Hybridization chain reaction enables a unified approach to multiplexed, quantitative, high-resolution immunohistochemistry and in situ hybridization.

RNA in situ hybridization based on the mechanism of the hybridization chain reaction (HCR) enables multiplexed, quantitative, high-resolution RNA imaging in highly autofluorescent samples, including whole-mount vertebrate embryos, thick brain slices and formalin-fixed paraffin-embedded tissue sections. Here, we extend the benefits of one-step, multiplexed, quantitative, isothermal, enzyme-free HCR signal amplification to immunohistochemistry, enabling accurate and precise protein relative quantitation with subcellular resolution in an anatomical context. Moreover, we provide a unified framework for simultaneous quantitative protein and RNA imaging with one-step HCR signal amplification performed for all target proteins and RNAs simultaneously.

A BRILLIANT-BRCA study: residual breast tissue after mastectomy and reconstruction.

INTRODUCTION: Different types of mastectomies leave different amounts of residual breast tissue. The significance of the residual breast volume (RBV) is not clear. Therefore, we developed an MRI tool that allows to easily assess the RBV. In this study we evaluated factors associated with RBV after skin or nipple sparing mastectomy (SSM/NSM) in breast cancer BRCA pathogenic variant (PV) carriers who underwent both therapeutic and risk reducing SSM/NSM and its relation to breast cancer outcomes using an innovative MRI-based tool. METHODS: Data of breast cancer BRCA PV who were treated between 2006 and 2020 were retrieved from of the oncogenetics unit databases. Only patients who underwent SSM/NSM and had a postoperative breast MRI available for analysis were included. Data collected included demographics, clinicopathological features, and outcomes. The MRI tool was developed by a breast cancer imaging laboratory. A logistic regression test and 95% confidence interval (CI) were used to assess the associated risk of increased RBV. A forward stepwise linear regression was used to correlate tumour-patient specific factors and RBV, and a Kaplan-Meier curve to show the probability of locoregional relapse. RESULTS: A total of 84 patients undergoing 89 mastectomies were included. At a median follow-up of 98 months, 5 local, 2 regional, and 4 distant recurrences were observed. RBV was not significantly related with breast cancer outcomes (p value = NS). A higher body mass index (BMI) was associated with a higher RBV (p < 0.0001). A larger number of involved axillary nodes was associated with a smaller RBV (p = 0.025). The RBV on the risk-reducing mastectomy side was significantly higher compared to the breast cancer side (p value = 0.007). Local recurrences occurred in the vicinity of the primary tumour.

Quantitative measurement of mammographic density in breast-tissue explants using portable NMR: Precision and accuracy.

PURPOSE: Single-sided portable NMR (pNMR) has previously been demonstrated to be suitable for quantification of mammographic density (MD) in excised breast tissue samples. Here we investigate the precision and accuracy of pNMR measurements of MD ex vivo as compared with the gold standards. METHODS: Forty-five breast-tissue explants from 9 prophylactic mastectomy patients were measured. The relative tissue water content was taken as the MD-equivalent quantity. In each sample, the water content was measured using some combination of three pNMR techniques (apparent T2, diffusion, and T1 measurements) and two gold-standard techniques (computed microtomography [µCT] and hematoxylin and eosin [H&E] histology). Pairwise correlation plots and Bland-Altman analysis were used to quantify the degree of agreement between pNMR techniques and the gold standards. RESULTS: Relative water content measured from both apparent T2 relaxation spectra, and diffusion decays exhibited strong correlation with the H&E and µCT results. Bland-Altman analysis yielded average bias values of -0.4, -2.6, 2.6, and 2.8 water percentage points (pp) and 95% confidence intervals of 13.1, 7.5, 11.2, and 11.8 pp for the H&E - T2, µCT - T2, H&E - diffusion, and µCT - diffusion comparison pairs, respectively. T1-based measurements were found to be less reliable, with the Bland-Altman confidence intervals of 27.7 and 33.0 pp when compared with H&E and µCT, respectively. CONCLUSION: Apparent T2-based and diffusion-based pNMR measurements enable quantification of MD in breast-tissue explants with the precision of approximately 10 pp and accuracy of approximately 3 pp or better, making pNMR a promising measurement modality for radiation-free quantification of MD.

