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Objective Male breast cancer (MBC) is rare. Information about breast cancer is usually designed for female patients. However, in males this disease and some side effects differ from its female counterpart. Therefore, there is a need for male‐specific information. The aim was to assess unmet information needs of (a) MBC patients and (b) health professionals. Methods Dutch MBC patients (diagnosed between 2011 and 2016 in 21 hospitals), patient advocates and partners were invited to participate in focus groups and/or complete a paper‐based questionnaire on information needs. In addition, an online questionnaire on information needs was sent to health professionals involved in MBC patient care. Results In three focus groups with MBC patients (N = 12) and partners (N = 2) the following unmet information themes were identified: patients' experiences/photographs, symptoms, (delay of) diagnosis, treatments, side effects, follow‐up, psychological impact/coping, genetics and family, research and raising awareness. 77 of 107 MBC patients (72%) completed the questionnaire: most patients lacked information about acute (65%) or late (56%) side effects, particularly sexual side effects. Among health professionals, 110 of 139 (79%) had searched for MBC‐related information, specifically: patient information, anti‐hormonal therapy, genetic testing, research, and psychosocial issues. Conclusions Unmet information needs in MBC patients and health professionals were identified. Specific information on MBC should be developed to improve timely diagnosis, quality of life, treatment, and survival. A targeted website is an ideal tool to meet these needs. Therefore, we integrated these results into a user‐centered design to develop an informative website, www.mannenmetborstkanker.nl.

Objective: Unmet health care needs require additional care resources to achieve optimal patient well-being. In this nationwide study we examined associations between a number of risk factors and unmet needs after treatment among women with breast cancer, while taking into account their health care practices. We expected that more care use would be associated with lower levels of unmet needs. Methods: A multicenter, prospective, observational design was employed. Women with primary breast cancer completed questionnaires 6 and 15 months post-diagnosis. Medical data were retrieved from medical records. Direct and indirect associations between sociodemographic and clinical risk factors, distress, care use, and unmet needs were investigated with structural equation modeling. Results: Seven hundred forty-six participants completed both questionnaires (response rate 73.7%). The care services received were not negatively associated with the reported levels of unmet needs after treatment. Comorbidity was associated with higher physical and daily living needs. Higher age was associated with higher health system-related and informational needs. Having had chemotherapy and a mastectomy were associated with higher sexuality needs and breast cancer-specific issues, respectively. A higher level of distress was associated with higher levels of unmet need in all domains. Conclusions: Clinicians may use these results to timely identify which women are at risk of developing specific unmet needs after treatment. Evidence-based, cost-effective (online) interventions that target distress, the most influential risk factor, should be further implemented and disseminated among patients and clinicians.

Paper spray ionization has been used as a fast sampling/ionization method for the direct mass spectrometric analysis of biological samples at ambient conditions. Here, we demonstrated that by utilizing paper spray ionization-mass spectrometry (PSI-MS) coupled with field asymmetric waveform ion mobility spectrometry (FAIMS), predictive metabolic and lipidomic profiles of routine breast core needle biopsies could be obtained effectively. By the combination of machine learning algorithms and pathological examination reports, we developed a classification model, which has an overall accuracy of 87.5% for an instantaneous differentiation between cancerous and noncancerous breast tissues utilizing metabolic and lipidomic profiles. Our results suggested that paper spray ionization-ion mobility spectrometry-mass spectrometry (PSI-IMS-MS) is a powerful approach for rapid breast cancer diagnosis based on altered metabolic and lipidomic profiles.

Significance: Early detection of oral cancer is vital for high-risk patients, and machine learning-based automatic classification is ideal for disease screening. However, current datasets collected from high-risk populations are unbalanced and often have detrimental effects on the performance of classification. Aim: To reduce the class bias caused by data imbalance. Approach: We collected 3851 polarized white light cheek mucosa images using our customized oral cancer screening device. We use weight balancing, data augmentation, undersampling, focal loss, and ensemble methods to improve the neural network performance of oral cancer image classification with the imbalanced multi-class datasets captured from high-risk populations during oral cancer screening in low-resource settings. Results: By applying both data-level and algorithm-level approaches to the deep learning training process, the performance of the minority classes, which were difficult to distinguish at the beginning, has been improved. The accuracy of “premalignancy” class is also increased, which is ideal for screening applications. Conclusions: Experimental results show that the class bias induced by imbalanced oral cancer image datasets could be reduced using both data- and algorithm-level methods. Our study may provide an important basis for helping understand the influence of unbalanced datasets on oral cancer deep learning classifiers and how to mitigate.

ObjectiveIncreased knowledge of breast cancer risk factors enables a shift from one‐size‐fits‐all breast cancer screening to a risk‐based approach, tailoring screening policy to a woman's individual risk. New opportunities for prevention will arise. However, before this novel screening and prevention program is introduced, its acceptability from a woman's perspective needs to be explored.MethodsWomen eligible for breast cancer screening in the Netherlands, United Kingdom, and Sweden were invited to take part in focus groups. A total of 143 women participated. Data were transcribed verbatim and analyzed using thematic analysis.ResultsAnalysis identified five themes across the three countries. The first theme “impact of knowledge” describes women's concern of not being able to unlearn their risk, perceiving it as either a motivator for change or a burden which may lead to stigma. The second theme “belief in science” explains women's need to trust the science behind the risk assessment and subsequent care pathways. Theme three “emotional impact” explores, eg, women's perceived anxiety and (false) reassurance, which may result from knowing their risk. Theme four “decision making” highlights cultural differences in shared versus individual decision making. Theme five “attitude to medication” explores the controversial topic of offering preventative medication for breast cancer risk reduction.ConclusionsAcceptability of risk‐based screening and prevention is mixed. Women's perceptions are informed by a lack of knowledge, cultural norms, and common emotional concerns, which highlights the importance of tailored educational materials and risk counselling to aid either shared or individual informed decision making.

Significance: Current imaging paradigms for differential diagnosis of suspicious breast lesions suffer from high false positive rates that force patients to undergo unnecessary biopsies. Diffuse optical spectroscopic imaging (DOSI) noninvasively probes functional hemodynamic and compositional parameters in deep tissue and has been shown to be sensitive to contrast between normal and malignant tissues. Aim: DOSI methods are under investigation as an adjunct to mammography and ultrasound that could reduce false positive rates and unnecessary biopsies, particularly in radiographically dense breasts. Methods: We performed a retrospective analysis of 212 subjects with suspicious breast lesions who underwent DOSI imaging. Physiological tissue parameters were z-score normalized to the patient’s contralateral breast tissue and input to univariate logistic regression models to discriminate between malignant tumors and the surrounding normal tissue. The models were then used to differentiate malignant lesions from benign lesions. Results: Models incorporating several individual hemodynamic parameters were able to accurately distinguish malignant tumors from both the surrounding background tissue and benign lesions with area under the curve (AUC) ≥0.85. Z-score normalization improved the discriminatory ability and calibration of these predictive models relative to unnormalized or ratio-normalized data. Conclusions: Findings from a large subject population study show how DOSI data normalization that accounts for normal tissue heterogeneity and quantitative statistical regression approaches can be combined to improve the ability of DOSI to diagnose malignant lesions. This improved diagnostic accuracy, combined with the modality’s inherent logistical advantages of portability, low cost, and nonionizing radiation, could position DOSI as an effective adjunct modality that could be used to reduce the number of unnecessary invasive biopsies.

