International Journal of Breast Cancer The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Everolimus-Based Therapy versus Chemotherapy among Patients with HR+/HER2− Metastatic Breast Cancer: Comparative Effectiveness from a Chart Review Study Wed, 20 May 2015 08:26:57 +0000 Objective. To compare the real-world effectiveness of everolimus-based therapy and chemotherapy in postmenopausal women with hormone-receptor-positive/human-epidermal-growth-factor-receptor-2-negative (HR+/HER2−) metastatic breast cancer (mBC). Methods. This retrospective chart review examined a nationwide sample of postmenopausal HR+/HER2− mBC women in community-based oncology practices. Patients received everolimus-based therapy or chemotherapy for mBC between 07/01/2012 and 04/15/2013, after failure of a non-steroidal aromatase inhibitor. Overall survival (OS), progression-free survival (PFS), and time on treatment (TOT) were compared using Kaplan-Meier analysis and Cox proportional hazards models adjusting for line of therapy and baseline characteristics. Results. 234 and 137 patients received everolimus-based therapy and chemotherapy. Patients treated with everolimus-based therapy tended to have less aggressive mBC than patients treated with chemotherapy. Multivariate-adjusted Cox models showed that everolimus-based therapy was associated with significantly longer OS [hazard ratio (HR) = 0.37, 95% confidence interval (CI): 0.22–0.63], PFS (HR = 0.70, 95% CI = 0.50–0.97), and TOT (HR = 0.34, 95% CI: 0.25–0.45) than chemotherapy. Adjusted comparative effectiveness results were generally consistent across lines of therapy. Conclusion. In this retrospective chart review of postmenopausal HR+/HER2− mBC patients, treatment with everolimus-based therapy was associated with longer OS, PFS, and TOT than chemotherapy. Nanxin Li, Yanni Hao, Jipan Xie, Peggy L. Lin, Valerie Koo, Erika Ohashi, and Eric Q. Wu Copyright © 2015 Nanxin Li et al. All rights reserved. SEMA6D Expression and Patient Survival in Breast Invasive Carcinoma Mon, 20 Apr 2015 11:29:27 +0000 Breast cancer (BC) is the second most common cancer diagnosed in American women and is also the second leading cause of cancer death in women. Research has focused heavily on BC metastasis. Multiple signaling pathways have been implicated in regulating BC metastasis. Our knowledge of regulation of BC metastasis is, however, far from complete. Identification of new factors during metastasis is an essential step towards future therapy. Our labs have focused on Semaphorin 6D (SEMA6D), which was implicated in immune responses, heart development, and neurogenesis. It will be interesting to know SEMA6D-related genomic expression profile and its implications in clinical outcome. In this study, we examined the public datasets of breast invasive carcinoma from The Cancer Genome Atlas (TCGA). We analyzed the expression of SEMA6D along with its related genes, their functions, pathways, and potential as copredictors for BC patients’ survival. We found 6-gene expression profile that can be used as such predictors. Our study provides evidences for the first time that breast invasive carcinoma may contain a subtype based on SEMA6D expression. The expression of SEMA6D gene may play an important role in promoting patient survival, especially among triple negative breast cancer patients. Dongquan Chen, Yufeng Li, Lizhong Wang, and Kai Jiao Copyright © 2015 Dongquan Chen et al. All rights reserved. Locoregional and Distant Recurrence Patterns in Young versus Elderly Women Treated for Breast Cancer Thu, 09 Apr 2015 11:11:34 +0000 Objective. This study examined recurrence patterns in breast cancer patients younger than age of 40 and older than age of 75, two groups that are underrepresented in clinical trials and not routinely screened by mammography. Methods. The records of 230 breast cancer patients ( less than 40 and greater than 75) who presented to the Emory University Department of Radiation Oncology for curative treatment between 1997 and 2010 were reviewed. Data recorded included disease presentation, treatment, and areas of locoregional recurrence. Results. Women less than 40 years of age had higher rates of locoregional recurrence (20% versus 7%, ) and distant recurrence (18% versus 5%, ) than patients above 75 years of age. On multivariate analysis, patient age less than 40 was the only significant predictor of locoregional recurrence (). In a univariate analysis of each age group, receptor status and postlumpectomy radiation were significant predictors of locoregional recurrence-free survival in younger women while mammography screening predicted for distant recurrence-free survival in older patients. Conclusion. The factors identified in our age-stratified analysis highlight patients who are at high risk of locoregional and