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1.  An Interesting Pathological Diagnosis – Adenoid Cystic Carcinoma in an Adolescent Girl 
Adenoid cystic carcinomas (ACCs) constitute 0.1–1 % of all malignant breast tumors. They have better prognosis than other breast malignancies. To date, there have been about 933 cases reported as per English literature. To the best of our knowledge, this case may be the second well-documented case of ACC of breast at younger age.
doi:10.4137/BCBCR.S22069
PMCID: PMC4294633
ACC; young age; core biopsy
2.  Hereditary Breast Cancer: Clinical, Pathological and Molecular Characteristics 
Pathogenic mutations in BRCA1 or BRCA2 are only detected in 25% of families with a strong history of breast cancer, though hereditary factors are expected to be involved in the remaining families with no recognized mutation. Molecular characterization is expected to provide new insight into the tumor biology to guide the search of new high-risk alleles and provide better classification of the growing number of BRCA1/2 variants of unknown significance (VUS). In this review, we provide an overview of hereditary breast cancer, its genetic background, and clinical implications, before focusing on the pathologically and molecular features associated with the disease. Recent transcriptome and genome profiling studies of tumor series from BRCA1/2 mutation carriers as well as familial non-BRCA1/2 will be discussed. Special attention is paid to its association with molecular breast cancer subtypes as well as the latest advances in predicting BRCA1/2 involvement (BRCAness) using molecular signatures, for improved diagnostics and selection of patients sensitive to targeted therapeutics.
doi:10.4137/BCBCR.S18715
PMCID: PMC4213954  PMID: 25368521
hereditary breast cancer; molecular profiling; microarray; review; clinical genetics; BRCA1/2
3.  RAD51B Activity and Cell Cycle Regulation in Response to DNA Damage in Breast Cancer Cell Lines 
Common genetic variants mapping to two distinct regions of RAD51B, a paralog of RAD51, have been associated with breast cancer risk in genome-wide association studies (GWAS). RAD51B is a plausible candidate gene because of its established role in the homologous recombination (HR) process. How germline genetic variation in RAD51B confers susceptibility to breast cancer is not well understood. Here, we investigate the molecular function of RAD51B in breast cancer cell lines by knocking down RAD51B expression by small interfering RNA and treating cells with DNA-damaging agents, namely cisplatin, hydroxyurea, or methyl-methanesulfonate. Our results show that RAD51B-depleted breast cancer cells have increased sensitivity to DNA damage, reduced efficiency of HR, and altered cell cycle checkpoint responses. The influence of RAD51B on the cell cycle checkpoint is independent of its role in HR and further studies are required to determine whether these functions can explain the RAD51B breast cancer susceptibility alleles.
doi:10.4137/BCBCR.S17766
PMCID: PMC4213955  PMID: 25368520
RAD51B; breast cancer; DNA damage; homologous recombination
4.  Update on Adjuvant Chemotherapy for Early Breast Cancer 
Breast cancer is the second most common cancer in women worldwide. Although most women are diagnosed with early breast cancer, a substantial number recur due to persistent micro-metastatic disease. Systemic adjuvant chemotherapy improves outcomes and has advanced from first-generation regimens to modern dose-dense combinations. Although chemotherapy is the cornerstone of adjuvant therapy, new biomarkers are identifying patients who can forego such treatment. Neo-adjuvant therapy is a promising platform for drug development, but investigators should recognize the limitations of surrogate endpoints and clinical trials. Previous decades have focused on discovering, developing, and intensifying adjuvant chemotherapy. Future efforts should focus on customizing therapy and reducing chemotherapy for patients unlikely to benefit. In some cases, it may be possible to replace chemotherapy with treatments directed at specific genetic or molecular breast cancer subtypes. Yet, we anticipate that chemotherapy will remain a critical component of adjuvant therapy for years to come.
doi:10.4137/BCBCR.S9454
PMCID: PMC4197909  PMID: 25336961
neoadjuvant; toxicity; pathologic response; metastases
5.  Breast Positioning during Mammography: Mistakes to be Avoided 
AIMS AND OBJECTIVES
Breast positioning is the key factor affecting a mammogram. If care is taken during positioning, it maximizes the amount of breast tissue being imaged, eliminates most of the artifacts, and increases sensitivity of the mammogram. This retrospective study was carried out in our department to assess correctness, and also the incorrectness of breast positioning, which need to be avoided to obtain an ideal mammogram.