This study is focused on identifying novel epithelial markers in circulating extracellular vesicles (EVs) through the development of a dual sandwich-type electrochemical paper-based immunosensor for Claudin 7 and CD81 determination, as well as its validation in breast cancer (BC) patients. This immunosensor allows for rapid, sensitive, and label-free detection of these two relevant BC biomarkers. Under optimum conditions, the limit of detection for Claudin 7 was 0.4 pg mL-1, with a wide linear range of 2 to 1000 pg mL-1, while for CD81, the limit of detection was 3 pg mL-1, with a wide linear range of 0.01 to 10 ng mL-1. Finally, we validated Claudin 7 and CD81 determination in EVs from 60 BC patients and 20 healthy volunteers, reporting higher diagnostic accuracy than the one observed with classical diagnostic markers. This analysis provides a low-cost, specific, versatile, and user-friendly strategy as a robust and reliable tool for early BC diagnosis. Fil: Ortega, Francisco G.. Balearic Islands Health Research Institute; España Fil: Regiart, Matías D.. Universidade de Sao Paulo; Brasil Fil: Rodríguez Martínez, Alba. Universidad de Granada; España Fil: De Miguel-Pérez, Diego. Universidad de Granada; España Fil: Serrano, María J.. Universidad de Granada; España Fil: Lorente, José A.. Universidad de Granada; España Fil: Tortella, Gonzalo. Universidad de La Frontera; Chile Fil: Rubilar, Olga. Universidad de La Frontera; Chile Fil: Sapag, Manuel Karim. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Física Aplicada "Dr. Jorge Andrés Zgrablich". Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto de Física Aplicada "Dr. Jorge Andrés Zgrablich"; Argentina Fil: Bertotti, Mauro. Universidade de Sao Paulo; Brasil Fil: Fernández Baldo, Martín Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Química de San Luis. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Química de San Luis; Argentina

The cytotoxicities of silica (SiO2s) particles against cancers are still controversial. In this study, the purchased submicron silica particles (SM-SiO2s) were identified by transmission electron microscopy and energy dispersive spectrometer, and it showed potent cytotoxicities on hepatocellular carcinoma (HCC), non-small cell lung cancer (NSCLC) and breast cancer (BC), which ranked the top in the incidence among the tumor types. Through the microarray assay on long noncoding RNAs (lncRNAs) from the SM-SiO2s-treated HCC, NSCLC and BC cells, followed by Venn analysis, we found that a series of lncRNAs were significantly regulated by SM-SiO2s, among of which XLOC_001659 was mostly decreased. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay confirmed that XLOC_001659 could be decreased in all the SM-SiO2s-treated HCC, NSCLC and BC cells, coupled to inhibited cell proliferation. Further, XLOC_001659 was recognized as a miR-98-5p sponge and therefore modulates the “pro-inflammatory tumor promoter” MAP3K2 expressions. The XLOC_001659/miR-98-5p/MAP3K2 axis uniformly mediated the regulation of SM-SiO2s on proliferation of HCC, NSCLC and BC cells. Further clinical experiments demonstrated that XLOC_001659 was negatively correlated with miR-98-5p level and positively correlated with MAP3K2 level, and XLOC_001659/miR-98-5p/MAP3K2 axis was significantly associated with progressions and prognosis in HCC, NSCLC and BC patients. These results provide a new clue for the anti-tumor mechanism of SM-SiO2s and a new way for drug development by using SM-SiO2s.

Significance: Decreasing the oxygen consumption rate (OCR) of tumor cells is a powerful method for ameliorating tumor hypoxia. However, quantifying the change in OCR is challenging in complex experimental systems. Aim: We present a method for quantifying the OCR of two tumor cell lines using oxygen-sensitive dual-emissive boron nanoparticles (BNPs). We hypothesize that our BNP results are equivalent to the standard Seahorse assay. Approach: We quantified the spectral emissions of the BNP and accounted for external oxygen diffusion to quantify OCR over 24 h. The BNP-computed OCR of two breast cancer cell lines, E0771 and 4T07, were compared with their respective Seahorse assays. Both cell lines were also irradiated to quantify radiation-induced changes in the OCR. Results: Using a Bland–Altman analysis, our BNPs OCR was equivalent to the standard Seahorse assay. Moreover, in an additional experiment in which we irradiated the cells at their 50% survival fraction, the BNPs were sensitive enough to quantify 24% reduction in OCR after irradiation. Conclusions: Our results conclude that the BNPs are a viable alternative to the Seahorse assay for quantifying the OCR in cells. The Bland–Altman analysis showed that these two methods result in equivalent OCR measurements. Future studies will extend the OCR measurements to complex systems including 3D cultures and in vivo models, in which OCR measurements cannot currently be made.

Significance: Optical coherence tomography (OCT) is widely used as a potential diagnostic tool for a variety of diseases including various types of cancer. However, sensitivity and specificity analyses of OCT in different cancers yield results varying from 11% to 100%. Hence, there is a need for more detailed statistical analysis of blinded reader studies. Aim: Extensive statistical analysis is performed on results from a blinded study involving OCT of breast tumor margins to assess the impact of reader variability on sensitivity and specificity. Approach: Five readers with varying levels of experience reading OCT images assessed 50 OCT images of breast tumor margins collected using an intraoperative OCT system. Statistical modeling and analysis was performed using the R language to analyze reader experience and variability. Results: Statistical analysis showed that the readers’ prior experience with OCT images was directly related to the probability of the readers’ assessment agreeing with histology. Additionally, results from readers with prior experience specific to OCT in breast cancer had a higher probability of agreement with histology compared to readers with experience with OCT in other (noncancer) diseases. Conclusions: The results from this study demonstrate the potential impact of reader training and experience in the assessment of sensitivity and specificity. They also demonstrate even greater potential improvement in diagnostic performance by combining results from multiple readers. These preliminary findings suggest valuable directions for further study.

Tumor tropism metastasis is a multi-step process that involves interactions between tumor cells and the microenvironment. Due to the limitations of experimental techniques, current studies are not able to gain insight into the dynamic process of such tropism migration. To overcome this issue, we developed a paper-supported co-culture system for dynamic investigations of the lung-tropic migration of breast cancer cells. This co-culture system contains a tumor layer, a recruitment layer, and several invasion layers between these two parts. The tumor and recruitment layers are impregnated with breast cancer cells and lung cells, respectively. Stacking these layers forms a co-culture device that comprises interactions between breast cancer and lung, destacking such a device represents cancer cells at different stages of the migration process. Thus, the paper-supported co-culture system offers the possibility of investigating migration from temporal and spatial aspects. Invasion assays using the co-culture system showed that breast cancer cells induced lung fibroblasts to convert to cancer-associated fibroblasts (CAFs), and the CAFs, in turn, recruited breast cancer cells. During migration, the local invasion of the cancer cells is a collective behavior, while the long-distance migration comes from individual cell behaviors. Breast cancer cells experienced repetitive processes of migration and propagation, accompanied by epithelial–mesenchymal and mesenchymal–epithelial transitions, and changes in stemness and drug resistance. Based on these results, the lung-tropic migration of breast cancer is interpreted as a process of bilateral interaction with the local and host-organ microenvironment. The developed paper-supported co-culture system offers the possibility of dynamically investigating tropism migration under the pre-metastatic niche, thus providing an advantageous tool for studying tumor metastasis.

Significance: Diffuse optical imaging (DOI) provides in vivo quantification of tissue chromophores such as oxy- and deoxyhemoglobin (HbO2 and HHb, respectively). These parameters have been shown to be useful for predicting neoadjuvant treatment response in breast cancer patients. However, most DOI devices designed for the breast are nonportable, making frequent longitudinal monitoring during treatment a challenge. Furthermore, hemodynamics related to the respiratory cycle are currently unexplored in the breast and may have prognostic value. Aim: To design, fabricate, and validate a high optode-density wearable continuous wave diffuse optical probe for the monitoring of breathing hemodynamics in breast tissue. Approach: The probe has a rigid-flex design with 16 dual-wavelength sources and 16 detectors. Performance was characterized on tissue-simulating phantoms, and validation was performed through flow phantom and cuff occlusion measurements. The breasts of N = 4 healthy volunteers were measured while performing a breathing protocol. Results: The probe has 512 unique source-detector (S-D) pairs that span S-D separations of 10 to 54 mm. It exhibited good performance characteristics: ma drift of 0.34%/h, ma precision of 0.063%, and mean SNR > 24 dB up to 41 mm S-D separation. Absorption contrast was detected in flow phantoms at depths exceeding 28 mm. A cuff occlusion measurement confirmed the ability of the probe to track expected hemodynamics in vivo. Breast measurements on healthy volunteers during paced breathing revealed median signal-to-motion artifact ratios ranging from 8.1 to 8.7 dB. Median DHbO2 and DHHb amplitudes ranged from 0.39 to 0.67 mM and 0.08 to 0.12 mM, respectively. Median oxygen saturations at the respiratory rate ranged from 82% to 87%. Conclusions: A wearable diffuse optical probe has been designed and fabricated for the measurement of breast tissue hemodynamics. This device is capable of quantifying breathing-related hemodynamics in healthy breast tissue.

