Hereditary cancer comprises more than 10% of all breast cancer cases. In patients with a family history suggestive of a hereditary component, a mutation is often identified in the high penetrant genesBRCA1andBRCA2. Several founder mutations have been detected in some Jewish communities, yet noBRCA1/2founder mutation had been known in Kurdish Jews. Here, we describe the validation of a 22 hereditary cancer gene panel and aBRCA1mutation found in 4 women from 2 unrelated Kurdish Jewish families utilizing this gene panel.A panel spanning the coding sequences of 22 familial cancer-related genes was planned. Genomic DNA was taken to create libraries using this panel, which were then sequenced using the Ion Torrent PGM. The panel's validity in detecting mutations was tested on 25 samples with previously identified point mutations in theBRCA1,BRCA2,MLH1andPMS2genes; the panel did not test for large deletions or insertions. All previously identified mutations were detected. Next, a different set of 40 cancer patients of Kurdish Jewish descent diagnosed with cancer before the age of 50 years was tested. We identified theBRCA1mutation,c.224_227delAAAG(dbSNP ID rs80357697), in 4 women from 2 unrelated Jewish Kurdish families. The probands were diagnosed with cancer at a young age and had significant family history, suggesting a founder mutation in this population. We suggest testing Kurdish Jewish women with a personal or family history of breast and/ or ovarian cancer for this mutation.
Breast cytology, in particularly fine needle aspiration biopsy (FNAB), has been used for many years as a diagnostic tool for managing patients with breast lesions. In experienced hands, FNAB is highly sensitive and specific. Other benefits include its low cost, minimal invasiveness, and ability to provide same-day diagnosis. Despite all these benefits, FNAB has gradually been replaced by core needle biopsy (CNB) because of its high error rates when there is a lack of experienced cytopathologists, its inability to distinguish between invasive and in situ carcinoma, and most importantly, its inability to provide adequate and suitable materials for quantitative evaluation of HER2 and other prognostic markers. Other uses of breast cytology include touch preparation cytology for intraoperative evaluation of sentinel lymph nodes and surgical margins of lumpectomy specimens and for providing same-day diagnosis of CNB. In addition, breast cytology, such as ductal lavage and nipple fluid cytology, has also found applications in risk assessment for women at high risk for developing breast cancer. With the increased utilization of molecular technologies, genomic and proteomic studies have been successfully applied to breast cytologic preparations. It would not be far fetched to predict that in the very near future, the clinical application of molecular analyses will be routine ancillary testing in breast cytology, thus allowing early cancer detection, and improved tumor characterization as well as prediction of patients' outcomes and therapeutic responses.
Breast cancer is the second leading cause of cancer death in women. Approximately 15-20% are triple negative breast cancer (TNBC: no protein expression of estrogen receptor, progesterone receptor, nor human epidermal growth factor receptor 2), representing one of the most challenging molecular subtypes of breast cancer. TNBC encompasses a heterogenous group of breast cancers that are not generally responsive to targeted therapies for hormone and growth factor receptors. Compared to their hormone receptor-positive counterparts, TNBC cases are associated with poor prognosis, worse overall survival and earlier recurrence. The purpose of this review is to describe the clinicopathologic features, molecular variants, associations with the BRCA genes, and therapeutic approaches for TNBC. New TNBC-targeted drug therapies are currently under investigation and include poly-ADP-ribose polymerase (PARP) inhibitors, platinum-based drugs, anti-epidermal growth factor receptor (EGFR) inhibitors, and anti-vascular endothelial growth factor receptor (VEGF) inhibitors. Both clinical trials and basic research are needed to further our understanding of the best treatment options for patients with TNBC. Keyword: Triple negative breast cancer.
Compared to epithelial lesions, spindle-cell lesions of the breast are relatively uncommon and, because of that, may cause diagnostic difficulty. The majority of these spindle cell lesions, such as fibromatosis, nodular fasciitis, spindle- cell carcinoma, inflammatory myofibroblatic tumor and angiosarcoma, resemble their more common non-mammary counterparts. A few others, such as pseudoangiomatous stromal hyperplasia for example, specifically arise in breast. This review discusses these mammary spindle cell lesions with a focus on their salient histological features.
