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International Journal of Particle... Mar 2024In breast cancer, improved treatment approaches that reduce injury to lung tissue and early diagnosis and intervention for lung toxicity are increasingly important in...
PURPOSE
In breast cancer, improved treatment approaches that reduce injury to lung tissue and early diagnosis and intervention for lung toxicity are increasingly important in survivorship. The aims of this study are to (1) compare lung tissue radiographic changes in women treated with conventional photon radiation therapy and those treated with proton therapy (PT), (2) assess the volume of lung irradiated to 5 Gy (V5) and 20 Gy (V20) by treatment modality, and (3) quantify the effects of V5, V20, time, and smoking history on the severity of tissue radiographic changes.
PATIENTS AND METHODS
A prospective observational study of female breast cancer patients was conducted to monitor postradiation subclinical lung tissue radiographic changes. Repeated follow-up x-ray computed tomography scans were acquired through 2 years after treatment. In-house software was used to quantify an internally normalized measure of pulmonary tissue density change over time from the computed tomography scans, emphasizing the 6- and 12-month time points.
RESULTS
Compared with photon therapy, PT was associated with significantly lower lung V5 and V20. Lung V20 (but not V5) correlated significantly with increased subclinical lung tissue radiographic changes 6 months after treatment, and neither correlated with lung effects at 12 months. Significant lung tissue density changes were present in photon therapy patients at 6 and 12 months but not in PT patients. Significant lung tissue density change persisted at 12 months in ever-smokers but not in never-smokers.
CONCLUSION
Patients treated with PT had significantly lower radiation exposure to the lungs and less statistically significant tissue density change, suggesting decreased injury and/or improved recovery compared to photon therapy. These findings motivate additional studies in larger, randomized, and more diverse cohorts to further investigate the contributions of treatment modality and smoking regarding the short- and long-term radiographic effects of radiation on lung tissue.
PubMed: 38757081
DOI: 10.1016/j.ijpt.2024.02.001 -
Translational Breast Cancer Research :... 2024We report the results of our retrospective analysis of the ability of standard chest computed tomography (CT) scans to correctly differentiate cystic from solid lesions....
We report the results of our retrospective analysis of the ability of standard chest computed tomography (CT) scans to correctly differentiate cystic from solid lesions. MModal Catalyst identified 27 women who had an ultrasound of the breast that was recommended because of a chest CT finding between January 1, 2010, and December 31, 2017. All images were reviewed by a radiologist fellowship trained in both breast imaging and cardiothoracic radiology (MS). Ultrasound characterization of lesion density as cystic or solid was considered the gold standard for this study. Analysis of CT scans was performed to identify lesions of interest corresponding to ultrasound abnormality; average, minimum, and maximum Hounsfield units (HUs) were measured. If masses had any solid component, they were considered solid. Twenty masses were solid, and 7 masses were cystic on ultrasound. Thirteen studies were performed without contrast and 14 were performed with contrast. On non-contrast studies, the average HU for cystic lesions was 19 compared to 38 HU for solid (P=0.007). On contrast studies, the average HU for cystic lesions was 16 compared to 53 HU for solid (P=0.002). Cystic lesions did not change with contrast significantly. Solid lesions enhanced with contrast; average HU 38 without contrast to 53 HU with contrast. Chest CT accurately diagnosed breast masses as cystic or solid with or without contrast.
PubMed: 38751680
DOI: 10.21037/tbcr-23-34 -
Translational Breast Cancer Research :... 2024Breast cancer (BC) is the most common neoplasm in women worldwide and one of the leading causes of female death. The triple-negative subtype, characterized by the... (Review)
Review
Breast cancer (BC) is the most common neoplasm in women worldwide and one of the leading causes of female death. The triple-negative subtype, characterized by the absence of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2), tends to occur in younger patients, be more aggressive and less differentiated. Furthermore, this subtype is considered the most immunogenic and associated with higher levels of tumor cell infiltration, mainly lymphocytes. Tumor-infiltrating lymphocytes (TILs) play a crucial role in the interaction of the host's immune system and cancer cells. The microenvironment is critical in tumor development and progression. Assessment of infiltrating lymphocytes can provide valuable information about the immune response and, given the lack of biomarkers to guide treatment decisions and predict outcomes in triple-negative tumors and can be considered as a potential biomarker. Some evidence suggests that higher levels of these lymphocytes are associated with better responses to systemic treatment, longer progression-free survival and overall survival (OS). However, treatment escalation or de-escalation strategies for triple-negative BC (TNBC) currently do not consider the presence or density of TILs for therapeutic decisions. TILs appear to be useful predictive and prognostic indicators. Further clinical studies are needed to confirm these relationships and integrate TILs as a biomarker consistently into clinical practice. This article summarizes key concepts relating to the role of the immune infiltrate in BC, along with the current status and future prospects regarding TILs as a predictive and prognostic biomarker.
