High-Resolution Full-3D Specimen Imaging for Lumpectomy Margin Assessment in Breast Cancer.

BACKGROUND: Two-dimensional (2D) specimen radiography (SR) and tomosynthesis (DBT) for breast cancer yield data that lack high-depth resolution. A volumetric specimen imager (VSI) was developed to provide full-3D and thin-slice cross-sectional visualization at a 360° view angle. The purpose of this prospective trial was to compare VSI, 2D SR, and DBT interpretation of lumpectomy margin status with the final pathologic margin status of breast lumpectomy specimens. METHODS: The study enrolled 200 cases from two institutions. After standard imaging and interpretation was performed, the main lumpectomy specimen was imaged with the VSI device. Image interpretation was performed by three radiologists after surgery based on VSI, 2D SR, and DBT. A receiver operating characteristic (ROC) curve was created for each method. The area under the curve (AUC) was computed to characterize the performance of the imaging method interpreted by each user. RESULTS: From 200 lesions, 1200 margins were interpreted. The AUC values of VSI for the three radiologists were respectively 0.91, 0.90, and 0.94, showing relative improvement over the AUCs of 2D SR by 54%, 13%, and 40% and DBT by 32% and 11%, respectively. The VSI has sensitivity ranging from 91 to 94%, specificity ranging from 81 to 85%, a positive predictive value ranging from 25 to 30%, and a negative predicative value of 99%. CONCLUSIONS: The ROC curves of the VSI were higher than those of the other specimen imaging methods. Full-3D specimen imaging can improve the correlation between the main lumpectomy specimen margin status and surgical pathology. The findings from this study suggest that using the VSI device for intraoperative margin assessment could further reduce the re-excision rates for women with malignant disease.

TARGIT-R (Retrospective): 5-Year Follow-Up Evaluation of Intraoperative Radiation Therapy (IORT) for Breast Cancer Performed in North America.

BACKGROUND: Intraoperative radiation therapy (IORT) has been investigated for patients with low-risk, early-stage breast cancer. The The North American experience was evaluated by TARGIT-R (retrospective) to provide outcomes for patients treated in "real-world" clinical practice with breast IORT. This analysis presents a 5-year follow-up assessment. METHODS: TARGIT-R is a multi-institutional retrospective registry of patients who underwent lumpectomy and IORT between the years 2007 and 2013. The primary outcome of the evaluation was ipsilateral breast tumor recurrence (IBTR). RESULTS: The evaluation included 667 patients with a median follow-up period of 5.1 years. Primary IORT (IORT at the time of lumpectomy) was performed for 72%, delayed IORT (after lumpectomy) for 3%, intended boost for 8%, and unintended boost (primary IORT followed by whole-breast radiation) for 17% of the patients. At 5 years, IBTR was 6.6% for all the patients, with 8% for the primary IORT cohort and 1.7% for the unintended-boost cohort. No recurrences were identified in the delayed IORT or intended-boost cohorts. Noncompliance with endocrine therapy (ET) was associated with higher IBTR risk (hazard ratio [HR], 3.67). Patients treated with primary IORT who were complaint with ET had a 5-year IBTR rate of 3.9%. CONCLUSION: The local recurrence rates in this series differ slightly from recent results of randomized IORT trials and are notably higher than in previous published studies using whole-breast radiotherapy for similar patients with early-stage breast cancer. Understanding differences in this retrospective series and the prospective trials will be critical to optimizing patient selection and outcomes going forward.

Local Transdermal Delivery of Telapristone Acetate Through Breast Skin, Compared With Oral Treatment: A Randomized Double-Blind, Placebo-Controlled Phase II Trial.

Oral breast cancer prevention medications entail systemic exposure, limiting acceptance by high-risk women. Delivery through the breast skin, although an attractive alternative, requires demonstration of drug distribution throughout the breast. We conducted a randomized double-blind, placebo-controlled phase II clinical trial comparing telapristone acetate, a progesterone receptor antagonist, administered orally (12 mg/day) or transdermally (12 mg/breast) for 4 ± 1 weeks to women planning mastectomy. Plasma and tissue concentrations, measured at five locations in the mastectomy specimen using liquid chromatography tandem mass spectrometry were compared. In 60 evaluable subjects, median drug concentration (ng/g tissue) was 103 (interquartile range (IQR): 46.3-336) in the oral vs. 2.82 (IQR: 1.4-5.5) in the transdermal group. Despite poor dermal permeation, within-breast drug distribution pattern was identical in both groups (R2  = 0.88, P = 0.006), demonstrating that transdermally and orally delivered drug is distributed similarly through the breast, and is strongly influenced by tissue adiposity (P < 0.0001). Other skin-penetrant drugs should be tested for breast cancer prevention.

