International Journal of Breast Cancer http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2013 , Hindawi Publishing Corporation . All rights reserved. Quantifying Potential Error in Painting Breast Excision Specimens Thu, 23 May 2013 16:33:15 +0000 http://www.hindawi.com/journals/ijbc/2013/854234/ Aim. When excision margins are close or involved following breast conserving surgery, many surgeons will attempt to reexcise the corresponding cavity margin. Margins are ascribed to breast specimens such that six faces are identifiable to the pathologist, a process that may be prone to error at several stages. Methods. An experimental model was designed according to stated criteria in order to answer the research question. Computer software was used to measure the surface areas of experimental surfaces to compare human-painted surfaces with experimental controls. Results. The variability of the hand-painted surfaces was considerable. Thirty percent of hand-painted surfaces were 20% larger or smaller than controls. The mean area of the last surface painted was significantly larger than controls (mean 58996 pixels versus 50096 pixels, CI 1477–16324, ). By chance, each of the six volunteers chose to paint the deep surface last. Conclusion. This study is the first to attempt to quantify the extent of human error in marking imaginary boundaries on a breast excision model and suggests that humans do not make these judgements well, raising questions about the safety of targeting single margins at reexcision. Thomas Fysh, Alex Boddy, and Amy Godden Copyright © 2013 Thomas Fysh et al. All rights reserved. The Mammary Gland Carcinogens: The Role of Metal Compounds and Organic Solvents Wed, 15 May 2013 09:36:40 +0000 http://www.hindawi.com/journals/ijbc/2013/640851/ The increased rate of breast cancer incidences especially among postmenopausal women has been reported in recent decades. Despite the fact that women who inherited mutations in the BRCA1 and BRCA2 genes have a high risk of developing breast cancer, studies have also shown that significant exposure to certain metal compounds and organic solvents also increases the risks of mammary gland carcinogenesis. While physiological properties govern the uptake, intracellular distribution, and binding of metal compounds, their interaction with proteins seems to be the most relevant process for metal carcinogenicity than biding to DNA. The four most predominant mechanisms for metal carcinogenicity include (1) interference with cellular redox regulation and induction of oxidative stress, (2) inhibition of major DNA repair, (3) deregulation of cell proliferation, and (4) epigenetic inactivation of genes by DNA hypermethylation. On the other hand, most organic solvents are highly lipophilic and are biotransformed mainly in the liver and the kidney through a series of oxidative and reductive reactions, some of which result in bioactivation. The breast physiology, notably the parenchyma, is embedded in a fat depot capable of storing lipophilic xenobiotics. This paper reviews the role of metal compounds and organic solvents in breast cancer development. Stephen Juma Mulware Copyright © 2013 Stephen Juma Mulware. All rights reserved. Time-Dependent Prognostic Impact of Circulating Tumor Cells Detection in Non-Metastatic Breast Cancer: 70-Month Analysis of the REMAGUS02 Study Thu, 09 May 2013 14:13:09 +0000 http://www.hindawi.com/journals/ijbc/2013/130470/ Introduction. In non-metastatic breast cancer patients, the REMAGUS02 neoadjuvant study was the first to report a significant impact of circulating tumor cells (CTCs) detection by the CellSearch system on the distant metastasis-free survival (DMFS) and overall survival (OS) endpoints. However, these results were only reported after a short follow-up. Here, we present the updated data, with a longer follow-up. Material and Methods. CTC count was performed before and after neoadjuvant chemotherapy in 118 patients and correlated to survival. Results. CTC count results were available before and/or after neoadjuvant chemotherapy in 115 patients. After a median follow-up of 70 months, detection of ≥1 CTC/7.5 mL before chemotherapy () was significantly associated with DMFS () and OS (), whereas postchemotherapy CTC detection () had no significant impact. In multivariable analysis, prechemotherapy CTC and triple negative phenotype were the two independent prognostic factors for survival. We observed that the CTC impact is most significant during the first three years of follow-up. Discussion. We confirm that the detection of CTC is independently associated with a significantly worse outcome, but mainly during the first 3-4 years of follow-up. No prognostic impact is seen in patients who are still relapse-free at this moment. François-Clément Bidard, Lisa Belin, Suzette Delaloge, Florence Lerebours, Charlotte Ngo, Fabien Reyal, Séverine Alran, Sylvie Giacchetti, Michel Marty, Ronald Lebofsky, and Jean-Yves Pierga Copyright © 2013 François-Clément Bidard et al. All rights reserved. Ductal Carcinoma In Situ: What the Pathologist Needs to Know and Why Wed, 06 Feb 2013 11:40:08 +0000 http://www.hindawi.com/journals/ijbc/2013/914053/ Ductal carcinoma in situ is a proliferation of malignant epithelial cells confined to the ductolobular system of the breast. It is considered a pre-cursor lesion for invasive breast cancer and when identified patients are treated with some combination of surgery, +/− radiation therapy, and +/adjuvant tamoxifen. However, no good biomarkers exist that can predict