Breast

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 [email protected] 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.

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.

Targeted mass spectrometry is a promising technology for site-specific quantification of posttranslational modifications. However, a major constraint is the limited sensitivity for quantifying low-abundance PTMs, requiring the use of affinity reagents for enrichment. Herein, we demonstrate the direct site-specific quantification of ERK phosphorylation isoforms (pT, pY, pTpY) and their relative stoichiometry using a sensitive targeted MS approach termed high-pressure, highresolution separations with intelligent selection, and multiplexing (PRISM). PRISM provides effective enrichment of target peptides into a given fraction from complex mixture, followed by selected reaction monitoring quantification. Direct quantification of ERK phosphorylation in human mammary epithelial cells (HMEC) was demonstrated from as little as 25 μg tryptic peptides from whole cell lysates. Compared to immobilized metal-ion affinity chromatography, PRISM provided ∼10-fold higher signal intensities, presumably due to the better peptide recovery of PRISM. This approach was applied to quantify ERK phosphorylation dynamics in HMEC treated by different doses of epidermal growth factor at both the peak activation (10 min) and steady state (2 h). The maximal ERK activation was observed with 0.3 and 3 ng/mL doses for 10 min and 2 h time points, respectively. The dose−response profiles of individual phosphorylated isoforms showed that singly phosphorylated pT-ERK never increases significantly, while the increase of pY-ERK paralleled that of pTpY-ERK. This data supports for a processive, rather than distributed model of ERK phosphorylation. The PRISM-SRM quantification of protein phosphorylation illustrates the potential for simultaneous quantification of multiple PTMs.

Background: Although radiotherapy (RT) after mastectomy was an established treatment for patients with 4 or more positive axillary lymph nodes, it is still unclear it role in women at moderate risk for locoregional recurrence such as patients with 1−3 positive nodes. The purpose of this analysis was to evaluate the results of postmastectomy RT in patients with 1−3 positive nodes and negative nodes with grade 3 tumors. Patients and Methods: We evaluated 482 early breast cancer patients (node negative with grade 3 tumors, or 1−3 positive nodes any grade tumors) who were treated with radical mastectomy and after that either with adjuvant chemotherapy cyclofophosphamide, methotrexate and fluorouracil (CMF) (N = 172) or adjuvant endocrine therapy [ovarian ablation by irradiation (N = 139) or Tamoxifen (N = 171)]. Adjuvant endocrine therapy was given to those patients with PgR positive tumors, regardless of ER content. In PgR negative patient's adjuvant chemotherapy was given. Among 482 patients 199 received postoperative radiotherapy to the regional lymph nodes (axillary, supra and infraclavicular and internal mammary nodes) with TD 48 Gy in 22 fractions over 4 and a half week (168 postmenopausal and 31 premenopausal patients were irradiated). Results: After median follow up was 79.5 months (range 2−232) there was a similar relapse rate in both groups (30.6% in RT group vs 36.7% in no RT group) (Chi-square test; p = 0.1). The frequency of local recurrence alone or with distant metastases was 4.52% in RT group vs 7.77% in no RT group (Chi-square test; p = 0.1). In premenopausal patients local relapse occurred in 3.2% in RT group vs 8.2% in no RT group (Fisher Exact test; p = 0.48). Also in postmenopausal patients there were more local relapses in no RT group 6.58% vs 4.76% in RT group, but this difference did not reach statistical significance (Chi-squared test; p = 0.55). After the end of follow-up, more than half of patients are alive without evidence of disease (56.5% in no RT vs 59.8% in RT group). Ten-year DFI for RT group was 63.3% and for patients without RT 55%. Ten-year OS for RT group was 68.7% and 75.2% in no RT group. There was no difference in DFS and OS between RT and no RT groups (Log-Rank test; p = 0.34 and p = 0.35, respectively). Conclusion: Our results did not show the significant difference in disease relapse occurrence, including local relapse between postoperative regional nodal irradiation and no radiotherapy in moderate risk breast cancer patients.

Purpose: External beam accelerated partial breast irradiation requires accurate localization of the target volume for each treatment fraction. Using the concept of target registration error (TRE), the performance of several methods of target localization was compared. Methods and Materials: Twelve patients who underwent external beam accelerated partial breast irradiation were included in this study. TRE was quantified for four methods of image guidance: standard laser-based setup, kilovoltage imaging of the chest wall, kilovoltage imaging of surgically implanted clips, and three-dimensional surface imaging of the breast. The use of a reference surface created from a free-breathing computed tomography scan and a reference surface directly captured with three-dimensional video imaging were compared. The effects of respiratory motion were also considered, and gating was used for 8 of 12 patients. Results: The median value of the TRE for the laser, chest wall, and clip alignment was 7.1 mm (n = 94), 5.4 mm (n = 81), and 2.4 mm (n = 93), respectively. The median TRE for gated surface imaging based on the first fraction reference surface was 3.2 mm (n = 49), and the TRE for gated surface imaging using the computed tomographybased reference surface was 4.9 mm (n = 56). The TRE for nongated surface imaging using the first fraction reference surface was 6.2 mm (n = 25). Conclusions: The TRE of surface imaging using a reference surface directly captured with three-dimensional video and the TRE for clip-based setup were within 1 mm. Gated capture is important for surface imaging to reduce the effects of respiratory motion in accelerated partial breast irradiation. Ó 2008 Elsevier Inc.