Toroidal multilayer mirrors for laboratory soft X-ray grazing emission X-ray fluorescence.

Efficient soft X-ray spectroscopy in the laboratory is still a challenging task. Here, we report on new toroidal multilayer optics designed and applied with the laser-produced plasma (LPP) source of the Berlin Laboratory for innovative X-ray technologies. The optics are described and characterized, and the application of the updated source to scanning-free grazing emission X-ray fluorescence is demonstrated on thermoelectric gold-doped copper oxide nanofilms. The comparison with synchrotron measurements allows estimating a flux on the sample of approximately 7.5 × 109 photons/s in the 1 keV range on a 100 µm × 100 µm spot, emphasizing the suitability of the updated LPP source for the application in photon hungry experiments.

The effect of post-deposition annealing conditions on structural and thermoelectric properties of sputtered copper oxide films.

The development of thin-film thermoelectric applications in sensing and energy harvesting can benefit largely from suitable deposition methods for earth-abundant materials. In this study, p-type copper oxide thin films have been prepared on soda lime silicate glass by direct current (DC) magnetron sputtering at room temperature from a pure copper metallic target in an argon atmosphere, followed by subsequent annealing steps at 300 °C under various atmospheres, namely air (CuO:air), nitrogen (CuO:N) and oxygen (CuO:O). The resultant films have been studied to understand the influence of various annealing atmospheres on the structural, spectroscopic and thermoelectric properties. X-ray diffraction (XRD) patterns of the films showed reflexes that could be assigned to those of crystalline CuO with a thin mixed Cu(I)Cu(II) oxide, which was also observed by near edge X-ray absorption fine structure spectroscopy (NEXAFS). The positive Seebeck coefficient (S) reached values of up to 204 µV K-1, confirming the p-type behavior of the films. Annealing under oxygen provided a significant improvement in the electrical conductivity up to 50 S m-1, resulting in a power factor of 2 µW m-1 K-2. The results reveal the interplay between the intrinsic composition and the thermoelectric performance of mixed copper oxide thin films, which can be finely adjusted by simply varying the annealing atmosphere.

Selective Progesterone Receptor Modulators in Early-Stage Breast Cancer: A Randomized, Placebo-Controlled Phase II Window-of-Opportunity Trial Using Telapristone Acetate.

PURPOSE: Selective progesterone receptor modulators (SPRMs) show preclinical activity against hormone-sensitive breast cancer, but have not been tested in patients with early, treatment-naïve tumors. PATIENTS AND METHODS: In a double-blind presurgical window trial of oral telapristone acetate (TPA) 12 mg daily versus placebo, 70 patients with early-stage breast cancer were randomized 1:1 (stratified by menopause) and treated for 2 to 10 weeks. The primary endpoint was change in Ki67 between diagnostic biopsy and surgical specimens. Gene expression pre- and posttherapy was assessed using RNA-sequencing and gene set enrichment analysis was performed to determine pathways enriched in response to TPA and placebo treatments. RESULTS: Among 61 evaluable women (29 placebo and 32 telapristone acetate), 91% of tumors were ER/PR positive. The mean Ki67 declined by 5.5% in all women treated with telapristone acetate (P = 0.003), and by 4.2% in all women treated with placebo (P = 0.04). After menopausal stratification, the Ki67 decline remained significant in 22 telapristone acetate-treated premenopausal women (P = 0.03). Differential gene expression analysis showed no significant modulation overall. However, in a subset of tumors that demonstrated ≥30% relative reduction in Ki67 in the telapristone acetate group, genes related to cell-cycle progression, and those in the HER2 amplicon were significantly downregulated. In contrast, no significantly enriched pathways were identified in the placebo group. CONCLUSIONS: Patients treated with telapristone acetate whose Ki67 decreased by ≥30% demonstrated a selective antiproliferative signal, with a potentially important effect on HER2 amplicon genes. Evaluation of SPRMs in a neoadjuvant trial is merited, with attention to predictors of response to SPRM therapy, and inclusion of pre- and postmenopausal women.