with accuracy those cases of DCIS destined to progress to invasive disease or once treated those patients that are likely to suffer a recurrence; thus, in the era of screening mammography it seems likely that many patients with DCIS are overtreated. This paper details the parameters that should be included in a pathology report for a case of DClS with some explanations as to their importance for good clinical decision making. Anita Bane Copyright © 2013 Anita Bane. All rights reserved. Diet across the Lifespan and the Association with Breast Density in Adulthood Sat, 02 Feb 2013 08:26:57 +0000 http://www.hindawi.com/journals/ijbc/2013/808317/ Studies have shown inconsistent results regarding the association between dietary factors across the lifespan and breast density and breast cancer in women. Breast density is a strong risk factor for breast cancer, and the mechanism through which it influences cancer risk remains unclear. Breast density has been shown to be modifiable, potentially through dietary modifications. The goal of this paper is to summarize the current studies on diet and diet-related factors across all ages, determine which dietary factors show the strongest association with breast density, the most critical age of exposure, and identify future directions. We identified 28 studies, many of which are cross-sectional, and found that the strongest associations are among vitamin D, calcium, dietary fat, and alcohol in premenopausal women. Longitudinal studies with repeated dietary measures as well as the examination of overall diet over time are needed to confirm these findings. Jessica Lindgren, Joanne Dorgan, Jennifer Savage-Williams, Donna Coffman, and Terryl Hartman Copyright © 2013 Jessica Lindgren et al. All rights reserved. Mechanisms Mediating the Effects of γ-Tocotrienol When Used in Combination with PPARγ Agonists or Antagonists on MCF-7 and MDA-MB-231 Breast Cancer Cells Mon, 28 Jan 2013 13:52:27 +0000 http://www.hindawi.com/journals/ijbc/2013/101705/ γ-Tocotrienol is a natural vitamin E that displays potent anticancer activity, and previous studies suggest that these effects involve alterations in PPARγ activity. Treatment with 0.5–6 μM  γ-tocotrienol, 0.4–50 μM PPARγ agonists (rosiglitazone or troglitazone), or 0.4–25 μM PPARγ antagonists (GW9662 or T0070907) alone resulted in a dose-responsive inhibition of MCF-7 and MDA-MB-231 breast cancer proliferation. However, combined treatment of 1–4 μM  γ-tocotrienol with PPARγ agonists reversed the growth inhibitory effects of γ-tocotrienol, whereas combined treatment of 1–4 μM  γ-tocotrienol with PPARγ antagonists synergistically inhibited MCF-7 and MDA-MB-231 cell growth. Combined treatment of γ-tocotrienol and PPARγ agonists caused an increase in transcription activity of PPARγ along with increased expression of PPARγ and RXR, and decrease in PPARγ coactivators, CBP p/300, CBP C-20, and SRC-1, in both breast cancer cell lines. In contrast, combined treatment of γ-tocotrienol with PPARγ antagonists resulted in a decrease in transcription activity of PPARγ, along with decreased expression of PPARγ and RXR, increase in PPARγ coactivators, and corresponding decrease in PI3K/Akt mitogenic signaling in these cells. These findings suggest that elevations in PPARγ are correlated with increased breast cancer growth and survival, and treatment that decreases PPARγ expression may provide benefit in the treatment of breast cancer. Abhita Malaviya and Paul W. Sylvester Copyright © 2013 Abhita Malaviya and Paul W. Sylvester. All rights reserved. Phenotypic and Molecular Characterization of MCF10DCIS and SUM Breast Cancer Cell Lines Wed, 16 Jan 2013 08:34:09 +0000 http://www.hindawi.com/journals/ijbc/2013/872743/ We reviewed the phenotypic and molecular characteristics of MCF10DCIS.com and the SUM cell lines based on numerous studies performed over the years. The major signaling pathways that give rise to the phenotype of these cells may serve as a good resource of information when researchers in drug discovery and development use these cells to identify novel targets and biomarkers. Major signaling pathways and mutations affecting the coding sequence are also described providing important information when using these cells as a model in a variety of studies. Nandita Barnabas and Dalia Cohen Copyright © 2013 Nandita Barnabas and Dalia Cohen. All rights reserved. A Comparison of Cholesterol Uptake and Storage in Inflammatory and Noninflammatory Breast Cancer Cells Mon, 31 Dec 2012 13:51:32 +0000 http://www.hindawi.com/journals/ijbc/2012/412581/ Although there are many subtypes of breast cancer, inflammatory breast cancer (IBC) is arguably the deadliest. Research over the past decade has demonstrated that IBC is a distinct entity from other forms of breast cancer. Important risk factors that have been associated with the development of aggressive breast cancers, such as IBC, include obesity and diet, which are evident in the United States, where the overconsumption of high-fat foods continues to contribute to obesity in the nation. Here we investigate differences in cholesterol uptake and storage between IBC, non-IBC, and mammary epithelial cell lines. Our results demonstrate that compared with human mammary epithelial cells (HMECs), both IBC and non-IBC cells have increased cholesterol content. IBC cells retain intracellular cholesterol esters, free cholesterol, and triglycerides in lipid-deficient environments. In contrast, we observe in cell-type-of-origin-matched non-IBC a significant decrease in lipid