MATERIAL AND METHODS
A total of 1369 female patients were included in this study. Mammography was performed on full field detector digital mammography equipment. Craniocaudal (CC) view and mediolateral oblique (MLO) view were carried out for each breast. Four views were done for 1322 patients. The remaining 47 patients had undergone a mastectomy and underwent two views for the other breast. Mistakes in improperly positioned mammogram were assessed with respect to proper visualization of nipple, position of pectoralis major, pectoral–nipple distance (PND), inframammary fold, and adequate coverage of all breast quadrants.
RESULTS
As per prescribed guidelines, mistakes in positioning were recognized in 2.879% of total mammograms. Improper positioning of the nipple was the commonest problem, seen in 3.827% of mammograms, CC view. On MLO view, bilaterally, pectoralis shadow was not seen in 0.520% mammograms, its margin was not straight/convex in 0.706%, lower edge of pectoralis was above pectoralis–nipple line in 2.081%, and inframammary fold was not seen in 1.189%. There was inadequate coverage of lower quadrants in 2.787%, and mismatch in PND was seen in 3.864%. In few of the patients, the shortcomings as a result of improper positioning were noted on one view, the rest being normal.
CONCLUSION
Positioning is the most important factor affecting the resultant mammography image. During mammography, many cases are improperly positioned and as a result the examination is inconclusive, which reduces the sensitivity of mammography.
doi:10.4137/BCBCR.S17617
PMCID: PMC4125373  PMID: 25125982
mammography; positioning; mistakes
6.  Breast Cancer Characteristics and Survival in a Hispanic Population of Costa Rica 
BACKGROUND
Breast cancer characteristics may vary according to the patient’s ethnic group. The goal of this cohort study was to evaluate the characteristics of a group of Costa Rican breast cancer patients and their relationship with survival.
METHODS
Age, stage, tumor grade, immunohistochemistry, lymphovascular invasion, recurrence, and survival data on 199 Hispanic patients with breast cancer diagnosis, treated between January 2009 and May 2010, were collected from a single institution in San Jose, Costa Rica. The data were statistically analyzed for significance.
RESULTS
Median age at diagnosis was 53 years. With a median follow-up of 46.5 months, there was an 88% overall survival rate. Thirty-seven percent of the patients (p < 0.001) were at stages III and IV during diagnosis. The hormone receptor human epidermal receptor negative phenotype (HR−HER2−) (p < 0.001) was present in 17% of the cases. In a multivariate analysis, local (risk ratio, RR: 7.2; confidence interval, CI 95%: 3.8–7.6; p = 0.06) and distant recurrence (RR: 14.9; CI 95%: 7.7–28.9; p = 0.01) showed the strongest association with the probability of death from the disease. Patients with HR−HER2− phenotype tumors reported more local recurrences (p = 0.04), a higher tumor grade (p < 0.01), and lower overall survival than patients with other breast cancer phenotypes (p = 0.01).
CONCLUSIONS
Although this study analyzes a modest number of cases, it is an initial insight into factors that may contribute to differences in breast cancer outcomes among Hispanic women in Costa Rica. The higher proportion of triple negative tumors, advanced stage, and younger median age at diagnosis could contribute to the inferior prognostic described among Hispanic women. There may be a different distribution of tumor subtypes compared to non-Hispanic white women. Further studies are necessary to confirm such findings.
doi:10.4137/BCBCR.S15854
PMCID: PMC4125366  PMID: 25125980
breast; cancer; Hispanic; Costa Rica; immunohistochemistry
7.  Current Approaches and Emerging Directions in HER2-resistant Breast Cancer 
Human epidermal growth factor receptor-2 (HER2) is overexpressed in up to 30% of breast cancers; HER2 overexpression is indicative of poor prognosis. Trastuzumab, an anti-HER2 monoclonal antibody, has led to improved outcomes in patients with HER2-positive breast cancer, including improved overall survival in adjuvant and first-line settings. However, a large proportion of patients with breast cancer have intrinsic resistance to HER2-targeted therapies, and nearly all become resistant to therapy after initial response. Elucidation of underlying mechanisms contributing to HER2 resistance has led to development of novel therapeutic strategies, including those targeting HER2 and downstream pathways, heat shock protein 90, telomerase, and vascular endothelial growth factor inhibitors. Numerous clinical trials are ongoing or completed, including phase 3 data for the mammalian target of rapamycin inhibitor everolimus in patients with HER2-resistant breast cancer. This review considers the molecular mechanisms associated with HER2 resistance and evaluates the evidence for use of evolving strategies in patients with HER2-resistant breast cancer.
