Breast Cancer

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"ABSTRACT


Objective: My objective was to investigate the experiences of women diagnosed with metastatic breast cancer.

Method: I did a qualitative study based on interview data. Fourteen women with metastatic breast cancer were recruited into a larger study of online support group use. Participants were interviewed by phone.

Results: The women indicated that they experience distress because of concerns about body image, declines in aspects of their sexual lives, and worries about the effect of stress on their illness. The stress that worries these women comes from fear of dying, fear of disease progression and debilitation, the loss of their future, and practical concerns. The women were also likely to experience a decline in daily activity after being diagnosed with metastatic disease. They become less active because of the physical symptoms of the illness and the side effects of treatments, the medicalization of their lifestyle, their desire to avoid stressful situations, the constraints imposed by their social world, and the need to maintain disability benefits. Although women are often in need of emotional and material support from others after they are diagnosed, social support can decrease, both because women find it difficult to be open about the difficulties they face and because the responses of others are not adequately supportive. Distress and declines in daily activity and social support can feed into each other to create a vicious circle.

Significance of results: This paper makes a significant contribution to the literature by providing a rich description of how metastatic breast cancer affects women. Further research, with more diverse samples, is needed in this understudied area."

This presentation is part of the Social Values in Medical Research track. Due to higher than national average breast cancer rates and deaths on Long Island the U.S. Congress in 1993 ordered a study of breast cancer on the island. The Long Island Breast Cancer Study Project (LIBCSP), federally funded under Public Law 103-43, conducted by the National Cancer Institute

Tumor microenvironment (TME) is a host for a complex network of heterogeneous stromal cells with overlapping or opposing functions depending on the dominant signals within this milieu. Reciprocal paracrine interactions between cancer cells with cells within the tumor stroma often reshape the TME in favor of the promotion of tumor. These complex interactions require more sophisticated approaches for cancer therapy, and, therefore, advancing knowledge about dominant drivers of cancer within the TME is critical for designing therapeutic schemes. This review will provide knowledge about TME architecture, multiple signaling, and cross communications between cells within this milieu, and its targeting for immunotherapy of cancer.

With the most recent advances in technology, computer programming has reached the capabilities of human brain to decide things for almost all healthcare systems. The implementation of convolutional neural network (CNN) and extreme gradient boosting (XGBoost) is expected to improve the accurateness of breast cancer detection. The aims of this research were to; i) determine the stages of CNN-XGBoost integration in diagnosis of breast cancer and ii) calculate the accuracy of the CNN-XGBoost integration in breast cancer detection. By combining transfer learning and data augmentation, CNN with XGBoost as a classifier was used. After acquiring accuracy results through transfer learning, this reasearch connects the final layer to the XGBoost classifier. Furthermore, the interface design for the evaluation process was established using the Python programming language and the Django platform. The results: i) the stages of CNN-XGBoost integration on histopathology images for breast cancer detection were discovered. ii) achieved a higher level of accuracy as a result of the CNN-XGBoost integration for breast cancer detection. In conclusion, breast cancer detection was revealed through the integration of CNN-XGBoost through histopathological images. The combination of CNN and XGBoost can enhance the accuracy of breast cancer detection.

A 41-year-old woman with breast cancer was referred to the pain management clinic for a course of acupuncture for intense pain following a subcutaneous mastectomy and a latissimus dorsi flap reconstruction. She was treated with a standard course of acupuncture for breast pain, using paravertebral segmental points, trigger points, plus contralateral LI4 on the non-lymphoedematous arm. She experienced an episode of galactorrhoea six days following the first treatment and during the second treatment. She had not previously lactated for four years. CT and MRI of the brain revealed no focal abnormality. Acupuncture has been used in to promote lactation in the Traditional Chinese literature using the ‘Tianzong’ acupoint SI11. This acupoint coincided with a trigger point over infraspinatus that was included in the neurophysiologically based acupuncture treatment. Quantitative analysis has shown an increase in the production of prolactin and oxytocin following acupuncture. These hormones ar...

Modulation of cellular antigens in chronically infected CEM cells by HTLV-IIIB. 0-propiolactone-treated cells were acetone-fixed and stained with monoclonal antibodies; hence membrane and cytoplasmic antigen is detected. Filled columns, infected; hatched columns, uninfected cells. Similar results were obtained by flow cytometnc analysis of intact cells. in pathogenicity among virus variants between and within HIVinfected individuals and AIDS patients.4

