International Journal of Breast Cancer The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. The Value of Intraoperative Frozen Section Analysis for Margin Status in Breast Conservation Surgery in a Nontertiary Institution Tue, 30 Sep 2014 11:43:14 +0000 Introduction. Breast conservation treatment (BCT) for early-stage breast malignancies requires negative margins and good cosmesis. Reoperations may be needed to achieve negative margins, which can have an adverse impact on outcomes. This study was performed to evaluate the efficacy of intraoperative frozen section analysis (IFSA) for margin assessment to reduce excision rates. Methods. All patients treated at the authors’ private healthcare facility between 2009 and 2011 for breast cancer were included in the study. Those for whom BCT was intended underwent wide excision with IFSA. Six margins of the excised tissue, and the sentinel lymph node (SLN), where appropriate, were submitted for IFSA. Patient demographics, tumour characteristics, number of operations performed, and outcomes were analysed. Results. Of the 161 patients analysed, 138 (85.7%) had successful breast conservation. Four patients required a reoperation for incomplete surgical extirpation. One had a false negative SLN assessment on IFSA, and was returned to the operating room for an axillary dissection. Three patients required reoperations for inadvertently missed multicentric disease. None had false negative margin evaluation with IFSA necessitating reexcision. Conclusion. The use of IFSA allows low rates of reoperation with BCT. Further research is needed to establish consistency in low reexcision rates for cost-effectiveness and optimum resource allocation. Mona P. Tan, Nadya Y. Sitoh, and Amanda S. Sim Copyright © 2014 Mona P. Tan et al. All rights reserved. Cosmetic Outcome Assessment following Breast-Conserving Therapy: A Comparison between BCCT.core Software and Panel Evaluation Mon, 22 Sep 2014 06:10:06 +0000 Purpose. Over recent decades, no consensus has yet been reached on the optimal approach to cosmetic evaluation following breast-conserving therapy (BCT). The present study compared the strengths and weaknesses of the BCCT.core software with a 10-member panel from various backgrounds. Methods. Digital photographs of 109 consecutive patients after BCT were evaluated for 7 items by a panel consisting of 2 breast surgeons, 2 residents, 2 laypersons, and 4 plastic surgeons. All photographs were objectively evaluated using the BCCT.core software (version 20), and an overall cosmetic outcome score was reached using a four-point Likert scale. Results. Based on the mean BCCT.core software score, 41% of all patients had fair or poor overall cosmetic results (10% poor), compared with 51% (14% poor) obtained with panel evaluation. Mean overall BCCT.core score and mean overall panel score substantially agreed (weighted kappa: 0.68). By contrast, analysis of the evaluation of scar tissue revealed large discrepancies between the BCCT.core software and the panel. The analysis of subgroups formed from different combinations of the panel members still showed substantial agreement with the BCCT.core software (range 0.64–0.69), independent of personal background. Conclusions. Although the analysis of scar tissue by the software shows room for improvement, the BCCT.core represents a valid and efficient alternative to panel evaluation. Max Hendrik Haloua, Nicole Marianna Alexandra Krekel, Gerrit Johannes Albertus Jacobs, Barbara Zonderhuis, Mark-Bram Bouman, Marlon Eugène Buncamper, Franciscus Bernardus Niessen, Henri Adolf Hubert Winters, Caroline Terwee, Sybren Meijer, and Monique Petrousjka van den Tol Copyright © 2014 Max Hendrik Haloua et al. All rights reserved. Comparison of Cantharidin Toxicity in Breast Cancer Cells to Two Common Chemotherapeutics Sun, 14 Sep 2014 10:41:06 +0000 As part of a larger study synthesizing a more directed form of chemotherapy, we have begun to assess the efficacy of different potential toxins that could be delivered locally rather than systemically. In doing so, we hope to reduce the systemic side effects commonly observed, while maintaining a high level of toxicity and eliminating the need for metabolic alterations. In a search for this more efficient method for killing cancerous cells, we have begun studying cantharidin, a toxin used in traditional Chinese medicine, as a potential chemotherapeutic. Using an MTT cell viability assay, the toxicity of cantharidin was compared to both cyclophosphamide and paclitaxel in three different breast cancer cell lines: MCF-7, MDA-MB-231, and