doi:10.4137/BCBCR.S9453
PMCID: PMC4125367  PMID: 25125981
HER2-positive; human epidermal growth factor receptor-2; HER2 therapy resistance
8.  Coping Strategies in Egyptian Ladies with Breast Cancer 
INTRODUCTION
A diagnosis of breast cancer regardless of the stage can be stressful, impact multiple spheres of life, and disrupt physical status, emotional and spiritual well-being, and personal relationships for the patient and family. In order to adapt, the patient ought to employ certain coping mechanisms. Individuals with terminal illness who utilize coping strategies have better quality of life compared to those who do not.
PATIENTS AND METHODS
This study aimed to determine the strategies used by females with breast cancer to cope with such stress by using Brief COPE scale and the hospital anxiety and depression scale. The study included 56 female patients diagnosed with operable breast cancer at Mansoura Oncology Center before surgery.
RESULTS
Large proportion of patients used acceptance, religion, and emotional support in coping with the stress of having breast cancer. Patients with depressive symptoms scored significantly higher venting while those with anxiety scored higher positive reframing, planning, and venting.
CONCLUSION
Efforts should be made to encourage women with breast cancer to use coping strategies that have been found to be helpful (eg, acceptance, emotional support, distraction, and active coping strategies).
doi:10.4137/BCBCR.S14755
PMCID: PMC4055407  PMID: 24940070
coping; depression; anxiety; breast cancer; Egypt
9.  Hyperactivated Signaling Pathways of Chemokine RANTES/CCL5 in Osteopathies of Jawbone in Breast Cancer Patients—Case Report and Research 
BACKGROUND
Hollow spaces in the jawbone have been defined as fatty degenerative osteonecrosis of jawbone (FDOJ) and have been linked with a dysregulated immune system. Little is known about the underlying relationship.
OBJECTIVES
Samples of FDOJ were analyzed to assess expression of cytokines which can play a role in the pathogenesis of breast cancer (MaCa).
MATERIAL AND METHODS
Samples of FDOJ extracted from 23 patients with MaCa and 19 healthy control jawbone samples were analyzed for 7 immune messengers.
RESULTS
RANTES was found to be highly overexpressed in disease samples. No change was observed in expression levels of the other immune mediators.
DISCUSSION
This data provides a compelling confirmation that FDOJ produces high levels of RANTES, a cytokine implicated in MaCa and metastasis. Levels detected in FDOJ are five-fold higher than that previously reported for MaCa tissue suggesting its role as a cytokine source in MaCa.
CONCLUSION
We thus hypothesize that FDOJ may serve as an expeditor of MaCa progression, through RANTES production.
doi:10.4137/BCBCR.S15119
PMCID: PMC4039184  PMID: 24899812
RANTES/CCL5; breast cancer; jawbone; osteonecrosis; metastasis; signaling pathways
10.  Pertuzumab in Combination with Trastuzumab and Chemotherapy in the Treatment of HER2-Positive Metastatic Breast Cancer: Safety, Efficacy, and Progression Free Survival 
Tyrosine kinase inhibitors have revolutionized the oncology community and were pioneered by the use in HER2-targeted therapies. Improved outcomes were seen with the advent of trastuzumab, leading investigators to develop newer agents to target the HER2 pathway such as the novel monoclonal antibody pertuzumab. In this paper, we describe the attributes of pertuzumab including: mechanism of action, pharmacokinetics and metabolism, safety/cardiotoxicity, drug interactions, efficacy, and role in HER2-positive breast cancer management. Newly reviewed here versus previously published reviews on pertuzumab oriented therapy are data of pertuzumab monotherapy as it is used in combination with other anti-HER2 agents derived from preclinical research and ongoing clinical trials.
MATERIALS AND METHODS
A computer based literature search was carried out using PubMed data reported at international meetings (ASCO) up to September 2013 were included.
doi:10.4137/BCBCR.S9032
PMCID: PMC4022699  PMID: 24855372
pertuzumab; trastuzumab; HER2; breast cancer
11.  Breast Cancer Knowledge, Beliefs, and Screening Practices among Women Seeking Care at District Hospitals in Dar es Salaam, Tanzania 
BACKGROUND
Limited disease awareness among women may impact breast cancer stage-at-diagnosis in Tanzania, reducing survival. This study assessed breast cancer knowledge, screening practices, and educational preferences among outpatients at Tanzanian government-supported hospitals.