Background: Most studies on cancer patient preferences and information needs have not focused specifically on elderly breast cancer patients. Objective: To determine factors which are taken into account by elderly breast cancer patients (>70 years of age) when deciding between primary endocrine therapy or surgery and between mastectomy or wide local excision. Methods: Cross-sectional study of 34 female breast cancer patients who were at least 70 years of age at the time of diagnosis. Structured interviews were conducted either after a follow-up clinic appointment or at home via a telephone interview. Results: Seventy-six per cent of patients were given a choice of treatment and the patients who felt that they were not given a choice did not prefer to choose. Forty-two per cent of patients chose primary endocrine therapy based on the surgeon's recommendation. The same proportion reported that they were afraid of surgery. A quarter wanted to try tablets first and were prepared to undergo surgery if unresponsive. All patients who chose a modified radical mastectomy +/- axillary node clearance or sampling felt that it was safer and wanted to avoid the possibility of further surgery. All patients were satisfied with the amount of information provided and emphasized that the service provided by breast care nurses was invaluable. Conclusion: Not all patients based their decision on the surgeon's recommendation. Some patients were not given any recommendation. Individual preferences of patients should be determined and the management plan should be tailored accordingly.
Primary cilia are non-motile, microtubule-based appendages extending from the surfaces of most vertebrate cells.The function of primary cilia is cell-type dependent.However, they are known to serve as sensors of the extracellular environment by sensing mechanical forces and chemical constituents in several different cell types.They also function as critical platforms for several signaling pathways, including hedgehog and platelet derived growth factor (PDGF) signaling, and function in maintaining cell polarity.While present on many types of normal cells, including epithelial cells of the breast, they have been shown to be decreased or absent in many cancers.This review discusses the relative decrease in primary cilia in a variety of cancers and the known consequences of the presence or absence of primary cilia during tumorigenesis.This review also addresses possible etiologies for the loss of primary cilia in cancer, potential functions for primary cilia in human breast epithelium and subsequent consequences of the loss of primary cilia during breast carcinogenesis.
Columnar cell change in breast epithelium is frequently encountered in biopsies performed for evaluation of radiographically detected microcalcifications.While columnar cell change by itself is typically of no clinical consequence, on occasion cytologic atypia may be present, a finding now termed "flat epithelial atypia (FEA)".Morphologic, immunophenotypic, and genetic associations between FEA and low grade in situ and invasive breast carcinomas provide compelling evidence that FEA represents a precursor lesion in the spectrum of low grade breast neoplasia.Despite this information, the ultimate clinical impact of FEA and, thus, the best management strategy for it remains unknown.Herein, current concepts regarding FEA are reviewed, including pathologic definition, evidence supporting its role as a neoplastic precursor, and suggested management strategies.
Breast cancer is the second leading cause of cancer death in women. Approximately 15-20% are triple negative breast cancer (TNBC: no protein expression of estrogen receptor, progesterone receptor, nor human epidermal growth factor receptor 2), representing one of the most challenging molecular subtypes of breast cancer. TNBC encompasses a heterogenous group of breast cancers that are not generally responsive to targeted therapies for hormone and growth factor receptors. Compared to their hormone receptor-positive counterparts, TNBC cases are associated with poor prognosis, worse overall survival and earlier recurrence. The purpose of this review is to describe the clinicopathologic features, molecular variants, associations with the BRCA genes, and therapeutic approaches for TNBC. New TNBC-targeted drug therapies are currently under investigation and include poly-ADP-ribose polymerase (PARP) inhibitors, platinum-based drugs, anti-epidermal growth factor receptor (EGFR) inhibitors, and anti-vascular endothelial growth factor receptor (VEGF) inhibitors. Both clinical trials and basic research are needed to further our understanding of the best treatment options for patients with TNBC. Keyword: Triple negative breast cancer.