Introduction: The standard treatment of stage IV breast cancer (stage IV) has thus far mainly involved palliative care with chemotherapy, hormonal therapy and/or radiation therapy. Resection of the primary tumor is not considered as curative treatment; solely as local therapy to maintain the quality of life. However, the overall survival (OS) after the diagnosis of stage IV is largely determined by the site of metastasis, i.e. less than 6 months for visceral, approximately 18 months for nodal, and 4-5 years for bony metastasis. Several retrospective studies have that surgery for the primary tumor may improve survival in patients with stage IV. Method: We therefore examined 141 stage IV patients treated between 1992 and 2010 in our institute. The patients ranged 26 to 83 years of age, with Eastern Cooperative Oncology Group performance status 0-1. Complete resection of the primary tumor was expected to be possible by total or partial mastectomy and standard systemic therapy of the time were administered. Adequate informed consent was given to all the patients before surgery. The subjects were classified into the following 2 groups: 77 patients, who received resection of the primary tumor, and 64 patients who did not. Distributions of anatomic site of distant metastasis and number of metastatic lesions were similar in the 2 groups. Results: The median OS was longer in patients treated with surgical resection (4.8 years) compared to patients not treated with surgical resection (2.9 years). The 5-year OS was better in women treated with surgery than in women who did not receive surgery (47.7% vs. 28.3%). The 10-year OS was 23.0% in patients with surgery but undetermined in patients without surgery. Among 77 patients treated with surgery, OS was better in patients with bone metastasis and one to four metastatic lesions. There were no significant OS differences with log-rank tests, but 7 cases with surgical resection survived more than 10 years after surgery. Conclusion: Our data obviously refer to a subset of patients who were selected for favorable prognostic factors, and any comparison with surgically untreated patients is threatened by serious biases. Our results, still, indicates that surgery for the primary tumor may provide better prognosis in stage IV patients. Well-conducted prospective trials are needed to examine the potential advantages of surgery. Surgery for the primary tumor could be one of the options in multidisciplinary treatment for stage IV, may provide better prognosis with low operative morbidity and less serious adverse events.

Incorporating various new and conventional risk factors, the 2005 St Gallen risk categorization is a potentially useful prognostic tool for breast cancers. We conducted a retrospective study to evaluate its application in Hong Kong. Of the 902 included female breast cancers with median follow-up of 5.4 years, 7%, 63% and 30% patients were classified as low-, intermediate-and high-risk categories, respectively. Their corresponding 5-year distant disease-free survivals (DDFS) were 100%, 92% and 72%, respectively (po0.00005). In the intermediate-risk category, node-positive patients had marginally inferior 5-year DDFS than node-negative patients (89% vs. 93%, p ¼ 0.0551). In the high-risk category, patients having HER2 overexpressed tumors and 1-3 positive nodes had significantly better DDFS than other patients with X4 positive nodes (89% vs. 65%, p ¼ 0.0001). Overall, the 2005 St Gallen risk categorization had high prognostic value. However, the impact of HER2 overexpression might be affected by reproducibility of HER2 tests. r

Reduction mammaplasty is one of the most common procedures performed by plastic surgeons all around the world. This procedure is performed for aesthetic or reconstructive purposes, but also offers the opportunity to examine all resected breast tissue histopathologically. The purpose of this study was to evaluate the histologic diagnoses of the reduction mammaplasty specimens retrospectively and to determine the incidence of breast lesions in otherwise asymptomatic and healthy women. Therefore, 149 patients who had undergone reduction mammaplasty were reviewed with regard to their histologic diagnoses. We found that 61% of these women have pathologic alterations in at least one of their breasts, so each patient who requests a breast reduction surgery should be evaluated carefully and the specimens should be handled with particular care.