content under the same lipid-deficient conditions. These data suggest that cholesterol storage may be affected by the cholesterol content of the environment where the tumor cell was isolated. Here, we suggest that breast cancer cells may migrate when they are unable to obtain cholesterol from their extracellular environments. Breonna J. Martin and Kenneth L. van Golen Copyright © 2012 Breonna J. Martin and Kenneth L. van Golen. All rights reserved. Preclinical Evaluation of Oncolytic Δγ134.5 Herpes Simplex Virus Expressing Interleukin-12 for Therapy of Breast Cancer Brain Metastases Mon, 31 Dec 2012 10:53:57 +0000 http://www.hindawi.com/journals/ijbc/2012/628697/ The metastasis of breast cancer to the brain and central nervous system (CNS) is a problem of increasing importance. As improving treatments continue to extend patient survival, the incidence of CNS metastases from breast cancer is on the rise. New treatments are needed, as current treatments are limited by deleterious side effects and are generally palliative. We have previously described an oncolytic herpes simplex virus (HSV), designated M002, which lacks both copies of the γ134.5 neurovirulence gene and carries a murine interleukin 12 (IL-12) expression cassette, and have validated its antitumor efficacy in a variety of preclinical models of primary brain tumors. However, M002 has not been yet evaluated for use against metastatic brain tumors. Here, we demonstrate the following: both human breast cancer and murine mammary carcinoma cells support viral replication and IL-12 expression from M002; M002 replicates in and destroys breast cancer cells from a variety of histological subtypes, including “triple-negative” and HER2 overexpressing; M002 improves survival in an immunocompetent model more effectively than does a non-cytokine control virus. Thus, we conclude from this proof-of-principle study that a γ134.5-deleted IL-12 expressing oncolytic HSV may be a potential new therapy for breast cancer brain metastases. James J. Cody, Pietro Scaturro, Alan B. Cantor, G. Yancey Gillespie, Jacqueline N. Parker, and James M. Markert Copyright © 2012 James J. Cody et al. All rights reserved. Effect of Berry Extracts and Bioactive Compounds on Fulvestrant (ICI 182,780) Sensitive and Resistant Cell Lines Mon, 31 Dec 2012 10:44:11 +0000 http://www.hindawi.com/journals/ijbc/2012/147828/ Fulvestrant (ICI 182,780; ICI) is approved for the treatment of advanced metastatic breast cancer that is unresponsive to other endocrine therapies. Berries are frequently consumed for their antioxidant, anti-inflammatory, and anticancer potential. In this study, we tested the efficacy of two berry extracts (Jamun-EJAE and red raspberry-RRE) and their bioactive compounds (Delphinidin-Del and Ellagic acid-EA) to inhibit cell proliferation with or without a sublethal dose of ICI in various breast cancer cell lines. ICI-sensitive (LCC1, ZR75-1, and BT474) and -resistant (LCC9, ZR75-1R) cells were subjected to treatment with berry extracts alone (0.1–100 μg/mL) or with a sub-lethal dose of ICI (<IC50 dose; 1 nM for sensitive; 1 μM for resistant cells). Extracts and Del enhanced the effect of ICI in sensitive ZR75-1 and BT474 cells primarily in an additive fashion (measured by relative index (RI)~1). In ZR75-1R cells, both EJAE and RRE synergistically enhanced the effects of ICI (15–50%; ; ). EA, in doses tested, did not have any significant effects on any of the cell lines. Finally, we found that the extracts were more effective at lower, physiologically relevant concentrations than at higher experimental doses. Denzel R. Woode, Harini S. Aiyer, Nicole Sie, Alan L. Zwart, Liya Li, Navindra P. Seeram, and Robert Clarke Copyright © 2012 Denzel R. Woode et al. All rights reserved. Large-Format Histology in Diagnosing Breast Carcinoma Thu, 27 Dec 2012 10:25:38 +0000 http://www.hindawi.com/journals/ijbc/2012/618796/ Tibor Tot, Vincenzo Eusebi, and Julio A. Ibarra Copyright © 2012 Tibor Tot et al. All rights reserved. 3D Pathology Volumetric Technique: A Method for Calculating Breast Tumour Volume from Whole-Mount Serial Section Images Sun, 23 Dec 2012 09:42:18 +0000 http://www.hindawi.com/journals/ijbc/2012/691205/ Tumour size, most commonly measured by maximum linear extent, remains a strong predictor of survival in breast cancer. Tumour volume, proportional to the number of tumour cells, may be a more accurate surrogate for size. We describe a novel “3D pathology volumetric technique” for lumpectomies and compare it with 2D measurements. Volume renderings and total tumour volume are computed from digitized whole-mount serial sections using custom software tools. Results are presented for two lumpectomy specimens selected for tumour features which may challenge accurate measurement of tumour burden with conventional, sampling-based pathology: (1) an infiltrative pattern admixed with normal breast elements; (2) a localized invasive mass separated from the in situ component by benign tissue. Spatial relationships between key features (tumour foci, close or involved margins) are clearly visualized in volume renderings. Invasive tumour burden can be underestimated using conventional pathology, compared to the volumetric technique (infiltrative pattern: 30% underestimation; localized mass: 3% underestimation for invasive tumour, 44% for in situ component). Tumour volume approximated from 2D measurements (i.e., maximum linear extent), assuming elliptical geometry, was seen to overestimate volume compared to the 3D volumetric calculation (by a