This study investigated whether valproic acid (VPA, a histone deacetylase inhibitor) can interfere with the carcinogenicity of polycyclic aromatic hydrocarbons (PAHs). A typical representative compound of PAHs, 7,12-Dimethylbenz[a]anthracene (DMBA), was used to induce rat breast cancer. The results showed that therapeutic concentration of VPA (50 and 100 mg/kg) delayed the occurrence of tumors, reduced tumor formation rate and attenuated tumors growth, and have a protective effect on normal tissues. The macrophage-mediated inflammatory response was found to be associated with the observed effect of VPA. In addition, we screened and validated a possible gene, Sema3c, which was involved in DMBA-induced breast cancer development and can be inhibited by VPA.

Significance: Re-excision rates for women with invasive breast cancer undergoing breast conserving surgery (or lumpectomy) have decreased in the past decade but remain substantial. This is mainly due to the inability to assess the entire surface of an excised lumpectomy specimen efficiently and accurately during surgery. Aim: The goal of this study was to develop a deep-ultraviolet scanning fluorescence microscope (DUV-FSM) that can be used to accurately and rapidly detect cancer cells on the surface of excised breast tissue. Approach: A DUV-FSM was used to image the surfaces of 47 (31 malignant and 16 normal/benign) fresh breast tissue samples stained in propidium iodide and eosin Y solutions. A set of fluorescence images were obtained from each sample using low magnification (4×) and fully automated scanning. The images were stitched to form a color image. Three nonmedical evaluators were trained to interpret and assess the fluorescence images. Nuclear–cytoplasm ratio (N/C) was calculated and used for tissue classification. Results: DUV-FSM images a breast sample with subcellular resolution at a speed of 1.0 min/cm2. Fluorescence images show excellent visual contrast in color, tissue texture, cell density, and shape between invasive carcinomas and their normal counterparts. Visual interpretation of fluorescence images by nonmedical evaluators was able to distinguish invasive carcinoma from normal samples with high sensitivity (97.62%) and specificity (92.86%). Using N/C alone was able to differentiate patch-level invasive carcinoma from normal breast tissues with reasonable sensitivity (81.5%) and specificity (78.5%). Conclusions: DUV-FSM achieved a good balance between imaging speed and spatial resolution with excellent contrast, which allows either visual or quantitative detection of invasive cancer cells on the surfaces of a breast surgical specimen.

OBJECTIVE: Troublesome hot flushes and night sweats (HFNS) are experienced by many women after treatment for breast cancer, impacting significantly on sleep and quality of life. Cognitive behavioural therapy (CBT) is known to be effective for the alleviation of HFNS. However, it is not known if it can effectively be delivered by specialist nurses. We investigated whether group CBT, delivered by breast care nurses (BCNs), can reduce the impact of HFNS.METHODS: We recruited women with primary breast cancer following primary treatment with seven or more HFNS/week (including 4/10 or above on the HFNS problem rating scale), from six UK hospitals to an open, randomised, phase 3 effectiveness trial. Participants were randomised to Group CBT or usual care (UC). The primary endpoint was HFNS problem rating at 26 weeks after randomisation. Secondary outcomes included sleep, depression, anxiety and quality of life.RESULTS: Between 2017 and 2018, 130 participants were recruited (CBT:63, control:67). We found a 46% (6.9-3.7) reduction in the mean HFNS problem rating score from randomisation to 26 weeks in the CBT arm and a 15% (6.5-5.5) reduction in the UC arm (adjusted mean difference -1.96, CI -3.68 to -0.23, P = .039). Secondary outcomes, including frequency of HFNS, sleep, anxiety and depression all improved significantly.CONCLUSION: Our results suggest that specialist nurses can be trained to deliver CBT effectively to alleviate troublesome menopausal hot flushes in women following breast cancer in the NHS setting.

Bone metastases are a frequent complication of breast cancer, and there has been little progress in the treatment of breast cancer patients with bone metastases. The cytotoxicity of selenium donors, including organic selenium and selenium nanoparticles (SeNPs), to cancer cells has been reported previously, but their relationship with bone metastases progression is not fully clear yet. In this study, multicenter clinical exploration was conducted to obtain dietary selenium intakes of breast cancer patients with or without bone metastasis, to study the relationship between selenium and breast cancer prognosis and bone metastasis. We found that dietary selenium intakes were significantly lower in breast cancer patients with bone metastasis, comparing with the non-bone metastasis cases. Selenium lower group of bone metastasis breast cancer patients had worse prognosis, whereas the daily selenium intakes could not predict the prognosis of breast cancer patients without bone metastasis. Subsequently, we study the regulatory role of selenium donors on bone metastasis at the cellular level, by challenging the cells with SeNPs. SeNPs showed potent cytotoxicity in breast cancer cells, no matter whether they were primary or bone-metastatic. SeNPs treated cancer cell inhibited the survival and differentiation of osteoclast progenitor cells. At the molecular level, we demonstrated that IL-6 partially mediated osteoclastogenesis suppression by SeNPs. These results provide a new way for biomarkers or drug development to treat and even prevent bone metastases of breast cancer by using selenium donors.

Author(s): Napoles, Anna Maria; Santoyo-Olsson, Jasmine; Stewart, Anita L; Ortiz, Carmen; Samayoa, Cathy; Torres-Nguyen, Alma; Palomino, Helen; Coleman, LaVerne; Urias, Aday; Gonzalez, Nayeli; Cervantes, Silvia Araceli; Totten, Vicken Y | Abstract: ObjectiveWe report results of a community-based multisite, randomized controlled trial of Nuevo Amanecer (NA-II), a 10-week stress management program for rural, low literacy Latina breast cancer survivors.MethodsTrained peers delivered NA-II to Spanish-speaking Latinas with non-metastatic breast cancer in three rural communities. Women were randomized to receive the program immediately or wait 6 months. Assessments were conducted at baseline, 3 months, and 6 months. Primary outcomes were breast cancer-specific quality of life domains; secondary outcomes included general distress symptoms and stress management skills. Intention-to-treat analyses using repeated-measures linear regression models estimated changes in slope between groups.ResultsOf 153 participants (76 randomized to intervention, 77 to control group), 92% were retained at 6 months. Mean age was 54.8 years (SD = 10.5); 80% had less than high school education. There were no statistically significant treatment × time effects on quality of life. Compared to women in the control group, intervention group women reported greater improvements in anxiety at 6 months (-0.20 vs -0.02, P = .049; range 0-4) as well as three stress management skills: relaxation at 3 months (+0.98 vs -0.07, P l .0001; range 0-4) and 6 months (+0.82 vs +0.04, P l .001), awareness of tension at 3 months (+0.31 vs -0.19, P l .01; range 0-4) and 6 months (+0.29 vs -0.11, P l .05), and coping confidence at 3 months (+0.12 vs -0.23, P l .01; range 0-4).ConclusionsStress management programs delivered by trained peers in rural community settings can reduce anxiety and improve stress management skills among Latina breast cancer survivors.