Risk factors for residual fibroglandular breast tissue following a mastectomy - an overview and retrospective cohort study.

BACKGROUND: Residual fibroglandular breast tissue (RFGT) following a mastectomy is associated with the remaining of occult breast cancer at the time of mastectomy as well as an increased local recurrence risk thereafter. Despite its oncologic implications, data on measures to prevent RFGT are lacking. Therefore, in a first step knowledge of risk factors for RFGT is of uttermost importance in order to allow identification of patients at risk and subsequently adaption of the surgical treatment and potentially prevention of RFGT a priori. METHODS: We performed a systematic literature review in PubMed using the MESH terms [residual fibroglandular breast tissue], [residual breast tissue], [mastectomy] and [risk factor] followed by a retrospective data analysis including all patients with a mastectomy treated at the Department of Obstetrics and Gynecology of the Medical University of Vienna, Austria, between 01.01.2015 and 26.02.2020 in order to identify risk factors of RFGT following a mastectomy. The primary aim of the study was to assess a potential difference in RFGT volume between the different types of mastectomy. The secondary objectives of the study were to identify other potential risk factors for RFGT as well as to compare the skin and subcutaneous fat tissue thickness pre- to postoperatively. RESULTS: Significantly higher RFGT volumes were observed following a nipple-sparing mastectomy (NSM) compared to a skin-sparing mastectomy (SSM) and radical mastectomy (RME) (p < .001). Furthermore, RFGT volume was significantly associated with the variables: reconstruction (p = .012), acellular dermal matrix (ADM) or mesh (p = .031), patient age (p = .022), preoperative fibroglandular tissue (FGT) volume (p = .012) and preoperative whole breast volume (including the skin envelope and nipple-areola-complex) (p = .030). The reduction in the postoperative compared to preoperative skin envelope thickness measured medially and laterally reached statistical significance in the NSM-cohort (medial p < .001, lateral p = .001) and showed a numerical difference in the RME and SSM-cohort. CONCLUSION: Mastectomy type, reconstruction, ADM or mesh, patient age, preoperative FGT volume and whole breast volume were identified as risk factors for RFGT in univariable analysis. The observed reduction in the post- compared to preoperative skin envelope thickness should be avoided considering the known associated increase in risk for ischemic complications.

Evaluation of a non-metallic dual-port expander for intensity modulated proton therapy.

PURPOSE: To provide a methodology for characterization of the technical properties of a newly developed non-metallic tissue expander for intensity modulated proton therapy. METHODS: Three tissue expanders (AlloX2-Pro: plastic-dual port, AlloX2: metal-dual port, and Dermaspan: metal-single port) were deconstructed, CT-scanned, and modeled in RayStation12A. A 165 MeV single spot was used to create RayStation dose planes, and the integrated depth dose profiles were calculated and the DR90 extracted to predict water equivalent thickness (WET). These predictions were compared to measurements taken with an IBA Giraffe MLIC. Native, water, and fully modelled overrides were compared for the AlloX2 Pro to quantify differences in override choices. Geometric considerations between expanders were compared using a ray-tracing technique to contour the "no-fly" zone around metallic components using a clinical, three beam arrangement. Lastly, a planning and evaluation framework was provided using a single plan as an illustration. RESULTS: The measured AlloX2-Pro WET values were within 0.22 cm of RayStation predictions while metallic values ranged from 0.08 to 0.46 cm. Using natively scanned density values for the AlloX2 Pro improved the discrepancy in WET between predicted and measured from -0.22 to -0.09 cm (drain) and from -0.17 to -0.12 cm (injection). The "no-fly" zone volume of all three beams reduced 95% between the AlloX2-Pro and Dermaspan, which geometrically allowed more uniform coverage behind the port and reduced need for beam modulation. CONCLUSION: The beam perturbation of the AlloX2-Pro is well modeled, but improved agreement with measured WET values was observed when utilizing native densities in calculations. The AlloX2 Pro can support beam arrangements that traverse the ports, which can enable simpler beam geometry and a reduction in dose modulation around the port to promote improved robustness and treatment delivery quality.

