International Journal of Breast Cancer The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Beyond DNA: An Integrated and Functional Approach for Classifying Germline Variants in Breast Cancer Genes Sun, 16 Oct 2016 13:52:38 +0000 Genetic testing for hereditary breast cancer is an integral part of individualized care in the new era of precision medicine. The accuracy of an assay is reliant on not only the technology and bioinformatics analysis utilized but also the experience and infrastructure required to correctly classify genetic variants as disease-causing. Interpreting the clinical significance of germline variants identified by hereditary cancer testing is complex and has a significant impact on the management of patients who are at increased cancer risk. In this review we give an overview of our clinical laboratory’s integrated approach to variant assessment. We discuss some of the nuances that should be considered in the assessment of genomic variants. In addition, we highlight lines of evidence such as functional assays and structural analysis that can be useful in the assessment of rare and complex variants. T. Pesaran, R. Karam, R. Huether, S. Li, S. Farber-Katz, A. Chamberlin, H. Chong, H. LaDuca, and A. Elliott Copyright © 2016 T. Pesaran et al. All rights reserved. Surgical Site Infections in Breast Surgery: The Use of Preoperative Antibiotics for Elective, Nonreconstructive Procedures Wed, 05 Oct 2016 08:51:23 +0000 Background. Antibiotic prophylaxis for surgical site infections (SSIs) for breast surgery is widespread, but the benefit in clean surgical cases is not well defined. Methods. A retrospective analysis of 855 patients undergoing elective, nonreconstructive breast operations was performed, with 401 patients receiving no antibiotics and 454 patients receiving a single dose of preoperative antibiotic. Results. Administration of a preoperative antibiotic did not decrease the SSI rate. In this community-based study, antibiotic use practices varied considerably by surgeon. In univariate analyses, SSI rates appeared to increase with prophylactic antibiotic use (12% SSI with antibiotics versus 4% without, ), likely because the use of underdosed antibiotics was associated with higher rates of SSI (13.2% SSI with cefazolin 1 gram, , and 15.4% SSI with clindamycin 300 mg or less, ). Methicillin-resistant Staphylococcus aureus was the most common isolate from SSI cultures, 31.8% (7 of 22). In multivariable analyses, increased risk of SSI was associated with BMI > 25 kg/m2 (OR: 1.08, 95% CI: 1.04–1.11, ). Conclusion. The administration of a single dose of preoperative antibiotic did not decrease the rate of SSI in this large series of patients undergoing clean breast operations. BMI >25 kg/m2 and the use of an inadequate dose of antibiotics for prophylaxis may increase risk of SSI. Christopher B. Crawford, James A. Clay, Anna S. Seydel, and Jessica A. Wernberg Copyright © 2016 Christopher B. Crawford et al. All rights reserved. Modified Lower Pole Autologous Dermal Sling for Implant Reconstruction in Women Undergoing Immediate Breast Reconstruction after Mastectomy Wed, 05 Oct 2016 07:59:48 +0000 Background. Autologous dermal sling with wise pattern skin reducing mastectomy allows one-stage implant reconstruction in women with large and ptotic breasts needing mastectomy for cancer or risk reduction. However, this technique is not suitable for women who lack ptosis and also carries risk of T-junction breakdown. Method. We have performed one-stage nipple sparing mastectomies with implant reconstruction in 5 women (8 breasts) by modifying the autologous dermal sling approach. All these women had small to moderate breasts with no ptosis or pseudoptosis. Results. Three women had bilateral procedures, two underwent bilateral mastectomies simultaneously, and one had contralateral risk reduction surgery a year after the cancer side operation. All women underwent direct to implant reconstruction with implant volumes varying from 320 to 375 cc. There were no implant losses and only one required further surgery to excise the nipple for positive nipple shaves. A low complication rate was encountered in this series with good aesthetic outcome. Conclusion. The modified lower pole dermal sling allows direct to implant reconstruction in selected women with small to moderate sized breasts with minimal ptosis. The approach is safe and cost-effective and results in more natural reconstruction with preservation of nipple. Pankaj G. Roy Copyright © 2016 Pankaj G. Roy. All rights reserved. Synthesis, Structural Characterization, and Preclinical Efficacy of a Novel Paclitaxel-Loaded Alginate Nanoparticle for Breast Cancer Treatment Tue, 30 Aug 2016 13:05:50 +0000 Purpose. The antitumor activity of a novel alginate (ALG) polymer-based particle that contained paclitaxel (PTX) was evaluated using human primary breast cancer cells. Materials and Methods. PTX was combined with ALG in a nanoparticle as a drug delivery system designed to improve breast cancer tumor cell killing. PTX-ALG nanoparticles were first synthesized by nanoemulsification polymer cross-linking methods that improved the aqueous solubility. Structural and biophysical properties of the PTX-ALG nanoparticles were then determined by transmission electron microscopy (TEM) and high performance liquid chromatography (HPLC) fluorescence. The effect on cell cycle progression and apoptosis was determined using flow cytometry. Results. PTX-ALG nanoparticles were prepared and characterized by ultraviolet (UV)/visible (VIS), HPLC fluorescence, and TEM. PTX-ALG nanoparticles demonstrated increased hydrophobicity and solubility over PTX alone. Synthetically engineered PTX-ALG nanoparticles promoted cell-cycle arrest, reduced viability, and induced apoptosis in human primary patient breast cancer cells superior to those of PTX alone. Conclusion. Taken together, our results demonstrate that PTX-ALG nanoparticles represent an innovative, nanoscale delivery system for the administration of anticancer agents that may avoid the adverse toxicities with enhanced antitumor