Fat necrosis is one of the most common complications following free flap breast reconstruction. Although a minor complication, fat necrosis can compromise esthetic results and confuse with cancer recurrence. Perfusion-related factors and post-operative radiotherapy are the known risks. However, the influence of adjuvant chemotherapy on fat necrosis prevalence remains unknown. Our initial experience of 88 consecutive breast reconstructions with free abdominal flaps was reviewed. The prevalence of fat necrosis was recorded and the risk factors were analyzed using univariate and multivariate logistic regression models. The overall prevalence of fat necrosis was 36.4% in this series. In a multivariate logistic regression model, adjuvant chemotherapy significantly increased the risk of fat necrosis. The relative risk was 4.762 (95% confidence interval (CI), 1.767-12.831; p = 0.002). There was no evidence of a specific chemotherapeutic agent causing fat necrosis. The first cycle of adjuva...

Two new supraglottic airway devices, the LMA Supreme TM (LMA) and the i-gel TM , offer potential benefits when inserted by inexperienced operators. This study compared the insertion success rate and ventilation profile between the LMA Supreme and the i-gel when inserted by operators without previous airway management expertise. Following a short lecture and manikin training, airway novices were randomly allocated to insert either the LMA Supreme or the i-gel into 80 patients undergoing breast surgery. The primary outcome was first-time success rate, and secondary outcomes were overall success rate, insertion time, airway leak pressure, tidal volume during pressure controlled ventilation at 17 cmH 2 O, and adverse events. First-time insertion success rate was significantly higher for the LMA Supreme than the i-gel (30 ⁄ 39 (77%) vs 22 ⁄ 41 (54%); p = 0.029). Significantly more placement failures occurred with the i-gel (6 vs 0, p = 0.025). Mean (SD) leak pressure (29 (8) vs 23 (11) cmH 2 O, p = 0.007) and expired tidal volume (PCV 17 cmH 2 O) (785 (198) vs 654 (91), p = 0.001) were significantly greater with the LMA Supreme than with the i-gel, respectively. More patients complained of pharyngolaryngeal pain with the LMA Supreme than with the i-gel (17 ⁄ 39 (44%) vs 8 ⁄ 41 (20%); p = 0.053). We found better first time success rate, fewer failures, and a better seal with the LMA Supreme compared with the i-gel, indicating that the LMA Supreme may be preferable for emergency airway use by novices.

Background: Electrical impedance tomography (EIT) is a new non-invasive, mobile screening method which does not use ionizing radiation to the human breast; allows conducting quantitative assessment of the images besides the visual interpretation. The aim of this study was to correlate the quantitative assessment and visual interpretation of breast electrical impedance tomographs and associated factors. Materials and Methods: One hundred and fifty mammography patients above 40 years and undergoing EIT were chosen using convenient sampling. Visual interpretation of the images was carried out by a radiologist with minimum of three years experience using the breast imaging-electrical impedance (BI-EIM) classification for detection of abnormalities. A set of thirty blinded EIT images were reinterpreted to determine the intra-rater reliability using kappa. Quantitative assessment was by comparison of the breast average electric conductivity with the norm and correlations with visual interpretation of the images were determined using Chi-square. One-way ANOVA was used to compare the mean electrical conductivity between groups and t-test was used for comparisons with pre-existing Caucasians statistics. Independent t-tests were applied to compare the mean electrical conductivity of women with factors like exogenous hormone use and family history of breast cancer. Results: The mean electrical conductivity of Malaysian women was significantly lower than that of Caucasians (p<0.05). Quantitative assessment of electrical impedance tomography was significantly related with visual interpretation of images of the breast (p<0.05). Conclusions: Quantitative assessment of electrical impedance tomography images was significantly related with visual interpretation.

Previous studies have suggested elevated estrogen production in tumour-bearing breast quadrants as well as in breast cancers versus benign tissue. Using highly sensitive assays, we determined breast cancer tissue estrogen concentrations together with plasma and benign tissue estrogen concentrations in each quadrant obtained from mastectomy specimens (34 postmenopausal and 13 premenopausal women). We detected similar concentrations of each of the three major estrogens estradiol (E 2 ), estrone (E 1 ) and E 1 S in tumour-bearing versus non-tumour-bearing quadrants. Considering malignant tumours, intratumour E 1 levels were reduced in cancer tissue obtained from pre-as well as postmenopausal women independent of tumour ER status (average ratio E 1 cancer: benign tissue of 0.2 and 0.3, respectively; p < 0.001 for both groups), suggesting intratumour aromatization to be of minor importance. The most striking finding was a significant (4.1-8.6-fold) increased E 2 concentration in ER positive tumours versus normal tissue (p < 0.05 and <0.001 for pre-and postmenopausal patients, respectively), contrasting low E 2 concentrations in ER− tumours (p < 0.01 and <0.001 comparing E 2 levels between ER+ and ER− tumours in pre-and postmenopausals, respectively). A possible explanation to our finding is increased ligand receptor binding capacity for E 2 in receptor positive tumours but alternative factors influencing intratumour estrogen disposition cannot be excluded.