Background: The relationship between lymphocyte infiltrates (LIs) and breast cancer outcome remains controversial.We performed this meta-analysis to elucidate the relationship.Methods: A literature search identified 21 eligible studies.Results: 16,097 patients were included.Multivariate analyses data for patients with unspecified receptors status showed that rich LIs expression was associated with 52% (hazard ratio [HR] = 0.48; 95% confidence interval [CI], 0.30-0.77),and 29% (HR = 0.71; 95% CI, 0.63-0.80)reduction in the risk of relapse and death, respectively.In the neoadjuvant setting, rich LIs predicted a 28% increase in complete pathological response rate.The prognostic and predictive utility of rich LIs was restricted to patients with estrogen receptor negative (ER-) or triple negative disease.Only rich CD8+ T cells tumors demonstrated clinical utility. Conclusion:LIs significantly correlated to outcome predominantly in ER-tumors.Integrating immunotherapy with conventional therapy may warrant future research in breast cancer.
For over 70 years, long chain fatty acids have been implicated in the development and progression of breast cancer.Although the exact role remains to be elucidated, dietary factors have been implicated in approximately 35% of cancer deaths.Currently, biomarker, animal and in vitro studies suggest that the individual fatty acids have differing roles in the promotion or prevention of breast cancer development and progression.The goal of this review is to assess epidemiological, animal and cellular studies with respect to the role of dietary long chain fatty acids in breast cancer risk.Subsequently we identify the common findings in these studies, discuss important factors that may influence human studies and evaluate the current dietary fat recommendations with respect to these findings.
In this issue of the Open Breast Cancer Journal we have assembled a group of manuscripts from experts in the field of diagnostic and experimental breast pathology to report on changes influencing clinical care and to provide new insights into the mechanistic underpinnings of mammary gland neoplastic progression.Harigopal and Chhieng, at Yale University, reviewed the changing face of breast cytology focusing, in part, on "the benefits and limitations of fine needle aspiration biopsies in diagnoses of breast lesions" as western societies increasingly abandon this technique for core biopsy interpretation.They weave into their historical tapestry the rise of molecular cytopathology and the continued use of cytology as part of intraoperative examination by pathologists.Adams reporting from Emory University covers one of the newly rediscovered human breast premalignant conditions, flat epithelial atypia, an outgrowth of the attempt for better defining of columnar cell lesions through breast core biopsies.Perhaps most critically, the realization that all such lesions are not flat and that via morphologic, immunophenotypic, and molecular criteria, these lesions are better tied to breast neoplasia ending in invasive carcinoma is more fully explored.Wei and Hammed take a different direction in breast pathology diagnoses by reporting on spindle cell lesions within this organ.They emphasize a broad range of lesions stretching from reactive conditions to the neoplastic and discuss entities such as fibromatosis and nodular fasciitis (traditionally thought of as soft tissue tumors) through pseudoangiomatous stromal hyperplasia, clearly a breast specific entity, and then turn to other, more exotic, entities including inflammatory myofibroblastic tumor and reactive spindle cell nodule ending with a highly malignant spindle cell carcinoma and angiosarcoma.
Introduction: Male breast cancer (MBC) is a rare condition, which accounts for less than 1% of all breast cancer diagnoses.Because of this, there is a paucity of focussed work available and most data is derived from female breast cancer studies.Recently, there has been speculation of increased incidence, and we sought to verify this by reviewing our own experience with MBC. Methods and Materials:A retrospective analysis was designed to include patients seen at our institution from 1 st July, 2000 until 31 st July 2009, and information was derived from the patients' records.Results: Seven (7) patients were found, with an average age of 66.6 years.All patients had discovered their lumps on selfbreast examination as their main presenting complaint, and none noted any other breast symptoms such as mastalgia, bleeding or discharge.Four (4) patients were found to have a family history for malignancy, including female breast, prostate, lung and gastric cancers and Hodgkin lymphoma.Two (2) patients were found to have been exposed to gynaecomastia-inducing agents for extended periods of time.One (1) patient had undergone chest wall irradiation for Hodgkin lymphoma 30 years prior to his diagnosis of MBC.86% were diagnosed on histology, with 100% of these having ductal cancer, with 100% oestrogen-receptor positivity and 86% progesterone-receptor positivity. Conclusion:Patients with MBC are an uncommon within our institution.Features associated with its presentation compare to what is published within the literature.