Assessment of hospital-level adjusted breast cancer sentinel lymph node positivity rates.

BACKGROUND/OBJECTIVES: Proficiency of performing sentinel lymph node biopsy (SLNB) for breast cancer varies among hospitals and may be reflected in the hospital's SLNB positivity rate. Our objectives were to examine whether hospital characteristics are associated with variation in SLNB positivity rates and whether hospitals with lower-than-expected SLNB positivity rates have worse patient survival. METHODS: Using the National Cancer Data Base, stage I to III breast cancer patients were identified (2004-2012). Hospital-level SLNB positivity rates were adjusted for tumor and patient factors. Hospitals were divided into terciles of SLNB positivity rates (lower-, higher-, as-expected). Hospital characteristics and survival were examined across terciles. RESULTS: Of 438 610 SLNB patients (from 1357 hospitals), 78 104 had one or more positive SLN (21.3%). Hospitals in the low and high terciles were more likely to be low volume (low: RRR, 4.40; 95% CI, 2.89-6.57; P < 0.001; and high: RRR, 1.79; 95% CI, 1.21-2.64; P < 0.001) compared to hospitals with as-expected (middle tercile) SLNB positivity rates. Stage I patients at low- and high-tercile hospitals had statistically worse survival. CONCLUSIONS: There is a wide variation in hospital SLNB positivity rates. Hospitals with lower- or higher-than-expected SLNB positivity rates were associated with survival differences. Hospital SLNB positivity rates may be a novel 'process measure' to report to hospitals for internal quality assessment.

Impact of breast MRI in women eligible for breast conservation surgery and intra-operative radiation therapy.

PURPOSE: The current standard of care for women diagnosed with early stage breast cancer is breast-conserving surgery (BCS) followed by external beam radiation therapy, commonly delivered over 3-6 weeks. As an alternative, select patients can undergo intra-operative radiation therapy (IORT) at the time of BCT. This technique delivers a single fraction of radiation at the time of surgery, enabling patients to undergo both surgery and radiation in a single session. Our current study analyzed the value of incorporating breast MRI into the routine work-up of patients deemed eligible for IORT, to quantify the impact on patient eligibility and requirement for additional work-up. MATERIALS AND METHODS: We retrospectively identified patients treated by a single surgeon who were eligible for IORT based on institutional eligibility criteria which included: women age ≥55, grades 1-2, size <3 cm, estrogen receptor (ER) positive, Her-2 neu non-amplified and low/intermediate Ki-67, unifocal invasive ductal/mixed histology carcinomas. All patients must have undergone a physical exam and bilateral diagnostic mammography with ultrasound. From this population, we identified all patients who had undergone bilateral breast MRI as part of pre-operative evaluation. RESULTS: A total of 215 women were identified who met all eligibility criteria. MRI detected additional abnormalities in the breast in 89 patients (41%). Sixty-eight women underwent additional biopsies, with a total of 117 separate lesions biopsied. Of these, pathology was benign in 61 (52.1%), atypical ductal hyperplasia (ADH) in 21 (18%), ductal carcinoma in-situ (DCIS) in 17 (14.5%) and invasive disease in 18 (15.4%). Six patients had MRI-detected abnormalities in the contralateral breast only, with biopsies identifying invasive disease (3), DCIS (1) and benign (2) findings. MRI showed abnormalities in both breasts in 6 patients and 18 additional lesions were biopsied which reveled invasive carcinoma (6), DCIS (7), ADH (3) and benign findings (2). Fifteen patients had either multifocal/multicentric disease or index lesion >3 cm on MRI and were deemed ineligible for IORT. Based on either MRI size or biopsy results, management was ultimately changed for 27 patients (12.5%). Extramammary findings were observed in 17 patients and 11 of these patients underwent further imaging studies all of which returned negative results. CONCLUSION: Preoperative bilateral breast MRI is a valuable tool in the proper selection of patients best suited for IORT. Even in highly selected, favorable risk patients, MRI detected additional lesions that changed surgical and radiation therapy recommendations in 12.5% of patients. However, the cost/benefit ratio needs to be taken into consideration given the high frequency of benign biopsies and additional radiological work-up.

Development of a nomogram to predict the clinical impact of a postexcision preirradiation mammogram.