effects to improve the treatment of breast cancer patients. Ahmed A. Markeb, Nagwa A. El-Maali, Douaa M. Sayed, Amany Osama, Mohamed A. Y. Abdel-Malek, Amen H. Zaki, Mostafa E. A. Elwanis, and James J. Driscoll Copyright © 2016 Ahmed A. Markeb et al. All rights reserved. Pattern of Breast Cancer Distribution in Ghana: A Survey to Enhance Early Detection, Diagnosis, and Treatment Thu, 18 Aug 2016 12:12:28 +0000 Background. Nearly 70% of women diagnosed with breast cancer in Ghana are in advanced stages of the disease due especially to low awareness, resulting in limited treatment success and high death rate. With limited epidemiological studies on breast cancer in Ghana, the aim of this study is to assess and understand the pattern of breast cancer distribution for enhancing early detection and treatment. Methods. We randomly selected and screened 3000 women for clinical palpable breast lumps and used univariate and bivariate analysis for description and exploration of variables, respectively, in relation to incidence of breast cancer. Results. We diagnosed 23 (0.76%) breast cancer cases out of 194 (6.46%) participants with clinically palpable breast lumps. Seventeen out of these 23 (0.56%) were premenopausal (<46.6 years) with 7 (0.23%) being below 35 years. With an overall breast cancer incidence of 0.76% in this study, our observation that about 30% of these cancer cases were below 35 years may indicate a relative possible shift of cancer burden to women in their early thirties in Ghana, compared to Western countries. Conclusion. These results suggest an age adjustment for breast cancer screening to early twenties for Ghanaian women and the need for a nationwide breast cancer screening to understand completely the pattern of breast cancer distribution in Ghana. Frank Naku Ghartey Jnr, Akwasi Anyanful, Sebastian Eliason, Saanid Mohammed Adamu, and Samuel Debrah Copyright © 2016 Frank Naku Ghartey Jnr et al. All rights reserved. Advanced Imaging and Receipt of Guideline Concordant Care in Women with Early Stage Breast Cancer Mon, 25 Jul 2016 08:34:20 +0000 Objective. It is unknown whether advanced imaging (AI) is associated with higher quality breast cancer (BC) care. Materials and Methods. Claims and Surveillance Epidemiology and End Results data were linked for women diagnosed with incident stage I-III BC between 2002 and 2008 in western Washington State. We examined receipt of preoperative breast magnetic resonance imaging (MRI) or AI (defined as computed tomography [CT]/positron emission tomography [PET]/PET/CT) versus mammogram and/or ultrasound (M-US) alone and receipt of guideline concordant care (GCC) using multivariable logistic regression. Results. Of 5247 women, 67% received M-US, 23% MRI, 8% CT, and 3% PET/PET-CT. In 2002, 5% received MRI and 5% AI compared to 45% and 12%, respectively, in 2008. 79% received GCC, but GCC declined over time and was associated with younger age, urban residence, less comorbidity, shorter time from diagnosis to surgery, and earlier year of diagnosis. Breast MRI was associated with GCC for lumpectomy plus radiation therapy (RT) (OR 1.55, 95% CI 1.08–2.26, and ) and AI was associated with GCC for adjuvant chemotherapy for estrogen-receptor positive (ER+) BC (OR 1.74, 95% CI 1.17–2.59, and ). Conclusion. GCC was associated with prior receipt of breast MRI and AI for lumpectomy plus RT and adjuvant chemotherapy for ER+ BC, respectively. Elizabeth Trice Loggers, Diana S. M. Buist, Laura S. Gold, Steven Zeliadt, Rachel Hunter Merrill, Ruth Etzioni, Scott D. Ramsey, Sean D. Sullivan, and Larry Kessler Copyright © 2016 Elizabeth Trice Loggers et al. All rights reserved. Coverage of Axillary Lymph Nodes with Tangential Breast Irradiation in Korea: A Multi-Institutional Comparison Study Thu, 21 Jul 2016 12:56:00 +0000 Introduction. To evaluate the dose distribution and coverage of axilla using only tangential field for whole breast radiotherapy (RT) at three institutions in Korea. Methods. We used computed tomography (CT) images of nine consecutive 1-2 sentinel lymph node-positive patients who underwent breast conserving surgery and whole breast RT without axillary lymph node (ALN) dissection for clinical T1-2N0 breast cancer. The CT data were transferred to three radiation oncologists in 3 institutions and each radiation oncologist created treatment plans for all nine patients; a total of 27 treatment plans were analyzed. Results. The mean doses delivered to levels I and II were 31.9 Gy (9.9–47.9 Gy) and 22.3 Gy (3.4–47.7 Gy). Ninety-five percent of levels I and II received a mean dose of 11.8 Gy (0.4–43.0 Gy) and 3.0 Gy (0.3–40.0 Gy). The percent volumes of levels I and II covered by 95% of the prescribed dose were only 29.0% (0.2–74.1%) and 11.5% (0.0–70.1%). The dose distribution and coverage of axilla were significantly different between three institutions (). Conclusion. There were discrepancies in ALN coverage between three institutions. A standardization of whole breast RT technique through further research with a nationwide scale is needed. Jinhong Jung, Moonkyoo Kong, Su Ssan Kim, and Won Sup Yoon Copyright © 2016 Jinhong Jung et al. All rights reserved. Promoter Methylation Status of Breast Cancer Susceptibility Gene 1 and 17 Beta Hydroxysteroid Dehydrogenase Type 1 Gene in Sporadic Breast Cancer Patients Mon, 20 Jun 2016 14:18:52 +0000 Epigenetic modifications are involved in breast carcinogenesis. Identifying genes that are epigenetically silenced via methylation could select target patients for diagnostic as well as therapeutic potential. We assessed promoter methylation of breast cancer susceptibility gene 1 (BRCA1) and 17 Beta Hydroxysteroid Dehydrogenase Type 1 (17βHSD-1) in normal and cancer breast tissues of forty sporadic breast cancer (BC) cases using restriction enzyme based methylation-specific PCR (REMS-PCR). In cancerous tissues, BRCA1 and 17βHSD-1 were methylated in 42.5% and 97.5%, respectively, while normal tissues had 35% and 95% methylation, respectively. BRCA1 methylation in normal tissues was 12.2-fold more likely to associate with