Spatial and Spectral Reconstruction of Breast Lumpectomy Hyperspectral Images.

(1) Background: Hyperspectral imaging has emerged as a promising margin assessment technique for breast-conserving surgery. However, to be implicated intraoperatively, it should be both fast and capable of yielding high-quality images to provide accurate guidance and decision-making throughout the surgery. As there exists a trade-off between image quality and data acquisition time, higher resolution images come at the cost of longer acquisition times and vice versa. (2) Methods: Therefore, in this study, we introduce a deep learning spatial-spectral reconstruction framework to obtain a high-resolution hyperspectral image from a low-resolution hyperspectral image combined with a high-resolution RGB image as input. (3) Results: Using the framework, we demonstrate the ability to perform a fast data acquisition during surgery while maintaining a high image quality, even in complex scenarios where challenges arise, such as blur due to motion artifacts, dead pixels on the camera sensor, noise from the sensor's reduced sensitivity at spectral extremities, and specular reflections caused by smooth surface areas of the tissue. (4) Conclusion: This gives the opportunity to facilitate an accurate margin assessment through intraoperative hyperspectral imaging.

The Role of Pre-Contrast Sequences of an MRI-Guided Breast Biopsy in Localizing a Target.

Objective: This retrospective study aims to assess the role of pre-contrast sequences of an MRI-guided breast biopsy (MRIB) exam in confident and accurate lesion site localization based on tissue landmarks. Methods: The charts of all consecutives MRIB that were performed between January 2018 and December 2020 were reviewed. The images of the eligible exams were analyzed by 3 breast radiologists. Each radiologist independently attempted to identify lesion site on pre-contrast MRIB sequences, while blinded to the post-contrast MRIB images. Confidence levels (I-confident, II-not confident, and III-unknown) were assigned by each reviewer. A fourth radiologist assessed the accuracy (≤5 mm-accurate, >5 mm-inaccurate) in lesion site localization using the actual biopsied lesion site and the post-contrast MRIB images as reference. Descriptive statistics were used to calculate the percentage of confidence and accuracy categories for each reviewer, with Chi-square tests applied to analyze relationships between categorical variables. Results: There were 174 female patients with 181 lesions eligible for the trial. When the lesion site is confidently identified on the pre-contrast MRIB images (level 1 confidence), mean grade 1 accuracy was 93.8% (P < .001). Accuracy decreased with Level II and III confidence (55.3% and 34.2% respectively). Up to 61.4% improved accuracy was demonstrated when combining the performance of 2 reviewers. No correlation was found between breast density, lesion morphology, or biopsy positioning with confidence level or accuracy grade. Conclusion: Careful review of the pre-contrast MRIB images and familiarization with the surrounding tissue landmarks are important steps in confidently and accurately detecting lesion site.

Host, reproductive, and lifestyle factors in relation to quantitative histologic metrics of the normal breast.