We aimed to better quantify the impact of a postexcision preirradiation mammogram (PPM), first by identifying factors associated with abnormal results and then incorporating these findings into a nomogram. Beginning February 2011, our institution made a practice change to obtain a PPM on all patients with any calcifications identified. A total of 530 patients underwent a PPM. Suspicious abnormalities were reported in 61 patients (11.5%), with the PPM leading to a change in management in 47 instances (8.9%). A nomogram was created based on patient and tumor characteristics to identify patients most likely to have an abnormal PPM.

The Surgical Impact of E-Cigarettes: A Case Report and Review of the Current Literature.

We report a case of a 51 years old female with a 25 pack year smoking history who underwent bilateral mastectomy and immediate tissue expander reconstruction for newly diagnosed right breast cancer. The patient reported herself as a non-smoker despite significant e-cigarette use, with resulting significant mastectomy skin flap necrosis and breast reconstruction failure. Little is known about the physiologic effect of e-cigarettes on wound healing and tissue perfusion. To this end, we provide an updated review of the impact of e-cigarettes on surgical outcomes. PubMed, Ovid MEDLINE, and PRS GO were searched for the terms "e-cigarette", "electronic cigarette", "e-cig", "electronic nicotine delivery system", "vaping", "surgery", "surgical", "peri-operative", "operate", "operative", and "wound healing". Abstract review of all articles was performed. 123 articles returned that contained both variants of e-cigarettes and surgery as keywords. Of those, manual assessment returned three articles which were found to be relevant to e-cigarette use in the surgical patient. No articles were found that compared perioperative complications in e-cigarette versus traditional cigarette users in humans. In conclusion, our case report depicts the potential dangers associated with e-cigarette use in the surgical patient. There is a public misconception that e-cigarettes are healthier than traditional cigarettes and as such their use may go unreported by patients. Early evidence suggests e-cigarettes may induce some of the same physiologic changes as traditional cigarettes, and may have a significant deleterious effect on wound healing.

In Situ Complementary Doping, Thermoelectric Improvements, and Strain-Induced Structure within Alternating PEDOT:PSS/PANI Layers.

Although the deposition of alternating layers from poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) and polyaniline (PANI) salts has recently provided a breakthrough in the field of conductive polymers, the cause for the conductivity improvement has remained unclear. In this work, we report a cooperative doping effect between alternating PANI base and PEDOT:PSS layers, resulting in electrical conductivities of 50-100 S cm-1 and power factors of up to 3.0 ± 0.5 µW m-1 K-2, which surpass some of the recent values obtained for protonated PANI/PEDOT:PSS multilayers by a factor of 20. In this case, the simultaneous improvement in the electrical conductivity of both types of layers is caused by the in situ protonation of PANI, which corresponds to the removal of the excess acidic PSS chains from the PEDOT:PSS grains. The interplay between the functional groups' reactivity and the supramolecular chain reorganization leads to an array of preparation-dependent phenomena, including a stepwise increase in the film thickness, an alternation in the electrical conductivity, and the formation of a diverse surface landscape. The latter effect can be traced to a buildup of strain within the layers, which results in either the formation of folds or the shrinkage of the film. These results open new paths for designing nanostructured thin-film thermoelectrics.

Tamoxifen Acceptance and Adherence among Patients with Ductal Carcinoma In Situ (DCIS) Treated in a Multidisciplinary Setting.

Tamoxifen and other endocrine agents have proven benefits for women with ductal carcinoma in situ (DCIS), but low patient acceptance is widely reported. We examined factors associated with tamoxifen acceptance and adherence among DCIS patients who received a recommendation for therapy in a multidisciplinary setting. Using our institutional database, we identified women diagnosed with DCIS, 1998 to 2009, who were offered tamoxifen. We recorded data on demographics, tumor and therapy variables, tamoxifen acceptance, and adherence to therapy for ≥4 years. Univariable and multivariable analyses were conducted using logistic regression to identify factors specific to each group that were related to acceptance and adherence. A total of 555 eligible women identified, of whom 369 were offered tamoxifen; 298 (81%) accepted, among whom 214 (72%) were adherent, 59 of 298 (20%) were nonadherent, and for 25 (8%), adherence was undetermined. After stepwise elimination in adjusted logistic regression models, acceptance of breast radiotherapy was associated with acceptance of tamoxifen [OR, 2.22; 95% confidence interval (CI), 1.26-3.90; P < 0.01], as was a medical oncology consultation (OR, 1.76; 95% CI, 0.99-3.15; P = 0.05). Insured patients were more likely to adhere to tamoxifen (OR, 6.03; 95% CI, 2.60-13.98; P < 0.01). The majority of nonadherent women (n = 38/56, 68%) discontinued the drug during the first year of treatment with 48 (86%) citing adverse effect(s) as the reason. In a multidisciplinary, tertiary care setting, we observed relatively high rates of acceptance and adherence of tamoxifen. Acceptance of tamoxifen and radiotherapy were associated, and adherence was influenced by insurance status.Key Message: Tamoxifen acceptance and adherence following resection of DCIS of the breast is related to acceptance of radiotherapy and may be improved by confirmation of the recommendation by a medical oncologist. Despite the low cost of tamoxifen, adherence to therapy is significantly impacted by lack of insurance; those who discontinue therapy report adverse effects as a major reason. Cancer Prev Res; 10(7); 389-97. ©2017 AACR.