METHODS
A convenience sample of women was surveyed regarding (1) knowledge/beliefs of breast cancer etiology, risk factors, symptoms, treatment, (2) early detection knowledge/practice, and (3) educational preferences.
RESULTS
Among 225 respondents, 98.2% knew of breast cancer; 22.2% knew someone affected by breast cancer. On average, 30% of risk factors and 51% of symptoms were identified. Most accepted one or more breast cancer myths. Among 126 aware of breast self-exam, 40% did not practice it; only 0.9% underwent regular clinical breast examinations despite 68% being aware of the procedure. Among treatments, 87% recognized surgery, 70% radiation, and fewer systemic therapy. Preferred educational sources were group sessions, television/radio, and meetings with breast cancer survivors.
CONCLUSIONS
This work reveals incomplete breast cancer awareness among Tanzanian women and promises to inform development of user-focused educational resources.
doi:10.4137/BCBCR.S13745
PMCID: PMC4022700  PMID: 24855371
breast cancer; awareness; urban; Tanzania; low income
12.  Diagnosis of a Nonpalpable Intraductal Papilloma without Radiological Abnormality by Nipple Discharge Smear Examination: A Case Report 
Nipple discharge is the third most common breast complaint after breast pain and breast mass, most commonly associated with endocrine alterations and/or medications, pregnancy, lactation, post lactation, fibrocystic disease, intraductal papilloma, duct ectasia, nipple adenoma, infection, chronic mastitis, subareolar abscess, and least frequently, breast carcinoma. Cytological examination of nipple discharge (ND) is a noninvasive method of diagnosing the underlying breast pathology. We report a 46 year old female, who presented with pain and blood-mixed ND from the right breast with an impalpable mass. Cytological examination of the discharge was done and diagnosis of papillary neoplasm with degeneration, metaplasia, and atypia was given, which was further confirmed on histology and positive IHC for HMWCK and p63. Final diagnosis was intraductal papilloma of the lactiferous duct with squamous metaplasia and infarction. Differentiating benign papilloma from a carcinoma is challenging to the cytopathologist and requires clinicopathological correlation and a good knowledge of cytology.
doi:10.4137/BCBCR.S14914
PMCID: PMC3981477  PMID: 24737934
nipple discharge; papillary neoplasms; infarction; HMWCK; p63
13.  Successful Remission of Hemolytic-Uremic Syndrome During the Third-line Weekly Gemcitabine for Metastatic Breast Cancer 
Sequential palliative chemotherapy for metastatic breast cancer incorporating weekly gemcitabine administered as three-weeks-on, one-week-off schedule is widely adopted throughout the East Asia region. Hemolytic-uremic syndrome (HUS) associated with weekly gemcitabine for a breast cancer patient is extremely rare. We report here a case of 43-year-old woman with metastatic breast cancer who received weekly gemcitabine as a third-line palliative chemotherapy for her disease. She developed HUS after a cumulative dose of 11,000 mg/m2 gemcitabine, evidenced by microangiopathic hemolytic anemia (MAHA) with schistocytes seen in peripheral blood smear, decreased haptoglobin level (<0.29 mmol/L), thrombocytopenia, negative direct Coombs test, and acute kidney injury. Owing to the ease of administration of weekly gemcitabine, gemcitabine-induced thrombocytopenia, multifactorial anemia in metastatic breast cancer, and possibility of cancer progression, HUS could have gone unnoticed. Breast cancer oncologist should be cognizant of this rare HUS even during weekly gemcitabine treatment.