Breast cancer is the most common cause of cancer-related death among women worldwide, with case fatality rates highest in low-resource countries. Despite significant scientific advances in its management, most of the world faces resource constraints that limit the capacity to improve early detection, diagnosis, and treatment of the disease. The Breast Health Global Initiative (BHGI) strives to develop evidence-based, economically feasible, and culturally appropriate guidelines that can be used in nations with limited health care resources to improve breast cancer outcomes. Using an evidence-based consensus panel process, four BHGI expert panels addressed the areas of early detection and access to care, diagnosis and pathology, treatment and resource allocation, and health care systems and public policy as they relate to breast health care in limited-resource settings. To update and expand on the BHGI Guidelines published in 2003, the 2005 BHGI panels outlined a stepwise, systematic approach to health care improvement using a tiered system of resource allotment into four levels-basic, limited, enhanced, and maximalbased on the contribution of each resource toward improving clinical outcomes. Early breast cancer detection improves outcome in a cost-effective fashion assuming treatment is available, but requires public education to foster active patient participation in diagnosis and treatment. Clinical breast examination combined with diagnostic breast imaging (ultrasound ± diagnostic mammography) can facilitate cost-effective tissue sampling techniques for cytologic or histologic diagnosis. Breast-conserving treatment with partial mastectomy and radiation therapy requires more health care resources and infrastructure than mastectomy, but can be provided in a thoughtfully designed limited-resource setting. The availability and administration of systemic therapies are critical to improving breast cancer survival. Estrogen receptor testing allows patient selection for hormonal treatments (tamoxifen, oophorectomy). Chemotherapy, which requires some allocation of resources and infrastructure, is needed to treat node-positive, locally advanced breast cancers, which represent the most common clinical presentation of disease in low-resource countries. When chemotherapy is not available, patients with locally advanced, hormone receptor-negative cancers can only receive palliative therapy. Future research is needed to better determine how these guidelines can best be implemented in limited-resource settings.

Currently there is no simple method available to assess milk ejection and breast milk flow in lactating women in both the clinical and research setting. The authors hypothesize that changes in milk flow rate are associated with milk ejection and therefore may provide a method suitable for the assessment of milk ejection and removal. Mothers (n = 23) expressed milk from one breast for a 15-minute period using both weak and strong vacuums on two to four separate occasions using an experimental electric breast pump (Medela AG, Baar, Switzerland). Breast milk flow rates were recorded at 5-second intervals by connecting a tube from the breast shield to a bottle placed on a balance that was connected to a computer. Milk ejection was determined by an acute increase in milk duct diameter in the contralateral breast using ultrasound (Acuson XP10, Siemens, Mountain View, CA), and the change in duct diameter was compared with milk flow rates. Milk flow rates ranged from 0 to 4.6 g per 5-second...

The purpose of this study was to evaluate prospectively the sensitivity and specificity of scintimammography in the detection of both primary breast cancer and axillary lymph node involvement. Sixty-five consecutive women referred for a suspicious breast lesion on clinical examination and/or with abnormal mammographies suggestive of malignancies were studied with scintimammography using planar prone imaging (with a chest positioning device with semicircular lateral aperture on the imaging table) performed 15 min postinjection of 25-30 mCi 99mTc-sestamibi. Three planar views, right and left lateral prone and anterior supine thoracic views, were obtained (8-10 min/view). The entire breast and ipsilateral axillary region were included in the field of view. Excisional breast biopsy and/or fine needle aspiration cytology were performed in all patients within 4 wk after scintimammography. Axillary node dissection was also performed. The largest primary tumor measured 2 x 3 cm. There were ...

To reevaluate breast aspirates showing extracellular hyaline material (EHM) and globules to assess if clinicoradiologic and cytologic features could help in differentiating between benign and malignant lesions, especially collagenous spherulosis (CS) and adenoid cystic carcinoma (ACC). Fine needle aspiration was performed on 884 patients with breast lumps. The cytomorphologic features of 6 cases showing EHM, including classic hyaline globules (HGs), were analyzed in detail. Three cases also had hemorrhagic nipple discharge. Tissue diagnosis (4) and mammography (6) were available. Aspirate smears revealed high cellularity composed of monolayers: clusters of uniform, small cells; EHM; and HGs surrounded by similar cells. Benign naked nuclei and stromal fragments (4), nuclear pleomorphism (3), apocrine cells (2), foam cells (2), naked HGs (2) and spindle cells in proximity to HGs were also seen (4). Nipple discharge smears showed foam cells, erythrocytes (3) and epithelial cell cluster...