Assessing long-term complications in patients undergoing immediate postmastectomy breast reconstruction and adjuvant radiation.

PURPOSE: The purpose of this article is to report the long-term rate and timing of complications associated with postmastectomy radiation therapy (PMRT) following immediate breast reconstruction in a large patient population. METHODS AND MATERIALS: We identified and reviewed the charts of all patients with stages I through IIIC breast cancer who underwent mastectomy with immediate reconstruction followed by subsequent radiation therapy between November 1997 and May 2010. We aimed to assess the rate of major complications, defined as events requiring a separate and distinct procedure. Statistical analysis between variables was evaluated using Fisher exact test and Pearson χ2 Elder et al. (2005) test. RESULTS: In total, 134 patients met inclusion criteria for having adequate long-term follow-up and documentation. The median follow-up for all patients was 77.4 months (range, 6-185 months). The overall major complication rate was found to be 44%. Nine patients (6.7%) experienced complications for which a secondary procedure could not be performed to retain a reconstructed breast. The average time between initiation of PMRT and the first major complication was 13.5 months, with 68.3% of first major complications occurring within 1 year of PMRT initiation and 81.7% within 2 years. The difference in incidence of major complications for patients undergoing immediate tissue expander/implant reconstruction followed by PMRT was not statistically different when compared with that for patients with immediate autologous tissue reconstruction followed by PMRT (47.3% vs 30.4%, P = .168). CONCLUSIONS: The risk of first major complications and reconstruction loss in patients undergoing PMRT on immediately reconstructed breasts is greatest within 1 year of beginning radiation therapy and decreases significantly with time. Immediate autologous tissue reconstruction followed by PMRT can be performed with reasonable complication rates.

Risk Factors Leading to Complications in Early-Stage Breast Cancer Following Breast-Conserving Surgery and Intraoperative Radiotherapy.

OBJECTIVE: The aim of this study was to evaluate outcomes after breast-conserving surgery (BCS) and intraoperative radiotherapy (IORT), and to identify risk factors associated with complications. MATERIALS/METHODS: We evaluated patients with early-stage breast cancer treated from January 1, 2011 to January 31, 2014 with BCS and IORT at a single institution. The presence of breast cancer recurrences, complications, or fat necrosis were assessed at subsequent follow-up visits using physical examination and breast imaging. RESULTS: Overall, 113 patients, of whom three were undergoing bilateral treatments, were identified. The median length of time for IORT was 29 min and 36 s (range 15:50-59:00). Fifteen patients received additional external beam radiotherapy (EBRT), and the median follow-up was 40.3 months (range 1.6-58.3) for all patients. To date, one biopsy-proven ipsilateral recurrence has been noted (0.9%), for which the patient elected to undergo a mastectomy. Nine patients were found to have wound complications (7.7%) and two had fat necrosis (1.7%) on follow-up. Of all the evaluated risk factors, only applicator size (p < 0.01) had a statistically significant association with an increase in complications. CONCLUSIONS: With a short follow-up, IORT appears to be a safe treatment modality for a select group of patients, leading to a reasonable increase in operating room time and complication rates following BCS. The utilization of larger applicators at the time of IORT was associated with an increase in wound complications and fat necrosis.

National Evaluation of the New Commission on Cancer Quality Measure for Postmastectomy Radiation Treatment for Breast Cancer.