SK-BR-3. Increasing the concentration of chemotherapy drugs did decrease cell viability in all cell lines when cantharidin and cyclophosphamide were applied; however differences for paclitaxel were cell-specific. Additionally, cantharidin exhibited the highest decrease in cell viability regardless of cell type, indicating it may be a much more potent and less specific chemotherapeutic. These results will help us move forward in developing a potentially more potent treatment for breast cancer that might eliminate the need for subtype-specific treatments. Katie M. Kern and Jennifer R. Schroeder Copyright © 2014 Katie M. Kern and Jennifer R. Schroeder. All rights reserved. Boost IORT in Breast Cancer: Body of Evidence Tue, 02 Sep 2014 13:07:56 +0000 The term IORT (intraoperative radiotherapy) is currently used for various techniques that show decisive differences in dose delivery. The largest evidence for boost IORT preceding whole breast irradiation (WBI) originates from intraoperative electron treatments with single doses around 10 Gy, providing outstandingly low local recurrence rates in any risk constellation also at long term analyses. Compared to other boost methods, an intraoperative treatment has evident advantages as follows. Precision. Direct visualisation of the tumour bed during surgery guarantees an accurate dose delivery. This fact has additionally gained importance in times of primary reconstruction techniques after lumpectomy to optimise cosmetic outcome. IORT is performed before breast tissue is mobilised for plastic purposes. Cosmesis. As a consequence of direct tissue exposure without distension by hematoma/seroma, IORT allows for small treatment volumes and complete skin sparing, both having a positive effect on late tissue tolerance and, hence, cosmetic appearance. Patient Comfort. Boost IORT marginally prolongs the surgical procedure, while significantly shortening postoperative radiotherapy. Its combination with a 3-week hypofractionated external beam radiotherapy to the whole breast (WBI) is presently tested in the HIOB trial (hypofractionated WBI preceded by IORT electron boost), a prospective multicenter trial of the International Society of Intraoperative Radiotherapy (ISIORT). Felix Sedlmayer, Roland Reitsamer, Christoph Fussl, Ingrid Ziegler, Franz Zehentmayr, Heinz Deutschmann, Peter Kopp, and Gerd Fastner Copyright © 2014 Felix Sedlmayer et al. All rights reserved. Effect of Melatonin on Cognitive Function and Sleep in relation to Breast Cancer Surgery: A Randomized, Double-Blind, Placebo-Controlled Trial Wed, 27 Aug 2014 00:00:00 +0000 Background. Sleep disturbances and cognitive dysfunction are common in patients with breast cancer. Disturbed sleep leads to poor cognitive performance and exogenous melatonin may improve sleep and attenuate cognitive dysfunction. We hypothesized that melatonin would improve sleep and cognitive function after surgery. Methods. This study reports secondary endpoints from a randomized, double-blind, placebo-controlled trial. Women, 30–75 years, were randomized to 6mg oral melatonin/placebo for 3 months. We assessed postoperative cognitive dysfunction (POCD) with a neuropsychological test battery, sleep with a diary, and sleep quality with VAS. Results. 54 patients were randomized to melatonin () or placebo (); 11 withdrew (10 placebo, 1 melatonin, ). The incidence of POCD was 0% (0/20) [95% CI 0.0%; 16.8%] in the placebo group and 0% (0/26) [95% CI 0.0%; 13.2%] in the melatonin group 2 weeks postoperatively () and 6.3% (1/16) [95% CI 0.0%; 30.2%] in the placebo group and 0% (0/26) [95% CI 0.0%; 13.2%] in the melatonin group 12 weeks postoperatively (). Sleep efficiency was significantly greater in the melatonin group; mean difference was 4.28% [95% CI 0.57; 7.82] (). The total sleep period was significantly longer in the melatonin group; mean difference was 37.0 min [95% CI 3.6; 69.7] (). Conclusion. Melatonin increased sleep efficiency and total sleep time but did not affect cognitive function. The dropout rate was significantly lower in the melatonin group. This trial is registered with NCT01355523. Melissa Voigt Hansen, Michael Tvilling Madsen, Lærke Toftegård Andersen, Ida Hageman, Lars Simon Rasmussen, Susanne Bokmand, Jacob Rosenberg, and Ismail Gögenur Copyright © 2014 Melissa Voigt Hansen et al. All rights reserved. Adopting Ambulatory Breast Cancer Surgery as the Standard of Care in an Asian Population Tue, 12 Aug 2014 12:55:43 +0000 Introduction. Ambulatory surgery is not commonly practiced in Asia. A 23-hour ambulatory (AS23) service was