We analysed telomerase activity in normal, benign and malignant breast tissues and in fine needle aspirates by a PCR-based assay. The tissue samples we used in this assay consisted of 20 cryostat sections, zyxwvutsr I0 pm thick, from each breast 'To whom correspondence and reprint requests should be sent, at

The early nursing-sucking relationship is not to be taken for granted in humans. A number of factors can either facilitate or mitigate its optimal establishment on the mother's or newborn's sides. Among these factors, a morphological feature of human mothers' breaststhe areolar glands (AG)has been identified as potentially important. Three day-old infants display attraction during the presentation of the native secretions of the AG, suggesting that they could influence the newborn's behaviour during breastfeeding. The present study assessed this topic in a sample of 121 Caucasian mother-infant dyads. The areolae of these women were screened during the first 3 postnatal days in parallel with the infant's sucking performance, body weight fluctuations and time to lactation onset. On average, 97% of the women bore AG, 80.2% having 1-20 units per areola and 33% showing AG excreting a visible fluid. The endowment in AG appeared positively linked with neonatal growth after birth and with the speed of lactation onset: infants of primiparous women with lower AG numbers had a lower weight gain than those of mothers with higher AG numbers. Further, it took longer to primiparae with lower AG counts to set on lactation. This study confirms and extends the fact that AG, in interaction with maternal experience, might influence the initiation of the breastfeeding relationship.

Current classification systems in proliferative mammary gland pathology are based on a two-cell system, recognizing only glandular and myoepithelial lines of differentiation. A third cell type has recently been characterized in normal breast tissue by doubleimmunofluorescence analysis to express cytokeratin 5 (Ck5) only. These cells were shown to represent progenitor or adult stem cells that give rise to the glandular and myoepithelial cell lineage. The double-labelling technique has been applied to characterize a spectrum of intraductal epithelial proliferations, namely benign usual ductal hyperplasia, atypical ductal hyperplasia, and ductal carcinoma in situ, all of which are thought to represent the gradual steps of a sequence in the development of breast cancer. Immunofluorescence studies with specific antibodies against Ck5, Ck8/18/19, and smooth muscle actin were complemented by western blotting analysis of Ck5 and Ck8/18/19 expression in normal breast tissue and in proliferative lesions. Usual ductal hyperplasia appears to be a Ck5positive committed stem (progenitor) cell lesion with the same differentiation potential as seen in the normal breast. This is in sharp contrast to atypical ductal hyperplasia/ductal carcinoma in situ, which display the differentiated glandular immunophenotype (Ck8/18/19positive, but Ck5-negative). These data require the abandonment of the idea of an obligate biological continuum of intraductal proliferations from benign to malignant. This study provides evidence that cells undergoing malignant transformation tend to be fairly advanced in the glandular lineage of differentiation. The committed stem (progenitor) cell model may contribute to a better understanding of both benign proliferative breast disease and breast cancer development.

The spectral reflectance measurements in tissue reveal physiological meaning. Normally, functional changes like, increase in total hemoglobin concentration, decrease in oxygen saturation, etc., are observed when there is an abnormality creeping in the normal tissue. These functional changes can act together to reveal disease by non-invasive near-infrared (NIR) spectroscopy, as it influence its optical properties. In the present study, a simple two dimensional, four layer model of breast is proposed. The four layers are (i) skin (ii) adipose layer (iii) glandular tissue and (iv) muscle. Each layer is modeled with appropriate biological chromophores like hemoglobin, water, lipid and melanin. From the literature, the concentrations and molar extinction coefficients of the chromophores in various layers of the model are obtained. These values are used to calculate the wavelength dependent absorption characteristics of a particular layer. Monte Carlo simulation of diffuse reflectance (percentage of back reflected photons after multiple scattering with the broad variety of angles) are simulated for the modeled breast tissue with and without diseased condition. Near-infrared wavelengths are chosen, as the depth of penetration in tissue is more compared to UV and visible region. Simulations are carried out on the modeled breast tissue for different races (skin colors) at different NIR wavelengths. Results show significant changes in diffuse reflectance and relative absorbance for normal and diseased breast tissues for differently pigmented model. This model can be used to study the photo dynamical therapy, drug delivery and prognosis of cancer.

We describe a unique case of a 67-year-old patient with primary uterine rhabdomyosarcoma with a history of breast cancer and gastrointestinal stromal tumor of the stomach. Uterine rhabdomyosarcoma was diagnosed in our patient during adjuvant treatment of breast cancer with anastrozole. To the best of our knowledge, the development of primary uterine rhabdomyosarcoma has never been described in patients treated with anastrozole. Due to the suggested causative role of tamoxifen in the development of uterine sarcomas, it is interesting to analyze whether the new drug, anastrozole, exerts any pathogenic effect on the development of uterine sarocomas.