BACKGROUND: Current guidelines recommend postmastectomy radiotherapy (PMRT) for patients with ≥4 positive lymph nodes and suggest strong consideration of PMRT in those with 1-3 positive nodes. These recommendations were incorporated into a Commission on Cancer quality measure in 2014. However, national adherence with these recommendations is unknown. Our objectives were to describe PMRT use in the United States in patients with stage I to III invasive breast cancer and to examine possible factors associated with the omission of PMRT. METHODS: From the National Cancer Data Base, 753,536 mastectomies at 1123 hospitals were identified from 1998 to 2011. PMRT use over time was examined using random effects logistic regression analyses, adjusting for patient, tumor, and hospital characteristics. Analyses were stratified by nodal status (≥4 nodes positive, 1-3 nodes positive, node negative). RESULTS: The proportion of patients receiving PMRT increased from 1998 to 2011 (>4 positive nodes: 56.2 to 66.6 %; 1-3 positive nodes: 28.0 to 39.1 %; node-negative: 8.3 to 10.0 %, p < 0.001 for all). In adjusted analyses, patients with ≥4 positive nodes were more likely to have PMRT omitted if they had smaller tumors. Patients with 1-3 positive nodes were more likely to have PMRT omitted if they had lower grade or smaller tumors. Irrespective of patients' nodal status, PMRT utilization rates decreased as age increased. CONCLUSIONS: Though PMRT rates increased over time in patients with ≥4 and 1-3 positive nodes, PMRT in patients with ≥4 positive nodes remains underutilized. Feedback to hospitals using the new Commission on Cancer PMRT measure may help to improve adherence rates.

TARGIT-R (Retrospective): North American Experience with Intraoperative Radiation Using Low-Kilovoltage X-Rays for Breast Cancer.

BACKGROUND: Single-dose intraoperative radiotherapy (IORT) is an emerging treatment for women with early stage breast cancer. The objective of this study was to define the frequency of IORT use, patient selection, and outcomes of patients treated in North America. METHODS: A multi-institutional retrospective registry was created, and 19 institutions using low-kilovoltage IORT for the treatment of breast cancer entered data on patients treated at their institution before July 31, 2013. Patient selection, IORT treatment details, complications, and recurrences were analyzed. RESULTS: From 2007 to July 31, 2013, a total of 935 women were identified and treated with lumpectomy and IORT. A total of 822 patients had at least 6 months' follow-up documented and were included in the analysis. The number of IORT cases performed increased significantly over time (p < 0.001). The median patient age was 66.8 years. Most patients had disease that was <2 cm in size (90 %) and was estrogen positive (91 %); most patients had invasive ductal cancer (68 %). Of those who had a sentinel lymph node procedure performed, 89 % had negative sentinel lymph nodes. The types of IORT performed were primary IORT in 79 %, secondary IORT in 7 %, or planned boost in 14 %. Complications were low. At a median follow-up of 23.3 months, crude in-breast recurrence was 2.3 % for all patients treated. CONCLUSIONS: IORT use for the treatment of breast cancer is significantly increasing in North America, and physicians are selecting low-risk patients for this treatment option. Low complication and local recurrence rates support IORT as a treatment option for selected women with early stage breast cancer.

Adjusting the thermoelectric properties of copper(I) oxide-graphite-polymer pastes and the applications of such flexible composites.

We present a facile alternative to other well known strategies for synthesizing flexible thermoelectric materials. Instead of printing thin active layers on flexible substrates or doping conductive polymers, we produce thermoelectric pastes, using a mixture of graphite, copper(I) oxide and polychlorotrifluoroethene. The Seebeck coefficient of the investigated pastes varies between 10 and 600 µV K(-1), while the electrical conductivity spans over an even wider range of 10(-4) to 10(2) S m(-1). Here, the influence of phenomena such as percolation on the electrical transport is revealed. The resulting power factor reaches 5.69 × 10(-4) ± 0.70 × 10(-4) µW m(-1) K(-2) for the graphite-polymer paste, with an unexpected minimum at a graphite molar fraction of approximately 0.4. The values are comparable to those of the powder mixtures, which are slightly higher, but less precisely tunable. Such compounds are further evaluated for practical applications. The graphite-polymer paste is used to exemplify, how a flexible thermoelectric sensor can be easily manufactured, step by step. Our results represent a proof of principle, that thermoelectric pastes are viable alternatives to current solutions. A further expansion of the scope for the composites can be achieved by using high performance thermoelectric materials and conductive polymers.

Decreasing the Effective Thermal Conductivity in Glass Supported Thermoelectric Layers.