Doses in mammography should be maintained as low as possible without reducing the high image quality needed for early detection of the breast cancer. The breast is composed of tissues with very close composition and densities. It increases the difficulty to detect small changes in the normal anatomical structures which may be associated with breast cancer. To achieve the standards of definition and contrast for mammography, the quality and intensity of the X-ray beam, the breast positioning and compression, the film-screen system, and the film processing have to be in optimal operational conditions. This study sought to evaluate average glandular dose (AGD) and image quality on a standard phantom in 134 mammography units in the state of Minas Gerais, Brazil, between December 2004 and May 2006. AGDs were obtained by means of entrance kerma measured with TL LiF100 dosimeters on phantom surface. Phantom images were obtained with automatic exposure technique, fixed 28 kV and molybdenum anode-filter combination. The phantom used contained structures simulating tumoral masses, microcalcifications, fibers and low contrast areas. High-resolution metallic meshes to assess image definition and a stepwedge to measure image contrast index were also inserted in the phantom. The visualization of simulated structures, the mean optical density and the contrast index allowed to classify the phantom image quality in a seven-point scale. The results showed that 54.5% of the facilities did not achieve the minimum performance level for image quality. It is mainly due to insufficient film processing observed in 61.2% of the units. AGD varied from 0.41 to 2.73 mGy with a mean value of 1.3270.44 mGy. In all optimal quality phantom images, AGDs were in this range. Additionally, in 7.3% of the mammography units, the AGD constraint of 2 mGy was exceeded. One may conclude that dose level to patient and image quality are not in conformity to regulations in most of the facilities. This indicates that ongoing actions are needed to optimize image quality and radiation dose for early detection of the breast cancer.

HE WOMEN'S HEALTH INITIAtive (WHI) focuses on defining the risks and benefits of strategies that could potentially reduce the incidence of heart disease, breast and colorectal cancer, and fractures in postmenopausal women. Between 1993 and 1998, the WHI enrolled 161809 postmenopausal women in the age range of 50 to 79 years into a set of clinical trials (trials of low-fat dietary pattern, calcium and vitamin D supplementation, and 2 trials of postmenopausal hormone use) and an observational study at 40 clinical centers in the United States. 1 This article reports principal results for the trial of combined estrogen and progestin in women with a uterus. The trial was stopped early based on health risks that exceeded health benefits over an average follow-up of 5.2 years. A parallel trial of estrogen alone in women who have had a hysterectomy is being continued, and the planned end of this trial is March 2005, by which time the average follow-up will be about 8.5 years. The WHI clinical trials were designed in 1991-1992 using the accumulated evidence at that time. The primary outcome for the trial of estrogen plus progestin was designated as coronary heart disease (CHD). Potential cardioprotection was based on generally Author Information and Financial Disclosures appear at the end of this article. Context Despite decades of accumulated observational evidence, the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain. Objective To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States. Design Estrogen plus progestin component of the Women's Health Initiative, a randomized controlled primary prevention trial (planned duration, 8.5 years) in which 16 608 postmenopausal women aged 50-79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993-1998. Interventions Participants received conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n=8506) or placebo (n=8102). Main Outcomes Measures The primary outcome was coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the primary adverse outcome. A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, and death due to other causes. Results On May 31, 2002, after a mean of 5.2 years of follow-up, the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits. This report includes data on the major clinical outcomes through April 30, 2002. Estimated hazard ratios (HRs) (nominal 95% confidence intervals [CIs]) were as follows: CHD, 1.29 (1.02-1.63) with 286 cases; breast cancer, 1.26 (1.00-1.59) with 290 cases; stroke, 1.41 (1.07-1.85) with 212 cases; PE, 2.13 (1.39-3.25) with 101 cases; colorectal cancer, 0.63 (0.43-0.92) with 112 cases; endometrial cancer, 0.83 (0.47-1.47) with 47 cases; hip fracture, 0.66 (0.45-0.98) with 106 cases; and death due to other causes, 0.92 (0.74-1.14) with 331 cases. Corresponding HRs (nominal 95% CIs) for composite outcomes were 1.22 (1.09-1.36) for total cardiovascular disease (arterial and venous disease), 1.03 (0.90-1.17) for total cancer, 0.76 (0.69-0.85) for combined fractures, 0.98 (0.82-1.18) for total mortality, and 1.15 (1.03-1.28) for the global index. Absolute excess risks per 10000 personyears attributable to estrogen plus progestin were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while absolute risk reductions per 10000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures. The absolute excess risk of events included in the global index was 19 per 10000 person-years. Conclusions Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women. All-cause mortality was not affected during the trial. The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD.

There is considerable argument concerning the number of sentinel node biopsy cases with axillary dissection that surgeons should perform before they are eligible on abandoning axillary dissection in negative sentinel node patients. Papers that (1) address directly or indirectly the subject of credentialing or of learning curve, (2) report on a surgeon's performance, (3) are reported as feasibility or learning curve studies, or both, (4) discuss the learning curve issue, and (5) express an expert's opinion on the learning curve. The number of procedures of the learning curve can not be fixed for all surgeons. Only surgeons in specialized breast cancer centers can succeed in meeting current recommendations with 20 to 30 cases. Surgeons from affiliated community hospitals will need more than 30 cases, whereas broad-based surgeons might need as many as 60 cases with their current caseload. Not all surgeons will be able to offer the procedure to their patients by the current reco...