PubMed: 38751669
DOI: 10.21037/tbcr-23-43 -
Translational Breast Cancer Research :... 2023Women are encouraged to have a yearly mammogram and in addition to screening for breast cancer, the radiologist reports the patient's breast density. High breast density... (Review)
Review
Women are encouraged to have a yearly mammogram and in addition to screening for breast cancer, the radiologist reports the patient's breast density. High breast density increases a woman's risk of developing breast cancer. The number of chest computed tomography (CT) scans performed each year is increasing. Chest CT scans for lung cancer screening in high-risk patients are the standard of care. Important additional findings can be identified on these exams including coronary artery calcifications, thyroid nodules, and breast density. Our previous research has shown that breast density can be reliably graded on chest CT and is comparable to mammographic grading. However, the inter-reader agreement was higher for chest CT. It is important that thoracic radiologists include the grading of breast density in their chest CT reports. According to mammography literature, this information has proven to be helpful for early detection of breast cancer. Federal legislation recommends notifying both providers and patients about breast density on mammography and so it follows that if we see the same information on chest CT, we should report it so that at the very least the clinician can encourage their patient to have a routine mammogram.
PubMed: 38751487
DOI: 10.21037/tbcr-23-36 -
Breast Cancer Research : BCR May 2024Mammographic density (MD) has been shown to be a strong and independent risk factor for breast cancer in women of European and Asian descent. However, the majority of...
BACKGROUND
Mammographic density (MD) has been shown to be a strong and independent risk factor for breast cancer in women of European and Asian descent. However, the majority of Asian studies to date have used BI-RADS as the scoring method and none have evaluated area and volumetric densities in the same cohort of women. This study aims to compare the association of MD measured by two automated methods with the risk of breast cancer in Asian women, and to investigate if the association is different for premenopausal and postmenopausal women.
METHODS
In this case-control study of 531 cases and 2297 controls, we evaluated the association of area-based MD measures and volumetric-based MD measures with breast cancer risk in Asian women using conditional logistic regression analysis, adjusting for relevant confounders. The corresponding association by menopausal status were assessed using unconditional logistic regression.
RESULTS
We found that both area and volume-based MD measures were associated with breast cancer risk. Strongest associations were observed for percent densities (OR (95% CI) was 2.06 (1.42-2.99) for percent dense area and 2.21 (1.44-3.39) for percent dense volume, comparing women in highest density quartile with those in the lowest quartile). The corresponding associations were significant in postmenopausal but not premenopausal women (premenopausal versus postmenopausal were 1.59 (0.95-2.67) and 1.89 (1.22-2.96) for percent dense area and 1.24 (0.70-2.22) and 1.96 (1.19-3.27) for percent dense volume). However, the odds ratios were not statistically different by menopausal status [p difference = 0.782 for percent dense area and 0.486 for percent dense volume].
CONCLUSIONS
This study confirms the associations of mammographic density measured by both area and volumetric methods and breast cancer risk in Asian women. Stronger associations were observed for percent dense area and percent dense volume, and strongest effects were seen in postmenopausal individuals.
Topics: Humans; Female; Breast Neoplasms; Case-Control Studies; Breast Density; Middle Aged; Asian People; Adult; Risk Factors; Mammography; Aged; Postmenopause; Premenopause; Odds Ratio; Mammary Glands, Human
PubMed: 38750574
DOI: 10.1186/s13058-024-01829-2 -
Plastic and Reconstructive Surgery.... May 2024Capsular contracture (CC) is a leading cause of morbidity in implant-based breast surgery. Implant surface texture has been implicated in CC development, yet its...
BACKGROUND
Capsular contracture (CC) is a leading cause of morbidity in implant-based breast surgery. Implant surface texture has been implicated in CC development, yet its etiopathogenesis remains unclear. We conducted a systematic review to determine the influence of implant surface texture on cellular and molecular mechanisms involved in the etiopathogenesis of CC.
METHODS
A systematic review of the MEDLINE, Embase, Web of Science, and Scopus databases was completed to examine the influence of implant texture on cellular and molecular pathways leading to CC. Excluded articles were reviews and those examining solely the clinical presentation of CC.