factor of 7x for the infiltrative pattern; 1.5x for the localized invasive mass). G. M. Clarke, M. Murray, C. M. B. Holloway, K. Liu, J. T. Zubovits, and M. J. Yaffe Copyright © 2012 G. M. Clarke et al. All rights reserved. Antibacterial-Coated Suture in Reducing Surgical Site Infection in Breast Surgery: A Prospective Study Wed, 19 Dec 2012 11:39:17 +0000 http://www.hindawi.com/journals/ijbc/2012/819578/ Background. To reduce the incidence of microbial colonization of suture material, Triclosan- (TC-)coated suture materials have been developed. The aim of this study was to assess the incidence of suture-related complications (SRC) in breast surgery with and without the use of TC-coated sutures. Methods. We performed a study on two consecutive periods: 92 patients underwent breast surgery with conventional sutures (Group 1) and 98 with TC-coated sutures (Group 2). We performed subgroups analyses and developed a model to predict SRC in Group 1 and tested its clinical efficacy in Group 2 using a nomogram-based approach. Results. The SRC rates were 13% in Group 1 and 8% in Group 2. We found that some subgroups may benefit from TC-coated sutures. The discrimination obtained from a logistic regression model developed in Group 1 and based on multifocality, age and axillary lymphadenectomy was 0.88 (95% CI 0.77–0.95) (). There was a significant difference in Group 2 between predicted probabilities and observed percentages (). The predicted and observed proportions of complications in the high-risk group were 38% and 13%, respectively. Conclusion. This study used individual predictions of SRC and showed that using TC-coated suture may prevent SRC. This was particularly significant in high-risk patients. Enora Laas, Cécile Poilroux, Corinne Bézu, Charles Coutant, Serge Uzan, Roman Rouzier, and Elisabeth Chéreau Copyright © 2012 Enora Laas et al. All rights reserved. Effects of Auraptene on IGF-1 Stimulated Cell Cycle Progression in the Human Breast Cancer Cell Line, MCF-7 Tue, 18 Dec 2012 16:32:30 +0000 http://www.hindawi.com/journals/ijbc/2012/502092/ Auraptene is being investigated for its chemopreventive effects in many models of cancer including skin, colon, prostate, and breast. Many mechanisms of action including anti-inflammatory, antiproliferative, and antiapoptotic effects are being suggested for the chemopreventive properties of auraptene. We have previously shown in the N-methylnitrosourea induced mammary carcinogenesis model that dietary auraptene (500 ppm) significantly delayed tumor latency. The delay in time to tumor corresponded with a significant reduction in cyclin D1 protein expression in the tumors. Since cyclin D1 is a major regulator of cell cycle, we further studied the effects of auraptene on cell cycle and the genes related to cell cycle in MCF-7 cells. Here we show that auraptene significantly inhibited IGF-1 stimulated S phase of cell cycle in MCF-7 cells and significantly changed the transcription of many genes involved in cell cycle. Prasad Krishnan and Heather Kleiner-Hancock Copyright © 2012 Prasad Krishnan and Heather Kleiner-Hancock. All rights reserved. Imaging-Assisted Large-Format Breast Pathology: Program Rationale and Development in a Nonprofit Health System in the United States Mon, 17 Dec 2012 16:43:18 +0000 http://www.hindawi.com/journals/ijbc/2012/171792/ Modern breast imaging, including magnetic resonance imaging, provides an increasingly clear depiction of breast cancer extent, often with suboptimal pathologic confirmation. Pathologic findings guide management decisions, and small increments in reported tumor characteristics may rationalize significant changes in therapy and staging. Pathologic techniques to grossly examine resected breast tissue have changed little during this era of improved breast imaging and still rely primarily on the techniques of gross inspection and specimen palpation. Only limited imaging information is typically conveyed to pathologists, typically in the form of wire-localization images from breast-conserving procedures. Conventional techniques of specimen dissection and section submission destroy the three-dimensional integrity of the breast anatomy and tumor distribution. These traditional methods of breast specimen examination impose unnecessary limitations on correlation with imaging studies, measurement of cancer extent, multifocality, and margin distance. Improvements in pathologic diagnosis, reporting, and correlation of breast cancer characteristics can be achieved by integrating breast imagers into the specimen examination process and the use of large-format sections which preserve local anatomy. This paper describes the successful creation of a large-format pathology program to routinely serve all patients in a busy interdisciplinary breast center associated with a community-based nonprofit health system in the United States. F. Lee Tucker Copyright © 2012 F. Lee Tucker. All rights reserved. Improving Breast Cancer Outcomes among Women in China: Practices, Knowledge, and Attitudes Related to Breast Cancer Screening Sun, 09 Dec 2012 15:54:16 +0000 http://www.hindawi.com/journals/ijbc/2012/921607/ Background. Breast cancer is a major public health issue and the most commonly diagnosed cancer for women worldwide. Despite lower incidence rates than those living in Western countries, breast cancer incidence among Chinese women has increased dramatically in the past 20 years. Nevertheless, there is a paucity of studies reporting the attitudes toward and practices of breast cancer screening among