Ontologies can represent large, multidimensional spaces: classi- cal music, research in computer science in the UK, health care for breast cancer are examples of rich domains. There have been no easy ways to represent meaningful slices through these multi- dimensional spaces to privilege the parts of the domain that are of interest to a given user. mSpace, an interaction model

Objective. Little is known about how cancer physicians communicate with limited English proficient (LEP) patients. We studied physician-reported use and availability of interpreters. Data Sources. A 2004 survey was fielded among physicians identified by a population-based sample of breast cancer patients. Three hundred and forty-eight physicians completed mailed surveys (response rate: 77 percent) regarding the structure and organization of care. Study Design and Settings. We used logistic regression to analyze use and availability of interpreters. Principal Findings. Most physicians reported treating LEP patients. Among physicians using interpreters within the last 12 months, 42 percent reported using trained medical interpreters, 21 percent telephone interpreter services, and 75 percent reported using untrained interpreters to communicate with LEP patients. Only one-third of physicians reported good availability of trained medical interpreters or telephone interpreter services when needed. Compared with HMO physicians, physicians in solo practice and single-specialty medical groups were less likely to report using trained medical interpreters or telephone interpreter services, and they were less likely to report good availability of these services. Conclusions. There were important practice setting differences predicting use and availability of trained medical interpreters and telephone interpretation services. These findings may have troubling implications for effective physician-patient communication critically needed during cancer treatment.

Prediction of patients at highest risk for ipsilateral breast tumor recurrence (IBTR) after local excision of ductal carcinoma in situ (DCIS) remains a clinical concern. The aim of our study was to evaluate a published nomogram from Memorial Sloan-Kettering Cancer Center to predict for risk of IBTR in patients with DCIS from our institution.

BACKGROUND: The aim was to describe cancer detection method and frequency of screening mammography in women undergoing breast cancer surgery in 2000. STUDY DESIGN: Patients undergoing breast cancer surgery were identified through an institutional database.

Fatigue is the most prevalent and distressing symptom experienced by patients receiving adjuvant chemotherapy for early stage breast cancer. Higher fatigue levels have been related to sleep maintenance problems and low daytime activity in patients who have received chemotherapy, but knowledge is sparse describing these relationships prior to chemotherapy. The Piper Integrated Fatigue Model© guided this study, which describes sleep/wake, activity/rest, circadian rhythms and fatigue, and how they inter-relate in women with Stage I, II or IIIA breast cancer during the 48 hours prior to the first adjuvant chemotherapy treatment. The present report describes these variables in 130 females, mean age = 51.4 years; the majority were married and employed. Subjective sleep was measured by the Pittsburgh Sleep Quality Index (PSQI) and fatigue was measured by the Piper Fatigue Scale (PFS). Wrist actigraphy was used to objectively measure sleep/wake, activity/rest, and circadian rhythms. Mean PSQI score was 6.73 ±3.4, indicating poor sleep. Objective sleep/wake results were within limits of normal (WNL) established for healthy individuals, except for the number and length of night awakenings. Objective activity/rest results were WNL except for low mean daytime activity. Circadian rhythm mesor was 132.3(24.6) and amplitude was 97.2(22.8). Mean PFS score was 2.56 ±2.0, with 72% reporting mild fatigue. There were significant relationships between subjective and objective sleep, but no consistent patterns. Higher total and subscale fatigue scores were correlated with most components of poorer subjective sleep quality (r= 0.25 to 0.42, P = <0.005).

Angiogenesis is essential for tumor growth and metastases. Studies in breast carcinomas suggest that microvessel quantitation as a measure of angiogenesis might be one of the most powerful prognostic tools available. Node negative breast cancer is a particular group for which better prognostic markers would be helpful. We therefore measured microvessel density in a series of well characterised node negative breast carcinomas to evaluate angiogenesis as a prognostic marker and assess its relationship to epidermal growth factor receptor (EGFR) and estrogen receptor (ER), which have previously been reported to be of value. 109 patients with a mean age of 55 years and a median follow-up of 25 months were examined. Vessels were immunohistochemically highlighted using an antibody to platelet endothelial cell adhesion molecule CD31, and microvessel density was quantified using a Chalkley point eyepiece graticule. No significant correlation was observed with patient age, tumor size, grade, ER, or EGFR expression. In a univariate analysis of survival, whereas ER expression was not a significant indicator of either relapse-free (RFS) or overall survival (OS), vascular count (VC) predicted both early RFS and OS (p=0.01 and p=0.028 respectively). Furthermore, in patients with ER positive tumors, a subgroup usually considered to have a good prognosis, there was a significant reduction in RFS and OS if tumors had high VCs (p=0.05 and p=0.002 respectively). A further statistically significant reduction in RFS (p=0.05) was observed for EGFR positive highly vascular tumors. In a Cox proportional hazard model, VC remained a significant prognostic indicator for both RFS and OS (p=0.04 and p=0.01) and conferred a 6.6 and 3.5 times respective increased risk of mortality and relapse. These findings suggest that quantitation of angiogenesis is an independent predictor of survival in node negative breast carcinomas, and due to these high hazard ratios might be more useful than other recently described prognostic markers in selecting patients who would benefit from adjuvant therapy.