A dynamic-contrast-enhanced magnetic resonance imaging (DCE-MRI) dataset consists of many imaging frames, often acquired both before and after contrast injection. Due to the length of time spent acquiring images, patient motion is likely and image re-alignment or registration is required before further analysis such as pharmacokinetic model fitting. Non-rigid image registration procedures may be used to correct motion artefacts; however, a careful choice of registration strategy is required to reduce misregistration artefacts associated with enhancing features. This work investigates the effect of registration on the results of model-fitting algorithms for 52 DCE-MR mammography cases for 14 patients. Results are divided into two sections: a comparison of registration strategies in which a DCE-MRI-specific algorithm is preferred in 50% of cases, followed by an investigation of parameter changes with known applied deformations, inspecting the effect of magnitude and timing of motion artefacts. Increased motion magnitude correlates with increased model-fit residual and is seen to have a strong influence on the visibility of strongly enhancing features. Motion artefacts in images close to the contrast agent arrival have a disproportionate effect on discrepancies in parameter estimation. The choice of algorithm, magnitude of motion and timing of the motion are each shown to influence estimated pharmacokinetic parameters even when motion magnitude is small.

n Abstract: This study aimed to determine the effects of demographic, clinical, and therapeutic variables in development of seromas. The relation between development of seromas and age, preference for surgery, tumor size, existence of axillary lymph nodes and lymph nodal metastases, number of lymph nodes removed, type of surgical equipments used, drainage duration, drainage flow rate, and whether or not neoadjuvant chemotherapy was received; dead volume was reduced; or pressure garment was used in patients who received surgery due to breast cancer between 2000 and 2005 years. Mean age of 119 patients included in the study was 53.13 ± 13.26 (range 26-79). Seromas were observed in 17 (14.28%) patients. In multivariate logistic regression analysis an association of postoperative seroma formation was noted with a drainage flow rate greater than 50 mL ⁄ day after 48th hours following breast surgery (p = 0.007), while other variables investigated herein are not associated with development of seromas. We conclude that a drainage flow rate greater than 50 mL ⁄ day after 48th hours is a predicting factor for seroma formation in breast cancer patients. Thus, we do not recommend terminating the drainage before flow rate at 48 hours is seen and daily drainage is lower than acceptable limit. n

Nonnegative matrix factorization (NMF), a popular part-based representation technique, does not capture the intrinsic local geometric structure of the data space. Graph regularized NMF (GNMF) was recently proposed to avoid this limitation by regularizing NMF with a nearest neighbor graph constructed from the input data set. However, GNMF has two main bottlenecks. First, using the original feature space directly to construct the graph is not necessarily optimal because of the noisy and irrelevant features and nonlinear distributions of data samples. Second, one possible way to handle the nonlinear distribution of data samples is by kernel embedding. However, it is often difficult to choose the most suitable kernel. To solve these bottlenecks, we propose two novel graph-regularized NMF methods, AGNMF FS and AGNMF MK , by introducing feature selection and multiple-kernel learning to the graph regularized NMF, respectively. Instead of using a fixed graph as in GNMF, the two proposed methods learn the nearest neighbor graph that is adaptive to the selected features and learned multiple kernels, respectively. For each method, we propose a unified objective function to conduct feature selection/multi-kernel learning, NMF and adaptive graph regularization simultaneously. We further develop two iterative algorithms to solve the two optimization problems. Experimental results on two challenging pattern classification tasks demonstrate that the proposed methods significantly outperform state-of-the-art data representation methods.

A 60-year-old female presented in the Department of Oncosurgery, A.H. Regional Cancer Centre, Cuttack with a lump in the left breast. The mass on examination was soft, irregular and nontender. It was in the inner and upper quadrant measuring 3 · 2 · 1.5 cm. Examination of the supraclavicular region and axillae did not reveal any palpable lymph nodes. Rest of the systemic examination was essentially normal. She was referred to the Department of Oncopathology for Aspiration Cytology with a clinical impression of Carcinoma of the breast. The material obtained by fine needle aspiration (FNA) was whitish and fluid like. Smears were stained with Papa-Figure 2. Aspiration Cytology showing sheathed microfilariae admixed with inflammatory cells. The microfilariae are sheathed, coiled and the tail tips are free of granules representing the species Wuchereria bancrofti.