Chinese women. Methods. This cross-sectional study examined the practices, knowledge, and attitudes toward breast cancer screening (BCS) on a convenience sample of 400 Chinese women. Results. Among study participants, 75% of the women never had a mammogram and the top three barriers reported were low priority, feeling OK, and lack of awareness/knowledge toward breast cancer screening. The results from the logistic regression model showed increased self-efficacy; having performed monthly self-exams, and having had clinical breast exams in the past two years were significant correlates while demographic variables were not correlated with screening behaviors. Conclusion. The findings provide a foundation to better understand beliefs and practices of Chinese women toward BCS and highlight the critical need for general public, health professionals, and the health care system to work collaboratively toward improving the quality of breast cancer care in this population. Tsu-Yin Wu, Yi-Lan Liu, and Scott Chung Copyright © 2012 Tsu-Yin Wu et al. All rights reserved. Adjuvant Hormonal Therapy in Postmenopausal Women with Breast Cancer: Physician’s Choices Sun, 09 Dec 2012 09:37:30 +0000 http://www.hindawi.com/journals/ijbc/2012/849592/ The choice of adjuvant hormonal therapy in postmenopausal women with hormone receptor positive breast cancer has remained a matter of controversy and debate. The variety of agents is available, with each claiming to be superior. This clinical survey was undertaken to get an impression of the physician’s first choice of therapy in an attempt to find out what questions still need to be answered in the making of “standard of care.” A web-based clinical survey was sent to the cancer physicians around the world, and 182 physicians responded to the survey. Most were medical oncologists in a tertiary care hospital. 36.3% preferred Anastrozole, 35.2% Tamoxifen, and 22.2% Letrozole as their first choice. Data support (67.8%) and safety concerns (30%) were given as the main reasons for the choice, 63.7% switched their therapy, and 24% had to switch because of side effects. 73.6% used 5 years of adjuvant hormonal therapy, 6.6% for 7 years, and 4.4% for 10 years. 61.5% follow their patients 3 times monthly, and 73.2% used laboratory and radiological assessment at each followup. Conclusion. Physicians show disagreement over the choice and duration of hormonal therapy in this patient population. Clinical trials leading to firm recommendations to set standards from which patients benefit the most are needed. Asim Jamal Shaikh, Shiyam Kumar, Sajjad Raza, Maria Mehboob, and Osama Ishtiaq Copyright © 2012 Asim Jamal Shaikh et al. All rights reserved. Identifying Patients Who May Be Candidates for a Clinical Trial of Salvage Accelerated Partial Breast Irradiation after Previous Whole Breast Irradiation Mon, 03 Dec 2012 14:47:41 +0000 http://www.hindawi.com/journals/ijbc/2012/937658/ Background and Objectives. Accelerated partial breast irradiation (APBI) has been proposed as an alternative to salvage mastectomy for patients with ipsilateral breast tumor recurrence (IBTR) after prior breast conservation. We studied factors that are associated with a more favorable local recurrence profile that could make certain patients eligible for APBI. Methods. Between 1980 and 2005, 157 Stage 0–II breast cancer patients had an IBTR treated by mastectomy. Clinical and pathological features were analyzed to identify factors associated with favorable IBTR defined as unifocal DCIS or T1 ≤ 2 cm, without skin involvement, and >2 year interval from initial treatment. Results. Median followup was 140 months and time to recurrence was 73 months. Clinical stage distribution at recurrence was DCIS in 32 pts (20%), T1 in 90 pts (57%), T2 in 14 pts (9%), T3 in 4 pts (3%), and T4 in 9 pts (6%). IBTR was classified as favorable in 71%. Clinical stage of IBTR predicted for pathologic stage –95% of patients with clinical T1 IBTR had pathologic T1 disease at salvage mastectomy . Conclusions. Clinical stage at presentation strongly correlated with pathologic stage at mastectomy. More than 70% of recurrences were favorable and may be appropriate candidates for salvage APBI trials. Linna Li, Tianyu Li, Randi J. Cohen, Penny R. Anderson, Lori J. Goldstein, Richard J. Bleicher, and Gary M. Freedman Copyright © 2012 Linna Li et al. All rights reserved. Age at Diagnosis and Breast Cancer Survival in Iran Thu, 22 Nov 2012 13:42:41 +0000 http://www.hindawi.com/journals/ijbc/2012/517976/ Background. Tumour characteristics are the most important prognostic factors in breast cancer. Patient-related factors such as young age at diagnosis, obesity, and smoking behaviour may also modify disease outcome. Due to the absence of a unique definition for “young age breast cancer” and the resulting variation in disease management, findings on the association between young age and prognosis of breast cancer are controversial. Methods. This study included 1500 patients with a primary diagnosis of breast cancer in six Iranian hospitals from 5 provinces. We modelled the relative excess risk (RER) of breast cancer death to age at diagnosis and tumour characteristics. Results. Excess risks of death were observed for stage IV disease and poorly differentiated tumours: RER of 4.3 (95% CI: 1.05–17.65) and 3.4 (95% CI: 1.17–9.87), respectively. “Older” patients, particularly those aged 50 and over, presented more often with advanced and poorly differentiated tumours (). After adjustment for stage, histological grade, Her-2 