BACKGROUND: Emerging data indicate that variations in quantitative epithelial and stromal tissue composition and their relative abundance in benign breast biopsies independently impact risk of future invasive breast cancer. To gain further insights into breast cancer etiopathogenesis, we investigated associations between epidemiological factors and quantitative tissue composition metrics of the normal breast. METHODS: The study participants were 4108 healthy women ages 18-75 years who voluntarily donated breast tissue to the US-based Susan G. Komen Tissue Bank (KTB; 2008-2019). Using high-accuracy machine learning algorithms, we quantified the percentage of epithelial, stromal, adipose, and fibroglandular tissue, as well as the proportion of fibroglandular tissue that is epithelium relative to stroma (i.e., epithelium-to-stroma proportion, ESP) on digitized hematoxylin and eosin (H&E)-stained normal breast biopsy specimens. Data on epidemiological factors were obtained from participants using a detailed questionnaire administered at the time of tissue donation. Associations between epidemiological factors and square root transformed tissue metrics were investigated using multivariable linear regression models. RESULTS: With increasing age, the amount of stromal, epithelial, and fibroglandular tissue declined and adipose tissue increased, while that of ESP demonstrated a bimodal pattern. Several epidemiological factors were associated with individual tissue composition metrics, impacting ESP as a result. Compared with premenopausal women, postmenopausal women had lower ESP [ß (95% Confidence Interval (CI)) = -0.28 (- 0.43, - 0.13); P < 0.001] with ESP peaks at 30-40 years and 60-70 years among pre- and postmenopausal women, respectively. Pregnancy [ß (95%CI) vs nulligravid = 0.19 (0.08, 0.30); P < 0.001] and increasing number of live births (P-trend < 0.001) were positively associated with ESP, while breastfeeding was inversely associated with ESP [ß (95%CI) vs no breastfeeding = -0.15 (- 0.29, - 0.01); P = 0.036]. A positive family history of breast cancer (FHBC) [ß (95%CI) vs no FHBC = 0.14 (0.02-0.26); P = 0.02], being overweight or obese [ß (95%CI) vs normal weight = 0.18 (0.06-0.30); P = 0.004 and 0.32 (0.21-0.44); P < 0.001, respectively], and Black race [ß (95%CI) vs White = 0.12 (- 0.005, 0.25); P = 0.06] were positively associated with ESP. CONCLUSION: Our findings revealed that cumulative exposure to etiological factors over the lifespan impacts normal breast tissue composition metrics, individually or jointly, to alter their dynamic equilibrium, with potential implications for breast cancer susceptibility and tumor etiologic heterogeneity.

Residual fibroglandular breast tissue after mastectomy is associated with an increased risk of a local recurrence or a new primary breast cancer".

BACKGROUND: Residual fibroglandular breast tissue (RFGT) following a mastectomy has been claimed to be associated with the occurrence of an in-breast local recurrence (IBLR) or new primary tumor (NP). Yet, scientific evidence proving this assumption is lacking. The primary aim of the study was to verify whether RFGT following a mastectomy is a risk factor for an IBLR or NP. METHODS: This retrospective analysis included all patients that underwent a mastectomy and were followed up at the Department of Obstetrics and Gynecology of the Medical University of Vienna between 01.01.2015 and 26.02.2020. RFGT volume (assessed on magnetic resonance imaging) was correlated with the prevalence of an IBLR and a NP. RESULTS: A total of 105 patients (126 breasts) following a therapeutic mastectomy were included. After a mean follow-up of 46.0 months an IBLR had occurred in 17 breasts and a NP in 1 breast. A significant difference in RFGT volume was observed between the disease-free cohort and the subgroup with an IBLR or NP (p = .017). A RFGT volume of ≥ 1153 mm3 increased the risk by the factor 3.57 [95%CI 1.27; 10.03]. CONCLUSIONS: RFGT volume is associated with an increased risk for an IBLR or NP.

A Comprehensive Landscape of Imaging Feature-Associated RNA Expression Profiles in Human Breast Tissue.