Objective: We investigated the effectiveness of a self-help intervention named PERANTARA, which aims to improve adherence to diagnostic procedures among women with breast cancer (BC) symptoms to reduce the time to a definitive diagnosis. Methods: With a cluster randomized crossover design across four hospitals, PERANTARA and treatment as usual (TAU) or TAU only was provided at successive periods in a randomly determined order. The main outcome was the time between the first medical consultation and the definitive diagnosis. Secondary outcomes were BC knowledge, measured by the Breast Cancer Knowledge Test (BCKT); symptoms of anxiety and depression, measured by the Hospital Anxiety and Depression Scale (HADS); quality of life, measured by the World Health Organization Quality of Life-BREF (WHOQOL-BREF); and health status, measured by the EQ-5D-5L. A linear mixed model analysis was conducted to analyse the outcomes. Results: We recruited 132 women with BC symptoms from four hospitals; 67 participants were in the intervention group, and 65 participants were in the control group. PERANTARA reduced the time to definitive diagnosis by 13.3 days (M [SD]: 25.90 [23.20] in the intervention group vs 39.29 [35.10] in the control group; mean difference = −13.26, 95% CI = −24.51 to −2.00, P =.02). No significant difference was found between the groups in BC knowledge, symptoms of anxiety, depression, quality of life, or health status. Conclusions: PERANTARA reduced the time to definitive diagnosis among Indonesian women with BC symptoms. Psychoeducation may be an important addition to regular BC care to prevent undue delays in diagnostic procedures.

Purpose:\ud \ud The pattern of dense tissue on a mammogram appears to provide additional information than overall density for risk assessment, but there has been little consistency in measures of texture identified. The purpose of this study is thus to validate a mammographic texture feature developed from a previous study in a new setting.\ud \ud Approach:\ud \ud A case–control study (316 invasive cases and 1339 controls) of women in Virginia, USA was used to validate a mammographic texture feature (MMTEXT) derived in a independent previous study. Analysis of predictive ability was adjusted for age, demographic factors, questionnaire risk factors (combined through the Tyrer-Cuzick model), and optionally BI-RADS breast density. Odds ratios per interquartile range (IQ-OR) in controls were estimated. Subgroup analysis assessed heterogeneity by mode of cancer detection (94 not detected by mammography).\ud \ud Results:\ud \ud MMTEXT was not a significant risk factor at 0.05 level after adjusting for classical risk factors (IQ-OR = 1.16, 95%CI 0.92 to 1.46), nor after further adjustment for BI-RADS density (IQ-OR = 0.92, 95%CI 0.76 to 1.10). There was weak evidence that MMTEXT was more predictive for cancers that were not detected by mammography (unadjusted for density: IQ-OR = 1.46, 95%CI 0.99 to 2.15 versus 1.03, 95%CI 0.79 to 1.35, Phet 0.10; adjusted for density: IQ-OR = 1.11, 95%CI 0.70 to 1.77 versus 0.76, 95%CI 0.55 to 1.05, Phet 0.21).\ud \ud Conclusions:\ud \ud MMTEXT is unlikely to be a useful imaging marker for invasive breast cancer risk assessment in women attending mammography screening. Future studies may benefit from a larger sample size to confirm this as well as developing and validating other measures of risk. This negative finding demonstrates the importance of external validation.

Purpose: Computer-aided detection (CAD) alerts radiologists to findings potentially associated with breast cancer but is notorious for creating false-positive marks. Although a previous paper found that radiologists took more time to interpret mammograms with more CAD marks, our impression was that this was not true in actual interpretation. We hypothesized that radiologists would selectively disregard these marks when present in larger numbers. Approach: We performed a retrospective review of bilateral digital screening mammograms. We use a mixed linear regression model to assess the relationship between number of CAD marks and ln (interpretation time) after adjustment for covariates. Both readers and mammograms were treated as random sampling units. Results: Ten radiologists, with median experience after residency of 12.5 years (range 6 to 24) interpreted 1832 mammograms. After accounting for number of images, Breast Imaging Reporting and Data System category, and breast density, the number of CAD marks was positively associated with longer interpretation time, with each additional CAD mark proportionally increasing median interpretation time by 4.35% for a typical reader. Conclusions: We found no support for our hypothesis that radiologists will selectively disregard CAD marks when they are present in larger numbers.

Significance: A key risk faced by oncological surgeons continues to be complete removal of tumor. Currently, there is no intraoperative imaging device to detect kidney tumors during excision. Aim: We are evaluating molecular chemical imaging (MCI) as a technology for real-time tumor detection and margin assessment during tumor removal surgeries. Approach: In exploratory studies, we evaluate visible near infrared (Vis-NIR) MCI for differentiating tumor from adjacent tissue in ex vivo human kidney specimens, and in anaesthetized mice with breast or lung tumor xenografts. Differentiation of tumor from nontumor tissues is made possible with diffuse reflectance spectroscopic signatures and hyperspectral imaging technology. Tumor detection is achieved by score image generation to localize the tumor, followed by application of computer vision algorithms to define tumor border. Results: Performance of a partial least squares discriminant analysis (PLS-DA) model for kidney tumor in a 22-patient study is 0.96 for area under the receiver operating characteristic curve. A PLS-DA model for in vivo breast and lung tumor xenografts performs with 100% sensitivity, 83% specificity, and 89% accuracy. Conclusion: Detection of cancer in surgically resected human kidney tissues is demonstrated ex vivo with Vis-NIR MCI, and in vivo on mice with breast or lung xenografts.

Significance: We introduce an application of machine learning trained on optical phase features of epithelial and mesenchymal cells to grade cancer cells’ morphologies, relevant to evaluation of cancer phenotype in screening assays and clinical biopsies. Aim: Our objective was to determine quantitative epithelial and mesenchymal qualities of breast cancer cells through an unbiased, generalizable, and linear score covering the range of observed morphologies. Approach: Digital holographic microscopy was used to generate phase height maps of noncancerous epithelial (Gie-No3B11) and fibroblast (human gingival) cell lines, as well as MDA-MB-231 and MCF-7 breast cancer cell lines. Several machine learning algorithms were evaluated as binary classifiers of the noncancerous cells that graded the cancer cells by transfer learning. Results: Epithelial and mesenchymal cells were classified with 96% to 100% accuracy. Breast cancer cells had scores in between the noncancer scores, indicating both epithelial and mesenchymal morphological qualities. The MCF-7 cells skewed toward epithelial scores, while MDA-MB-231 cells skewed toward mesenchymal scores. Linear support vector machines (SVMs) produced the most distinct score distributions for each cell line. Conclusions: The proposed epithelial–mesenchymal score, derived from linear SVM learning, is a sensitive and quantitative approach for detecting epithelial and mesenchymal characteristics of unknown cells based on well-characterized cell lines. We establish a framework for rapid and accurate morphological evaluation of single cells and subtle phenotypic shifts in imaged cell populations.

PubMed: 31983145 Obesity is associated with a higher risk of developing breast cancer and with worse disease outcomes for women of all ages. The composition, density, and organization of the breast tissue stroma are also known to play an important role in the development and progression of the disease. However, the connections between obesity and stromal remodeling are not well understood. We sought to characterize detailed organization features of the collagen matrix within healthy and cancerous breast tissues acquired from mice exposed to either a normal or high fat (obesity inducing) diet. We performed second-harmonic generation and spectral two-photon excited fluorescence imaging, and we extracted the level of collagen-associated fluorescence (CAF) along with metrics of collagen content, three-dimensional, and two-dimensional organization. There were significant differences in the CAF intensity and overall collagen organization between normal and tumor tissues; however, obesity-enhanced changes in these metrics, especially when three-dimensional organization metrics were considered. Thus, our studies indicate that obesity impacts significantly collagen organization and structure and the related pathways of communication may be important future therapeutic targets..