expression, estrogen and progesterone receptors, and place of residency, breast cancer mortality was not significantly different across age groups. Conclusion. We conclude that there is no prognostic effect of age at diagnosis of breast cancer among breast cancer patients treated at cancer centres in different parts of Iran; young and relatively old women have similar risks of dying from breast cancer. Fatemeh Asadzadeh Vostakolaei, Mireille J. M. Broeders, Nematollah Rostami, Jos A. A. M. van Dijck, Ton Feuth, Lambertus A. L. M. Kiemeney, and André L. M. Verbeek Copyright © 2012 Fatemeh Asadzadeh Vostakolaei et al. All rights reserved. The Value of Large Sections in Surgical Pathology Wed, 21 Nov 2012 14:31:33 +0000 http://www.hindawi.com/journals/ijbc/2012/785947/ Large format sections (LS) first have been introduced in breast pathology more than a century ago. Since then, they constituted for longtime a research tool to better understand breast microanatomy and the relationship between radiological images and pathological features. Similarly LS have been used to study neoplastic, inflammatory, and degenerative diseases affecting various organs, as brain, lung, gastrointentinal tract, bone, urinary tract, prostate, and placenta. Currently LS are mostly applied to diagnostic routine to better stage tumours such as prostate and breast carcinomas or to correlate radiologic imaging to gross specimens. The purpose of the present paper is to review the historical background and the basis of the applications of LS in surgical pathology, with special emphasis on breast tumours. Maria P. Foschini, Chiara Baldovini, Yuko Ishikawa, and Vincenzo Eusebi Copyright © 2012 Maria P. Foschini et al. All rights reserved. The Role of Large-Format Histopathology in Assessing Subgross Morphological Prognostic Parameters: A Single Institution Report of 1000 Consecutive Breast Cancer Cases Sun, 21 Oct 2012 15:15:25 +0000 http://www.hindawi.com/journals/ijbc/2012/395415/ Breast cancer subgross morphological parameters (disease extent, lesion distribution, and tumor size) provide significant prognostic information and guide therapeutic decisions. Modern multimodality radiological imaging can determine these parameters with increasing accuracy in most patients. Large-format histopathology preserves the spatial relationship of the tumor components and their relationship to the resection margins and has clear advantages over traditional routine pathology techniques. We report a series of 1000 consecutive breast cancer cases worked up with large-format histology with detailed radiological-pathological correlation. We confirmed that breast carcinomas often exhibit complex subgross morphology in both early and advanced stages. Half of the cases were extensive tumors and occupied a tissue space ≥40 mm in its largest dimension. Because both in situ and invasive tumor components may exhibit unifocal, multifocal, and diffuse lesion distribution, 17 different breast cancer growth patterns can be observed. Combining in situ and invasive tumor components, most cases fall into three aggregate growth patterns: unifocal (36%), multifocal (35%), and diffuse (28%). Large-format histology categories of tumor size and disease extent were concordant with radiological measurements in approximately 80% of the cases. Noncalcified, low-grade in situ foci, and invasive tumor foci <5 mm were the most frequent causes of discrepant findings. Tibor Tot Copyright © 2012 Tibor Tot. All rights reserved. The Value of Combined Large Format Histopathology Technique to Assess the Surgically Removed Breast Tissue following Neoadjuvant Chemotherapy: A Single Institution Study of 40 Cases Thu, 18 Oct 2012 11:29:44 +0000 http://www.hindawi.com/journals/ijbc/2012/361707/ Historically, neoadjuvant chemotherapy has been used to treat patients with advanced breast disease in an attempt to convert them into candidates for breast conservation surgery. The ultimate goal of histopathologic examination of the specimens removed after neoadjuvant chemotherapy is the identification of either residual disease or positive identification of the tumor bed. We report a series of 40 patients treated with neoadjuvant chemotherapy and evaluation of the surgical specimens by a combination of standard histopathology and the use of large format histopathology techniques. Julio A. Ibarra Copyright © 2012 Julio A. Ibarra. All rights reserved. Comparison of the Subgross Distribution of the Lesions in Invasive Ductal and Lobular Carcinomas of the Breast: A Large-Format Histology Study Sun, 14 Oct 2012 14:19:41 +0000 http://www.hindawi.com/journals/ijbc/2012/436141/ To compare the lesion distribution and the extent of the disease in ductal and lobular carcinomas of the breast, we studied 586 ductal and 133 lobular consecutive cancers. All cases were documented on large-format histology slides. The invasive component of ductal carcinomas was unifocal in 63.3% (371/586), multifocal in 35.5% (208/586), and diffuse in 1.2% (7/586) of the cases. The corresponding figures in the lobular group were 27.8% (37/133), 45.9% (61/586), and 26.3% (35/133), respectively. When the distribution of the in situ and invasive component in the same tumors was combined to give an aggregate pattern, the ductal carcinomas were unifocal in 41.6% (244/586), multifocal in 31.6% (185/586), and diffuse in 26.8% (157/586) of the cases. The corresponding figures in the lobular category were 15.0% (20/133), 54.2% (72/133), and 30.8% (41/133), respectively. Ductal cancers were