implemented at our institute in March 2004 to allow more surgeries to be performed as ambulatory procedures. In this study, we reviewed the impact of the AS23 service on breast cancer surgeries and reviewed surgical outcomes, including postoperative complications, length of stay, and 30-day readmission. Methods. Retrospective review was performed of 1742 patients who underwent definitive breast cancer surgery from 1 March 2004 to 31 December 2010. Results. By 2010, more than 70% of surgeries were being performed as ambulatory procedures. Younger women (), those undergoing wide local excision () and those with ductal carcinoma-in situ or early stage breast cancer (), were more likely to undergo ambulatory surgery. Six percent of patients initially scheduled for ambulatory surgery were eventually managed as inpatients; a third of these were because of perioperative complications. Wound complications, 30-day readmission and reoperation rates were not more frequent with ambulatory surgery. Conclusion. Ambulatory breast cancer surgery is now the standard of care at our institute. An integrated workflow facilitating proper patient selection and structured postoperativee outpatient care have ensured minimal complications and high patient acceptance. Yvonne Ying Ru Ng, Patrick Mun Yew Chan, Juliana Jia Chuan Chen, Melanie Dee Wern Seah, Christine Teo, and Ern Yu Tan Copyright © 2014 Yvonne Ying Ru Ng et al. All rights reserved. Intraoperative Radiotherapy for Breast Cancer: The Lasting Effects of a Fleeting Treatment Sun, 10 Aug 2014 09:00:14 +0000 In well-selected patients who choose to pursue breast conservation therapy (BCT) for early-stage breast cancer, partial breast irradiation (PBI) delivered externally or intraoperatively, may be a viable alternative to conventional whole breast irradiation. Two large, contemporary randomized trials have demonstrated breast intraoperative radiotherapy (IORT) to be noninferior to whole breast external beam radiotherapy (EBRT) when assessing for ipsilateral breast tumor recurrence in select patients. Additionally, IORT and other PBI techniques are likely to be more widely adopted in the future because they improve patient convenience by offering an accelerated course of treatment. Coupled with these novel techniques for breast radiotherapy (RT) are distinct toxicity profiles and unique cosmetic alterations that differ from conventional breast EBRT and have the potential to impact disease surveillance and patient satisfaction. This paper will review the level-one evidence for treatment efficacy as well as important secondary endpoints like RT toxicity, breast cosmesis, quality of life, patient satisfaction, and surveillance mammography following BCT with IORT. Harriet B. Eldredge-Hindy, Anne L. Rosenberg, and Nicole L. Simone Copyright © 2014 Harriet B. Eldredge-Hindy et al. All rights reserved. Healthcare Resource Use and Expenditures among Metastatic Breast Cancer Patients Treated with HER2-Targeted Agents Thu, 07 Aug 2014 08:38:11 +0000 Objective. To compare healthcare utilization (HCU) and costs of women newly diagnosed with metastatic breast cancer (mBC) by receipt of HER2-targeted agents (H2T) and among H2T subgroups. Methods. Adult women newly diagnosed with mBC (index date) during 2008–2012 were followed until enrollment end or inpatient death. Study cohorts were antineoplastic ± H2Ts, and no treatment; and subgroups of H2T patients stratified by receipt of hormonal therapy (HT+/HT−), by de novo versus recurrent disease status, and by age group. All-cause (ALL) and breast cancer related (BCR) HCU and costs (in 2012 dollars) were estimated using a generalized linear model. Results. Of 18,059 women, 14.6% were H2T users 71.1% nonusers, and 14.3% untreated. No treatment patients had the highest ALL and BCR inpatient HCU, and ALL emergency room HCU. H2Ts users had the highest ALL and BCR office visits, lab and diagnostic radiology, radiation treatments, other outpatient services, and prescription antineoplastics. Adjusted ALL and BCR costs were the highest for H2T users and, in H2T subgroups, higher for HT—versus HT+ and de novo versus recurrent, and declined with older age. Conclusions. Receipt of H2Ts was associated with greater levels of ALL and BCR HCU and costs. H2T subgroups of , de novo, and younger age had higher HCU and costs, possibly indicating more aggressive treatments. Nicole Meyer, Yanni Hao, Xue Song, Nianwen Shi, William Johnson, Jaqueline Willemann Rogerio, and Denise A. Yardley Copyright © 2014 Nicole Meyer et al. 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.