To investigate the efficacy of classical massage on stress perception and mood disturbances, 34 women diagnosed with primary breast cancer were randomized into an intervention or control group. For a period of 5 weeks, the intervention group (n = 17) received biweekly 30-min classical massages. The control group (n = 17) received no additional treatment to their routine health care. The Perceived Stress Questionnaire (PSQ) and the Berlin Mood Questionnaire (BSF) were used and the patients’ blood was collected at baseline (T1), at the end of the intervention period (T2), and 6 weeks after T2 (T3). Compared with control group, women in the intervention group reported significantly lower mood disturbances, especially for anger (p = 0.048), anxious depression (p = 0.03) at T2, and tiredness at T3 (p = 0.01). No group differences were found in PSQ scales, cortisol and serotonin concentrations at T2 and T3. However, perceived stress and cortisol serum levels (p = 0.03) were significantly reduced after massage therapy (T2) compared with baseline in the intervention group. Further research is needed to validate our findings.

Background and purpose: Investigation of the use of TomoTherapy and TomoDirect versus conventional radiotherapy for the treatment of post-operative breast carcinoma. This study concentrates on the evaluation of the planning protocol for the TomoTherapy and TomoDirect TPS, dose verification and the implementation of in vivo dosimetry. Materials and methods: Eight patients with different breast cancer indications (left/right tumor, axillary nodes involvement (N+)/no nodes (N0), tumorectomy/mastectomy) were enrolled. TomoTherapy, Tomo-Direct and conventional plans were generated for prone and supine positions leading to six or seven plans per patient. Dose prescription was 42 Gy in 15 fractions over 3 weeks. Dose verification of a TomoTherapy plan is performed using TLDs and EDR2 film inside a home-made wax breast phantom fixed on a randoalderson phantom. In vivo dosimetry was performed with TLDs. Results: It is possible to create clinically acceptable plans with TomoTherapy and TomoDirect. TLD calibration protocol with a water equivalent phantom is accurate. TLD verification with the phantom shows measured over calculated ratios within 2.2% (PTV). An overresponse of the TLDs was observed in the low dose regions (<0.1 Gy). The film measurements show good agreement for high and low dose regions inside the phantom. A sharp gradient can be created to the thoracic wall. In vivo dosimetry with TLDs was clinically feasible. Conclusions: The TomoTherapy and TomoDirect modalities can deliver dose distributions which the radiotherapist judges to be equal to or better than conventional treatment of breast carcinoma according to the organ to be protected.

This paper presents a new approach for breast cancer diagnosis using a combination of an Adaptive Network based Fuzzy Inference System (ANFIS) and the Information Gain method. In this approach, the ANFIS is to build an input-output mapping using both human knowledge and machine learning ability and the information gain method is to reduce the number of input features to ANFIS. An experimental result shows 98.23% accuracy which underlines the capability of the proposed algorithm.

Breast cancer is the most common malignancy among women worldwide. There is extensive literature on the relationship between body weight and breast cancer risk but some doubts still remain about the role of adipokines per se, the role of insulin and glucose regardless of obesity, as well as the crosstalk between these players. Thus, in this study, we intend to determine the relation between body mass index (BMI), glycaemia, insulinemia, insulin-resistance, blood adipokine levels and tumour characteristics in a Portuguese group of pre- and postmenopausal overweight/obese women with breast cancer. We evaluated clinical and biochemical data in 154 participants, divided in 4 groups: (1) control with BMI &lt;25 kg/m(2), n = 29 (CT); (2) control with BMI &gt;25 kg/m(2), n = 48 (CTOb); (3) breast cancer with BMI &lt;25 kg/m(2), n = 30 (BC); and (4) breast cancer with BMI &gt;25 kg/m(2), n = 47 (BCOb). In women with breast cancer, we also performed tumour characterization. We found that BCO...

Breast cancer radiotherapy can be an emotionally difficult experience. Despite this, few studies have examined the effectiveness of psychological interventions to reduce negative affect, and none to date have explicitly examined interventions to improve positive affect among breast cancer radiotherapy patients. The present study examined the effectiveness of a multimodal psychotherapeutic approach, combining cognitive-behavioral therapy and hypnosis (CBTH), to reduce negative affect and increase positive affect in 40 women undergoing breast cancer radiotherapy. Participants were randomly assigned to receive either CBTH or standard care. Participants completed weekly self-report measures of positive and negative affect. Repeated and univariate analyses of variance revealed that the CBTH approach reduced levels of negative affect [F(1, 38)=13.49; p=.0007, ω2=.56], and increased levels of positive affect [F(1, 38)=9.67; p=.0035, ω2=.48], during the course of radiotherapy. Additionally,...