Purpose: To compare seven techniques for irradiation of the postmastectomy chest wall (CW) using normal tissue complication probability (NTCP) predictions for pneumonitis and ischemic heart disease and dose-volume histogram analyses for normal and target tissues. Methods and Materials: Plan comparisons were performed for 20 left-sided postmastectomy CW RT cases using target volumes based on clinical delineation of standard field borders. Seven common treatment techniques were planned for each case, using a prescription of 50 Gy in 25 fractions to the CW and internal mammary node (IMN) targets. NTCP model metrics were used to quantify the risks of pneumonitis and ischemic heart disease, supplemented by dose-volume metrics to assess the target coverage to the CW and IMNs, as well as normal tissue dose (lung and heart). Results: Overlap in the distributions of the CW mean dose for all plans was found, except cobalt, which was significantly less than the remaining techniques (global F test, F ‫؍‬ 21.90, p <0.0001). Standard tangents produced a significantly lower IMN mean dose than all other methods, as expected (F ‫؍‬ 59.55, p < 0.0001); the reverse hockey stick and cobalt techniques were lower than the other methods, which were statistically similar. Cobalt produced a significantly higher percentage of the heart that received >30 Gy (V30) than the other methods (F ‫؍‬ 49.76, p <0.0001). Use of partially wide tangent fields (PWTFs) resulted in the smallest heart V30. Use of cobalt fields resulted in a significantly greater NTCP estimate for ischemic heart disease than all the remaining techniques (F ‫؍‬ 70.39, p <0.0001). Standard tangents resulted in a percentage of the lung receiving >20 Gy (V20) significantly less than with PWTFs, 30/70 and 20/80 photon/electron mix, and reverse hockey stick techniques. NTCP estimates for pneumonitis revealed significantly better results with standard tangents (F ‫؍‬ 6.57, p <0.0001). Conclusion: No one technique studied combines the best CW and IMN coverage with minimal lung and heart complication probabilities. The choice of technique should be based on clinical discretion and the technical expertise available to implement these complex plans. Of the seven techniques studied, this analysis supports PWTFs as the most appropriate balance of target coverage and normal tissue sparing when irradiating the CW and IMN.

Background Augmentation of tuberous breasts classified as grade 3 is a challenge to surgeons. The authors describe their technique for correcting grade 3 tuberous breasts with a book-shaped opening of the breast, insertion of an anatomic prosthesis, and fat grafting. Methods The authors' technique for correcting grade 3 tuberous breasts consists of reducing the areolar diameter and performing a book-shaped opening of the breast, applying a modified version of Puckett's technique. The modification consists of opening each breast, remodeling the glandular flap on each side to make them symmetric, inserting the same size subglandular anatomic prosthesis, and covering the prosthesis with the glandular flaps held in place by transcutaneous fixation stitches. After 6 months, fat grafting of the remaining constricting ring and the cleavage is performed. Results The study enrolled 28 patients with asymmetric bilateral tuberous breasts ages 18 to 39 years. At 12 months, using a questionnaire to rate their results, 68% of the patients were ''very satisfied,'' 25% were ''satisfied,'' and 7% were ''not satisfied.'' The medical team's ratings at 12 months were ''excellent'' for 82% of the cases and ''good'' for 18% of the cases. Conclusion For patients with grade 3 tuberous breasts, the authors perform aesthetic breast enlargement by reducing the size of the areola, making a book-shaped opening in the breast, and carrying out fat grafting to correct the cleavage and the remaining constricting ring. The patients and the medical team both expressed high levels of satisfaction with the results.

Literature data suggest that breast cancers occurring in young patients may be different from those arising in older women. In this study the clinicopathologic characteristics of 50 patients under 40 years of age were compared with those of patients aged over 60. Patients under 40 years old more frequently had a family history of breast cancer than did older patients (24% vs 17%) and had more often used oral contraceptives (29% vs 13%); on average they had experienced menarche 1 year earlier. For early onset breast carcinomas there was a higher frequency of grade 3 tumours (38% vs 17%) and oestrogen receptor negativity (46% vs 20%). In addition, in younger patients the carcinomas were mostly DNA aneuploid (78% vs 58%), with a higher proliferation rate (48% vs 26%) and more frequent c-erbB-2 overexpression (48% vs 26%) and p53 alteration (30% vs 8%). Our data demonstrate that breast cancers arising in young women have a significantly different biopathological profile from those in older patients, with a predominance of unfavourable prognostic parameters.

The aim of immediate breast reconstruction is to improve well-being and quality of life for women undergoing mastectomy for breast cancer. This prospective study used the SF-36 Health Survey questionnaire to assess quality of life before and 12 months after mastectomy and immediate breast reconstruction together with patients' expectations of and satisfaction with the immediate breast reconstruction with implant. Scores for 76 participants were compared with those in 920 age-matched women from the general population. Preoperative scores for emotional well-being and physical role functioning were lower than in the reference population, while after 12 months the scores in all domains had improved and were comparable with those in the reference population. The most common reason for immediate reconstruction was the desire to avoid an external prosthesis. Most women were satisfied with immediate reconstruction, and the major determinant of aesthetic satisfaction was completion of the procedure. Although many factors may influence quality of life, 1 year after breast cancer surgery with immediate reconstruction scores are equivalent to those of the normal population.