Aim: The aim of this study was to correlate breast cancer by common breast cancer risk factors in the Sudan.Methodology: Using a purposeful questionnaire 150 female breast cancer patients and 100 apparently health controls were asked detailed information on about risk factors.Results: Out of the 150 women with breast cancer, 38 (25.3%), 22(14.7%),26(17.3%),20(13.3%),21(14%), 11(7.3%),72(48%), and 86(57.3%)were identified as having a previous history of oral contraceptives usage, a family history of breast cancer, a past history of benign breast disease, a previous history of breast cancer, a previous breast biopsy, claimed other cancers in their families, confessed a pesticides exposure, and over weigh in most of their lives respectively.Out of the 150 women, 44(29.3%)were found to have a previous physical activity.Moreover, 44.8% and 66.9% have attended the menarge at the age of 13 and 14 respectively.Of these factors, statistical significant risks were found with, past history of benign breast disease (P < 0.04), previous breast biopsies (P <0.07), pesticides and plasticizers exposure (P < 0.01 and 0.04), period of being over weight (P <0.001), practice physical activities (P <0.0001), unmarried (P <0.002), decreased number of children (P <0.002).According to the ethnic group, Gaalyaeen tribes represented 61(40.7%) of the study subjects.Most of the patients were from Khartoum state, constituting 37.3%. Conclusion:There was variable exposure to many risk factors for breast cancer in the Sudan.The study suggests further separate measurement of risk factors for breast cancer, as well as, factors that might reduce those risk factors.Cohort mean of evaluation is highly recommended.
Background: Cancer Antigen 15-3 (CA 15-3) is a tumor-associated antigen used as serum marker for breast cancer surveillance in patients and for monitoring the response to treatment.Aim of this study was to retrospectively evaluate CA 15-3 as a prognostic factor in early detection of breast cancer relapse as well as to analyze the statistical correlation between CA 15-3 levels and clinical-pathological parameters including staging, grading, estrogen and progesterone receptors.Methods: Sera of 726 women with breast carcinoma obtained preoperatively and postoperatively were assayed for CA 15-3 by chemoluminescent immunometric assay.Results: We found that the mean serum CA 15-3 levels in patients before surgery were significantly higher (36.59U/ml) compared with those of CA 15-3 after surgery (27.11U/ml).We also found that elevated preoperative serum levels of CA 15-3 were significantly correlated with the presence of metastatic disease.In particular, among 305/700 patients (43,6%) that displayed over cut-off (>40U/ml) preoperative levels of CA 15-3, 94 patients (30,8%) developed advanced disease (metastases to distant sites).By contrast, in a subgroup of 395/700 patients (56.4%) with CA 15.3 serum levels < 40U/ml, only 32/305 patients (8%) showed signs of advanced disease during follow-up.Cox regression analysis revealed that only the presence of metastasis and the increased serum levels of CA 15-3 after surgery are significant risk factors for relapse of disease. Conclusion:Elevated preoperative concentrations of CA 15-3 may be a useful predictive factor for cancer progression in postoperative patients.