Background: Inadequate photosynthesis or oral intake of Vitamin D are associated with high incidence and mortality rates of breast cancer in ecological and observational studies, but the dose-response relationship in individuals has not been adequately studied. Methods: A literature search for all studies that reported risk by of breast cancer by quantiles of 25(OH)D identified two studies with 1760 individuals. Data were pooled to assess the dose-response association between serum 25(OH)D and risk of breast cancer. Results: The medians of the pooled quintiles of serum 25(OH)D were 6, 18, 29, 37 and 48 ng/ml. Pooled odds ratios for breast cancer from lowest to highest quintile, were 1.00, 0.90, 0.70, 0.70 and 0.50 (p trend < 0.001). According to the pooled analysis, individuals with serum 25(OH)D of approximately 52 ng/ml had 50% lower risk of breast cancer than those with serum <13 ng/ml. This serum level corresponds to intake of 4000 IU/day. This exceeds the National Academy of Sciences upper limit of 2000 IU/day. A 25(OH)D level of 52 ng/ml could be maintained by intake of 2000 IU/day and, when appropriate, about 12 min/day in the sun, equivalent to oral intake of 3000 IU of Vitamin D 3. Conclusions: Intake of 2000 IU/day of Vitamin D 3 , and, when possible, very moderate exposure to sunlight, could raise serum 25(OH)D to 52 ng/ml, a level associated with reduction by 50% in incidence of breast cancer, according to observational studies.

To correlate the clinical features of women presenting with locally advanced breast cancer with event-free survival (EFS) and overall survival (OS) and to evaluate the patterns of relapse. A total of 200 patients presenting consecutively over 9 years with Stage III breast cancer were evaluated for age, socio-economic status (SES), tumour size and grade, number of involved lymph nodes, stage III sub-categories, estrogen and progesterone receptor (ER/PR) status, treatment profiles and responses, and sites of relapse. EFS and OS at 5 and 10 years were calculated. Median age was 45 years. Poorly differentiated tumours were found in 127 patients, while 128 had larger tumours (T3 and T4). Eighty women had extensive nodal involvement (N2 and N3), and 86 had Stage IIIA tumours. Chemotherapy was given to 44 patients before surgery and one of these patients achieved pathological complete response. At 5 and 10 years, EFS was 25% and 7%, and OS was 52% and 31%, respectively. By Cox regression a...

might influence breast tumor angiogenesis. Although angiogenesis is currently under intense investigation in breast cancer, the expression of VEGF in this tumor has yet to be studied. We show here evidence of hypoxic induction of VEGF up-regulation in human mammary fibroblasts, suggesting the possibility of paracrine influences by fibroblasts on endothelium within hypoxic regions of these tumors. Materials and Methods Cells were grown in monolayer cultures for detection of VEGF mRNA via protection assays, following hypoxic exposure [VEGF is also called vascular permeability factor (8, 9)]. Cells were grown in multicellular sandwich cultures to study both the levels and the subcellular location of VEGF protein on a cell-by-cell basis over oxygen/nutrient gradients via immunohistochemistry and digitized imaging. RNA Detection. Monolayers of early culture (third) passage mammary fibroblast cells, isolated from both breast tumor (B437) and normal breast tissue derived from reduction mammoplasty (B106) were plated in DMEM (GIBCO)with 20%fetalbovine serum(GIBCO)at 4 X 10@ cells/60-mmglass Petri dish. Cells were obtained from Dr. Michael Gould (Department of Human Oncology, University of Wisconsin). Fibroblast origin was verified by immunostaining with a monoclonal antibody against vimentin (Dako). Hy poxia (â€oe100 ppm 02) was achieved using a Bactron IV anaerobic chamber (Sheldon) with a self-contained incubator unit that uses a 5% H2-5%C02-90% N2-injected atmosphere and a palladium catalyst. Some cultures that had undergone a 24-h hypoxic period were reoxygenated with an additional 24-h oxygen (21%) incubation. For mRNA collection cells were lysed on site in 4 M guanidinium thiocyanate, 25 mM sodium citrate, 0.5% N-lauroylsarcosine and 0.1 M 2-mercapthoethanol, and total RNA was isolated using acid phenol. From human VEGF-165 cDNA (Calbio California Technology), a 146-base pair clone extending from nucleotides 440 to 585 was subcloned in a Blue script Il-KS vector (Stratagene) and utilized as the probe template. The solution hybridization RNase protection assay was performed using a high specific activity antisense riboprobe transcribed in vitro (10). For reference, cyclophilin mRNA was analyzed in each sample simultaneously with the VEGF mRNA. This technique afforded the simultaneous probing of the cyclophilin control and the VEGF bands, assuring no artifactual probing differences due to variations in gel workup. Human granulosa-lutein cells were used as positive controls (11). Total RNA was dissolved in 25-@.tl hybridization solution (4 Mguanidinium thiocyanate-0.! MEDTA, pH 7) and mixed with 250 pg of each probe. The protected materials were resolved through nondenatur ing 5% PAGE. Quantitation of the bands was performed using a phosphoim ager (Molecular Dynamics). Tumor-mimetic Sandwich CUltUres. Mixed-cell sandwich cultures were set up by plating on microscope slides breast-fibroblasts (isolated either from tumor or normal mammary tissue after reduction mammoplasty) along with MCF7 cells, each at a density of 1.7 X 10@ cells/slide. Single-cell sandwiches were cultured using either tumor or normal mammary fibroblasts plated at 1.7 X 10@ cells/slide. After 24-h incubation, a top slide (coated with Prosil) was placed on the cultures, sandwiching the cells and restricting cell access of medium to the 75-pm gap between the slides (Fig. 2). The medium reservoir functions as the vasculature feeding the cell population. In much the same manner as in a tumor, cell consumption and diffusion constraints (due to the narrow gap between slides) decrease the oxygen/nutrient availability as a function of distance into the sandwich.