doi:10.4137/BCBCR.S14920
PMCID: PMC3972075  PMID: 24701120
breast neoplasms; gemcitabine; hemolytic-uremic syndrome
14.  Protein Kinase C-ε Promotes EMT in Breast Cancer 
Protein kinase C (PKC), a family of serine/threonine kinases, plays critical roles in signal transduction and cell regulation. PKCε, a member of the novel PKC family, is known to be a transforming oncogene and a tumor biomarker for aggressive breast cancers. In this study, we examined the involvement of PKCε in epithelial to mesenchymal transition (EMT), the process that leads the way to metastasis. Overexpression of PKCε was sufficient to induce a mesenchymal phenotype in non-tumorigenic mammary epithelial MCF-10 A cells. This was accompanied by a decrease in the epithelial markers, such as E-cadherin, zonula occludens (ZO)-1, and claudin-1, and an increase in mesenchymal marker vimentin. Transforming growth factor β (TGFβ) induced Snail expression and mesenchymal morphology in MCF-10 A cells, and these effects were partially reversed by the PKCε knockdown. PKCε also mediated cell migration and anoikis resistance, which are hallmarks of EMT. Thus, our study demonstrates that PKCε is an important mediator of EMT in breast cancer.
doi:10.4137/BCBCR.S13640
PMCID: PMC3972078  PMID: 24701121
PKCε; EMT; breast cancer
15.  Host Cell Reactivation and Transcriptional Activation of Carboplatin-Modified BRCA1 
The breast cancer susceptibility gene 1 (BRCA1) has been shown to maintain genomic stability through multiple functions in the regulation of DNA damage repair and transcription. Its translated BRCT (BRCA1 C-terminal domain) acts as a strong transcriptional activator. BRCA1 damaged by carboplatin treatment may lead to a loss of such functions. To address the possibility of the BRCA1 gene as a therapeutic target for carboplatin, we investigated the functional consequences of the 3′-terminal region of human BRCA1 following in vitro platination with carboplatin. A reduction in cellular BRCA1 repair of carboplatin-treated plasmid DNA, using a host cell reactivation assay, was dependent on the platination levels on the reporter gene. The transcriptional transactivation activity of the drug-modified BRCA1, assessed using a one-hybrid GAL4 transcriptional assay, was inversely proportional to the carboplatin doses. The data emphasized the potential of the BRCA1 gene to be a target for carboplatin treatment.
doi:10.4137/BCBCR.S14224
PMCID: PMC3964185  PMID: 24678242
BRCA1; carboplatin; host cell reactivation; transcriptional activity; cancer chemotherapy
16.  Novel PI3K and mTOR Inhibitor NVP-BEZ235 Radiosensitizes Breast Cancer Cell Lines under Normoxic and Hypoxic Conditions 
In the present study, we assessed, if the novel dual phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor NVP-BEZ235 radiosensitizes triple negative (TN) MDA-MB-231 and estrogen receptor (ER) positive MCF-7 cells to ionizing radiation under various oxygen conditions, simulating different microenvironments as occurring in the majority of breast cancers (BCs). Irradiation (IR) of BC cells cultivated in hypoxic conditions revealed increased radioresistance compared to normoxic controls. Treatment with NVP-BEZ235 completely circumvented this hypoxia-induced effects and radiosensitized normoxic, reoxygenated, and hypoxic cells to similar extents. Furthermore, NVP-BEZ235 treatment suppressed HIF-1α expression and PI3K/mTOR signaling, induced autophagy, and caused protracted DNA damage repair in both cell lines in all tested oxygen conditions. Moreover, after incubation with NVP-BEZ235, MCF-7 cells revealed depletion of phospho-AKT and considerable signs of apoptosis, which were significantly enhanced by radiation. Our findings clearly demonstrate that NVP-BEZ235 has a clinical relevant potential as a radiosensitizer in BC treatment.
doi:10.4137/BCBCR.S13693
PMCID: PMC3964191  PMID: 24678241
radiosensibility; Akt; DNA repair protraction; apoptosis; hypoxia; autophagy
17.  A Proposal to Unify the Classification of Breast and Prostate Cancers Based on the Anatomic Site of Cancer Origin and on Long-term Patient Outcome 
The similarity between the structure and function of the breast and prostate has been known for a long time, but there are serious discrepancies in the terminology describing breast and prostate cancers. The use of the large, thick-section (3D) histology technique for both organs exposes the irrationality of the breast cancer terminology. Pathologists with expertise in diagnosing prostate cancer take the anatomic site of cancer origin into account when using the terms AAP (acinar adenocarcinoma of the prostate) and DAP (ductal adenocarcinoma of the prostate) to distinguish between the prostate cancers originating primarily from the fluid-producing acinar portion of the organ (AAP) and the tumors originating either purely from the larger ducts (DAP) or from both the acini and the main ducts combined (DAP and AAP). Long-term patient outcome is closely correlated with the terminology, because patients with DAP have a significantly poorer prognosis than patients with AAP.