methylation in cancer tissues (). It correlated significantly with increased age at menopause, mitosis, the negative status of Her2, and the molecular subtype “luminal A” (, , , and , resp.). Methylation of BRCA1 and 17βHSD-1 related to luminal A subtype of breast cancer. Since a small proportion of normal breast epithelial cells had BRCA1 methylation, our preliminary findings suggest that methylation of BRCA1 may be involved in breast tumors initiation and progression; therefore, it could be used as a biomarker for the early detection of sporadic breast cancer. Methylation of 17βHSD-1 in normal and cancer tissue could save patients the long term use of adjuvant antiestrogen therapies. Marwa M. Hosny, Nagwan A. Sabek, Taghrid B. El-Abaseri, Fathalla M. Hassan, and Sherif H. Farrag Copyright © 2016 Marwa M. Hosny et al. All rights reserved. Breast Cancer in Africa: Limitations and Opportunities for Application of Genomic Medicine Thu, 16 Jun 2016 10:20:42 +0000 As genomic medicine gains clinical applicability across a spectrum of diseases, insufficient application in low-income settings stands to increase health disparity. Breast cancer screening, diagnosis, and treatment have benefited greatly from genomic medicine in high-income settings. As breast cancer is a leading cause of both cancer incidence and mortality in Africa, attention and resources must be applied to research and clinical initiatives to integrate genomic medicine into breast cancer care. In terms of research, there is a paucity of investigations into genetic determinants of breast cancer specific to African populations, despite consensus in the literature that predisposition and susceptibility genes vary between populations. Therefore, we need targeted strengthening of existing research efforts and support of new initiatives. Results will improve clinical care through screening and diagnosis with genetic testing specific to breast cancer in African populations. Clinically, genomic medicine can provide information capable of improving resource allocation to the population which most stands to benefit from increased screening or tailored treatment modalities. In situations where mammography or chemotherapy options are limited, this information will allow for the greatest impact. Implementation of genomic medicine will face numerous systemic barriers but is essential to improve breast cancer outcomes and survival. Allison Silverstein, Rachita Sood, and Ainhoa Costas-Chavarri Copyright © 2016 Allison Silverstein et al. All rights reserved. Associations between Reoperations and Psychological Factors after Contralateral Risk-Reducing Mastectomy: A Two-Year Follow-Up Study Thu, 26 May 2016 15:12:52 +0000 Introduction. The aim of the study was to investigate associations between reoperations after contralateral risk-reducing mastectomies (CRRM) and emotional problems, body image, sexuality, and health related quality of life (HRQoL) in women with breast cancer and hereditary high risk. Patients and Methods. Patients scheduled for CRRM with breast reconstruction between 1998 and 2010 completed questionnaires, comprised of SF-36, the Hospital Anxiety and Depression Scale, the Body Image Scale, and the Sexual Activity Questionnaire, preoperatively and two years after CRRM. Data on reoperations was collected from medical charts. Results. A total of 80 women participated, with a response rate of 61 (76%) preoperatively and 57 (71%) at the two-year follow-up. At the two-year assessment, 44 (55%) patients had undergone ≥1 reoperation (reoperation group), whereas 36 (45%) had not (no reoperation group). No statistically significant differences between the groups were found for HRQoL, sexuality, anxiety, or depression. A higher proportion of patients in the “reoperation group” reported being dissatisfied with their bodies (81% versus 48%, ). Conclusion. The results suggest associations between reoperation following CRRM with breast reconstruction and body image problems. Special attention should be paid to body image problems among women who are subject to reoperations after CRRM. Dmytro Unukovych, Marie Wickman, Kerstin Sandelin, Brita Arver, Hemming Johansson, and Yvonne Brandberg Copyright © 2016 Dmytro Unukovych et al. All rights reserved. Unmet Supportive Care Needs among Breast Cancer Survivors of Community-Based Support Group in Kuching, Sarawak Wed, 27 Apr 2016 09:58:24 +0000 Background. Recognizing the needs of cancer survivors is one of the important aspects in healthcare delivery. This study aimed to determine the prevalence of unmet supportive care needs and its associated factors among the breast cancer survivors of community-based support group in Kuching, Sarawak. Materials and Methods. This was a cross-sectional study using Supportive Care Needs Survey (SCNS-SF34). All the members of community-based breast cancer support groups in Kuching were invited. A total of 101 respondents were face-to-face interviewed after the consent was obtained. Data was entered and analyzed using SPSS version 20. Results. The respondents endorsed health system and information domain with the highest mean score (2.48; 95% CI: 2.32–2.64). Top 10 items with “moderate to high” level unmet needs had a prevalence of 14.9% to 34.7% of respondents indicating need. Significantly higher level of unmet needs was associated with survivors who were younger (less than 60 years old), had higher education attainment, were unemployed, had survival duration of up to 5 years, and were undergoing active treatment. Conclusion. Systematic delivery of health information which is targeted, culturally sensitive, and linguistically appropriate for addressing younger age, education level, employment status, length of survivorship, and treatment stage should be considered not only at hospital-based setting but also at the community-based support groups. Emmanuel Joseph Fong and Whye Lian Cheah Copyright © 2016 Emmanuel Joseph Fong and Whye Lian Cheah. All rights reserved. The Role of Forkhead Box Protein M1 in Breast Cancer Progression and Resistance to Therapy Sun, 31 Jan 2016 11:38:31 +0000 