The MammaPrint™ gene signature, currently used in clinical practice, provides prognostic information regarding the recurrence and potential metastasis in breast cancer patients. However, the prognostic information of the 70 genes included can only be estimated at the RNA expression level. In this study, we investigated whether copy number information of MammaPrint™ genes at the DNA level can be used as a prognostic tool for breast cancer, as copy number variations (CNVs) are major contributors to cancer progression. We performed CNV profiling of MammaPrint™ genes in 59 breast cancer cell lines and 650 breast cancer patients, using publicly available data in The Cancer Genome Atlas (TCGA) database. Statistical analyses including Fisher exact test, chi-square test, and Kaplan-Meier survival analyses were performed. All MammaPrint™ genes showed recurrent CNVs, particularly in TCGA cohort. CNVs of 32 and 36 genes showed significant associations with progesterone receptor and estrogen re...

To evaluate the difference between pre- and post-menopausal breast cancer regarding menstrual and reproductive risk factors The case-control study was conducted in Mayo Hospital, Lahore, between October 2008 and April 2009. Cases were breast cancer patients admitted in the surgical and oncology floors of the hospital. Controls were hospital patients without breast cancer. The study enrolled 150 cases and 300 controls. Menstrual and reproductive history was taken from both the cases and the controls. For every risk factor age-adjusted odds ratio (OR) and 95% confidence interval (CI) was calculated by logistic regression analysis, separate for pre- and post-menopausal women. Among the breast cancer patients, 42.7% were pre-menopausal and 57.3% were post-menopausal. Age at menarche had no association with breast cancer for both pre- and post-menopausal women. Nulliparity was a risk factor for both pre-menopausal (OR 4.1, 95% CI 1.4-12.6) and post-menopausal breast cancer (OR 8.2, 95% C...

A case of high-grade endometrial stromal sarcoma, confi ned into an intrauterine polypoid growth, in a woman with a history of breast cancer who was treated with adjuvant tamoxifen. Based on the fi ndings, a high-grade endometrial stromal sarcoma was diagnosed. The patient underwent a total hysterectomy and bilateral salpingo-oophorectomy with multiple omental biopsies. Pathological examination on multiple uterine sections showed the absence of residual tumor cells in the uterus. The endometrium showed patterns of glandular cystic hyperplasia. After 14 months of follow-up, the patient is well and free of disease. In deciding if tamoxifen therapy is warranted, all potentially life-threatening adverse events associated with tamoxifen should be considered, including endometrial adenocarcinoma or uterine sarcoma.

From September 1977 to November 1987 high-risk (i.e. with positive axillary lymph nodes, or tumor size >5 cm or skidfascia invasion) premenopausal and menopausal breast cancer patients have been included in 2 randomized trials. In both trials the primary surgical treatment was total mastectomy with axillary sampling. In the first trial (DBCG 77-B) 1034 patients all received postoperative radiotherapy (RT) and were further randomized to 1) no systemic treatment (O), 2) cyclophosphamide (C), or 3) cyclophosphamide + methotrexate + 5-fluorouracil (CMF). The chemotherapy was given for 1 year. With a median observation time of 7 years the actuarial survival after 9 years is 50, 60 and 65% respectively. Retrospectively, the survival benefit was observed to be most pronounced in patients with tumor size C5 cm and with <3 positive lymph nodes. In the subsequent study initiated in 1982 (82-B) all patients received CMF for 9 months. Furthermore they were randomized to 1) RT, 2) no further treatment, or 31 tamoxifen (TAM) for 1 year. As of November 1, 1987, 1308 patients have been included. At 4 years and with a median observation time of 2 years the survival is similar in the 3 groups. In conclusion, in high-risk premenopausal and menopausal patients adjuvant chemotherapy combined with RT resulted in a 20-30% relative reduction in mortality at 9 years compared with RT alone. Preliminary analysis of adjuvant CMF + RT, compared with CMF alone or with CMF + TAM, shows after a median observation time of more than 2 years no significant survival differences.