Objective Internet‐delivered interventions may alleviate distress in cancer survivors with limited access to psychological face‐to‐face treatment. In collaboration with a group of cancer survivors, we developed and tested the efficacy of a therapist‐assisted internet‐delivered mindfulness‐based cognitive therapy (iMBCT) program for anxiety and depression in cancer survivors. Methods A total of 1282 cancer survivors were screened for anxiety and depression during their routine oncology follow‐up; eligible breast (n = 137) and prostate cancer (n = 13) survivors were randomized to iMBCT or care‐as‐usual (CAU) wait‐list. Primary outcomes of anxiety and depression were assessed at baseline, 5 weeks, 10 weeks (post intervention), and 6 months. Results Significant effects were found for both anxiety (Cohen's d = 0.45; P = .017) and depressive symptoms (d = 0.42; P = .024) post intervention. The effects were maintained at follow‐up for anxiety (d = 0.40; P = .029), but not for depressive symptoms (d = 0.28; P = .131). Conclusions Our preliminary findings suggest iMBCT to be a helpful intervention for cancer survivors suffering from symptoms of anxiety. Further studies on the efficacy for symptoms of depression are needed.

Objective: This study examined the course and predictors of supportive care needs among Mexican breast cancer patients for different cancer treatment trajectories.Methods: Data from 172 (66.4% response rate) patients were considered in this observational longitudinal study. Participants were measured after diagnosis, neoadjuvant treatment, surgery, adjuvant treatment, and the first post-treatment follow-up visit. Psychological, Health System and Information, Physical and Daily Living, Patient Care and Support, Sexual, and Additional care needs were measured with the Supportive Care Needs Survey (SCNS-SF34). Linear mixed models with maximum-likelihood estimation were computed.Results: The course of supportive care needs was similar across the different cancer treatment trajectories. Supportive care needs declined significantly from diagnosis to the first post-treatment follow-up visit. Health System and Information care needs were the highest needs over time. Depressive symptoms and time since diagnosis were the most consistent predictors of changes in course of supportive care needs of these patients.Conclusions: Health system and information care needs of Mexican breast cancer patients need to be addressed with priority because these needs are the least met. Furthermore, patients with high depressive symptoms at the start of the disease trajectory have greater needs for supportive care throughout the disease trajectory.

Altres ajuts: the ICN2 is funded by the CERCA Programme/Generalitat de Catalunya. The development of paper-based electroanalytical strips as powerful diagnostic tools has gained a lot of attention within the sensor community. In particular, the detection of nucleic acids in complex matrices represents a trending topic, especially when focused toward the development of emerging technologies, such as liquid biopsy. DNA-based biosensors have been largely applied in this direction, and currently, there are two main approaches based on target/probe hybridization reported in the literature, namely Signal ON and Signal OFF. In this technical note, the two approaches are evaluated in combination with paper-based electrodes, using a single strand DNA relative to H1047R (A3140G) missense mutation in exon 20 in breast cancer as the model target. A detailed comparison among the analytical performances, detection protocol, and cost associated with the two systems is provided, highlighting the advantages and drawbacks depending on the application. The present work is aimed to a wide audience, particularly for those in the field of point-of-care, and it is intended to provide the know-how to manage with the design and development stages, and to optimize the platform for the sensing of nucleic acids using a paper-based detection method.

© 2018 The Authors. Psycho-Oncology Published by John Wiley & Sons Ltd. Objective: Despite the physical and psychological health benefits associated with physical activity (PA) for breast cancer (BC) survivors, up to 70% of female BC survivors are not meeting minimum recommended PA guidelines. The objective of this study was to evaluate acceptability and satisfaction with Project MOVE, an innovative approach to increase PA among BC survivors through the combination of microgrants and financial incentives. Methods: A mixed-methods design was used. Participants were BC survivors and support individuals with a mean age of 58.5 years. At 6-month follow-up, participants completed a program evaluation questionnaire (n = 72) and participated in focus groups (n = 52) to explore their experience with Project MOVE. Results: Participants reported that they were satisfied with Project MOVE (86.6%) and that the program was appropriate for BC survivors (96.3%). Four main themes emerged from focus groups: (1) acceptability and satisfaction of Project MOVE, detailing the value of the model in developing tailored group-base PA programs; (2) the importance of Project MOVE leaders, highlighting the value of a leader that was organized and a good communicator; (3) breaking down barriers with Project MOVE, describing how the program helped to address common BC related barriers; and (4) motivation to MOVE, outlining how the microgrants enabled survivors to be active, while the financial incentive motivated them to increase and maintain their PA. Conclusion: The findings provide support for the acceptability of Project MOVE as a strategy for increasing PA among BC survivors.

OBJECTIVE: Patients and partners both cope individually and as a dyad with challenges related to a breast cancer diagnosis. The objective of this study was to evaluate the effect of a psychological attachment-oriented couple intervention for breast cancer patients and partners in the early treatment phase.METHODS: A randomised controlled trial including 198 recently diagnosed breast cancer patients and their partners. Couples were randomised to the Hand in Hand (HiH) intervention in addition to usual care or to usual care only. Self-report assessments were conducted for both patients and partners at baseline, postintervention (5 months), and follow-up (10 months), assessing cancer-related distress, symptoms of anxiety and depression, and dyadic adjustment. Patients' cancer-related distress was the primary outcome.RESULTS: Cancer-related distress decreased over time in both patients and partners, but the intervention did not significantly affect this decrease at postintervention (P = .08) or follow-up (P = .71). A significant positive effect was found on dyadic adjustment at follow-up for both patients (P = .04) and partners (P = .02).CONCLUSIONS: There was no significant effect of the HiH intervention cancer-related distress. The results suggest that most couples can cope with cancer-related distress in the context of usual care. However, the positive effect on dyadic adjustment implies that the HiH intervention benefitted both patients and partners. Future studies should investigate how to integrate a couple focus in usual cancer care to improve dyadic coping in the early treatment phase.

Inexpensive near-infrared microscopy (NIRM) was developed as a convenient technique to detect the medulla loss of scalp hair while reducing analytical time with easy sample preparation, leading to a field screening tool for breast cancer. NIRM has been evaluated as an alternative to synchrotron-based nanoscopy and to the relatively expensive method of conventional infrared microscopy to determine the degree and pattern of medulla loss of scalp hairs of patients with breast cancer and benign diseases, as well as normal healthy individuals. NIR imaging showed a strong, scattering-based hyperintense contrast of the medulla compared to the fully attenuated cortex in medullated healthy hair. Complete medulla loss (CML) per hair strand was more extensively (60.9 ± 10.2 %) (p

Author(s): Escalera, Cristian; Santoyo-Olsson, Jasmine; Stewart, Anita L; Ortiz, Carmen; Napoles, Anna Maria | Abstract: ObjectiveIntrusive thoughts, defined as unwanted and recurrent thoughts about a stressful experience, are associated with psychological distress in women with breast cancer. This study assessed moderating effects of various social support dimensions on associations between intrusive thoughts and psychological distress among Latina breast cancer survivors.MethodsWe used baseline data from a randomized controlled trial of a stress management intervention delivered to 151 Spanish-speaking Latinas with nonmetastatic breast cancer within 1 year of diagnosis. Intrusive thoughts, four dimensions of social support (emotional/informational, tangible, affectionate, and positive social interaction), and symptoms of anxiety and depression were assessed through in-person interviews. Information on age, time since diagnosis, breast cancer variables, history of depression, and marital status served as covariates. Generalized linear models were used to investigate bivariate and multivariate associations and to explore moderation effects of the four dimensions of social support.ResultsIn bivariate models, intrusive thoughts were associated positively with depression (β = .024, .001) and anxiety (β = .047, P l .001) symptoms. Adjusting for other factors, intrusive thoughts remained associated with depression symptoms (β = .022, .008), regardless of level of social support (for all support dimensions). For anxiety, there were significant interactions of tangible (β = -.013, .034) and affectionate (β = -.022, .005) support with intrusive thoughts. Intrusive thoughts were associated more strongly with anxiety symptoms among women reporting less tangible and affectionate support than those with higher levels of these types of support.ConclusionsTangible and affectionate support have protective effects on anxiety symptoms among Spanish-speaking Latina breast cancer survivors experiencing intrusive thoughts, but not depression symptoms.