The current breast cancer terminology could be improved by modeling it after the method of classifying prostate cancer to reflect the anatomic site of breast cancer origin and the patient outcome. The long-term survival curves of our consecutive breast cancer cases collected since 1977 clearly show that the non-palpable, screen-detected breast cancers originating from the milk-producing acini have excellent prognosis, irrespective of their histologic malignancy grade or biomarkers. Correspondingly, the breast cancer subtypes of truly ductal origin have a significantly poorer outcome, despite recent improvements in diagnosis and therapy. The mammographic appearance of breast cancers reflects the underlying tissue structure. Addition of these “mammographic tumor features” to the currently used histologic phenotypes makes it possible to distinguish the breast cancer cases of ductal origin with a poor outcome, termed DAB (ductal adenocarcinoma of the breast), from the more easily managed breast cancers of acinar origin, termed AAB (acinar adenocarcinoma of the breast), which have a significantly better outcome. This simple and easily communicable terminology could lead to better communication between the diagnostic and therapeutic team members and result in more rational treatment planning for the benefit of their patients.
doi:10.4137/BCBCR.S13833
PMCID: PMC3948717  PMID: 24653647
breast cancer terminology; prostate cancer terminology; ductal adenocarcinoma of the breast (DAB); acinar adenocarcinoma of the breast (AAB); subgross 3-D histology; neoductgenesis
18.  Challenges to the Control of Breast Cancer in A Small Developing Country 
OBJECTIVE
The aim of this study is to determine the clinicopathological features of breast cancer in two dedicated cancer treatment centers in north Trinidad. The histological types and stage at presentation were also investigated.
DESIGN AND METHODS
A retrospective cohort design was used; data were collected from a review of medical records of patients meeting the entry criteria. Clinical and demographic data were extracted.
RESULTS
A total of 640 patients were selected for the study and were available for the analysis. The annual cumulative incidence rate of breast cancer for the calendar years 2010 and 2011 in north Trinidad was 32.4 per 100,000 and 24.6 per 100,000 of the population. The age group between 51–60 years had the highest proportion of cases of breast cancer. There was a significant ethnic disparity in the occurrence of breast cancer, as it was more common in people of African origin than among South East Asians. Surgery and chemotherapy were the major interventions employed.
CONCLUSION
Breast cancer prevalence continues to be high in Trinidad; we provide evidence of the extent of and the degree of sophistication required to care for patients with breast cancer in a health care system in a small developing country.
doi:10.4137/BCBCR.S12780
PMCID: PMC3921156  PMID: 24526837
breast cancer; epidemiology; developing countries
19.  Oncotype Dx Results in Multiple Primary Breast Cancers 
PURPOSE
To determine whether multiple primary breast cancers have similar genetic profiles, specifically Oncotype Dx Recurrence Scores, and whether obtaining Oncotype Dx on each primary breast cancer affects chemotherapy recommendations.
METHODS
A database of patients with hormone receptor-positive, lymph node-negative, breast cancer was created for those tumors that were sent for Oncotype Dx testing from the University of Michigan Health System from 1/24/2005 to 2/25/2013.
Retrospective chart review abstracted details of tumor location, histopathology, distance between tumors, Oncotype Dx results, and chemotherapy recommendations.
RESULTS
Six hundred and sixty-six patients for whom Oncotype Dx testing was sent were identified, with 22 patients having multiple breast tumor specimens sent. Of the 22 patients who had multiple samples sent for analysis, chemotherapy recommendations were changed in 6 of 22 patients (27%) based on significant differences in Oncotype Dx Recurrence Scores. Qualitatively, there seems to be a greater difference in genetic profile in tumors appearing simultaneously on different breasts when compared to multiple tumors on the same breast. There was no association between distance between tumors and difference in Oncotype Dx scores for tumors on the same breast.
CONCLUSIONS
Oncotype Dx testing on multiple primary breast cancers altered management in regards to chemotherapy recommendations and should be considered for multiple primary breast cancers.
doi:10.4137/BCBCR.S13727
PMCID: PMC3891573  PMID: 24453493
breast cancer; oncotype dx; recurrence score
20.  Hormone Receptors and Age Distribution in Breast Cancer Patients at a University Hospital in Northern Egypt 
Introduction:
Breast cancer is the most common cancer among Egyptian women. The disease is often advanced at diagnosis. Since molecular profiling is not feasible in routine practice, we sought to examine the association of age distribution with hormone receptor profile, disease stage and outcome among Egyptian women.