Purpose: Ongoing symptoms and impairments in quality of life (QOL) among breast cancer survivors remain a significant problem. We tested the feasibility and acceptability of a manualized Ayurvedic nutrition and lifestyle intervention for breast cancer survivors. Methods: Eligible participants had Stage I-III breast cancer, underwent treatment within the past year that included che-motherapy, and were without active disease. The 4-month individualized Ayurvedic intervention included counseling on nutrition, lifestyle, yoga, and marma (like acupressure) during 8 one-on-one visits with an Ayurvedic practitioner. Feasibility and acceptability were the primary outcomes. QOL (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ C30]) and symptoms-sleep disturbance (General Sleep Disturbance Scale [GSDS]), fatigue (Lee Fatigue Scale [LFS]), depressive symptoms (Center for Epidemiological Studies-Depression Scale [CES-D]), anxiety (Spielberger State-Trait Anxiety Inventory [STAI-S, STAI-T]), and stress (Perceived Stress Scale [PSS])-were measured prior to, at midpoint, and at the end of the 4-month intervention. Effect sizes (Cohen's d) were calculated along with paired t tests comparing baseline to end of month 4 time points. Mixed effects models were used for repeated measures analyses. Results: Participants (n ¼ 32) had a mean age of 48 years (SD ¼ 10). Retention at the end of the intervention was 84%. Among those who completed the intervention (n ¼ 27), adherence was high (99.5% of visits with practitioners attended). Large improvements were seen in QLQ-C30 emotional functioning (d ¼ 0.84, P < 0.001), QLQ-C30 cognitive functioning (d ¼ 0.86, P < 0.001), GSDS (d ¼-1.23, P < 0.001), and CES-D (d ¼-1.21, P < 0.001). Moderate improvements were seen in QLQ-C30 global health (d ¼ 0.65, p ¼ 0.003), LFS (d ¼-0.68, P ¼ 0.002), and PSS (d ¼-0.75, P < 0.001). No adverse events were observed due to the intervention.

The propeptides PICP and PINP are derived from the synthesis of type I collagen, a major matrix protein of bone and soft tissues. The aim of this cross-sectional study was to investigate their value as indicators of the aggressivity of breast cancer. Serum PINP, PICP, and total alkaline phosphatase were determined from 89 breast cancer patients. Forty had major bone and/or soft tissue metastases with an aggressive disease course: the progressive disease (PD) group. Forty-nine had either none or minor bone and/or soft tissue metastases with a stable clinical course: the stable disease group (SD). The mean value of PINP in the PD group was 7.2 times higher than that in the SD group (276 +/- 79 microg/l versus 38 +/- 3 microg/l, respectively; P = 0.005), whereas PICP mean value was only 1.7 times higher in the PD group (174 +/- 20 microg/l versus 100 +/- 5 microg/l; P = 0.001). The ratio of PICP to PINP was 1.02 +/- 0.07 in the PD group and 3.07 +/- 0.18 in the SD group (P &lt; 0.001)....

Topotecan (TPT), a highly active anticancer camptothecin drug, would benefit from nanocarrier-mediated site-specific and intracellular delivery because of a labile lactone ring whose hydrolysis inactivates the drug, poor cellular uptake resulting from both lactone hydrolysis and a titratable phenol hydroxyl, and the schedule-dependency of its efficacy due to its mechanism of action. We have encapsulated topotecan in liposomes using transmembrane gradients of triethylammonium salts of polyphosphate (Pn) or sucroseoctasulfate (SOS). Circulation lifetimes were prolonged, and the rate of drug release in vivo depended on the drug load (T 1/2 = 5.4 h vs. 11.2 h for 124 and 260 g TPT/mol PL, respectively) and the nature of intraliposomal drug complexing agent used to stabilize the nanoliposome formulation (T 1/2 = 11.2 h vs. 27.3 h for Pn and SOS, respectively). Anti-EGFR and anti-HER2-immunoliposomal formulations dramatically increased uptake of topotecan compared to nontargeted nanoliposomal topotecan and poorly permeable free topotecan in receptor-overexpressing cancer cell lines, with a corresponding increase in cytotoxicity in multiple breast cancer cell lines and improved antitumor activity against HER2-overexpressing human breast cancer (BT474) xenografts. We conclude that stabilization of topotecan in nanoliposomes significantly improves the targetability and pharmacokinetic profile of topotecan, allowing for highly active formulations against solid tumors and immunotargeting to cancer-overexpressing cell surface receptors.

Background: 1E10 monoclonal antibody is a murine anti-idiotypic antibody that mimics N-glycolyl-GM3 gangliosides. This antibody has been tested as an anti-idiotypic cancer vaccine, adjuvated in Al(OH) 3 , in several clinical trials for melanoma, breast, and lung cancer. During early clinical development this mAb was obtained in vivo from mice ascites fluid. Currently, the production process of 1E10 is being transferred from the in vivo to a bioreactor-based method.