Neoadjuvant chemotherapy (NACT) is routinely administered to subsets of breast cancer patients, including triple negative (TN) or human epidermal growth factor receptor 2-positive (HER2+) cancers. After NACT and subsequent surgical resection, 5% to 30% of patients have no residual invasive carcinoma, termed pathological complete response. Unfortunately, many patients experience little-to-no response after NACT and unnecessarily suffer its side effects. Methods are needed to predict an individual patient’s response to NACT. Core needle biopsies, taken before NACT, consist of tumor cells and the surrounding extracellular matrix. We performed second-harmonic generation (SHG) imaging of fibrillar collagen in core needle biopsy sections as a possible predictor of response to NACT. The ratio of forward-to-backward scattering (F/B) SHG was assessed in the “tumor bulk” and “tumor–host interface” in HER2+ and TN core needle biopsy sections. Patient response was classified post-treatment using the Residual Cancer Burden (RCB) score. In HER2+ biopsies, RCB class was associated with F/B derived from the tumor–stromal interface, but not tumor bulk. F/B was not associated with RCB class in TN biopsies. These findings suggest that F/B from needle biopsy sections may be a useful predictor of which patients will respond favorably to NACT, with the potential to help reduce overtreatment.

Breast cancer is one of the leading causes for cancer related deaths in women, and early detection is extremely important to improve survival rates. Currently, x-ray mammogram is the only modality for mass screening of asymptomatic women. However, it has decreased sensitivity in radiographically dense breasts, which is also associated with a higher risk for breast cancer. Photoacoustic (PA) imaging is an emerging modality that enables deep tissue imaging of optical contrast at ultrasonically defined spatial resolution, which is much higher than that can be achieved in purely optical imaging modalities. Because of high optical absorption from hemoglobin molecules, PA imaging can map out hemo distribution and dynamics in breast tissue and identify malignant lesions based on tumor associated angiogenesis and hypoxia. We review various PA breast imaging systems proposed over the past few years and summarize the PA features of breast cancer identified in these systems.

Relatively few imaging and sensing technologies are employed to study human lactation physiology. In particular, human mammary development during pregnancy as well as mammary involution after lactation have been poorly described, despite their importance for breast cancer diagnosis and treatment during these phases. Our case study shows the potential of diffuse optical spectroscopic imaging (DOSI) to uniquely study the spatiotemporal changes in mammary tissue composition during the involution of the lactating breast toward its pre-pregnant state. At nine time intervals over a period of eight months after the cessation of breastfeeding, we reconstructed 2-D maps of mammary water content, lipid content, total hemoglobin (THb) concentration, oxygen saturation (StO2), and tissue optical scattering. Mammary lipid content in the nonareolar region showed a significant relative increase of 59%, whereas water content and THb concentration showed a significant relative decrease of 50% and 48%, respectively. Significant changes were also found in StO2 and tissue optical scattering. Our findings are consistent with the gradual replacement of fibroglandular tissue by adipose tissue and vascular regression during mammary involution. Moreover, our data provide unique insight into the dynamics of breast tissue composition and demonstrate the effectiveness of DOSI as a technique to study human lactation physiology.

Early stage diagnosis of breast cancer by monitoring the proteins in human biological fluids is the best method and the first section toward efficient therapy, delaying metastasis and hindrance mortality. In this study, graphite ink was synthesized and combined with CA 15-3 antibody in order to develop a novel immunosensor for detection of CA 15-3, breast cancer biomarker. Conductivity of bioink was examined by designing various conductive patterns on paper using a rollerball pen. Electrochemical behavior of engineered immunosensor was evaluated through employing sensitive diagnostic technique, DPV (differential pulse voltammetry). Under optimal conditions, the linear concentration range and low limit of quantification (LLOQ) of designed immunosensor was 15–250 U/mL and 15 U/mL, respectively. The process was successfully applied to assay of breast cancer biomarker (CA15-3) in unprocessed human plasma specimens.

Genome-wide association studies have demonstrated that combinations of single nucleotide polymorphisms (SNPs), rather than individual SNPs, represent genetic signatures that correlate with heterogeneous and complex diseases. In this context, we developed a paper-based device that provides visual detection of a 10-SNP panel as a genetic signature associated with the risk for breast cancer. The method involves multiplex PCR amplification, multiplex extension reaction of allele-specific primers, without prior purification of the amplified sequences, and, finally, capture and visualization of the extension products within minutes on the device. Detection and monitoring are accomplished either by naked eye or by scanning with a common flatbed scanner. The total assay time is ∼ 2 h. The method was evaluated by using 21 clinical samples of known genotypes. The results were fully concordant with the reference method (sequencing). The proposed method is accurate, simple, rapid, and cost-effective. Visual detection does not require specialized instrumentation or highly trained technical personnel. We anticipate that the proposed device will become a useful analytical tool for precision medicine of breast cancer.

Objective Medical cancer treatment is often accompanied by appearance‐related side effects such as hair loss, skin irritation, and paleness, which can subsequently lead to psychosocial distress. Initial evidence suggests that beauty care interventions may reduce distress and improve quality of life (QoL), body image, and self‐esteem immediately. Methods We investigated the effects of a brief beauty care intervention on self‐reported symptoms of depression, quality of life, body image, and self‐esteem in 39 female primary breast cancer patients with appearance‐related treatment side effects. Patients were randomly assigned either to an immediate intervention group (IG) or to a wait‐list control (WL). The intervention consisted of a single‐session group makeup workshop, a photo shooting, and of receiving professionally edited portrait and upper‐body photos. Results While groups did not differ regarding any measure at the pretreatment baseline assessment, IG patients reported less symptoms of depression, higher QoL, and higher self‐esteem compared with baseline and compared with WL. Follow‐up at 8 weeks indicated moderate stability of these improvements. Conclusions In contrast to previous research, results indicate beneficial short‐term and midterm effects of beauty care on psychological outcomes in patients with early breast cancer. These results emphasize the utility of this type of brief, low‐cost intervention in women undergoing medical cancer treatment in order to improve their well‐being.

Diffuse reflectance spectroscopy (DRS) can discriminate different tissue types based on optical characteristics. Since this technology has the ability to detect tumor tissue, several groups have proposed to use DRS for margin assessment during breast-conserving surgery for breast cancer. Nowadays, an increasing number of patients with breast cancer are being treated by neoadjuvant chemotherapy. Limited research has been published on the influence of neoadjuvant chemotherapy on the optical characteristics of the tissue. Hence, it is unclear whether margin assessment based on DRS is feasible in this specific group of patients. We investigate whether there is an effect of neoadjuvant chemotherapy on optical measurements of breast tissue. To this end, DRS measurements were performed on 92 ex-vivo breast specimens from 92 patients, treated with neoadjuvant chemotherapy and without neoadjuvant chemotherapy. Generalized estimating equation (GEE) models were generated, comparing the measurements of patients with and without neoadjuvant chemotherapy in datasets of different tissue types using a significance level of 5%. As input for the GEE models, either the intensity at a specific wavelength or a fit parameter, derived from the spectrum, was used. In the evaluation of the intensity, no influence of neoadjuvant chemotherapy was found, since none of the wavelengths were significantly different between the measurements with and the measurements without neoadjuvant chemotherapy in any of the datasets. These results were confirmed by the analysis of the fit parameters, which showed a significant difference for the amount of collagen in only one dataset. All other fit parameters were not significant for any of the datasets. These findings may indicate that assessment of the resection margin with DRS is also feasible in the growing population of breast cancer patients who receive neoadjuvant chemotherapy. However, it is possible that we did not detect neoadjuvant chemotherapy effect in the some of the datasets due to the small number of measurements in those datasets.