The Forkhead box M1 (FOXM1) is a transcription factor that has been implicated in normal cell growth and proliferation through control of cell cycle transition and mitotic spindle. It is implicated in carcinogenesis of various malignancies where it is activated by either amplification, increased stability, enhanced transcription, dysfunction of regulatory pathways, or activation of PI3K/AKT, epidermal growth factor receptor, Raf/MEK/MAPK, and Hedgehog pathways. This review describes the role of FOXM1 in breast cancer. This includes how FOXM1 impacts on different subtypes of breast cancer, that is, luminal/estrogen receptor positive (ER+), expressing human epidermal growth factor receptor 2 (HER2), basal-like breast cancer (BBC), and triple negative breast cancer (TNBC). The review also describes different tested preclinical therapeutic strategies targeting FOXM1. Developing clinically applicable therapies that specifically inhibit FOXM1 activity is a logical next step in biomarker-driven approaches against breast cancer but will not be without its challenges due to the unique properties of this transcription factor. Raya Saba, Alhareth Alsayed, James P. Zacny, and Arkadiusz Z. Dudek Copyright © 2016 Raya Saba et al. All rights reserved. Quality of Life and Volume Reduction in Women with Secondary Lymphoedema Related to Breast Cancer Wed, 30 Dec 2015 06:28:09 +0000 Purpose. To assess the quality of life (QOL) as a predictor of volume reduction in women undergoing complex physical therapy (CPT) for lymphoedema following breast cancer. Methods. Clinical trial in 57 women undergoing CPT. Results. At baseline, in measuring quality of life for the EORTC QLQ-C30 questionnaire subscale of functionality, the worst scores for emotional function (55 points) and better social function (89 points) were observed. The symptom scales showed the worst pain averaged (66 points). The overall quality of life showed a low score (40 points). In the BR 23 module, low scores were observed in the field of future perspective (47 points). After treatment of lymphoedema, absolute reduction of excess volume between the upper limbs of 282 mL was observed, representing a reduction of 15%. No association was observed between the domains of quality of life and response to treatment of lymphoedema. Conclusion. This study included 57 women with advanced and chronic lymphoedema in early treatment with CPT and low scores for quality of life. The lymphoedema therapeutic response was not influenced by the QOL at the beginning of treatment. Marcus Lanza, Anke Bergmann, Maria Giseli da Costa Leite Ferreira, Suzana Sales de Aguiar, Ricardo de Almeida Dias, Karen de Souza Abrahão, Ester M. Paltrinieri, Ruy G. Martínez Allende, and Mauro Figueiredo Carvalho de Andrade Copyright © 2015 Marcus Lanza et al. All rights reserved. Green Tea Catechin, EGCG, Suppresses PCB 102-Induced Proliferation in Estrogen-Sensitive Breast Cancer Cells Sun, 13 Dec 2015 11:27:52 +0000 The persistence of polychlorinated biphenyls (PCBs) in the environment is of considerable concern since they accumulate in human breast tissue and may stimulate the growth of estrogen-sensitive tumors. Studies have shown that EGCG from green tea can modify estrogenic activity and thus may act as a cancer chemopreventive agent. In the present study, we evaluated the individual and combined effects of PCB 102 and EGCG on cell proliferation using an estrogen-sensitive breast cancer cell line MCF-7/BOS. PCB 102 (1–10 μM) increased cell proliferation in a dose-dependent manner. Furthermore, the proliferative effects of PCB 102 were mediated by ERα and could be abrogated by the selective ERα antagonist MPP. EGCG (10–50 μM) caused a dose-dependent inhibition of PCB 102-induced cell proliferation, with nearly complete inhibition at 25 μM EGCG. The antiproliferative action of EGCG was mediated by ERβ and could be blocked by the ERβ-specific inhibitor PHTPP. In conclusion, EGCG suppressed the proliferation-stimulating activity of the environmental estrogen PCB 102 which may be helpful in the chemoprevention of breast cancer. Kimberly Mantzke Baker and Angela C. Bauer Copyright © 2015 Kimberly Mantzke Baker and Angela C. Bauer. All rights reserved. A Nationwide Cross-Sectional Survey of UK Breast Surgeons’ Views on the Management of Ductal Carcinoma In Situ Mon, 30 Nov 2015 11:26:30 +0000 Background. There is wide variation in the management of Ductal Carcinoma In Situ (DCIS) nationwide. We aimed to investigate whether the attitudes of surgeons towards different aspects of DCIS treatment varied by seniority of surgeon or by geographical region within the UK. Materials and Methods. A nationwide online survey targeted at UK breast surgeons was undertaken. The anonymous survey contained questions regarding demographics of respondents and specific questions regarding DCIS management that were identified as areas of uncertainty during a systematic search of the literature. Results. Responses from 80 surgeons were obtained. Approximately 57% were male and the majority were consultant or specialist registrar. Approximately 63% of participants were based in district general hospitals with all training deaneries represented. Surgeons’ views on the prognosis and management of DCIS varied geographically across the UK and terminology for DCIS varied with surgeon seniority. Surgeons’ views particularly differed from national guidance on indications for SLNB, tamoxifen, and follow-up practice. Conclusion. Our survey reaffirms that, irrespective of national guidelines and attempts at uniformity, there continues to be a wide variety of views amongst breast surgeons regarding the ideal management of DCIS. However, by quantifying this variation, it may be possible to take it into account when examining long-term trends in nationwide treatment data. Gurdeep S. Mannu, Joao H. Bettencourt-Silva, Farid Ahmed, and Giles Cunnick Copyright © 2015 Gurdeep S. Mannu et al. All rights reserved. Assessment of Pathological Response of Breast Carcinoma in Modified Radical Mastectomy Specimens after Neoadjuvant Chemotherapy Mon, 30 