distant recurrence. Future studies aimed at enhancing therapies in young patients are warranted. Soumon Rudra, David S. Yu, Esther S. Yu, Jeffrey M. Switchenko, Donna Mister, and Mylin A. Torres Copyright © 2015 Soumon Rudra et al. All rights reserved. Green Synthesis of Silver Nanoparticles Using Extract of Oak Fruit Hull (Jaft): Synthesis and In Vitro Cytotoxic Effect on MCF-7 Cells Thu, 01 Jan 2015 09:47:04 +0000 A green synthetic approach by using oak fruit hull (Jaft) extract for preparation of silver nanoparticles (AgNPs) was developed and optimized. Parameters affecting the synthesis of AgNPs, such as temperature, extract pH, and concentration of extract (ratio of plant sample to extraction solvent), were investigated and optimized. Optimum conditions for the synthesis of silver nanoparticles are as follows: Ag+ concentration, 1 mM; extract concentration, 40 g/L (4% w/v); pH = 9 and temperature, 45°C. Biosynthesized silver nanoparticles were characterized using UV-visible absorption spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). TEM and DLS analyses have shown the synthesized AgNPs were predominantly spherical in shape with an average size of 40 nm. The cytotoxic activity of the synthesized AgNPs and Jaft extract containing AgNPs against human breast cancer cell (MCF-7) was investigated and the half maximal inhibitory concentrations (IC50) were found to be 50 and 0.04 μg/mL at 24 h incubation, respectively. This eco-friendly and cost-effective synthesis method can be potentially used for large-scale production of silver nanoparticles. Rouhollah Heydari and Marzieh Rashidipour Copyright © 2015 Rouhollah Heydari and Marzieh Rashidipour. All rights reserved. Metabolic Syndrome Is Associated with Increased Breast Cancer Risk: A Systematic Review with Meta-Analysis Mon, 29 Dec 2014 10:08:46 +0000 Background. Although individual metabolic risk factors are reported to be associated with breast cancer risk, controversy surrounds risk of breast cancer from metabolic syndrome (MS). We report the first systematic review and meta-analysis of the association between MS and breast cancer risk in all adult females. Methods. Studies were retrieved by searching four electronic reference databases [PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, and ProQuest through June 30, 2012] and cross-referencing retrieved articles. Eligible for inclusion were longitudinal studies reporting associations between MS and breast cancer risk among females aged 18 years and older. Relative risks and 95% confidence intervals were calculated for each study and pooled using random-effects models. Publication bias was assessed quantitatively (Trim and Fill) and qualitatively (funnel plots). Heterogeneity was examined using and statistics. Results. Representing nine independent cohorts and 97,277 adult females, eight studies met the inclusion criteria. A modest, positive association was observed between MS and breast cancer risk (RR: 1.47, 95% CI, 1.15–1.87; ; ; , ; %). No publication bias was observed. Conclusions. MS is associated with increased breast cancer risk in adult women. Ruchi Bhandari, George A. Kelley, Tara A. Hartley, and Ian R. H. Rockett Copyright © 2014 Ruchi Bhandari et al. All rights reserved. Intraoperative Boost Radiotherapy during Targeted Oncoplastic Breast Surgery: Overview and Single Center Experiences Wed, 17 Dec 2014 11:57:35 +0000 Breast-conserving surgery followed by whole-breast irradiation is the standard local therapy for early breast cancer. The international discussion of reduced importance of wider tumor-free resection margins than “tumor not touching ink” leads to the development of five principles in targeted oncoplastic breast surgery. IORT improves local recurrence risk and diminishes toxicity since there is less irradiation of healthy tissue. Intraoperative radiotherapy (IORT) can be delivered in two settings: an IORT boost followed by a conventional regimen of external beam radiotherapy or a single IORT dose. The data from TARGIT-A and ELIOT reinforce the conviction that intraoperative radiotherapy during breast-conserving surgery is a reliable alternative to conventional postoperative fractionated irradiation, but only in a carefully selected population at low risk of local recurrence. We describe our experiences with IORT boost (50 kV energy X-rays; 20 Gy) in combination with targeted oncoplastic breast surgery in a routine clinical setting. Our experiences demonstrate the applicability and reliability of combining IORT boost with targeted oncoplastic breast surgery in breast-conserving therapy of early breast cancer. Wolfram Malter, Verena Kirn, Lisa Richters, Claudius Fridrich, Birgid Markiefka, Rudolf Bongartz, Robert Semrau, Peter Mallmann, and Stefan Kraemer Copyright © 2014 Wolfram Malter et al. All