The expression abundance of transcripts in nondiseased breast tissue varies among individuals. The association study of genotypes and imaging phenotypes may help us to understand this individual variation. Since existing reports mainly focus on tumors or lesion areas, the heterogeneity of pathological image features and their correlations with RNA expression profiles for nondiseased tissue are not clear. The aim of this study is to discover the association between the nucleus features and the transcriptome-wide RNAs. We analyzed both microscopic histology images and RNA-sequencing data of 456 breast tissues from the Genotype-Tissue Expression (GTEx) project and constructed an automatic computational framework. We classified all samples into four clusters based on their nucleus morphological features and discovered feature-specific gene sets. The biological pathway analysis was performed on each gene set. The proposed framework evaluates the morphological characteristics of the cell nucleus quantitatively and identifies the associated genes. We found image features that capture population variation in breast tissue associated with RNA expressions, suggesting that the variation in expression pattern affects population variation in the morphological traits of breast tissue. This study provides a comprehensive transcriptome-wide view of imaging-feature-specific RNA expression for healthy breast tissue. Such a framework could also be used for understanding the connection between RNA expression and morphology in other tissues and organs. Pathway analysis indicated that the gene sets we identified were involved in specific biological processes, such as immune processes.

Ectopic breast tissue of the vulva.

Ectopic mammary gland tissue in the vulva is an exceptionally rare disease. We present a case of a 62-year-old woman with a left vulvar mass of 30 years duration that progressively increased in size. The patient reported having pressure and discomfort, especially during movement. Surgical excision was performed, and a histopathological examination revealed a well-differentiated ectopic breast. We also review other cases of vulvar ectopic breast to further comprehend the characteristics of this rare disease.  Clinicians and pathologists should always consider it as a differential diagnosis when presented with a vulvar mass.

Exposure to polycyclic aromatic hydrocarbons during pregnancy and breast tissue composition in adolescent daughters and their mothers: a prospective cohort study.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAH), which are found in air pollution, have carcinogenic and endocrine disrupting properties that might increase breast cancer risk. PAH exposure might be particularly detrimental during pregnancy, as this is a time when the breast tissue of both the mother and daughter is undergoing structural and functional changes. In this study, we tested the hypothesis that ambient PAH exposure during pregnancy is associated with breast tissue composition, measured one to two decades later, in adolescent daughters and their mothers. METHODS: We conducted a prospective analysis using data from a New York City cohort of non-Hispanic Black and Hispanic mother-daughter dyads (recruited 1998-2006). During the third trimester of pregnancy, women wore backpacks containing a continuously operating air sampling pump for two consecutive days that measured ambient exposure to eight carcinogenic higher molecular weight nonvolatile PAH compounds (Σ8 PAH) and pyrene. When daughters (n = 186) and mothers (n = 175) reached ages 11-20 and 29-55 years, respectively, optical spectroscopy (OS) was used to evaluate measures of breast tissue composition (BTC) that positively (water content, collagen content, optical index) and negatively (lipid content) correlate with mammographic breast density, a recognized risk factor for breast cancer. Multivariable linear regression was used to evaluate associations between ambient PAH exposure and BTC, overall and by exposure to household tobacco smoke during pregnancy (yes/no). Models were adjusted for race/ethnicity, age, and percent body fat at OS. RESULTS: No overall associations were found between ambient PAH exposure (Σ8 PAH or pyrene) and BTC, but statistically significant additive interactions between Σ8 PAH and household tobacco smoke exposure were identified for water content and optical index in both daughters and mothers (interaction p values < 0.05). Σ8 PAH exposure was associated with higher water content (ßdaughters = 0.42, 95% CI = 0.15-0.68; ßmothers = 0.32, 95% CI = 0.05-0.61) and higher optical index (ßdaughters = 0.38, 95% CI = 0.12-0.64; ßmothers = 0.38, 95% CI = 0.12-0.65) in those exposed to household tobacco smoke during pregnancy; no associations were found in non-smoking households (interaction p values < 0.05). CONCLUSIONS: Exposure to ambient Σ8 PAH and tobacco smoke during pregnancy might interact synergistically to impact BTC in mothers and daughters. If replicated in other cohorts, these findings might have important implications for breast cancer risk across generations.

Serum hormone levels and normal breast histology among premenopausal women.

