nicolino Lia Neto, Hélio Humberto Angotti Carrara, Eduardo Antônio Donadi, Maria Alice Guimarães Gonçalves, Edson Garcia Soares, and Christiane Pienna Soares Copyright © 2013 Gisela Bevilacqua Rolfsen Ferreira da Silva et al. All rights reserved. Tannic Acid Preferentially Targets Estrogen Receptor-Positive Breast Cancer Wed, 27 Nov 2013 10:07:14 +0000 Research efforts investigating the potential of natural compounds in the fight against cancer are growing. Tannic acid (TA) belongs to the class of hydrolysable tannins and is found in numerous plants and foods. TA is a potent collagen cross-linking agent; the purpose of this study was to generate TA-cross-linked beads and assess the effects on breast cancer cell growth. Collagen beads were stable at body temperature following crosslinking. Exposure to collagen beads with higher levels of TA inhibited proliferation and induced apoptosis in normal and cancer cells. TA-induced apoptosis involved activation of caspase 3/7 and caspase 9 but not caspase 8. Breast cancer cells expressing the estrogen receptor were more susceptible to the effects of TA. Taken together the results suggest that TA has the potential to become an anti-ER+ breast cancer treatment or preventative agent. Brian W. Booth, Beau D. Inskeep, Hiral Shah, Jang Pyo Park, Elizabeth J. Hay, and Karen J. L. Burg Copyright © 2013 Brian W. Booth et al. All rights reserved. Staging Investigations in Breast Cancer: Collective Opinion of UK Breast Surgeons Wed, 20 Nov 2013 18:54:32 +0000 Introduction. Certain clinicopathological factors are associated with a higher likelihood of distant metastases in primary breast cancer. However, there remains inconsistency in which patients undergo formal staging for distant metastasis and the most appropriate investigation(s). Aims. To identify UK surgeon preferences and practice with regard to staging investigations for distant metastases. Methods. A survey was disseminated to members of the Association of Breast Surgery by e-mail regarding surgeon/breast unit demographics, use of staging investigations, and local policy on pre/postoperative staging investigations. Several patient scenarios were also presented. Results. 123 of 474 (25.9%) recipients completed the survey. Investigations routinely employed for patients diagnosed with early breast cancer included serological/haematological tests (72% respondents), axillary ultrasound (67%), liver ultrasound (2%), chest radiograph (36%), and computed tomography (CT) (1%). Three areas contributed to decisions to undertake staging by CT scan: tumour size, axillary nodal status, and plan for chemotherapy. There was widespread variation as to criteria for CT staging based on tumour size and nodal status, as well as the choice of staging investigation for the clinical scenarios presented. Conclusions. There remains variation in the use of staging investigations for distant disease in early breastcancer despite available guidelines. N. Chand, R. I. Cutress, R. S. Oeppen, and A. Agrawal Copyright © 2013 N. Chand et al. All rights reserved. Sex Hormone Receptor Repertoire in Breast Cancer Wed, 13 Nov 2013 13:48:52 +0000 Classification of breast cancer as endocrine sensitive, hormone dependent, or estrogen receptor (ER) positive refers singularly to ERα. One of the oldest recognized tumor targets, disruption of ERα-mediated signaling, is believed to be the mechanistic mode of action for all hormonal interventions used in treating this disease. Whereas ERα is widely accepted as the single most important predictive factor (for response to endocrine therapy), the presence of the receptor in tumor cells is also of prognostic value. Even though the clinical relevance of the two other sex hormone receptors, namely, ERβ and the androgen receptor remains unclear, two discordant phenomena observed in hormone-dependent breast cancers could be causally related to ERβ-mediated effects and androgenic actions. Nonetheless, our understanding of regulatory molecules and resistance mechanisms remains incomplete, further compromising our ability to develop novel therapeutic strategies that could improve disease outcomes. This review focuses on the receptor-mediated actions of the sex hormones in breast cancer. Gerald M. Higa and Ryan G. Fell Copyright © 2013 Gerald M. Higa and Ryan G. Fell. All rights reserved. Assessment of Factors Associated with Breast Self-Examination among Health Extension Workers in West Gojjam Zone, Northwest Ethiopia Tue, 05 Nov 2013 09:07:27 +0000 Background. Early detection of breast cancer using breast self-examination (BSE) plays an important role in decreasing its morbidity and mortality. Objective. To identify factors associated with BSE among health extension workers in Northwest Ethiopia. Methods. Cross-sectional study design was employed from October to November, 2012 in West Gojjam Zone of Amhara region. Simple random sampling technique was used to recruit a total of 390 health extension workers (HEWs). A structured Amharic questionnaire was used to collect the data. Data were entered and analyzed using SPSS