The double Debye model has been used to understand the dielectric response of different types of biological tissues at terahertz (THz) frequencies but fails in accurately simulating human breast tissue. This leads to limited knowledge about the structure, dynamics, and macroscopic behavior of breast tissue and hence constrains the potential of THz imaging in breast cancer detection. The first goal of this paper is to propose a new dielectric model capable of mimicking the spectra of human breast tissue's complex permittivity in THz regime. Namely, a non-Debye relaxation model is combined with a single Debye model to produce a mixture model of human breast tissue. A sampling gradient algorithm of non-smooth optimization is applied to locate the optimal fitting solution. Samples of healthy breast tissue and breast tumour are used in the simulation to evaluate the effectiveness of the proposed model. Our simulation demonstrates exceptional fitting quality in all cases. The second goal is to confirm the potential of using the parameters of the proposed dielectric model to distinguish breast tumour from healthy breast tissue, especially fibrous tissue. Statistical measures are employed to analyse the discrimination capability of the model parameters while support vector machines (SVM) are applied to assess the possibility of using the combinations of these parameters for higher classification accuracy. The obtained analysis confirms the classification potential of these features.

Breast cancer is a major health problem in underdeveloped countries including Sudan. Immunohistochemical typing is important for diagnosing and understanding the biology of such heterogeneous disease. To the best of our knowledge, no study has investigated the association between estrogen receptors (ER) expression and carbohydrates in breast tissue. Mammographic high density, a major risk factor, is partially attributed to carbohydrates. This study aimed to determine the type of carbohydrates in malignant and benign breast lesions and detect if there is any association between ER expression and carbohydrates using histochemical and immunohistochemical methods. A total of 60 diagnosed samples of different breast lesions were reexamined for ER status by immunohistochemistry (IHC) and for carbohydrates by histochemical staining methods i.e. periodic acid Schiff (PAS) and alcian blue. Strong relationship was discovered between ER positivity and presence of acid mucin, but not with sulfated mucin. Furthermore, strong relationship was found between ER positivity and PAS positive materials, but not with glycogen. Since there was a significant correlation between ER and carbohydrates, these positive PAS materials might be PAS positive acid mucin. These findings are useful in understanding the behavior of breast lesions. Also, these findings suggested an underlying molecular relationships and that ER expression might be predicted using histochemical demonstration of carbohydrates in female breast tissue particularly when immunohistochemistry is out of reach.

Background Gestational gigantomastia (GGM) is a rare complication of pregnancy. Management usually is initiated with bromocriptine. If this is unsuccessful, surgery may be required. The surgical management may be by breast reduction or by mastectomy and delayed reconstruction. Case A 24-year-old woman (G1P0) presented at 24 weeks gestation with massive hypertrophy of her breasts. A decision to operate was made by a multidisciplinary team. At 30 weeks gestation, bilateral mastectomies were performed, with removal of more than 8 kg per side. Reconstruction was started 10 months after delivery using tissue expanders followed by definitive implants. Conclusion GGM can be successfully reconstructed. Knowledge of the treatment process and the expected outcomes can help clinicians inform their patients.

Various histopathologic components in benign and malignant breast lesions may generate hyperintense signal at T2-weighted magnetic resonance (MR) imaging. A comparison of the specific histologic features found in breast lesions with a high-signal-intensity appearance on unenhanced T2-weighted turbo spin-echo MR images obtained without spectral fat suppression shows that this MR imaging characteristic is often suggestive of the differential diagnosis. Histopathologic features that may produce high signal intensity in breast lesions include extensive necrosis, a cystic or microcystic component, an adipose or sebaceous component, mucinous stroma, loose myxoid stroma, stromal edema, and hemorrhagic changes. A more nuanced understanding of the correlation between the MR imaging appearance and specific pathologic findings may help radiologists achieve earlier and more accurate differentiation among this group of breast lesions. ©

Telomerase reverse transcriptase (TERT) promoter mutations have been discovered in solid and hematological malignancies, where they reflect TERT activation and cell-cycle progression. In melanoma, glioma, and thyroid cancers, TERT promoter mutations are associated with a poor prognosis. However, no studies have evaluated the prevalence and prognostic significance of TERT promoter mutations in breast cancer. We analyzed TERT promoter hotspot mutations (C228T and C250T) using direct sequencing of DNA from 319 tumor tissues. We also collected clinical data from cases that were positive for TERT promoter mutations. We detected TERT promoter mutations in three (0.9%) of the 319 cases. Two patients had hormone receptor-positive and human epidermal growth factor receptor 2-negative cancer, while the third patient had triple-negative cancer. All three patients had initially been diagnosed with operable breast cancer and undergone surgical treatment. The relapse-free survivals of these patie...