RESULTS
Development of CC includes prolonged inflammation, increased myofibroblast density, parallel arrangement of collagen fibers, and biofilm formation. When compared with textured implants, smooth implants are associated with reduction in parallel collagen, capsule thickness, and sheer frictional force. Microtextured implants trigger a reduced macrophage response and decreased fibroblast activation as compared with smooth and macrotextured surfaces. Bacterial counts on microtextured and smooth surfaces are significantly lower than that of macrotextured surfaces. Both micro- and macrotextured implants have increased matrix metalloproteinases and activation of tumor necrosis factor α pathway, with increased activation of the transforming growth factor β1 pathway relative to smooth implants.
CONCLUSIONS
Implant surface texture alters the cellular and molecular mechanisms in the chronic inflammatory process leading to CC. Given the complex biological system of cellular and molecular events in CC, a mathematical model integrating these influences may be optimal to deduce the etiopathogenesis.
PubMed: 38746946
DOI: 10.1097/GOX.0000000000005802 -
BioRxiv : the Preprint Server For... May 2024Cells regulate their shape and metabolic activity in response to the mechano-chemical properties of their microenvironment. To elucidate the impact of matrix stiffness...
Cells regulate their shape and metabolic activity in response to the mechano-chemical properties of their microenvironment. To elucidate the impact of matrix stiffness and ligand density on a cell's bioenergetics, we developed a non-equilibrium, active chemo-mechanical model that accounts for mechanical energy of the cell and matrix, chemical energy from ATP hydrolysis, interfacial energy, and mechano-sensitive regulation of stress fiber assembly through signaling. By integrating the kinetics and energetics of these processes we introduce the concept of the metabolic potential of the cell that, when minimized, gives experimentally testable predictions of the cell contractility, shape, and the ATP consumption. Specifically, we show that MDA-MB-231 breast cancer cells in 3D collagen gels follow a spherical to spindle to spherical change in morphology with increasing matrix stiffness consistent with experimental observations. This biphasic transition in cell shape emerges from a competition between increased contractility accompanied by ATP hydrolysis enabled by mechano-sensitive signaling, which lowers the volumetric contribution to the metabolic potential of elongated cells and the interfacial energy which is lower for spherical shapes. On 2D hydrogels, our model predicts a hemispherical to spindle to disc shape transition with increasing gel stiffness. In both cases, we show that increasing matrix stiffness monotonically increases the cell's contractility as well as ATP consumption. Our model also predicts how the increased energy demand in stiffer microenvironments is met by AMPK activation, which is confirmed through experimental measurement of activated AMPK levels as a function of matrix stiffness carried out here in both 2D and 3D micro-environments. Further, model predictions of increased AMPK activation on stiffer micro-environments are found to correlate strongly with experimentally measured upregulation of mitochondrial potential, glucose uptake and ATP levels. The insights from our model can be used to understand mechanosensitive regulation of metabolism in physiological events such as metastasis and tumor progression during which cells experience dynamic changes in their microenvironment and metabolic state.
PubMed: 38746096
DOI: 10.1101/2024.04.30.591879 -
Scientific Reports May 2024The diagnostic accuracy of clinically significant prostate cancer (csPCa) of Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) is limited by subjectivity...
The diagnostic accuracy of clinically significant prostate cancer (csPCa) of Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) is limited by subjectivity in result interpretation and the false positive results from certain similar anatomic structures. We aimed to establish a new model combining quantitative contrast-enhanced ultrasound, PI-RADSv2, clinical parameters to optimize the PI-RADSv2-based model. The analysis was conducted based on a data set of 151 patients from 2019 to 2022, multiple regression analysis showed that prostate specific antigen density, age, PI-RADSv2, quantitative parameters (rush time, wash-out area under the curve) were independent predictors. Based on these predictors, we established a new predictive model, the AUCs of the model were 0.910 and 0.879 in training and validation cohort, which were higher than those of PI-RADSv2-based model (0.865 and 0.821 in training and validation cohort). Net Reclassification Index analysis indicated that the new predictive model improved the classification of patients. Decision curve analysis showed that in most risk probabilities, the new predictive model improved the clinical utility of PI-RADSv2-based model. Generally, this new predictive model showed that quantitative parameters from contrast enhanced ultrasound could help to improve the diagnostic performance of PI-RADSv2 based model in detecting csPCa.