PURPOSE: Breast terminal duct lobular units (TDLUs) are the main source of breast cancer (BC) precursors. Higher serum concentrations of hormones and growth factors have been linked to increased TDLU numbers and to elevated BC risk, with variable effects by menopausal status. We assessed associations of circulating factors with breast histology among premenopausal women using artificial intelligence (AI) and preliminarily tested whether parity modifies associations. METHODS: Pathology AI analysis was performed on 316 digital images of H&E-stained sections of normal breast tissues from Komen Tissue Bank donors ages ≤ 45 years to assess 11 quantitative metrics. Associations of circulating factors with AI metrics were assessed using regression analyses, with inclusion of interaction terms to assess effect modification. RESULTS: Higher prolactin levels were related to larger TDLU area (p < 0.001) and increased presence of adipose tissue proximate to TDLUs (p < 0.001), with less significant positive associations for acini counts (p = 0.012), dilated acini (p = 0.043), capillary area (p = 0.014), epithelial area (p = 0.007), and mononuclear cell counts (p = 0.017). Testosterone levels were associated with increased TDLU counts (p < 0.001), irrespective of parity, but associations differed by adipose tissue content. AI data for TDLU counts generally agreed with prior visual assessments. CONCLUSION: Among premenopausal women, serum hormone levels linked to BC risk were also associated with quantitative features of normal breast tissue. These relationships were suggestively modified by parity status and tissue composition. We conclude that the microanatomic features of normal breast tissue may represent a marker of BC risk.

Association of breast cancer risk, density, and stiffness: global tissue stiffness on breast MR elastography (MRE).

PURPOSE: Quantify in vivo biomechanical tissue properties in various breast densities and in average risk and high-risk women using Magnetic Resonance Imaging (MRI)/MRE and examine the association between breast biomechanical properties and cancer risk based on patient demographics and clinical data. METHODS: Patients with average risk or high-risk of breast cancer underwent 3.0 T breast MR imaging and elastography. Breast parenchymal enhancement (BPE), density (from most recent mammogram), stiffness, elasticity, and viscosity were recorded. Within each breast density group (non-dense versus dense), stiffness, elasticity, and viscosity were compared across risk groups (average versus high). Separately for stiffness, elasticity, and viscosity, a multivariable logistic regression model was used to evaluate whether the MRE parameter predicted risk status after controlling for clinical factors. RESULTS: 50 average risk and 86 high-risk patients were included. Risk groups were similar in age, density, and menopausal status. Among patients with dense breasts, mean stiffness, elasticity, and viscosity were significantly higher in high-risk patients (N = 55) compared to average risk patients (N = 34; all p < 0.001). Stiffness remained a significant predictor of risk status (OR = 4.26, 95% CI [1.96, 9.25]) even after controlling for breast density, BPE, age, and menopausal status. Similar results were seen for elasticity and viscosity. CONCLUSION: A structurally based, quantitative biomarker of tissue stiffness obtained from MRE is associated with differences in breast cancer risk in dense breasts. Tissue stiffness could provide a novel prognostic marker to help identify high-risk women with dense breasts who would benefit from increased surveillance and/or risk reduction measures.

Investigation of the effect of metoclopramide on proliferation signal molecules in breast tissue.

Metoclopramide (MCP) is a drug that has been widely used in recent years due to its hyperprolactinaemia effect on mothers during breastfeeding. The aim of this study was to investigate the proliferative changes that MCP may cause in the maternal breast tissue. In this study, 18 Wistar albino young-adult breastfeeding mothers with their offspring were divided into three groups: control group, low-dose MCP-applied group and high-dose MCP-applied group. The experiment was carried out during the lactation period and at the end of 21 days. Prolactin, BrdU and Ki-67 breast tissue distributions were evaluated by immunohistochemistry, and tissue levels were evaluated biochemically by the ELISA method. According to ELISA and immunohistochemistry results in breast tissue, there was no significant difference between Ki-67 and BrdU results in all groups. Metoclopramide did not change the expression of proliferation molecules Ki-67 and BrdU in breast tissue. These results suggested that while metoclopramide increases breast proliferation, it does not have the risk of transforming the tissue into a tumour.