The purpose of this study was to perform an initial investigation of the possibility to determine breast cancer growth rate with (14)C bomb-pulse dating. Tissues from 11 breast cancers, diagnosed in 1983, were retrieved from a regional biobank. The estimated average age of the majority of the samples overlapped the year of collection (1983) within 3σ Thus, this first study of tumour tissue has not yet demonstrated that (14)C bomb-pulse dating can obtain information on the growth of breast cancer. However, with further refinement, involving extraction of cell types and components, there is a possibility that fundamental knowledge of tumour biology might still be gained by the bomb-pulse technique. Additionally, δ (13)C and δ (15)N analyses were performed to obtain dietary and metabolic information, and to serve as a base for improvement of the age determination.

We propose a new intrinsic cancer marker in fixed tissue biopsy slides, which is based on the local spatial autocorrelation length obtained from quantitative phase images. The spatial autocorrelation length in a small region of the tissue phase image is sensitive to the nanoscale cellular morphological alterations and can hence inform on carcinogenesis. Therefore, this metric can potentially be used as an intrinsic cancer marker in histopathology. Typically, these correlation length maps are calculated by computing 2D Fourier transforms over image sub-regions – requiring long computational times. In this paper, we propose a more time efficient method of computing the correlation map and demonstrate its value for diagnosis of benign and malignant breast tissues. Our methodology is based on highly sensitive quantitative phase imaging data obtained by spatial light interference microscopy (SLIM).

Objective A dearth of studies focusing on young women (

To the Editor: Breast cancer is a frequently diagnosed solid tumor in women worldwide (1). MicroRNAs (miRNAs), small noncoding RNAs that regulate protein expression, are potential biomarkers in the diagnosis, prognosis, and prediction of response to treatment in breast cancer (2). We recently reported a paper-based method to extract miRNAs from plasma and circulating tumor cells (3). Here, we applied this method to plasma of patients with breast cancer and age- and gender-matched healthy controls, after treating the plasma with a commercial exosome isolation kit employing a nonspecific precipitation step; we compared the miRNA expression profiles from the plasma with and without the use of the precipitation method. After informed consent and institutional approval, we obtained peripheral blood samples from 9 patients with breast cancer and 9 healthy controls. Plasma was isolated by centrifugation at 3000 g for 10 min and stored at −80 °C. All plasma samples were visually inspected to exclude any discernible hemolysis. Then, 60 μL of Total Exosome Isolation reagent …

High re-excision rates in breast-conserving surgery call for a new intraoperative approach to the lumpectomy margin evaluation problem. The unique intraoperative imaging system, presented here, demonstrated the capability of photoacoustic tomography (PAT) to deliver optical sensitivity and specificity, along with over 2-cm imaging depth, in a clinical setting. The system enabled the evaluation of tumor extent, shape, morphology, and position within lumpectomy specimens measuring up to 11 cm in diameter. The investigation included all major breast cancer-related lesions, such as invasive ductal carcinoma (IDC), multifocal IDC, ductal carcinoma in situ and combinations of these variants. Coregistration with established ultrasound (US) technology, as well as comparison to specimen radiography, validated the performance of PAT, which appeared to facilitate better tumor visualization. Contrary to expected PA contrast mechanisms, PAT images of hemoglobin distribution correlated poorly with US-determined tumor location, while hypointense regions in lipid-weighted PAT images were in better agreement with US.

Diffuse optical tomography has demonstrated significant potential for clinical utility in the diagnosis and prognosis of breast cancer, and its use in combination with other structural imaging modalities improves lesion localization and the quantification of functional tissue properties. Here, we introduce a hybrid diffuse optical imaging system that operates concurrently with magnetic resonance imaging (MRI) in the imaging suite, utilizing commercially available MR surface coils. The instrument acquires both continuous-wave and time-domain diffuse optical data in the parallel-plate geometry, permitting both absolute assignment of tissue optical properties and three-dimensional tomography; moreover, the instrument is designed to incorporate diffuse correlation spectroscopic measurements for probing tissue blood flow. The instrument is described in detail here. Image reconstructions of a tissue phantom are presented as an initial indicator of the system’s ability to accurately reconstruct optical properties and the concrete benefits of the spatial constraints provided by concurrent MRI. Last, we briefly discuss how various data combinations that the instrument could facilitate, including tissue perfusion, can enable more comprehensive assessment of lesion physiology.

Pathological examination has been the gold standard for diagnosis in cancer and its role has also included the elucidation of etiology, pathogenesis, clinicopathological correlation, and prognostication. The advent of newer technologies and the realization that breast cancer is heterogeneous has shifted the focus to prognostication, with increased attention being paid to the identification of morphological features and immunohistochemical markers of prognostic relevance. However, despite the massive efforts invested in the identification of immunohistochemical biomarkers in breast cancer the majority have not proven to be of value in multivariate analyses and only estrogen receptor, progesterone receptor, and Her2/neu expression have remained essential components of pathological examination. These 3 markers were initially employed for prognostication but their role in treatment also rendered them of predictive value. Newer molecular methods, especially high-throughput technologies, have shown that even morphologically similar subtypes of breast cancer can show molecular heterogeneity; moreover, infiltrating ductal carcinoma can be separated into at least 4 molecular subtypes designated luminal (ER+, PR+, and Her2/neu–), Her2 overexpressing (ER–, PR–, and Her2/neu+), basal-like (ER–, PR–, Her2/neu–, and CK5/6+, EGFR+), and normal breast-like (ER–, PR–, and Her2/neu–), each with different clinical outcomes. The importance of proliferative gene expression in these subtypes has been demonstrated and surrogate immunohistochemical markers include ER, PR, Her2/neu, and Ki67 for the more expensive molecular tests. Molecular technologies, importantly, have not only provided further insights into the heterogeneity of breast cancer but have also opened new avenues for treatment through the identification of signaling molecules important in the proliferation and survival of the neoplastic cells. The treatment of cancer thus shifts from the conventional approach of ‘one size fits all’ to one of personalized treatment tailored to the specific characteristics of the tumor. Pathologists continue to play their traditional role in diagnosis but, as purveyors of the excised tissue, pathologists now have the additional role of identifying biomarkers responsive to therapeutic manipulation, thus playing an inextricable role as diagnostic oncologists in the management of breast cancer.

Venous thromboembolism (VTE) is a common complication in patients with malignant disease. First recognised by Bouillard in 1823 and later described by Trousseau in 1844, multiple studies have since provided considerable evidence for a clinical association between VTE and cancer. Across all cancers, the risk for VTE is elevated 7-fold; in certain malignancies, the risk for VTE may be increased up to 28-fold. Venous thromboembolism is the second leading cause of death in patients with cancer; among survivors, complications commonly include recurrent VTE and post-thrombotic syndrome, and (more rarely) chronic thromboembolic pulmonary hypertension, which are costly, and have a profound impact on the patient's quality of life. Tumour cells can activate blood coagulation through multiple mechanisms, including production of procoagulant, fibrinolytic, and proaggregating activities, release of proinflammatory and proangiogenic cytokines, and interacting directly with host vascular and blood cells (e.g., endothelial cells, leukocytes, and platelets) through adhesion molecules. Increasing evidence suggests that elements of the haemostatic system also have a direct role in eliciting or enhancing angiogenesis, cell survival, and metastasis. Despite the problem posed by VTE in the setting of cancer, it is evident that a significant number of oncologists do not recognise the link between cancer, its treatment, and thrombogenesis. On 22 May 2009, a group of UK-based physicians met in London, UK, to evaluate recent data on cancer thrombosis. This article (1 of 4) briefly reviews key data on the epidemiology and pathophysiology of VTE as a context for a discussion and consensus statement developed by meeting attendees, on the implications of this information for UK clinical practice.