Background: Breast Cancer (BC) is molecularly diverse disease that has been sub-classified in four major subtypes; (a) luminal A [estrogen and/or progesterone positive and Her 2neu negative], (b) luminal B [estrogen and/or progesterone positive and Her 2 neu positive], (c) Basal [triple negative] and (d) Her 2 neu [estrogen and/or progesterone negative and Her 2 neu positive].Luminal A and luminal B are less aggressive subtypes and are associated with better prognosis as compared to basal and Her 2 neu subtypes.We aimed to evaluate the pattern of breast cancer subtypes and response to treatment and outcomes in Saudi women.Materials and Methods: Between February 1988 and August 2008, confirmed BC from a cohort of 112 patients were subtyped according to the hormone receptor status and Her 2 neu overexpression which were determined by immunohistochemistry (IHC) and Fluorescence in situ hybridization (FISH).The prognostic value of the BC subtypes for locoregional control (LRC), distant metastases control (DMC), disease free survival (DFS) and overall survival (OS) was investigated using Kaplan-Meier curves and multivariable Cox regression model.Results: Pattern of BC subtypes in Saudi women were as; luminal A (32.1%), Her 2 neu ((32.1%),luminal B (25.9%) and basal (9.8%).Luminal A and Her 2 neu subtypes were predominant (34.4% and 33.3%) in premenopausal and basal subtype (26.3%) was predominant in postmenopausal women.Ten year DFS was 95%, 62%, 50% and 42.8% in luminal A, B, Her 2 neu and basal types respectively (p 0.003).No difference in LRC among different subtypes was seen (p 0.9) and DMC was found poor in Her 2 neu and basal subtypes (p 0.03). Conclusion:Luminal A subtypes has favorable prognosis in Saudi women with breast cancer as compared to other subtypes.Molecular subtyping can be helpful in predicting the treatment outcomes in breast cancer patients.
162 Background: Use of survivorship care plans (SCPs) was recommended by the IOM in 2005, but benefits are a subject of ongoing debate. ASCO’s Cost of Cancer Care Task Force cited use of unnecessary imaging and tumor markers in breast cancer follow up amongst the “top five” list to improve quality. Communication with breast cancer survivors about guideline based post-treatment follow-up may be improved with SCPs, however few studies have addressed measurable outcomes. We describe use of SCPs to coordinate follow-up care in a multidisciplinary practice. Methods: In 2009, our breast surgeons, medical oncologists, and nurse practitioners agreed upon guidelines for follow up of breast cancer patients, developed a Survivorship Care Program to follow active treatment and implemented use of SCPs. Prior to 2009, follow up was partly determined at physician discretion and partly patient-driven, often with both medical and surgical providers seeing patients within short spans of time. To improve access to two part-time breast surgeons, guidelines were established to shift follow-up to medical oncologists and nurse practitioners. After diagnosis, patients were given comprehensive SCPs, which included recommended follow-up visits and testing. Wait times and numbers of new surgical patients were measured before and after use of SCPs. Results: Implementation of SCPs occurred during 2009; data from time periods two years before and after SCPs is listed below. Wait times were measured from call to first appointment. New patients included both benign and malignant breast disease. Conclusions: SCPs were useful in re-engineering follow-up habits of clinicians, adding value to each visit and gaining acceptance from established patients regarding recommended surveillance. Patients expressed that uncertainty experienced at the end of active treatment is mitigated by remaining in an environment that can be easily transitioned back to other clinical services. SCPs contributed to reduced wait times and increase in volume of new patients seen by breast surgeons. Future studies should assess contribution of SCPs to reducing unnecessary tests and improving compliance with ASCO guidelines. [Table: see text]
An anti-cancer agent containing benzene-poly-carboxylic acids complex with cis-diammineplatinum (II) dichloride (BP-C1) was developed to establish a low toxic and cost effective treatment of breast cancer.The study was aimed to investigate if BP-C1 could be given continuously without rest periods and to estimate Maximum Tolerated (MTD) and Minimum Efficient Dose (MED) in metastatic breast cancer (MBC) treatment.A non-randomized, multicentre trial with 3-level Response Surface Pathway design was performed.Five MBC patients were included at each of the three design levels.BP-C1 was daily administrated intramuscularly during 32 days.The first five patients were given a cumulative dose of 0.64 mg/kg bodyweight.Based on the obtained results, the dose was increased /decreased for the next five patients in the next design level.The main variable was the National Cancer Institute Common Toxicity Criteria (NCI-CTC).Cumulative doses of 0.96 mg/kg or higher were defined as high-dose.One moderate and one mild increase in maximum NCI-CTC were found on 0.64 mg/kg, one mild increase occurred on 0.96 mg/kg and no changes were detected on 1.12 mg/kg.The Sum NCI-CTC increased (p=0.07) in the low-dose group, but reduced (p=0.09) in the high-dose group.In the high-dose group, 62.5% of the patients were classified as responders including one complete responder compared to 28.6% in the low-dose group.In conclusion, BP-C1 can safely be administrated continuously during 32 days.The MTD is larger than 1.12 mg/kg and MED estimated to 0.96 mg/kg.