extensive in 45.7% (268/586), lobular in 65.4% (87/133) of the cases. All these differences were statistically highly significant (). While the histological tumor type itself (ductal versus lobular) did not influence the lymph node status, multifocal and diffuse distribution of the lesions were associated with significantly increased risk of lymph node metastases in both ductal and lobular cancers. Syster Hofmeyer, Gyula Pekár, Mária Gere, Miklós Tarján, Dan Hellberg, and Tibor Tot Copyright © 2012 Syster Hofmeyer et al. All rights reserved. Evaluating Surveillance Breast Imaging and Biopsy in Older Breast Cancer Survivors Sun, 14 Oct 2012 10:33:29 +0000 http://www.hindawi.com/journals/ijbc/2012/347646/ Background. Patterns of surveillance among breast cancer survivors are not well characterized and lack evidence-based practice guidelines, particularly for imaging modalities other than mammography. We characterized breast imaging and related biopsy longitudinally among breast cancer survivors in relation to women’s characteristics. Methods. Using data from a state-wide (New Hampshire) breast cancer screening registry linked to Medicare claims, we examined use of mammography, ultrasound (US), magnetic resonance imaging (MRI), and biopsy among breast cancer survivors. We used generalized estimating equations (GEE) to model associations of breast surveillance with women’s characteristics. Results. The proportion of women with mammography was high over the follow-up period (81.5% at 78 months), but use of US or MRI was much lower (8.0%—first follow-up window, 4.7% by 78 months). Biopsy use was consistent throughout surveillance periods (7.4%–9.4%). Surveillance was lower among older women and for those with a higher stage of diagnosis. Primary therapy was significantly associated with greater likelihood of breast surveillance. Conclusions. Breast cancer surveillance patterns for mammography, US, MRI, and related biopsy seem to be associated with age, stage, and treatment, but need a larger evidence-base for clinical recommendations. Tracy Onega, Julie Weiss, Roberta diFlorio, Todd MacKenzie, Martha Goodrich, and Steven Poplack Copyright © 2012 Tracy Onega et al. All rights reserved. Metastatic Breast Cancer to the Gastrointestinal Tract: Report of Five Cases and Review of the Literature Thu, 04 Oct 2012 15:34:23 +0000 http://www.hindawi.com/journals/ijbc/2012/439023/ Luminal gastrointestinal (GI) metastases from breast cancer are rare, reports are fragmentary and poor. The purposes of this study are to assess the gastrointestinal involvement from breast cancer in a retrospective study at a single institution and reviewing the related literature. Between January 2007 and December 2011 a total of 980 patients with breast cancer were treated at our institution, patients’ records and report database were analysed. Institutional Review Board approval was obtained for this study. A search of the literature using PubMed, CancerLit, Embase, was performed. Selected for the present review were papers published in English before June 2012. Five of 980 patients (0.5%) showed gastrointestinal metastases from breast cancer, 3 patients had gastric involvement, 1 jejunum, and 1 rectum. Reviewing the literature, 206 patients affected by gastrointestinal metastasis from breast cancer were identified: the most frequent site of metastasis was the stomach (60%). The majority of the patients underwent chemotherapy and endocrine therapy, someone surgery and radiotherapy. GI metastases from breast cancer are rare, but possible, and a very late recurrence can also occur. Cyto-histological diagnosis is mandatory, to differentiate GI metastases from breast cancer to other diseases and to allow an adequate treatment. Massimo Ambroggi, Elisa Maria Stroppa, Patrizia Mordenti, Claudia Biasini, Adriano Zangrandi, Emanuele Michieletti, Elena Belloni, and Luigi Cavanna Copyright © 2012 Massimo Ambroggi et al. All rights reserved. Radiation Therapy for Locally Recurrent Breast Cancer Wed, 03 Oct 2012 18:55:01 +0000 http://www.hindawi.com/journals/ijbc/2012/571946/ Approximately one-third of all breast cancer patients experience local recurrence of their tumor after initial treatment. As initial treatment often employs the use of radiation therapy (RT), the standard of care for local breast cancer recurrence after initial breast conserving therapy has traditionally been surgical intervention with mastectomy. However, recent attempts to preserve the intact breast after recurrence with local excision have revealed a potential need for RT in addition to repeat breast conserving surgery as rates of local failure with resection alone remain high. Additionally, local recurrence following initial mastectomy and chest wall RT can be treated with reirradiation to increase local control. Repeating RT, however, in a previously irradiated area, is a complex treatment strategy, as the clinician must carefully balance maximizing treatment effectiveness while minimizing treatment-related toxicity. As a result, physicians have been hesitant to treat recurrent disease with repeat RT with limited data. Results from the current literature are promising and current clinical trials are underway to explore reirradiation modalities which will provide additional information on treatment-related toxicity and outcomes. This paper will review the current literature on repeat radiation therapy for locally recurrent breast cancer. Joshua Siglin, Colin E. Champ, Yelena Vakhnenko, Pramila R. Anne, and Nicole L. Simone Copyright © 2012 Joshua Siglin et al. All rights reserved. Incidence of Occult Carcinoma and High-Risk Lesions in Mammaplasty Specimens Wed, 03 Oct 2012 09:20:15 +0000 http://www.hindawi.com/journals/ijbc/2012/145630/ Objectives. To determine the incidence and type of premalignant or malignant changes in mammaplasty specimens and to determine the incidence of these changes according to age distribution. Methods. Retrospective database review of patients who underwent a reduction mammaplasty between 1999 and 2009 was performed from pathology records at a single institution. Results. 