Intraoperative electron radiotherapy (IOERT), which is an accelerated partial breast irradiation method, has been used for early-stage breast cancer treatment. In IOERT, a protective disk is inserted behind the target volume to minimize the dose received by normal tissues. However, to use such a disk, the surgical incision must be larger than the field size because the disk is manufactured from stiff and unyielding materials. In this study, the applicability of newly developed tungsten-based functional paper (TFP) was assessed as an alternative to the existing protective disk. The radiation-shielding performance of the TFP was verified through experimental measurements and Monte Carlo simulations. Percentage depth dose curves and lateral dose profiles with and without TFPs were measured and simulated on a dedicated IOERT accelerator. The number of piled-up TFPs was changed from 1 to 40. In the experimental measurements, the relative doses at the exit plane of the TFPs for 9 MeV were 42.7%, 9.2%, 0.2%, and 0.1% with 10, 20, 30, and 40 TFPs, respectively, whereas those for 12 MeV were 63.6%, 27.1%, 8.6%, and 0.2% with 10, 20, 30, and 40 TFPs, respectively. Slight dose enhancements caused by backscatter radiation from the TFPs were observed at the entrance plane of the TFPs at both beam energies. The results of the Monte Carlo simulation indicated the same tendency as the experimental measurements. Based on the experimental and simulated results, the radiation-shielding performances of 30 TFPs for 9 MeV and 40 TFPs for 12 MeV were confirmed to be acceptable and close to those of the existing protective disk. The findings of this study suggest the feasibility of using TFPs as flexible chest wall protectors in IOERT for breast cancer treatment., ファイル公開日: 2019/01/01

Paraneoplastic neuropathy is a clinical and immunological heterogeneous disorder and attempts have been made to classify subgroups of this disease. Only 30-50% of the clinical defined cases have antineuronal antibodies.The clinical and immunological features of 36 patients with paraneoplastic neuropathy from the authors' database were analysed including the type and course of the neuropathy, associated tumours, and the presence of antineuronal and other autoantibodies.Antineuronal antibodies were detected in 17/36 patients (47%) and anti-Hu was the most frequent antineuronal antibody. Nine patients had high titre antinuclear antibodies (ANA, median titre 1/1000) without antineuronal antibodies. ANA reactivities were different in most patients. Comparison of the ANA positive and ANA negative patients revealed that ANA positive paraneoplastic neuropathy is more frequently associated with breast cancer but is not associated with lung cancer (p0.05). The main clinical type in these patients was sensorimotor neuropathy. No ANA positive patient had central nervous system involvement. Although the Rankin score at the time of diagnosis was not different, the functional outcome in ANA positive patients was better than in ANA negative patients (p0.05).Paraneoplastic neuropathy is a heterogeneous disorder. ANA may define a subgroup of paraneoplastic neuropathy with different clinical and immunological features and may be related to better prognosis of the neuropathic symptoms.

Aims —An increased concentration of insulin-like growth factor 1 (IGF-1) is an independent risk factor for premenopausal breast cancer. Tamoxifen is thought initially to reduce concentrations of IGF-1 and increase concentrations of the IGF binding proteins. The aim of this study was to compare concentrations of IGF-1, IGF binding protein 1 (IGF-BP1), and IGF-BP3 in patients with breast cancer (n = 14) with those seen in control subjects (n = 23) and to assess the effect of tamoxifen on IGF status in these patients. Methods —Non-fasting blood samples were collected from patients with breast cancer before surgery and after nine, 18, and 27 months of tamoxifen treatment. The baseline concentrations were compared with those of age and sex matched healthy control subjects. Results —IGF-1, IGF-BP3, and IGF-BP1 concentrations were not significantly different in cases and controls. Tamoxifen treatment significantly increased IGF-BP1 after 18 and 27 months (baseline: mean, 21.6 ng/ml; SD, 16.6; 18 months: mean, 52.0 ng/ml; SD, 41.8; p = 0.019; 27 months: mean, 40.7 ng/ml; SD, 24.9; p = 0.043) and IGF-BP3 after nine, 18, and 27 months (baseline: mean, 3119 ng/ml; SD, 507; nine months: mean, 3673 ng/ml; SD, 476; p = 0.004; 18 months: mean, 3445 ng/ml; SD, 634; p = 0.034; 27 months: 3409 ng/ml; SD, 501; p = 0.043) when compared with baseline values. IGF-1 was not altered significantly from baseline at any time point. However, the IGF-1 to IGF-BP3 ratio was significantly decreased at both nine and 18 months (baseline: mean, 0.058; SD, 0.014; nine months: mean, 0.039; SD, 0.008; p = 0.033; 18 months: mean, 0.044; SD, 0.012; p = 0.01). This ratio was not significantly different from baseline at 27 months (mean, 0.054; SD, 0.01; p = 0.08). Conclusions —Tamoxifen increases IGF-BP3 and IGF-BP1 concentrations. It also decreases the IGF-1 to IGF-BP3 ratio but this effect may be limited after long term use. Longer follow up, with larger numbers of patients, should determine when, and for how long, tamoxifen can reduce circulating IGF-1.

Background/Aims—It was recently reported that significantly fewer breast tumours of BRCA1 mutation carriers overexpressed cyclin D1 and HER2 protein than tumours of age matched breast cancer cases unselected for family history. This study aimed to examine the genetic basis of this reduction by determining the frequency of tumours within this cohort showing DNA amplification of these genes. Methods—Paraffin wax embedded sections of breast tumours from BRCA1 mutation carriers and age, grade, histological type, and tumour size matched non-familial controls that had previously been stained for cyclin D1 and HER2 protein overexpression were analysed for CCND1 and HER2 gene amplification using fluorescence in situ hybridisation. Results—CCND1 amplification was detected in none of the 30 tumours of the BRCA1 mutation carriers and in 19 of 74 tumours of the matched controls. Of those samples previously determined to overexpress the HER2 protein, HER2 amplification was detected in one of three tumours from BRCA1 mutation carriers and in 13 of 17 tumours of the age matched non-familial cases. Conclusion—None of the tumours of BRCA1 mutation carriers showed CCND1 amplification and only one tumour showed HER2 amplification. In contrast, a large proportion of cyclin D1 and HER2 overexpression in tumours of non-familial breast cancer cases could be accounted for by amplification of these genes. These data suggest that breast tumorigenesis in BRCA1 mutation carriers occurs by a molecular mechanism distinct from that of age matched non-familial cases.

Aims—The relation between lobular carcinoma in situ (LCIS) and invasive breast cancer is unresolved. In an attempt to establish whether LCIS is a precursor of invasive cancer the mutational status and the expression of E-cadherin was analysed in LCIS and associated invasive breast carcinoma in 23 patients. Methods—Foci of LCIS and associated invasive carcinoma were individually microdissected from tissue from 23 patients. Exons 4–16 of the E-cadherin gene were analysed using single strand conformation polymorphism (SSCP); protein expression and the localisation of E-cadherin and β-catenin were assessed with the use of immunohistochemistry. Results—Immunohistochemistry revealed a lack of expression of E-cadherin and β-catenin in most LCIS samples and invasive foci. In all but four cases, the staining pattern was identical in the LCIS and associated invasive areas. When E-cadherin was absent, β-catenin was also undetected, suggesting a lack of expression of alternative classic cadherin members in these lesions. Coincident E-cadherin mutations in LCIS and associated invasive carcinoma were not identified in this series of patients. However, mutational analysis of E-cadherin in multiple foci of carcinoma in situ surrounding an invasive lesion provided evidence to support ductal carcinoma in situ as a precursor of invasive ductal carcinoma. Conclusion—These data support the hypothesis that LCIS is not a precursor of invasive breast carcinoma but a marker of increased risk of developing invasive disease.