Interindividual variation contributes to differential PCB 126 induced gene expression in primary breast epithelial cells and tissues.

PCB 126 is a pervasive, dioxin-like chemical pollutant which can activate the aryl hydrocarbon receptor (AhR). Despite being banned from the market, PCB 126 can be detected in breast milk to this day. The extent to which interindividual variation impacts the adverse responses to this chemical in the breast tissue remains unclear. This study aimed to investigate the impact of 3 nM PCB 126 on gene expression in a panel of genetically diverse benign human breast epithelial cell (HBEC) cultures and patient derived breast tissues. Six patient derived HBEC cultures were treated with 3 nM PCB 126. RNAseq was used to interrogate the impact of exposure on differential gene expression. Gene expression changes from the top critical pathways were confirmed via qRT-PCR in a larger panel of benign patient derived HBEC cultures, as well as in patient-derived breast tissue explant cultures. RNAseq analysis of HBEC cultures revealed a signature of 144 genes significantly altered by 3 nM PCB 126 treatment. Confirmation of 8 targets using a panel of 12 HBEC cultures and commercially available breast cell lines demonstrated that while the induction of canonical downstream target gene, CYP1A1, was consistent across our primary HBECs, other genes including AREG, S100A8, IL1A, IL1B, MMP7, and CCL28 exhibited significant variability across individuals. The dependence on the activity of the aryl hydrocarbon receptor was confirmed using inhibitors. PCB 126 can induce significant and consistent changes in gene expression associated with xenobiotic metabolism in benign breast epithelial cells. Although the induction of most genes was reliant on the AhR, significant variability was noted between genes and individuals. These data suggest that there is a bifurcation of the pathway following AhR activation that contributes to the variation in interindividual responses.

Correlation analysis of resected breast tissue and implant volume after mastectomy and its association with breast density.

BACKGROUND: The current methods for calculating the ideal implant volume for breast reconstruction are based on pre- or intraoperative volume measurements of the existing breast volume and do not take into account the individual breast density of the woman. This study aims is to identify objective parameters that can help to improve the optimal implant selection. MATERIALS AND METHODS: This retrospective analysis includes 198 breast cancer patients who underwent mastectomy. Breast densities (ACR) measured in mammography and MRI were compared with the removed breast tissue weight and volume of the implants used. In addition, the resected weight was compared directly with the implant volume to calculate a mathematical function. RESULTS: There was no significant correlation between the ACR values and the resected weights [correlation coefficient: mammography:- 0.117 (p = 0.176), MRI - 0.033 (p = 0.756)]. A negative correlation between the implant volumes and both imaging methods could be demonstrated [correlation coefficient: mammography - 0.268; p = 0.002; MRI was - 0.200 (p = 0.055)]. A highly significant correlation between the resected weights and the implant volumes (correlation coefficient 0.744; p < 0.001) was observed. This correlation corresponds to a power function (y = 34.71 x0.39), in which any resected weight can be used for the variable x to calculate the implant volume. CONCLUSION: We were able to show that there is a significant correlation between the resected breast tissue and the implant volume. With our novel potency function, the appropriate implant volume can be calculated for any resected weight making it easier for the surgeon to choose a fitting implant in a simple and more objective manner.

Robustness of three external beam treatment techniques against inter-fractional positional variations of the metal port in breast tissue expanders.