Patients and methods:
We conducted a retrospective review of breast cancer patients treated at Mansoura University Cancer Center in the Nile Delta from 2006 through 2011. Age groups were examined in relation to hormone receptors status and tumor clinicopathological criteria. Additionally, the effect of receptor status on disease relapse and disease-free survival was examined with logistic regression and Kaplan–Meier analysis.
Results:
A total of 263 patients were included in the current analysis. About 66.9% (n = 176) of patients were hormone receptor positive, 14.1% (n = 37) were Her2/neu positive, and 19.0% (n = 50) were triple negative. Median age of the patients was 52 years and was equal across all receptor status types. Triple negative status correlated with increased risk of disease relapse (odds ratio = 1.8, P = 0.03) and with shortened disease-free survival (hazards ratio = 2.6, P < 0.01).
Conclusion:
The age distribution and receptor status pattern in the Nile Delta region does not explain the aggressive behavior of the disease. The age of the patients at diagnosis is older than patients in earlier studies from Egypt emphasizing the importance of implementing mammographic screening programs.
doi:10.4137/BCBCR.S12214
PMCID: PMC3694824  PMID: 23825439
breast cancer; hormone receptors; Egypt; prognosis
21.  Dose Distribution in the Heart and Cardiac Chambers Following 4-field Radiation Therapy of Breast Cancer: a Retrospective Study 
Purpose:
To evaluate cardiac doses in breast cancer patients with stage II/III treated with 4-field radiotherapy based on computed tomography (CT) dose planning.
Methods and Materials:
Based on archived CT images, whole heart and cardiac chamber radiation doses were analyzed in 216 (111 left-sided and 105 right-sided) mastectomized or lumpectomized breast cancer patients treated at a single institution, the Norwegian Radium Hospital, between 2000–2002. Individual dose volume histograms for the whole heart and for the four cardiac chambers were obtained, and mean, median and maximum doses to these structures were calculated. The dose (Gy) delivered to the 5% of the volume of each cardiac structure (D5%), and the volume percentage of each structure receiving ≥ 25 Gy (V25Gy) were reported. Normal tissue complication probability (NTCP) calculations were used to estimate the risk for ischemic heart disease (IHD).
Results:
Cohort-based medians of the whole heart mean dose (Dmean) for left- and right-sided tumors were 3.2 Gy and 1.3 Gy, respectively, with similar ventricular but lower atrial values. The atrial doses did not differ according to laterality of the breast tumor. In 13 patients with left-sided cancer, 5% of the heart volume was exposed to >25 Gy. The NTCP estimates were generelly low, with a maximum of 2.8%.
Conclusions:
During adjuvant CT-based locoregional radiotherapy of women with breast cancer, the cardiac radiation doses are, at the group level, below recommended threshold values (D5% < 25 Gy), though individual patients with left-sided disease may exceed these limits.
doi:10.4137/BCBCR.S11118
PMCID: PMC3615991  PMID: 23589693
heart; cardiac chambers; breast cancer and radiation therapy
22.  Axillary Ultrasound for Breast Cancer Staging: an Attempt to Identify Clinical/Histopathological Factors Impacting Diagnostic Performance 
Aim:
To assess the diagnostic value of pre-surgery axillary ultrasound for nodal staging in patients with primary breast cancer and to identify clinical/histopathological factors impacting diagnostic performance.
Study design:
Single-center, retrospective chart analysis. We assessed sensitivity, specificity, and positive and negative predictive value of clinical examination as well as axillary ultrasound vs. clinical examination alone. The histopathological results were the standard of truth. In addition, we analyzed clinical and histopathological factors regarding their potential to impact sensitivity and specificity.
Results:
We enrolled a total of 172 women in the study. Sensitivity of clinical examination plus ultrasound was significantly higher than for clinical examination alone (58% vs. 31.6%). Specificity and positive predictive value were similar while the negative predictive value increased from 63.4% to 73% when additionally applying ultrasound. Sensitivity and specificity of axillary ultrasound were impacted by tumor size (P = 0.2/0.04), suspicious axillary palpation (P < 0.01/<0.01), number of affected lymph nodes (P < 0.01/−) and distant metastases (P = 0.04/<0.01). All other factors had no impact.