statistical package version 16.0. Result. This study found that 37% of HEWs had ever practiced BSE and 14.4% practiced it regularly. The three main reasons for not doing regular BSE were no breast problem (53.2%), not knowing the technique of BSE (30.6%), and not knowing the importance of BSE (21.4%). Discussion with families on BSE and history of breast examination by health professionals were found significantly associated with ever practice of BSE. Conclusion. BSE practice was found low in this study. Having information on the importance of BSE was predictor of BSE practice. Therefore, it is important to give training on BSE techniques and its role on breast cancer prevention for HEWs. Muluken Azage, Gedefaw Abeje, and Alemtsehay Mekonnen Copyright © 2013 Muluken Azage et al. All rights reserved. Microcalcifications Detected as an Abnormality on Screening Mammography: Outcomes and Followup over a Five-Year Period Tue, 01 Oct 2013 09:22:23 +0000 Objectives. This study reviewed the outcome of women attending a breast screening program recalled for assessment of microcalcifications and examined the incidence of a breast carcinoma detected during the following five years in any of the women who were given a benign diagnosis at assessment. Method. A retrospective study consisted of 235 clients attending an Australian BreastScreen program in 2003, who were recalled for investigation of microcalcifications detected on screening mammography. Records for the following five years were available for 168 women in the benign outcome group including those who did not require biopsy at initial assessment. Results. Malignant disease was detected in 26.0% () of the women who underwent biopsy. None of the women in the benign outcome group, with available five-year follow-up records, developed a subsequent breast cancer, arising from the calcifications initially recalled in 2003. Conclusions. This study highlights the effectiveness of an Australian screening program in diagnosing malignancy in women with screen detected microcalcification. This has been achieved by correctly determining 38% () of the women as benign without the need for biopsy or early recall. A low rate of open surgical biopsies was performed with no cancer diagnoses missed at the time of initial assessment. Melissa Craft, Anne M. Bicknell, Georges J. Hazan, and Karen M. Flegg Copyright © 2013 Melissa Craft et al. All rights reserved. Dose-Dense Epirubicin and Cyclophosphamide Followed by Docetaxel as Adjuvant Chemotherapy in Node-Positive Breast Cancer Wed, 25 Sep 2013 09:02:14 +0000 Background. Adding taxanes to anthracycline-based adjuvant chemotherapy has shown significant improvement particularly in node-positive patients, but optimal dose and schedule remain undetermined. Objectives. This study aimed to assess the feasibility of dose-dense epirubicin and cyclophosphamide followed by docetaxel in node-positive breast cancer. Methods. All Patients first received 4 cycles of epirubicin (100 mg/m2) and cyclophosphamide (600 mg/m2) at 2-week interval then followed by docetaxel (100 mg/m2) at 2-week interval for 4 cycles, with daily Pegfilgrastim (G-CSF) that was administered in all patients on days 3–10 after each cycle of epirubicin and cyclophosphamide infusion. Results. Fifty-eight patients with axillary lymph node-positive breast cancer were enrolled in the study, of whom 42 (72.4%) completed the regimen. There were two toxicity-related deaths, one patient due to grade 4 febrile neutropenia and the other due to congestive heart failure. Grade 3/4 neutropenia and febrile neutropenia were 13.8% and 5.1%. The most common grade 3/4 nonhematological complications were as follows: skin-nail disorders (48.3%), hand-foot syndrome (34.4%), paresthesia (38%), arthralgia (27.5%), and paresis (24.1%). Conclusions. Dose-dense epirubicin and cyclophosphamide followed by docetaxel with G-CSF support are not feasible, and it is not recommended for further investigation. Hamid Reza Mirzaei, Parisa Sabet Rasekh, Fatemeh Nasrollahi, Parto Sabet Rasekh, Zahra Akbari Tirabad, Hamid Reza Moein, Taban Ghaffari Pour, and Parastoo Hajian Copyright © 2013 Hamid Reza Mirzaei et al. All rights reserved. Histopathological Correlation of Atypical (C3) and Suspicious (C4) Categories in Fine Needle Aspiration Cytology of the Breast Mon, 23 Sep 2013 13:33:20 +0000 Introduction. According to the National Cancer Institute (NCI) guidelines in 1996, breast lesions are categorized as C1 to C5 on fine needle aspiration (FNA) cytology. Very few studies are available in the English literature analyzing histopathology outcome of C3 (atypical, probably benign) and C4 (suspicious, probably malignant) lesions. Our study aims to correlate FNA cytology of breast lump diagnosed as C3 and C4 lesion with histopathological examination. Methods. During a period of 2 years, 59 cases of C3 and 26 cases of C4 were retrieved from total 1093 cases of breast FNA. All the cases were reviewed by two cytopathologists independently. The final 24 cases of C3 and 16 cases of C4 categories were correlated with histopathological