Metastatic Breast Research Articles

Incidental findings involving the temporomandibular joint on computed tomography and magnetic resonance imaging.

The temporomandibular joint (TMJ) is frequently imaged in head and neck computed tomography (CT) and magnetic resonance imaging (MRI) studies. Depending on the indication for the study, an abnormality of the TMJ may be an incidental finding. These findings encompass both intra- and extra-articular disorders. They may also be related to local, regional or systemic conditions. Familiarity with these findings along with pertinent clinical information helps narrow the list of differential diagnoses. While definitive diagnosis may not be immediately apparent, a systematic approach contributes to improved discussions between clinicians and radiologists and better patient management.

Non-Small Cell Lung Cancer Metastases to Breast, Colon and Skin: A Case Report

Bronchogenic carcinoma is a leading cause of cancer mortality worldwide. Of lung cancer cases overall, 50% have metastasis at presentation, mostly to the brain, bone, liver, the adrenal glands ,thoracic cavity and non-regional lymph nodes .This case report presents a female patient with three rare sites of lung cancer metastasis: breast, colon, and skin. Her initial presentation was a several-month history of a mass in the left breast and in the upper abdominal wall, dyspepsia, weight loss, and intermittent per rectal bleeding. Diagnosis of this case was difficult because of the challenge to differentiate between primary breast cancer and metastasis. However, the diagnosis was made by the interpretation of images and immunohistochemistry.

Basal Cell Carcinoma of Breast Metastasis to Axillary Lymph Node: A Case Report and Comprehensive Literature Review

Basal cell carcinoma (BCC) metastasis incidence is rare and occurs in advanced, neglected, recurrent tumors or tumors with high risk histopathologic features like perineural invasion. The mainstay of management remains surgical excision with clear margins wherever possible followed by radiotherapy. We are presenting a case of metastatic BCC of an uncommon site i.e., anterior shoulder with metastasis to axillary lymph nodes and to review literature regarding the current standard of management.

Immune subtype identification and multi-layer perceptron classifier construction for breast cancer.

Breast cancer is a heterogeneous tumor. Tumor microenvironment (TME) has an important effect on the proliferation, metastasis, treatment, and prognosis of breast cancer. In this study, we calculated the relative proportion of tumor infiltrating immune cells (TIICs) in the breast cancer TME, and used the consensus clustering algorithm to cluster the breast cancer subtypes. We also developed a multi-layer perceptron (MLP) classifier based on a deep learning framework to detect breast cancer subtypes, which 70% of the breast cancer research cohort was used for the model training and 30% for validation. By performing the K-means clustering algorithm, the research cohort was clustered into two subtypes. The Kaplan-Meier survival estimate analysis showed significant differences in the overall survival (OS) between the two identified subtypes. Estimating the difference in the relative proportion of TIICs showed that the two subtypes had significant differences in multiple immune cells, such as CD8, CD4, and regulatory T cells. Further, the expression level of immune checkpoint molecules (PDL1, CTLA4, LAG3, TIGIT, CD27, IDO1, ICOS) and tumor mutational burden (TMB) also showed significant differences between the two subtypes, indicating the clinical value of the two subtypes. Finally, we identified a 38-gene signature and developed a multilayer perceptron (MLP) classifier that combined multi-gene signature to identify breast cancer subtypes. The results showed that the classifier had an accuracy rate of 93.56% and can be robustly used for the breast cancer subtype diagnosis. Identification of breast cancer subtypes based on the immune signature in the tumor microenvironment can assist clinicians to effectively and accurately assess the progression of breast cancer and formulate different treatment strategies for different subtypes.

Papillary Thyroid Carcinoma With Breast and Bone Metastasis.

Papillary thyroid carcinoma is the most common thyroid malignant tumor and usually has a fine prognosis. The most common metastatic site is the cervical lymph node, and distant metastasis is rare. This report describes a female patient with papillary thyroid carcinoma who presented with multiple metastases in the cervical lymph nodes, breast, and spine. The patient's disease course lasted 11 years, and eventually metastatic cancer led to the patient's death. We also analyzed the survival rate and median survival time of papillary thyroid carcinoma with multiple organ metastases using data in the literature.

Predicting of axillary lymph node metastasis in invasive breast cancer using multiparametric MRI dataset based on CNN model.