INTRODUCTION: Temporary breast tissue expanders contain a metal port that varies in position throughout the course of radiation treatments. The purpose of this study was to quantify the robustness of the three most common external beam treatment techniques (tangential three-dimensional conformal radiation therapy [3DCRT], volumetric modulated arc therapy [VMAT], and helical tomotherapy) against our measured inter-fractional positional variations of the port. METHODS: For eight breast cases, a clinical plan was created for each of the three techniques. The dosimetric effect of our previously measured inter-fractional port errors was evaluated for two classes of error: internal port errors (IPEs) and patient registration errors (PREs). For both classes of error, daily variable and systematic errors were modeled, and their cumulative effects were compared against the originally planned doses. RESULTS: For systematic IPE, the 1%-99% range in point dose differences inside a 5-mm target abutting the implant was the highest for tangential 3DCRT, and it was within 6% and 9% when calculated with Monte Carlo and collapsed cone calculation engines, respectively. Daily variable PRE resulted in mean changes of -3.0% and -3.5% to V100%Rx of the target for VMAT and tomotherapy, respectively. For nearby organs, daily variable PRE resulted in changes to V20Gy of the ipsilateral lung of less than 2% in all three techniques, while V5Gy of the heart increased by as much as 6% in VMAT and 10% in tomotherapy. CONCLUSIONS: When IPEs were modeled, dose variability was the largest in tangential 3DCRT, leading to areas of underdosage in the shadow of the port. When PREs were modeled, the target coverage and nearby organs were affected the most in VMAT and helical tomotherapy. In reality, port positional errors result from a combination of IPE and PRE, suggesting that VMAT and tomotherapy are more robust when patient registration errors are minimized, despite the presence of IPE.

Review of Thermal and Physiological Properties of Human Breast Tissue.

Electromagnetic thermal therapies for cancer treatment, such as microwave hyperthermia, aim to heat up a targeted tumour site to temperatures within 40 and 44 °C. Computational simulations used to investigate such heating systems employ the Pennes' bioheat equation to model the heat exchange within the tissue, which accounts for several tissue properties: density, specific heat capacity, thermal conductivity, metabolic heat generation rate, and blood perfusion rate. We present a review of these thermal and physiological properties relevant for hyperthermia treatments of breast including fibroglandular breast, fatty breast, and breast tumours. The data included in this review were obtained from both experimental measurement studies and estimated properties of human breast tissues. The latter were used in computational studies of breast thermal treatments. The measurement methods, where available, are discussed together with the estimations and approximations considered for values where measurements were unavailable. The review concludes that measurement data for the thermal and physiological properties of breast and tumour tissue are limited. Fibroglandular and fatty breast tissue properties are often approximated from those of generic muscle or fat tissue. Tumour tissue properties are mostly obtained from approximating equations or assumed to be the same as those of glandular tissue. We also present a set of reliable data, which can be used for more accurate modelling and simulation studies to better treat breast cancer using thermal therapies.

Target-filter combination effects on breast tissue characterization using mammographic X-rays: A Monte Carlo simulation study.

BACKGROUND: Characterization of normal and malignant breast tissues using X-ray scattering techniques has shown promising results and applications. OBJECTIVE: To examine possibility of characterizing normal and malignant breast tissues using the scattered photon distribution of polyenergetic beams of 30 kV X-rays. METHODS: A Monte Carlo simulation is upgraded so that it is capable of simulating input mammographic X-ray spectra from different target-filter combinations, tracing photon transport, and producing the distribution of scattered photons. The target-filter combinations include Mo-Mo, Mo-Al, Mo-Rh, Rh-Rh, Rh-Al, W-Rh, and W-Al. Analysis of obtained scattered photon distribution is carried out by comparing the ratio of count under the peak in the momentum transfer region from 0 to 1.55 nm-1, to that in the region from 1.6 to 9.1 nm-1 (covering the regions of scattering from fat and soft tissue, respectively) for breast samples with different percentages of normal tissue (0-100%). RESULTS: Mo-Mo target-filter combination shows a high linear dependence of the count under peak ratio on the percentage of normal tissue in breast samples (R2 = 0.9513). Despite slightly less linear than Mo-Mo, target-filter combinations other than Rh-Rh, W-Rh, and W-Al produce high linear responses (R2 > 0.9)CONCLUSION:Mo-Mo target-filter combination would probably be the most relevant in characterizing normal and malignant breast tissues from their scattered photon distribution.