diagnosis. Result. Among C3 category, 37.5% revealed malignant findings, whereas of C4 category, 87.5% were malignant on histopathology. This difference was statistically significant (). Sensitivity, specificity, positive predictive values, and negative predictive value of C4 category in diagnosing breast malignancy were 60.8%, 88.2%, 87.5%, and 62.5%, respectively. Conclusion. Although FNAC is simple, safe, cost-effective and accurate method for diagnosis of breast masses, one must be aware of its limitations particularly in C3 and C4 categories. Also, since both these categories carry different probabilities of malignancy and thus different management, we therefore, support maintaining C3 and C4 categories. Prashant Goyal, Shelly Sehgal, Soumyesh Ghosh, Deepti Aggarwal, Pritesh Shukla, Awanindra Kumar, Ruchika Gupta, and Sompal Singh Copyright © 2013 Prashant Goyal et al. All rights reserved. Screening prior to Breast Cancer Diagnosis: The More Things Change, the More They Stay the Same Wed, 18 Sep 2013 14:20:03 +0000 Purpose. In November 2009, the U.S. Preventative Service Task Force (USPSTF) revised their breast cancer screening guidelines. We evaluated the pattern of screening subsequent to the altered guidelines in a cohort of women. Methods. Our database was queried for the following variables: age, race, method of diagnosis, mass palpability, screening frequency, histology, and stage. Statistical analyses were performed using Pearson’s chi-square and Fisher’s exact tests. Results. 1112 women were diagnosed with breast cancer from January 2010 to 2012. The median age at diagnosis was 60 years. Most cancers were detected on mammography (61%). The majority of patients had invasive ductal carcinoma (59%), stage 0 (23%), and stage 1 (50%) cancers. The frequency of screening did not change significantly over time (). However, nonregular screeners had an increased risk of being diagnosed with later stage breast cancer () and were more likely to present with a palpable mass compared to regular screeners (56% versus 21%; ). Conclusions. In our study, screening behavior did not significantly change in the years following the USPSTF guidelines. These results suggest that women who are not screened annually are at increased risk of a delay in breast cancer diagnosis, which may impact treatment options and outcomes. Erica B. Friedman, Jennifer Chun, Freya Schnabel, Shira Schwartz, Sidney Law, Jessica Billig, Erin Ivanoff, Linda Moy, Deborah Axelrod, and Amber Guth Copyright © 2013 Erica B. Friedman et al. All rights reserved. Drug Resistance and the Role of Combination Chemotherapy in Improving Patient Outcomes Mon, 24 Jun 2013 13:16:20 +0000 Resistance to cancer chemotherapy is a common phenomenon especially in metastatic breast cancer (MBC), a setting in which patients typically have had exposure to multiple lines of prior therapy. The subsequent development of drug resistance can result in rapid disease progression during or shortly after completion of treatment. Moreover, cross-class multidrug resistance limits patient treatment choices, particularly in a setting where treatments options are few. One attempt to minimize the impact of drug resistance has been the concurrent use of two or more chemotherapy agents with unrelated mechanisms of action and differing modes of drug resistance, with the intent of blocking the development of multiple intracellular escape pathways essential for tumor survival. Within the past decade, an array of mechanistically diverse agents has augmented the list of combination regimens that may be both synergistic and efficacious in pretreated MBC. The aim of this paper is to review mechanisms of resistance to common chemotherapy agents and to consider current combination treatment options for heavily pretreated and/or drug-resistant patients with MBC. Denise A. Yardley Copyright © 2013 Denise A. Yardley. All rights reserved. Pretreatment Thrombocytosis as a Prognostic Factor in Metastatic Breast Cancer Mon, 24 Jun 2013 11:56:12 +0000 Background. An elevated platelet count is often associated with malignancies, and it has been confirmed as an adverse prognostic factor in various cancers including early stage breast cancer. We sought to determine if thrombocytosis is also a prognostic factor in metastatic breast cancer. Patients and Methods. The records of 165 metastatic breast cancer patients with complete follow-up that had thrombocytosis or normal platelet counts were reviewed. Kaplan-Meier curves were constructed, and the survivals of the two groups were compared using the LogRank test. A Cox regression analysis was used to determine if thrombocytosis is an independent factor for overall and progression free survival. Results. There was a statistically significant difference in overall and progression free survival favoring the normal platelets group (LogRank test and 0.008, resp.). Thrombocytosis remained a significant adverse prognostic factor in multivariate analysis. Other independent prognostic factors for overall survival included age, ER/PR status, and