As thermoelectric devices begin to make their way into commercial applications, the emphasis is put on decreasing the thermal conductivity. In this purely theoretical study, finite element analysis is used to determine the effect of a supporting material on the thermal conductivity of a thermoelectric module. The simulations illustrate the heat transfer along a sample, consisting from Cu, Cu2O and PbTe thermoelectric layers on a 1 mm thick Pyrex glass substrate. The influence of two different types of heating, at a constant temperature and at a constant heat flux, is also investigated. It is revealed that the presence of a supporting material plays an important role on lowering the effective thermal conductivity of the layer-substrate ensemble. By using thinner thermoelectric layers the effective thermal conductivity is further reduced, almost down to the value of the glass substrate. As a result, the temperature gradient becomes steeper for a fixed heating temperature, which allows the production of devices with improved performance under certain conditions. Based on the simulation results, we also propose a model for a robust thin film thermoelectric device. With this suggestion, we invite the thermoelectric community to prove the applicability of the presented concept for practical purposes.

Cytologic atypia in the contralateral unaffected breast is related to parity and estrogen-related genes.

PURPOSE: The contralateral unaffected breast (CUB) of women with unilateral breast cancer provides a model for the study of breast tissue-based risk factors. Using random fine needle aspiration (rFNA), we have investigated hormonal and gene expression patterns related to atypia in the CUBs of newly diagnosed breast cancer patients. METHODS: 83 women underwent rFNA of the CUB. Cytologic analysis was performed using the Masood Score (MS), atypia was defined as MS > 14. RNA was extracted using 80% of the sample. The expression of 20 hormone related genes was quantified using Taqman Low Density Arrays. Statistical analysis was performed using 2-tailed t tests and linear regression. RESULTS: Cytological atypia was more frequent in multiparous women (P = 0.0392), and was not associated with any tumor-related features in the affected breast. Masood Score was higher with shorter interval since last pregnancy (R = 0.204, P = 0.0417), higher number of births (R = 0.369, P = 0.0006), and estrogen receptor (ER) negativity of the index cancer (R = -0.203, P = 0.065). Individual cytologic features were associated with aspects of parity. Specifically, anisonucleosis was correlated with shorter interval since last pregnancy (R = 0.318, P = 0.0201), higher number of births (R = 0.382, P = 0.0004), and ER status (R = -0.314, P = 0.0038). Eight estrogen-regulated genes were increased in atypical samples (P < 0.005), including TFF1, AGT, PDZK1, PGR, GREB1, PRLR, CAMK2B, and CCND1. CONCLUSIONS: Cytologic atypia, and particularly anisonucleosis, is associated with recent and multiple births and ER negative status of the index tumor. Atypical samples showed increased expression of estrogen-related genes, consistent with the role of estrogen exposure in breast cancer development.

Local transdermal therapy to the breast for breast cancer prevention and DCIS therapy: preclinical and clinical evaluation.

PURPOSE: Women at high risk of breast cancer and those with carcinoma in situ need non-toxic, well-tolerated preventive interventions. One promising approach is drug delivery through the breast skin (local transdermal therapy, LTT). Our goal was to test novel drugs for LTT, to establish that LTT is applicable to non-steroidal drugs. METHODS: Athymic nude rats were treated with oral tamoxifen, transdermal 4-hydroxytamoxifen (4-OHT) or endoxifen gel applied daily to the axillary mammary gland for 6 weeks (Study 1). Study 2 was identical to Study 1, testing transdermal telapristone acetate (telapristone) gel versus subcutaneous implant. At euthanasia, mammary glands and blood were collected. In Study 3, consenting women requiring mastectomy were randomized to diclofenac patch applied to the abdomen or the breast for 3 days preoperatively. At surgery, eight tissue samples per breast were collected from predetermined locations, along with venous blood. Drug concentrations were measured using liquid chromatography-tandem mass spectroscopy. RESULTS: Mammary tissue concentrations of 4-OHT, endoxifen, and telapristone were significantly higher in the axillary glands of the gel-treated animals, compared to inguinal glands or to systemically treated animals. Plasma concentrations were similar in gel and systemically treated animals. The clinical trial showed significantly higher mammary concentrations when diclofenac was applied to the breast skin versus the abdominal skin, but concentrations were variable. CONCLUSIONS: These results demonstrate that lipophilic drugs can be developed for LTT; although the nude rat is suitable for testing drug permeability, delivery is systemic. In human, however, transdermal application to the breast skin provides local delivery.