rights reserved. Intraoperative Full-Dose of Partial Breast Irradiation with Electrons Delivered by Standard Linear Accelerators for Early Breast Cancer Wed, 17 Dec 2014 08:17:10 +0000 Purpose. To assess feasibility, efficacy, toxicity, and cosmetic results of intraoperative radiotherapy (IORT) with electrons delivered by standard linear accelerators (Linacs) during breast conserving surgeries for early infiltrating breast cancer (BC) treatment. Materials and Methods. A total of 152 patients with invasive ductal carcinoma ( cm) at low risk for local relapses were treated. All had unicentric lesions by imaging methods and negative sentinel node. After a wide local excision, 21 Gy were delivered on the parenchyma target volume with electron beams. Local recurrences (LR), survival, toxicity, and cosmetic outcomes were analyzed. Results. The median age was 58.3 years (range 40–85); median follow-up was 50.7 months (range 12–101.5). There were 5 cases with LR, 2 cases with distant metastases, and 2 cases with deaths related to BC. The cumulative incidence rates of LR, distant metastases, and BC death were 3.2%, 1.5%, and 1.5%, respectively. Complications were rare, and the cosmetic results were excellent or good in most of the patients. Conclusions. IORT with electrons delivered by standard Linacs is feasible, efficient, and well tolerated and seems to be beneficial for selected patients with early infiltrating BC. Alfredo Carlos S. D. Barros, Samir A. Hanna, Heloísa A. Carvalho, Eduardo Martella, Felipe Eduardo M. Andrade, José Roberto M. Piato, and José Luiz B. Bevilacqua Copyright © 2014 Alfredo Carlos S. D. Barros et al. All rights reserved. Prevalence of HER-2 and Hormone Receptors and P53 Mutations in the Pathologic Specimens of Breast Cancer Patients Wed, 12 Nov 2014 07:16:43 +0000 Prognostic factors are in interest for breast cancer as the second cause of malignancy deaths. Some have predictive values as human epidermal growth factor receptor-2 (HER-2) and estrogen receptor (ER). To access the incidence of HER2 and its relations to other factors, like age, pathology, ER, progesterone receptor (PR), and P53, 2000 pathologic blocks from 2750 total samples have been selected from 2011 to 2013 in Cancer Institute of Tehran. Incidence of HER2, ER, PR, and P53 was; 58.5%, 33.4%, 43.3%, and 65.4%, respectively. Invasive ductal carcinoma was the most pathologic type (82.2%) and 60%–70% positive HER2 and P53 had negative ER and PR (poor prognosis). The peak age of incidence of breast cancer was perimenopausal age group (46–55 years). Our cases had more positive HER2 and P53 and less positive PR and ER compared to other studies. High perimenopausal incidence as another finding assures the importance of breast cancer screening in these age groups. Seyed Abbas Mirmalek, Maryam Hajilou, Seyed Alireza Salimi Tabatabaee, Yekta Parsa, Soheila Yadollah-Damavandi, and Tina Parsa Copyright © 2014 Seyed Abbas Mirmalek et al. All rights reserved. Dermoglandular Rotation Flaps for Breast-Conserving Therapy: Aesthetic Results, Patient Satisfaction, and Morbidity in Comparison to Standard Segmentectomy Tue, 04 Nov 2014 09:24:45 +0000 We compared a dermoglandular rotation flap (DGR) in the upper inner, lower inner, and upper outer quadrant regarding similar aesthetic results, patient satisfaction, and comfort after breast-conserving therapy with standard segmentectomy (SE). Between 2003 and 2011, 69 patients were treated with breast-conserving surgery using DGR for cancers with high tumor-to-breast volume ratios or skin resection in the three above mentioned quadrants; 161 patients with tumors in the same quadrants were treated with SE. The outcome of the procedures was assessed at least 7 months after completed radiation therapy using a patient and breast surgeon questionnaire and the BCCT.core software. Symmetry, visibility of the scars, the position of the nipple-areola complex, and the appearance of the treated breast were each assessed on a scale from 1 to 4 by an expert panel and by the patients. Univariate and multivariate analysis were used to evaluate the relationship between patient-, tumor-, and treatment-dependent factors and patient satisfaction. 