Nov 2015 08:06:26 +0000 Aim. Paclitaxel based neoadjuvant chemotherapy regimen (NAT) in the setting of locally advanced breast cancer (LABC) can render inoperable tumor (T4, N2/N3) resectable. The aim of this study was to assess the status of carcinoma in the breast and lymph nodes after paclitaxel based NAT in order to find out the patient and the tumor characteristics that correspond to the pathological responses which could be used as a surrogate biomarker to assess the treatment response. Materials and Methods. Clinical and tumor characteristics of patients with breast carcinoma () were assessed preoperatively. These patients were subjected to modified radical mastectomy after 3 courses of paclitaxel based NAT regimen. The pathological responses of the tumor in the breast and the lymph nodes were studied by using Chevallier’s system which graded the responses into pathological complete response (pCR), pathological partial response (pPR), and pathological no response (pNR). Results. Our studies showed a pCR of 27.1% and a pPR of 70.9% . Clinically small sized tumors (2–5 cms) and Bloom Richardson’s grade 1 tumors showed a pCR. Mean age at presentation was 50.58 yrs. 79.2% of cases were invasive ductal carcinoma NOS; only 2.1% were invasive lobular carcinoma, their response to NAT being the same. There was no downgrading of the tumor grades after NAT. Ductal carcinoma in situ and lymphovascular invasion were found to be resistant to chemotherapy. The histopathological changes noted in the lymph nodes were similar to that found in the tumor bed. Discussion and Conclusion. From our study we conclude that histopathological examination of the tumor bed is the gold standard for assessing the chemotherapeutic tumor response. As previous studies have shown pCR can be used as a surrogate biomarker to assess the tumor response. Dhanya Vasudevan, P. S. Jayalakshmy, Suresh Kumar, and Siji Mathew Copyright © 2015 Dhanya Vasudevan et al. All rights reserved. Preoperative Peripheral Blood Count in Breast Carcinoma: Predictor of Prognosis or a Routine Test Mon, 30 Nov 2015 06:47:24 +0000 Background. Peripheral blood count is the first investigation to be done in every patient before surgery. As strong relationship exists between cancer and immune response of the body, clinical stage at presentation and altered hematological parameters can influence the progression of cancer and vice versa. Settings and Design. It is a case control study of total 50 cases (35 cases of carcinoma breast and 15 cases of benign breast disease). Methods. A case control study was carried out; 35 cases of breast cancer patients were taken prior to surgery and chemotherapy with 15 cases of benign breast disease as control. Clinical staging according to the tumor, node, and metastasis classification (TNMc) was done and was correlated with complete blood count (CBC). Results. All the cancer patients were females with overall mean age of years. Amongst all altered blood parameters, correlation of absolute lymphocytic count ( value 0.001) with TNMc staging was found significant. Particularly, decrease in absolute leucocytic count was observed with increase in stage of breast carcinoma. Conclusions. The stage-specific mean values of absolute lymphocytic counts of preoperative breast cancer patients can be used as an economical tool to know the evolution of disease. Amrit Pal Singh Rana, Manjit Kaur, B. Zonunsanga, Arun Puri, and Amarjit Singh Kuka Copyright © 2015 Amrit Pal Singh Rana et al. All rights reserved. C-Reactive Protein and Breast Cancer: New Insights from Old Molecule Thu, 26 Nov 2015 06:57:08 +0000 Recently an association between breast cancer and inflammation has emerged as the seventh hallmark of cancer. Chronic inflammation is a key contributor in the development and progression of carcinogenesis. Inflammatory pathways play an important role in the causation of breast cancer. C-reactive protein (CRP) an acute-phase reactant inflammatory protein is synthesized in hepatocytes in response to cytokines that are released from leucocytes within the tumor microenvironment. Several epidemiological studies appraised an association of CRP with breast cancer risk with inconsistent findings. Elevated levels at the time of diagnosis of breast cancer indicate aggressiveness of the tumor. CRP is also a well-established independent prognostic marker. Breast cancer survivors with the state of chronic inflammation are at risk of recurrence and metabolic disturbances. CRP lowering agents along with chemotherapeutic drugs will improve the survival of breast cancer patients. Also, it is a risk predictor for subsequent cardiotoxicity in patients receiving chemotherapy. The present review is aimed at elucidating the role of C-reactive protein, as an inflammatory risk marker and prognostic predictor of breast cancer. It also focuses on conflicting views on the role of CRP in breast cancer and its impact on therapeutic interventions. Shilpa Balaji Asegaonkar, Balaji Narayanrao Asegaonkar, Unmesh Vidyadhar Takalkar, Suresh Advani, and Anand Pandurang Thorat Copyright © 2015 Shilpa Balaji Asegaonkar et al. All rights reserved. Synergistic Apoptotic Effect of Crocin and Paclitaxel or Crocin and Radiation on MCF-7 Cells, a Type of Breast Cancer Cell Line Thu, 26 Nov 2015 06:39:17 +0000 Background. Chemotherapy, radiotherapy, and surgery are routine treatments of breast cancer. However, these methods could only improve the living survival. Nowadays the combined therapy including herbals such as crocin is to study for improving breast cancer treatment. The purpose of this study was to evaluate the effects of crocin, paclitaxel, and radiation on MCF-7 cell. Methods. To evaluate the effect of crocin, paclitaxel, and radiation on survival rate of MCF-7 cells MTT assay was done. To investigate the apoptotic effect of experimental groups PI-flow cytometry was used and expression of apoptotic proteins (caspase-7, caspase-9, PARP, and p53) was studied by western blot. Results. This study revealed that the combined therapy of 0.01µmol/mL paclitaxel and 2.5 mg/mL crocin after 48 h could cause IC50 for MCF-7 cell line. This study showed that the combined therapy of 2 Gy gamma radiation with crocin could rise apoptosis in MCF-7 cell line from 21% (related to using 2 Gy gamma radiation alone) to 46.6%. Conclusion. Crocin and paclitaxel and crocin and gamma radiation had synergistic effect on MCF-7 cell line to get more significant apoptosis. Faeze Vali, Vahid Changizi, and Majid Safa Copyright © 2015 Faeze Vali et al. All rights reserved. Race/Ethnicity, Primary Language, and Income Are Not Demographic Drivers of Mortality in Breast Cancer Patients at a Diverse Safety Net Academic Medical Center Wed, 28 Oct 2015 11:34:20 +0000 Objective. To examine the impact of patient demographics on mortality in breast cancer patients receiving care at a safety net academic medical center. Patients and Methods. 