Conclusion:
Since pre-surgery axillary nodal staging is currently used to determine disease management, axillary ultrasound is a useful add-on tool in the diagnostic armamentarium for breast cancer patients. Tumor size, suspicious axillary palpation, number of affected lymph nodes and distant metastases increase diagnostic performance of this diagnostic modality.
doi:10.4137/BCBCR.S11215
PMCID: PMC3595984  PMID: 23515655
breast cancer; axillary ultrasound; staging
23.  Combining mTOR Inhibitors with Chemotherapy and Other Targeted Therapies in Advanced Breast Cancer: Rationale, Clinical Experience, and Future Directions 
Improvements in survival of patients with breast cancer have been attributed to the development of agents that target key components of dysregulated pathways involved in oncogenesis and progression of breast cancer. Aberrant mammalian target of rapamycin (mTOR) activation has been implicated in oncogenesis, angiogenesis, and the development of estrogen independence and resistance to chemotherapy in breast tumors. Several mTOR inhibitors (sirolimus, everolimus, temsirolimus, and ridaforolimus) have demonstrated antitumor activity in breast cancer cells. Combining mTOR inhibitors with endocrine therapies has demonstrated clinical antitumor activity in patients with metastatic breast cancer. In addition, mTOR inhibitor combinations with various targeted biologic agents or cytotoxic chemotherapeutic agents are being examined in more than 40 clinical trials with some early promising results. Combination therapies targeting multiple components of these central signaling pathways may be an optimal treatment strategy for patients with advanced breast cancer.
doi:10.4137/BCBCR.S10071
PMCID: PMC3579426  PMID: 23492649
mTOR; hormone receptor; HER2; advanced breast cancer
24.  ER, PR, HER2, Ki-67 and CK5 in Early and Late Relapsing Breast Cancer—Reduced CK5 Expression in Metastases 
Breast cancer can recur even decades after the primary therapy. Markers are needed to predict cancer progression and the risk of late recurrence. The estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), proliferation marker Ki-67, and cytokeratin CK5 were studied to find out whether their expression or occurrence in subgroups of breast cancers correlated with the time of recurrence. The expression of HER2, ER, PR, Ki-67, and CK5 was studied by IHC in 72 primary breast cancers and their corresponding recurrent/metastatic lesions. The patients were divided into three groups according to the time of the recurrence/metastasis: before two years, after 5 years, and after 10 years. Based on their IHC profiles, the tumors were divided into surrogates of the genetically defined subgroups of breast cancers and the subtype definitions were as follows: luminal A (ER or PR+HER2–), luminal B (ER or PR+HER2+), HER2 overexpressing (ER–PR–HER2+), triple-negative (ER–PR–HER2–), basal-like (ER–PR–HER2–CK5+), non-classified (ER–PR–HER2–CK5–) and luminobasal (ER or PR+CK5+). In multivariate analysis, tumor size and HER2 positivity were a significant risk of early cancer relapse. The metastases showed a significantly lower CK5 expression. CK5 positivity distinguished triple negative tumors into rapidly and slowly recurring cancers. The IHC subtype ER or PR+HER2– luminal A presented a significantly lower risk of early tumor recurrence. Ki-67 expression denoted early-relapsing tumors and correlated linearly with tumor progression, since Ki-67 positivity declined gradually from early-relapsing toward late-recurring cancers.
doi:10.4137/BCBCR.S10701
PMCID: PMC3579427  PMID: 23514931
early and late relapsing breast cancers; CK5; immunohistochemistry
25.  Adjuvant Chemotherapy for Breast Cancer in a Patient with Primary Autoimmune Neutropenia 
We report an extremely rare and complex case of a 44-year-old woman diagnosed with an early stage triple negative breast cancer in the setting of primary autoimmune neutropenia with a pre-existing severe neutropenia. This case-report demonstrates that adjuvant chemotherapy for breast cancer can be administered in a patient with severe neutropenia. The management is however complicated and requires careful monitoring of side-effects related to both chemotherapy and treatment of autoimmune neutropenia. The role of chemotherapy in the treatment of triple negative breast cancer, the approach to autoimmune neutropenia and potential interactions are reviewed. To our knowledge, this is the first case reporting on the use of chemotherapy in a patient with severe pre-existing primary autoimmune neutropenia.
doi:10.4137/BCBCR.S10767
PMCID: PMC3572877  PMID: 23440399
breast cancer; autoimmune neutropenia; chemotherapy

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