grade. Conclusion. Thrombocytosis represents an independent adverse prognostic factor in patients with metastatic breast cancer. Thus metastatic breast cancer joins a range of cancers in which this easily measurable value can be used for clinical prognostication. Further use as a predictive value for specific treatments has a rationale and deserves to be investigated. Athina Stravodimou and Ioannis A. Voutsadakis Copyright © 2013 Athina Stravodimou and Ioannis A. Voutsadakis. All rights reserved. Risk Factors of Lymph Edema in Breast Cancer Patients Wed, 05 Jun 2013 15:36:14 +0000 Background. Lymphedema secondary to breast cancer treatment is a common and serious problem for disease survivors. The objective of the current study was to identify the risk factors of secondary lymphedema after breast carcinoma treatment. Materials & Methods. The breast cancer patients who were followed up in three centers in Tehran and Mashhad in 2010 were recruited in the study. The circumference measurement was used for defining lymphedema. Results. Among 410 breast cancer patients, 123 cases (30%) developed lymphedema. Variables such as low educational level, body mass index (BMI), higher stage of disease, number of involved lymph nodes, comorbid diseases, trauma, infection, and the time after surgery showed significant correlation with the development of lymphedema. In logistic regression analysis, increase of 1 kg/m2 in BMI (OR = 1.09; 95%  CI 1.05–1.15), each number increase in lymph node involvement (OR = 1.15; 95%  CI 1.08–1.21) and the increase of every 1 month after surgery (OR = 1.01; 95%  CI 1.01–1.02) significantly increased the risk of lymphedema. Conclusion. The results of this study demonstrated that preserving a fitted BMI, emphasis on self-care, and educating preventive activities may have important roles in decreasing the lymphedema incidence and improving the patients’ quality of life. Haghighat Shahpar, Akbari Atieh, Ansari Maryam, Homaei Shandiz Fatemeh, Najafi Massoome, Ebrahimi Mandana, Yunesian Masud, Mirzaei Hamid Reza, and Akbari Mohammad Esmaeil Copyright © 2013 Haghighat Shahpar et al. All rights reserved. Quantifying Potential Error in Painting Breast Excision Specimens Thu, 23 May 2013 16:33:15 +0000 Aim. When excision margins are close or involved following breast conserving surgery, many surgeons will attempt to reexcise the corresponding cavity margin. Margins are ascribed to breast specimens such that six faces are identifiable to the pathologist, a process that may be prone to error at several stages. Methods. An experimental model was designed according to stated criteria in order to answer the research question. Computer software was used to measure the surface areas of experimental surfaces to compare human-painted surfaces with experimental controls. Results. The variability of the hand-painted surfaces was considerable. Thirty percent of hand-painted surfaces were 20% larger or smaller than controls. The mean area of the last surface painted was significantly larger than controls (mean 58996 pixels versus 50096 pixels, CI 1477–16324, ). By chance, each of the six volunteers chose to paint the deep surface last. Conclusion. This study is the first to attempt to quantify the extent of human error in marking imaginary boundaries on a breast excision model and suggests that humans do not make these judgements well, raising questions about the safety of targeting single margins at reexcision. Thomas Fysh, Alex Boddy, and Amy Godden Copyright © 2013 Thomas Fysh et al. All rights reserved. The Mammary Gland Carcinogens: The Role of Metal Compounds and Organic Solvents Wed, 15 May 2013 09:36:40 +0000 The increased rate of breast cancer incidences especially among postmenopausal women has been reported in recent decades. Despite the fact that women who inherited mutations in the BRCA1 and BRCA2 genes have a high risk of developing breast cancer, studies have also shown that significant exposure to certain metal compounds and organic solvents also increases the risks of mammary gland carcinogenesis. While physiological properties govern the uptake, intracellular distribution, and binding of metal compounds, their interaction with proteins seems to be the most relevant process for metal carcinogenicity than biding to DNA. The four most predominant mechanisms for metal carcinogenicity include (1) interference with cellular redox regulation and induction of oxidative stress, (2) inhibition of major DNA repair, (3) deregulation of cell proliferation, and (4) epigenetic inactivation of genes by DNA hypermethylation. On the other hand, most organic solvents are highly lipophilic and are biotransformed mainly in the liver and the kidney through a series of oxidative and reductive reactions, some of which result in bioactivation. The breast physiology, notably the parenchyma, is embedded in a fat depot capable of storing lipophilic xenobiotics. This paper reviews the role of metal compounds and organic solvents in breast cancer development. Stephen Juma Mulware Copyright © 2013 Stephen Juma Mulware. All rights reserved.