The research of body image among breast cancer patients is characterized by some limitations, such as the lack of longitudinal studies or the absence of a multidimensional perspective of body image. This study intends to overcome these limitations, by examining the evolution of body image dimensions (investment, emotions and evaluations) from the period of surgery (T1) to 6-months after the treatment’s ending (T2). It also aims to explore the predictors of body image at T2 and, simultaneously, the predictive role of initial body image to psychosocial adjustment at T2.A total of 56 breast cancer patients participated in both assessments and completed a battery of instruments that included measures of body image dimensions (appearance investment, self-consciousness of appearance, shame and appearance satisfaction) and psychosocial adjustment (quality of life and emotional distress).Within the dimensions of body image, only shame increased over time. In general, initial levels of investment predicted subsequent body image dimensions and having a mastectomy done was associated with higher shame and lower appearance satisfaction at T2. Initial body image did not predict later adjustment, with the exception of depression, where appearance investment played a relevant role.Our findings contributed to the advance of knowledge in this area, providing relevant data about the evolution of body image dimensions, its predictors and its predictive role on psychosocial adjustment among breast cancer patients. This study also suggested some clinical implications that can assist health professionals to implement strategies focused on body image throughout the disease.

hemoglobin and serum albumin level, operating time, operative blood loss, and blood transfusions. The febrile morbidity rates and the operative site infection rates were similar in the two groups. Ninety vaginal drains were removed by day 3. By day 6, 55% of patients in group 1 had at least one sidewall drain, with a mean drainage of 150 ml/day. The median postoperative stay was similar in both groups. A pelvic lymphocyst developed in one patient in each group. The single vaginal closed-suction drain is safe, efficient, more acceptable to patients and more cost-effective.

Light emitting diodes (LED), which are available as small monochromatic light sources with characteristic features such as maximum illumination power combined with minimum energy consumption and extremely long lifespan have already proved as a highly potential low-cost alternative for specific diagnostic applications in clinical medicine such as tuberculosis fluorescence microscopy. Likewise, the most reliable evaluation of Her-2/neu (c-erbB2) gene amplification, which has been established in the last few years for routine diagnosis in clinical pathology as determinant towards Herceptin-based treatment of patients with breast cancer, is based on fluorescence in situ hybridization (FISH) and corresponding high priced fluorescence equipment. In order to test the possibility to utilize the advantages of low-cost LED technology on FISH analysis of c-erbB2 gene expression for routine diagnostic purposes, the applicability of a standard bright field Carl Zeiss Axiostar Plus microscope equipped with a Fraen AFTER* LED Fluorescence Microscope Kit for the detection of Her-2/neu gene signals was compared to an advanced Nikon Eclipse 80i fluorescence microscope in combination with a conventional 100W mercury vapor lamp. Both microscopes were fitted with the same Quicam FAST CCD digital camera to unequivocally compare the quality of the captured images. C-erbB2 gene expression was analyzed in 30 different human tissue samples of primary invasive breast cancer, following formalin fixation and subsequent paraffin-embedding. The Her2/neu gene signals (green) were identifiable in the tumor cells in all cases and images of equal quality were captured under almost identical conditions by 480 nm (blue) LED module equipped standard Axiostar microscope as compared to conventional fluorescence microscopy. In this first attempt, these monochromatic LED elements proved in principle to be suitable for the detection of Her-2/neu gene expression by FISH. Thus, our own experiences emphasize the high potential of this technology to provide a serious alternative to conventional fluorescence microscopy in routine pathology; representing a sustainable technological progress, this low-cost technology will clearly give direction also to the growing field of molecular pathology.

Heparin-like polysaccharides possess the capacity to inhibit cancer cell proliferation, angiogenesis, heparanase-mediated cancer cell invasion, and cancer cell adhesion to vascular endothelia via adhesion receptors, such as selectins. The clinical applicability of the antitumor effect of such polysaccharides, however, is compromised by their anticoagulant activity. We have compared the potential of chemically O-sulfated and N,O-sulfated bacterial polysaccharide (capsular polysaccharide from E. coli K5 [K5PS]) species to inhibit metastasis of mouse B16-BL6 melanoma cells and human MDA-MB-231 breast cancer cells in two in vivo models. We demonstrate that in both settings, O-sulfated K5PS was a potent inhibitor of metastasis. Reducing the molecular weight of the polysaccharide, however, resulted in lower antimetastatic capacity. Furthermore, we show that O-sulfated K5PS efficiently inhibited the invasion of B16-BL6 cells through Matrigel and also inhibited the in vitro activity of heparanase. Moreover, treatment with O-sulfated K5PS lowered the ability of B16-BL6 cells to adhere to endothelial cells, intercellular adhesion molecule-1, and P-selectin, but not to E-selectin. Importantly, O-sulfated K5PSs were largely devoid of anticoagulant activity. These findings indicate that O-sulfated K5PS polysaccharide should be considered as a potential antimetastatic agent.

The study measured the prevalence and costs of complementary therapy use by women diagnosed with breast cancer in the South Thames NHS region. A postal questionnaire was sent to a sample of 1023 women from the Thames Cancer Registry who had been diagnosed with breast cancer in the previous 7 years. Just over a ®fth (22.4%) had consulted a complementary practitioner in the previous 12 months. Almost one third (31.5%) had done so since diagnosis. Almost £17 000 had been spent on visits in the previous year. The women using complementary medicine after diagnosis were slightly younger, more educated and more likely to have used complementary medicine before their diagnosis than non-complementary medicine users. In conclusion, signi®cant numbers of women are visiting complementary therapists for health reasons following a breast cancer diagnosis. The out of pocket costs per user, with notable exceptions, are modest. Use of practitioners of complementary therapies following diagnosis is a signi®cant and possibly growing phenomenon. #