In order to know the associations between multifocality (MF), without related multicentricity (MC), and common clinical and biological parameters, and posterior influence in breast carcinoma behavior, we have developed this study. 816 successive women affected from invasive breast carcinomas, of which 96 were multifocal and 720 non- multifocal were included in the study. We considered age, size, lymph node involvement, distant metastasis, histological grade, ploidy, cellular synthesis phase, as well as expression of estrogen receptor (ER), progesterone receptor (PgR), androgen receptor (AR), p53, bcl2 and Ki67 by immunohistochemical assays. Taken as a whole, multifocal invasive carcinomas (11%) showed exclusively more distant metastasis and more tumor- related-deaths. However, when tumors were classified according to histological type, in ductal carcinomas MF courses exclusively with greater lymph node involvement, while in non ductal carcinomas MF showed higher percentage of distant metastasis, higher proliferation and higher number of recurrences. Also, there were NO differences between axillary lymph node involvement and tumor size in multifocal tumors regardless of histology. Our results suggest: 1) MF was found in 11% of invasive breast carcinomas and was associated with higher distant metastasis and number of tumor-related-deaths. 2) in invasive ductal carcinomas, MF was associated, exclusively, with increased axillary node involvement, whereas in other histological types, with a predominance of lobular, it did with higher distant metastasis, cell proliferation and recurrence number, suggesting, in this subtype of tumors where there is higher prognostic/diagnostic value has the MF presence.
In 2006 Myriad Genetic Laboratories, Inc. introduced BRACAnalysis Large Rearrangement Test (BART) to detect additional large genomic rearrangements in BRCA1 and BRCA2, which went undetected by Comprehensive BRACAnalysis. We retrospectively identified all patients within our community oncology practice that underwent Comprehensive BRACAnalysis testing from 2002 through 2006 and evaluated each of the 37 negative patients for BART eligibility to identify potential candidates for the additional testing. Two patients met published criteria, of which one was deceased and the other is considering BART testing. Overall, retrospective systematic review to identify patients eligible to undergo BART testing who have previously tested negative by BRACAnalysis will have a very low yield. We recommend patients with prior negative Comprehensive BRACAnalysis be evaluated for BART eligibility as they are seen in clinic for follow-up and offered the additional testing at that time if clinically appropriate.
Introduction: Breast cancer is the most common cancer among women in Jordan.Age standardized incidence rate for cervical cancer has been estimated at 3.6 per 100,000 women.This report presents the results of breast and cervical cancer screening practicesamong a nationally representative sample of Jordanian women aged 35 years or above.Method: We used data from the third Jordan Behavioural Risk Factor Surveillance System (2007) among a nationally representative sample of Jordanian women aged 35 years (n=1,157).Logistic regression was used to examine the associations between each of breast and cervical cancer screening practices and selected socio-demographic characteristics.Results: Only 12.4% of women aged 35 years or older reported ever having a mammography.One fifth reported ever having a clinical breast examination at least once in their life time.Over one quarter (27.1%) of the women reported that they perform self-breast examination on monthly basis, and 41.7% reported ever having performed a self-breast examination.Among ever-married women aged 35 years or more, Pap smear test was performed by 27.8% during their life.The reported low practices have shown substantial differences across regions, age groups, level of education, family income, marital status, and source of medical services. Conclusion:The low reported cancer screening activities among women in Jordan calls for action.Data on current screening practices is a primary step to provide health professionals, and policy-makers with the information necessary to identify priorities and to facilitate cancer control, policy development, and planning.