Topics: Humans; Male; Prostatic Neoplasms; Ultrasonography; Nomograms; Aged; Contrast Media; Middle Aged; Prostate-Specific Antigen; Prostate; Aged, 80 and over
PubMed: 38745087
DOI: 10.1038/s41598-024-61866-x -
Frontiers in Medicine 2024Retroperitoneal fibrosis, a condition of uncertain origin, is rarely linked to 8% of malignant cases, including breast, lung, gastrointestinal, genitourinary, thyroid,...
BACKGROUND
Retroperitoneal fibrosis, a condition of uncertain origin, is rarely linked to 8% of malignant cases, including breast, lung, gastrointestinal, genitourinary, thyroid, and carcinoid. The mechanism leading to peritoneal fibrosis induced by tumors is not well understood, possibly encompassing direct infiltration of neoplastic cells or the initiation of inflammatory responses prompted by cytokines released by tumor cells. We report a case of breast cancer with renal metastasis and retroperitoneal fibrosis detected using F-FDG PET/CT, providing help for clinical diagnosis and treatment.
CASE REPORT
A 49-year-old woman was referred to the hospital with elevated creatinine and oliguria for over a month. Abdominal computer tomography (CT) and magnetic resonance imaging (MRI) showed a retroperitoneal fibrosis-induced acute kidney injury (AKI) was suspected. However, a percutaneous biopsy of the kidney lesion confirmed metastasis from breast cancer. The physical examination revealed inverted nipples and an orange peel appearance on the skin of both breasts. Ultrasonography revealed bilateral hyperplasia (BIRADS 4a) of the mammary glands and bilateral neck and axillary lymphadenopathy. Subsequently, F-deoxyglucose positron emission tomography/computer tomography (F-FDG PET/CT) detected abnormally high uptake (SUVmax) in the bilateral mammary glands and axillary lymph nodes, suggesting bilateral breast cancer. Furthermore, abnormal F-FDG uptake was detected in the kidney, suggesting renal metastasis. In addition, abnormal F-FDG uptake was observed in the vertebrae, accompanied by an elevation in inhomogeneous bone mineral density, raising suspicion of bone metastases. However, the possibility of myelodysplasia cannot be dismissed, and further investigations will be conducted during close follow-ups. There was significant F-FDG uptake in the retroperitoneal position indicating a potential association between retroperitoneal fibrosis and breast cancer. The final pathological diagnosis of the breast tissue confirmed bilateral invasive ductal carcinoma. The patient had been treated with 11 cycles of albumin-bound (nab)-paclitaxel (0.3 mg) and had no significant adverse reaction.
CONCLUSION
In this case, neither the bilateral breast cancer nor the kidney metastatic lesion showed typical nodules or masses, so breast ultrasound, abdominal CT, and MRI did not suggest malignant lesions. PET/CT played an important role in detecting occult metastases and primary lesions, thereby contributing to more accurate staging, monitoring treatment responses, and prediction of prognosis in breast cancer.
PubMed: 38741768
DOI: 10.3389/fmed.2024.1353822 -
Nature Communications May 2024The unexplained protective effect of childhood adiposity on breast cancer risk may be mediated via mammographic density (MD). Here, we investigate a complex relationship...
The unexplained protective effect of childhood adiposity on breast cancer risk may be mediated via mammographic density (MD). Here, we investigate a complex relationship between adiposity in childhood and adulthood, puberty onset, MD phenotypes (dense area (DA), non-dense area (NDA), percent density (PD)), and their effects on breast cancer. We use Mendelian randomization (MR) and multivariable MR to estimate the total and direct effects of adiposity and age at menarche on MD phenotypes. Childhood adiposity has a decreasing effect on DA, while adulthood adiposity increases NDA. Later menarche increases DA/PD, but when accounting for childhood adiposity, this effect is attenuated. Next, we examine the effect of MD on breast cancer risk. DA/PD have a risk-increasing effect on breast cancer across all subtypes. The MD SNPs estimates are heterogeneous, and additional analyses suggest that different mechanisms may be linking MD and breast cancer. Finally, we evaluate the role of MD in the protective effect of childhood adiposity on breast cancer. Mediation MR analysis shows that 56% (95% CIs [32%-79%]) of this effect is mediated via DA. Our finding suggests that higher childhood adiposity decreases mammographic DA, subsequently reducing breast cancer risk. Understanding this mechanism is important for identifying potential intervention targets.
Topics: Humans; Breast Neoplasms; Female; Breast Density; Adiposity; Mammography; Mendelian Randomization Analysis; Risk Factors; Menarche; Child; Body Size; Adult; Polymorphism, Single Nucleotide; Middle Aged
PubMed: 38740751
DOI: 10.1038/s41467-024-48105-7