94.2% of the patients with rotation flaps and 83.5% of the patients with lumpectomy were very satisfied with the cosmetic appearance of their breast. Younger patient age was significantly associated with a lower degree of satisfaction. DGR provides good cosmetic results compared with SE and shows high patient satisfaction despite longer scarring and higher median resection volume. Ursula Hille-Betz, Bernhard Vaske, Helga Henseler, Philipp Soergel, Sudip Kundu, Lars Makowski, Sophia Schelcher, Sebastian Wojcinski, and Peter Hillemanns Copyright © 2014 Ursula Hille-Betz et al. All rights reserved. Factors Associated with the Incidence of Local Recurrences of Breast Cancer in Women Who Underwent Conservative Surgery Tue, 04 Nov 2014 08:27:54 +0000 Conservative surgery is considered the procedure of choice for women who are affected by early stage tumours. The local recurrence of cancer as a consequence of breast tissue conservation is a growing concern. This study aimed to describe the sociodemographic and clinical profiles of women who had local recurrences of breast cancer after conservative surgery and to examine the associations between sociodemographic and clinical variables and the incidence of tumour recurrence in these women. The retrospective cohort included 880 women who were diagnosed with breast cancer and underwent conservative surgery between January 2000 and December 2010. Recurrences occurred in 60 patients, and the mean age of the women at diagnosis was 48.8 years. Predictive factors for local recurrence were young age (<39 years) ( and ), surgical margin involvement ( and ), and Her-2 overexpression ( and ). The establishment of sociodemographic and clinical characteristics might help to select optimum treatments, which is a crucial challenge for public health in Brazil, especially with regard to reductions of surgery and hospitalisation expenditures in the Unified Health System (Sistema Único de Saúde—SUS). Juliana Rodrigues Tovar, Eliana Zandonade, and Maria Helena Costa Amorim Copyright © 2014 Juliana Rodrigues Tovar et al. All rights reserved. Sentinel Node Biopsy Alone versus Completion Axillary Node Dissection in Node Positive Breast Cancer: Systematic Review and Meta-Analysis Tue, 14 Oct 2014 08:01:37 +0000 Introduction. There has been recent interest in validity of completion axillary node dissection after a positive sentinel node. This systematic review aims to ascertain if sentinel lymph node dissection alone was noninferior to axillary lymph node dissection for breast cancer patients who have a positive sentinel node. Method. A systematic review of the electronic databases Embase, MEDLINE, and Cochrane Register of Controlled Trials was carried out. Only randomised trials that had patients with positive sentinel node as the study sample were included in the meta-analysis using the reported hazard ratios with a fixed effect model. Results. Three randomised controlled trials and five retrospective studies were identified. The pooled effect for overall survival was HR 0.94, 95% CI [0.79, 1.19], and for disease free survival was HR 0.83, 95% CI [0.60, 1.14]. The reported rates for locoregional recurrence were similar in both groups. The surgical morbidity was found to be significantly more in patients who had underwent axillary dissection. Conclusion. Amongst patients with micrometastasis in the sentinel node, no further axillary dissection is necessary. For patients with macrometastasis in the sentinel node, it is reasonable to consider omitting axillary dissection to avoid the morbidity of the procedure. Rachna Ram, Jasprit Singh, and Eddie McCaig Copyright © 2014 Rachna Ram et al. All rights reserved. Breast Cancer with Neoductgenesis: Histopathological Criteria and Its Correlation with Mammographic and Tumour Features Wed, 08 Oct 2014 00:00:00 +0000 Introduction. Breast cancer with mammographic casting type calcifications, high grade DCIS with an abnormal number of ducts, periductal desmoplastic reaction, lymphocyte infiltration, and tenascin-C (TN-C) overexpression has been proposed to represent a more aggressive form of breast cancer and has been denominated as breast cancer with neoductgenesis. We developed histopathological criteria for neoductgenesis in order to study reproducibility and correlation with other tumour markers. Methods. 74 cases of grades 2 and 3 DCIS, with or without an invasive component, were selected. A combined score of the degree(s) of concentration of ducts, lymphocyte infiltration, and periductal fibrosis was used to classify cases as showing neoductgenesis, or not. Diagnostic reproducibility, correlation with tumour markers, and mammographic features were studied. Results. Twenty-three of 74 cases were diagnosed with neoductgenesis. The kappa value between pathologists showed moderate reproducibility (0.50) (95% CI; 0.41–0.60). Neoductgenesis correlated significantly with malignant type microcalcifications and TN-C expression ( and 0.04) and with ER, PR, and HER2 status ( for all three markers). Conclusions. We developed histological criteria for breast cancer with neoductgenesis. Neoductgenesis, by our applied histopathological definition was related to more aggressive tumour biology and malignant mammographic calcifications. Wenjing Zhou, Thomas Sollie, Tibor Tot, Sarah E. Pinder, Rose-Marie Amini, Carl Blomqvist, Marie-Louise Fjällskog, Gunilla Christensson, Shahin Abdsaleh, and Fredrik