1128 patients were diagnosed with breast cancer at our institution between August 2004 and October 2011. Patient demographics were determined as follows: race/ethnicity, primary language, insurance type, age at diagnosis, marital status, income (determined by zip code), and AJCC tumor stage. Multivariate logistic regression analysis was performed to identify factors related to mortality at the end of follow-up in March 2012. Results. There was no significant difference in mortality by race/ethnicity, primary language, insurance type, or income in the multivariate adjusted model. An increased mortality was observed in patients who were single (OR = 2.36, CI = 1.28–4.37, ), age > 70 years (OR = 3.88, CI = 1.13–11.48, ), and AJCC stage IV (OR = 171.81, CI = 59.99–492.06, ). Conclusions. In this retrospective study, breast cancer patients who were single, presented at a later stage, or were older had increased incidence of mortality. Unlike other large-scale studies, non-White race, non-English primary language, low income, or Medicaid insurance did not result in worse outcomes. Divya A. Parikh, Rani Chudasama, Ankit Agarwal, Alexandar Rand, Muhammad M. Qureshi, Taylor Ngo, and Ariel E. Hirsch Copyright © 2015 Divya A. Parikh et al. All rights reserved. Comparison of the Explantation Rate of Poly Implant Prothèse, Allergan, and Pérouse Silicone Breast Implants within the First Four Years after Reconstructive Surgery before the Poly Implant Prothèse Alert by the French Regulatory Authority Mon, 12 Oct 2015 08:45:32 +0000 Background. In March 2010, ANSM (Agence Nationale de Sécurité du Medicament), the French Medical Regulatory Authority, withdrew Poly Implant Prothèse (PIP) breast implants from the market due to the use of non-medical-grade silicone gel. The aim of this study was to compare the removal rate (and reasons thereof) of breast implants produced by different manufacturers before the ANSM alert. Materials and Methods. From October 2006 to January 2010, 652 women received 944 implants after breast cancer surgery at the Gustave Roussy Comprehensive Cancer Center, Paris (France). The complications and removal rates of the different implant brands used (PIP, Allergan, and Pérouse) were evaluated and compared. Results. PIP implants represented 50.6% of the used implants, Allergan 33.4%, and Pérouse 16%. The main reasons for implant removal were patient dissatisfaction due to aesthetic problems (43.2%), infection (22.2%), and capsular contracture (13.6%). Two years after implantation, 82% of Pérouse implants, 79% of PIP, and 79% of Allergan were still in situ. There was no difference in removal rate among implant brands. Conclusion. Before the ANSM alert concerning the higher rupture rate of PIP breast implants, our implant removal rate did not predict PIP implant failure related to the use of nonapproved silicone gel. Alexandre Leduey, Chafika Mazouni, Nicolas Leymarie, Heba Alkhashnam, Benjamin Sarfati, Jean-Rémi Garbay, Amélie Gaudin, Frédéric Kolb, and Françoise Rimareix Copyright © 2015 Alexandre Leduey et al. All rights reserved. Correlation between Fine-Needle Aspiration Cytology and Histology for Palpable Breast Masses in a Nigerian Tertiary Health Institution Thu, 08 Oct 2015 09:06:34 +0000 Background. Management of breast lumps can be challenging in resource poor settings. Fine-needle aspiration cytology (FNAC) especially when used with cell block can help improve affordability for the patients. Objective. To determine the diagnostic accuracy of FNAC of palpable breast lesions within a 5-year period. Methods. The findings obtained from FNAC of palpable breast lumps seen at the FNAC clinic of our department from January 2007 to December 2011 were retrieved and correlated with findings on histology of excisional biopsies. Results. A total of 1790 patients had FNAC of breast lumps during the 5-year period; 436 of them subsequently had biopsies. Our results compare favourably with the measures of test performance of the UK NHS Breast Screening Programme shown in brackets: absolute sensitivity 95.4% (>70%), complete sensitivity 99.2% (>90%), full specificity 88.9% (>65%), positive predictive value 99.6% (>99%), false-negative rate 0.8% (<4%), false-positive rate 0.4% (<0.5%), inadequate rate 3.2% (<15%), and suspicious rate 10.2% (<15%). Conclusion. Breast FNACs compare very well with histology of excisional biopsies and in experienced hands are extremely useful in the management of breast lumps. Further studies assessing the diagnostic accuracy of FNAC and cell blocks in our setting are recommended. Adetola Olubunmi Daramola, Mosebolatan Olatokunboh Odubanjo, Fred John Obiajulu, Nzechukwu Zimudo Ikeri, and Adekunbiola Aina Fehintola Banjo Copyright © 2015 Adetola Olubunmi Daramola et al. All rights reserved. Perspectives of Cosmesis following Breast Conservation for Multifocal and Multicentric Breast Cancers Sun, 04 Oct 2015 16:56:12 +0000 Background. Contemporary data suggest that breast conservation treatment (BCT) for multifocal and multicentric breast cancer (MFMCBC) may be appropriate with noninferior local control rates. However, there is a paucity of data to evaluate patient’s satisfaction with cosmetic outcomes after BCT for MFMCBC. This study was performed to bridge