700 patients were identified. Of the 644 patients who had bilateral reductions, 25 (4%) had significant pathologic findings. The likelihood of finding premalignant changes or cancer increased with advancing patient age (0.8 percent for patients <40 years old and 10 percent for patients >60 years old). Of the 56 patients who underwent unilateral mammaplasty, 12 patients (21%) had significant pathologic findings. The incidence of finding premalignant changes or cancer in this population also increased with advancing patient age (0 for patients <40 years old to 25 percent for patients >60 years old). Conclusions. When a unilateral mammaplasty is performed to match a breast reconstructed after cancer surgery, the likelihood of identifying premalignant changes or cancer increases more than fourfold. Therefore, one should consider additional radiologic imaging in the preoperative workup of patients with a history of carcinoma prior to undergoing unilateral mammaplasty. Beth C. Freedman, Sharon M. Rosenbaum Smith, Alison Estabrook, Jasminka Balderacchi, and Paul I. Tartter Copyright © 2012 Beth C. Freedman et al. All rights reserved. The Ongoing Revolution in Breast Imaging Calls for a Similar Revolution in Breast Pathology Sun, 30 Sep 2012 09:57:54 +0000 http://www.hindawi.com/journals/ijbc/2012/489345/ Communication between pathologists and radiologists suffers from a lack of common ground: the pathologists examine cells in ultrathin tissue slices having the area of a postage stamp, while the radiologists examine images of an entire organ, but without seeing the cellular details. The current practice of examining breast cancer specimens is analogous to scrutinizing individual pieces of a jigsaw puzzle, without examining all of them and never putting all the pieces into place. The routine use of large section histopathology technique could help to alleviate much of this problem, especially with nonpalpable, screen-detected breast cancers. The study of three-dimensional (3D) images of subgross, thick section pathology specimens by both radiologists and pathologists could greatly assist in the communication of findings. L. Tabár, P. B. Dean, N. Lindhe, and M. Ingvarsson Copyright © 2012 L. Tabár et al. All rights reserved. Weight Gain, Metabolic Syndrome, and Breast Cancer Recurrence: Are Dietary Recommendations Supported by the Data? Mon, 24 Sep 2012 09:39:42 +0000 http://www.hindawi.com/journals/ijbc/2012/506868/ Metabolic syndrome, which can include weight gain and central obesity, elevated serum insulin and glucose, and insulin resistance, has been strongly associated with breast cancer recurrence and worse outcomes after treatment. Epidemiologic and prospective data do not show conclusive evidence as to which dietary factors may be responsible for these results. Current strategies employ low-fat diets which emphasize supplementing calories with increased intake of fruit, grain, and vegetable carbohydrate sources. Although results thus far have been inconclusive, recent randomized trials employing markedly different dietary strategies in noncancer patients may hold the key to reducing multiple risk factors in metabolic syndrome simultaneously which may prove to increase the long-term outcome of breast cancer patients and decrease recurrences. Since weight gain after breast cancer treatment confers a poor prognosis and may increase recurrence rates, large-scale randomized trials are needed to evaluate appropriate dietary interventions for our breast cancer patients. Colin E. Champ, Jeff S. Volek, Joshua Siglin, Lianjin Jin, and Nicole L. Simone Copyright © 2012 Colin E. Champ et al. All rights reserved. Large Format Histology May Aid in the Detection of Unsuspected Pathologic Findings of Potential Clinical Significance: A Prospective Multiyear Single Institution Study Thu, 20 Sep 2012 14:30:38 +0000 http://www.hindawi.com/journals/ijbc/2012/532547/ Large format histology offers several unique advantages over traditional tissue processing. Over 12 years of experience with this technique provide insight into its limitations and benefits. We conducted a prospective multiyear analysis of the potential advantages of large format histology. 656 cases were examined prospectively over an eight-year period. In 172 cases the sign-out pathologist documented an unexpected finding of potential clinical significance as present only on the large format sections and not present on the accompanying standard format slides. These include closer margins, a change in size or extent of disease, and previously undocumented invasive and/or in situ carcinoma. Based on over a decade of experience and eight years of data, our results demonstrate that a quarter of cases had an unexpected finding of potential clinical significance that may not have been fully realized without the use of the large format technique. Matthew R. Foster, Lauren Harris, and Karl W. Biesemier Copyright © 2012 Matthew R. Foster et al. All rights reserved.