Wärnberg Copyright © 2014 Wenjing Zhou et al. All rights reserved. Effect of Formalin Fixation on Surgical Margins in Breast Cancer Surgical Specimen Thu, 02 Oct 2014 08:07:04 +0000 Margin analysis in breast surgery is an important predictor of local recurrence and can have vital impact on the postoperative treatment planning. Objective. The aim was to assess the mean reduction in the closest tumor-free surgical margin in millimeters of breast cancer specimens following formalin fixation. Materials and Methods. We conducted a cross-sectional study at the Aga Khan University Hospital from March 30, 2010 to January 20, 2011. One hundred consecutive breast tumour surgical specimens which had macroscopically visible tumour were included. The cancer type included both in situ and invasive cancers. Excluded were the patients who had previous surgery or systemic/radiation therapy. The closest tumor-free margin was recorded and compared with the margin after formalin fixation. value of <0.05 was considered significant. Results. The mean age of our 100 patients was 53 years with the majority of the patients having undergone mastectomy for predominantly invasive ductal carcinoma. Following formalin fixation, the mean reduction of the closest tumor-free margin was noted as 2.14 mm which was found statistically significant. Conclusion. Considerable shrinkage of tumor-free surgical margins of breast cancer specimen was noted after formalin fixation. This inference can have implications on the postoperative management plan. Masooma Zaidi, Shaista Khan, Najiha Bilal Farooqi, Kashif Abbas, and Romana Idrees Copyright © 2014 Masooma Zaidi et al. All rights reserved. The Impact of Race in Male Breast Cancer Treatment and Outcome in the United States: A Population-Based Analysis of 4,279 Patients Thu, 02 Oct 2014 00:00:00 +0000 The purpose of this study is to compare the racial differences in treatment and overall survival (OS) of male breast cancer (MBC) patients. Data were extracted from the NCI SEER database that included population-based registries from 1988 to 2010 and analyzed using SPSS 20.0. 4,279 MBC patients were identified. 3,266 (76.3%) patients were White, 552 (12.9%) Black, 246 (5.7%) Hispanic, and 215 (5.0%) Asian. Black patients were more likely to be diagnosed at younger age , have advanced stage disease , and be unmarried and less likely to undergo lymph node dissection . When stratified by stage, there was no difference in receipt of primary treatment by race. The 5-year OS for White, Black, Hispanic, and Asian races was 73.8%, 66.3%, 74.0%, and 85.3% . This significant worse 5-year OS for Blacks persisted regardless of age, stage II or III disease, and grade 2 or 3 disease. On multivariate analysis, Black race was a significant independent prognostic factor for worse OS. Blacks were less likely to receive lymph node dissection of which patients may derive benefit, though we did not observe receipt of primary treatment, after stratifying for disease stage, to be an underlying factor contributing to racial outcome differences. Jacob Y. Shin, Lisa A. Kachnic, and Ariel E. Hirsch Copyright © 2014 Jacob Y. Shin et al. All rights reserved. Pain in Breast Cancer Treatment: Aggravating Factors and Coping Mechanisms Wed, 01 Oct 2014 09:01:26 +0000 The objective of this study was to evaluate pain in women with breast cancer-related lymphedema and the characteristics of aggravating factors and coping mechanisms. The study was conducted in the Clinica Godoy, São Jose do Rio Preto, with a group of 46 women who had undergone surgery for the treatment of breast cancer. The following variables were evaluated: type and length of surgery; number of radiotherapy and chemotherapy sessions; continued feeling of the removed breast (phantom limb), infection, intensity of pain, and factors that improve and worsen the pain. The percentage of events was used for statistical analysis. About half the participants (52.1%) performed modified radical surgery, with 91.3% removing only one breast; 82.6% of the participants did not perform breast reconstruction surgery. Insignificant pain was reported by 32.60% of the women and 67.3% said they suffered pain; it was mild in 28.8% of the cases (scale 1–5), moderate in 34.8% (scale 6–9), and severe in 4.3%. The main mechanisms used to cope with pain were painkillers in 41.30% of participants, rest in 21.73%, religious ceremonies in 17.39%, and chatting with friends in 8.69%. In conclusion, many mastectomized patients with lymphedema complain of pain, but pain is often underrecognized and undertreated. Maria de Fatima Guerreiro Godoy, Livia Maria Pereira de Godoy, Stelamarys Barufi, and José Maria Pereira de Godoy Copyright © 2014 Maria de Fatima Guerreiro Godoy et al. 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.