this information gap. Methods. All patients treated at the authors’ healthcare facility were included in the study. Patients with MFMCBC who were assessed to be eligible for BCT underwent tumour resection using standard surgical techniques with direct parenchymal closure through a single incision. After at least three years of follow-up, they were invited to participate in a survey regarding their cosmetic outcomes. Results. Of a total of 160 patients, 40 had MFMCBC, of whom 34 (85%) underwent successful BCT. Five-year cancer-specific survival and disease-free survival were 95.7%. Twenty of the 34 patients responded to the survey. No patient rated her cosmetic outcome as “poor.” Analysis indicated low agreement between patients’ self-assessment and clinician-directed evaluation of aesthetic results. Conclusion. BCT for MFMCBC is feasible with acceptable survival and cosmetic outcomes. However, there appears to be a disparity between patient and clinician-directed evaluation of cosmetic results which warrant further research. Mona P. Tan, Nadya Y. Sitoh, and Yih-Yiow Sitoh Copyright © 2015 Mona P. Tan et al. All rights reserved. Assessment of MRI Issues at 3 Tesla for a New Metallic Tissue Marker Wed, 22 Jul 2015 06:02:59 +0000 Purpose. To assess the MRI issues at 3 Tesla for a metallic tissue marker used to localize removal areas of tissue abnormalities. Materials and Methods. A newly designed, metallic tissue marker (Achieve Marker, CareFusion, Vernon Hills, IL) used to mark biopsy sites, particularly in breasts, was assessed for MRI issues which included standardized tests to determine magnetic field interactions (i.e., translational attraction and torque), MRI-related heating, and artifacts at 3 Tesla. Temperature changes were determined for the marker using a gelled-saline-filled phantom. MRI was performed at a relatively high specific absorption rate (whole body averaged SAR, 2.9-W/kg). MRI artifacts were evaluated using T1-weighted, spin echo and gradient echo pulse sequences. Results. The marker displayed minimal magnetic field interactions (2-degree deflection angle and no torque). MRI-related heating was only 0.1°C above background heating (i.e., the heating without the tissue marker present). Artifacts seen as localized signal loss were relatively small in relation to the size and shape of the marker. Conclusions. Based on the findings, the new metallic tissue marker is acceptable or “MR Conditional” (using current labeling terminology) for a patient undergoing an MRI procedure at 3 Tesla or less. Charlotte M. Cronenweth and Frank G. Shellock Copyright © 2015 Charlotte M. Cronenweth and Frank G. Shellock. All rights reserved. Locoregional Recurrence Risk in Breast Cancer Patients with Estrogen Receptor Positive Tumors and Residual Nodal Disease following Neoadjuvant Chemotherapy and Mastectomy without Radiation Therapy Tue, 21 Jul 2015 07:37:00 +0000 Among breast cancer patients treated with neoadjuvant chemotherapy (NAC) and mastectomy, locoregional recurrence (LRR) rates are unclear in women with ER+ tumors treated with adjuvant endocrine therapy without postmastectomy radiation (PMRT). To determine if PMRT is needed in these patients, we compared LRR rates of patients with ER+ tumors (treated with adjuvant endocrine therapy) with women who have non-ER+ tumors. 85 consecutive breast cancer patients (87 breast tumors) treated with NAC and mastectomy without PMRT were reviewed. Patients were divided by residual nodal disease (ypN) status (ypN+ versus ypN0) and then stratified by receptor subtype. Among ypN+ patients (), five-year LRR risk in patients with ER+, Her2+, and triple negative tumors was 5%, 33%, and 37%, respectively (). Among ypN+/ER+ patients, lymphovascular invasion and grade three disease increased the five-year LRR risk to 13% and 11%, respectively. Among ypN0 patients (), five-year LRR risk in patients with ER+, Her2+, and triple negative tumors was 7%, 22%, and 6%, respectively (). In women with ER+ tumors and residual nodal disease, endocrine therapy may be sufficient adjuvant treatment, except in patients with lymphovascular invasion or grade three tumors where PMRT may still be indicated. Shravan Kandula, Jeffrey M. Switchenko, Saul Harari, Carolina Fasola, Donna Mister, David S. Yu, Amelia B. Zelnak, and Mylin A. Torres Copyright © 2015 Shravan Kandula et al. All rights reserved. Evaluation of the Quilting Technique for Reduction of Postmastectomy Seroma: A Randomized Controlled Study Sun, 12 Jul 2015 09:33:17 +0000 Background. Postmastectomy seroma causes patients’ discomfort, delays starting the adjuvant therapy, and may increase the possibility of surgical site infection. Objective. To evaluate quilting of the mastectomy flaps with obliteration of the axillary space in reducing postmastectomy seroma. Methods. A randomized controlled study was carried out among 120 females who were candidates for mastectomy and axillary clearance. The intervention group () with quilting and the control group without quilting. All patients were followed up routinely for immediate and late complications. Results. There were no significant differences between the two groups as regards the demographic characteristics, postoperative pathological finding, and the immediate postoperative complications. The incidence of seroma was significantly lower in the intervention group compared with the control group (20% versus 78.3%, ). Additionally, the intervention group had a shorter duration till seroma resolution (9 days versus 11 days, ) and a smaller volume of drainage (710 mL versus 1160 mL, ) compared with the control group. Conclusion. The use of mastectomy with quilting of flaps and obliteration of the axillary space is an efficient method to significantly reduce the postoperative seroma in addition to significantly reducing the duration and volume of wound drainage. Therefore we recommend quilting of flaps as a routine step at the end of any mastectomy. Ashraf Khater, Waleed Elnahas, Sameh Roshdy, Omar Farouk, Ahmed Senbel, Adel Fathi, EmadEldeen Hamed, Mohamed Abdelkhalek, and Hosam Ghazy Copyright © 2015 Ashraf Khater et al. All rights reserved. Risk Factors for Premenopausal Breast Cancer in Bangladesh Wed, 01 Jul 2015 12:03:48 +0000 Background. The incidence of premenopausal breast cancer is rising throughout South Asia. Our objective was to determine the role of risk factors associated with Westernization for premenopausal breast cancer in Bangladesh. Methods. We conducted a matched case-control study between January 1, 2007, and December 31, 2010, at four hospitals in Bangladesh. Cases were premenopausal women diagnosed with invasive breast cancer. Controls were premenopausal women with no personal history of breast cancer. Logistic regression was used to calculate the odds ratios (OR) for breast cancer. Results. We identified 129 age-matched pairs. The mean age of breast cancer diagnosis was 37.5 years. Each year decrease in the age of menarche significantly increased the risk of breast cancer (OR = 1.67, 95% CI 1.09–2.56, ). The risk was also increased with a current body mass index of ≥25 kg/m2 (OR = 5.24, 95% CI 1.10–24.9, ). Age at first childbirth, parity, and breastfeeding were not significantly associated with premenopausal breast cancer risk (). Conclusions. Age at menarche and adult weight gain were associated with premenopausal breast cancer risk. Other factors associated with Westernization may not be relevant to premenopausal breast cancer risk in Bangladesh. Javaid Iqbal, Tahmina Ferdousy, Rahela Dipi, Reza Salim, Wei Wu, Steven A. Narod, Joanne Kotsopoulos, Mohammad G. Mostafa, and Ophira Ginsburg Copyright © 2015 Javaid Iqbal et al. All rights reserved. Evaluation of Sentinel Lymph Node Dose Distribution in 3D Conformal Radiotherapy Techniques in 67 pN0 Breast Cancer Patients Sun, 28 Jun 2015 07:35:13 +0000 Introduction. The anatomic position of the sentinel lymph node is variable. The purpose of the following study was to assess the dose distribution delivered to the surgically marked sentinel lymph node site by 3D conformal radio therapy technique. Material and Method. We retrospectively analysed 70 radiotherapy (RT) treatment plans of consecutive primary breast cancer patients with a successful, disease-free, sentinel lymph node resection. Results. In our case series the SN clip volume received a mean dose of 40.7 Gy (min 28.8 Gy/max 47.6 Gy). Conclusion. By using surgical clip markers in combination with 3D CT images our data supports the pathway of tumouricidal doses in the SN bed. The target volume should be defined by surgical clip markers and 3D CT images to give accurate dose estimations. Gerlo Witucki, Nikolaus Degregorio, Andreas Rempen, Lukas Schwentner, Dirk Bottke, Wolfgang Janni, and Florian Ebner Copyright © 2015 Gerlo Witucki et al. All rights reserved. Expression of Tropomyosin 1 Gene Isoforms in Human Breast Cancer Cell Lines Thu, 11 Jun 2015 12:24:03 +0000 Nine malignant breast epithelial cell lines and 3 normal breast cell lines were examined for stress fiber formation and expression of TPM1 isoform-specific RNAs and proteins. Stress fiber formation was strong (++++) in the normal cell lines and varied among the malignant cell lines (negative to +++). Although TPM1γ and TPM1δ were the dominant transcripts of TPM1, there was no clear evidence for TPM1δ protein expression. Four novel human TPM1 gene RNA isoforms were discovered (λ, μ, ν, and ξ), which were not identified in adult and fetal human cardiac tissues. TPM1λ was the most frequent isoform expressed in the malignant breast cell lines, and it was absent in normal breast epithelial cell lines. By western blotting, we were unable to distinguish between TPM1γ, λ, and ν protein expression, which were the only TPM1 gene protein isoforms potentially expressed. Some malignant cell lines demonstrated increased or decreased expression of these isoforms relative to the normal breast cell lines. Stress fiber formation did not correlate with TPM1γ RNA expression but significantly and inversely correlated with TPM1δ and TPM1λ expression, respectively. The exact differences in expression of these novel isoforms and their functional properties in breast epithelial cells will require further study. Syamalima Dube, Santhi Yalamanchili, Joseph Lachant, Lynn Abbott, Patricia Benz, Charles Mitschow, Dipak K. Dube, and Bernard J. Poiesz Copyright © 2015 Syamalima Dube et al. All rights reserved. A Review on Automatic Mammographic Density and Parenchymal Segmentation Thu, 11 Jun 2015 07:12:56 +0000 Breast cancer is the most frequently diagnosed cancer in women. However, the exact cause(s) of breast cancer still remains unknown. Early detection, precise identification of women at risk, and application of appropriate disease prevention measures are by far the most effective way to tackle breast cancer. There are more than 70 common genetic susceptibility factors included in the current non-image-based risk prediction models (e.g., the Gail and the Tyrer-Cuzick models). Image-based risk factors, such as mammographic densities and parenchymal patterns, have been established as biomarkers but have not been fully incorporated in the risk prediction models used for risk stratification in screening and/or measuring responsiveness to preventive approaches. Within computer aided mammography, automatic mammographic tissue segmentation methods have been developed for estimation of breast tissue composition to facilitate mammographic risk assessment. This paper presents a comprehensive review of automatic mammographic tissue segmentation methodologies developed over the past two decades and the evidence for risk assessment/density classification using segmentation. The aim of this review is to analyse how engineering advances have progressed and the impact automatic mammographic tissue segmentation has in a clinical environment, as well as to understand the current research gaps with respect to the incorporation of image-based risk factors in non-image-based risk prediction models. Wenda He, Arne Juette, Erika R. E. Denton, Arnau Oliver, Robert Martí, and Reyer Zwiggelaar Copyright © 2015 Wenda He et al. All rights reserved.