To develop a multiparametric MRI model for predicting axillary lymph node metastasis in invasive breast cancer. Clinical data and T2WI, DWI, and DCE-MRI images of 252 patients with invasive breast cancer were retrospectively analyzed and divided into the axillary lymph node metastasis (ALNM) group and non-ALNM group using biopsy results as a reference standard. The regions of interest (ROI) in T2WI, DWI, and DCE-MRI images were segmented using MATLAB software, and the ROI was unified into 224 × 224 sizes, followed by image normalization as input to T2WI, DWI, and DCE-MRI models, all of which were based on ResNet 50 networks. The idea of a weighted voting method in ensemble learning was employed, and then T2WI, DWI, and DCE-MRI models were used as the base models to construct a multiparametric MRI model. The entire dataset was randomly divided into training sets and testing sets (the training set 202 cases, including 78 ALNM, 124 non-ALNM; the testing set 50 cases, including 20 ALNM, 30 non-ALNM). Accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of models were calculated. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the diagnostic performance of each model for axillary lymph node metastasis, and the DeLong test was performed, P< 0.05 statistically significant. For the assessment of axillary lymph node status in invasive breast cancer on the test set, multiparametric MRI models yielded an AUC of 0.913 (95% CI, 0.799-0.974); T2WI-based model yielded an AUC of 0.908 (95% CI, 0.792-0.971); DWI-based model achieved an AUC of 0.702 (95% CI, 0.556-0.823); and the AUC of the DCE-MRI-based model was 0.572 (95% CI, 0.424-0.711). The improvement in the diagnostic performance of the multiparametric MRI model compared with the DWI and DCE-MRI-based models were significant (P< 0.01 for both). However, the increase was not meaningful compared with the T2WI-based model (P = 0.917). Multiparametric MRI image analysis based on an ensemble CNN model with deep learning is of practical application and extension for preoperative prediction of axillary lymph node metastasis in invasive breast cancer.

Synthesis of PAMAM dendrimers anchored to WS2 nano-sheets for controlled delivery of docetaxel: Design, characterization and in vitro drug release

The oral delivery of anti-cancer agents is typically challenging due to low bioavailability and significant gastrointestinal side effects of drugs. Docetaxel is a lipophilic anti-cancer agent used to treat some cancers, such as metastatic breast and prostate cancer. Herein, we represent a highly effective strategy for the delivery of docetaxel using a near-infrared responsive nano-carrier based on WS2 nano-sheets. To do this, Poly (N-vinylcaprolactam) and allyl amine were grafted on the surface of nano-sheets as thermo-sensitive polymer and functional monomer, respectively. Next, three generations of PAMAM dendrimers were anchored to the grafted polymer chains by using methyl acrylate and ethylenediamine. The produced nano-carrier was characterized by using FT-IR, TGA, XRD, FE-SEM systems. The adsorption isotherm and kinetic results were well fitted to Langmuir and second-order models. The results of thermodynamic factors including Gibb's free energy, enthalpy, and entropy supported the drug adsorption process. The thermo-sensitive nano-carrier released a maximum of 88.25% and 32.94% drug in the simulated human blood fluid at 50 °C and 37 °C within 6 h. The in vitro release curves were analyzed using several mathematical models to determine the drug release mechanism. Using the near-infrared irradiation, the drug release was reached at 100% in 12 min, which was about 4.4 times faster than without laser irradiation. The findings show that the produced smart nano-carrier could be a promising choice for sustained delivery of docetaxel.

“A sheep in a wolf's clothing”. Case report of tubercular axillary lymph nodes mimicking metastasis in a case of breast carcinoma with brief review of literature

“Appearances can be deceptive” – the saying holds true in our case where sinister appearing enlarged axillary lymph nodes draining breast carcinoma were surprisingly found to be tubercular. A 60-year-old nulliparous female presented with complaints of a right breast lump with no comorbidities. Examination and evaluation revealed a retro areolar non – metastatic breast … Continued

Breast metastasis of signet ring cell carcinoma from the colon: a case report

BackgroundColon cancer is one of the most common diagnosed malignancies. Despite the use of surgery, chemotherapy, radiotherapy, targeted therapy, immunotherapy, and other comprehensive treatments, distant metastasis is still one of the main causes for dying of colon cancer. The common metastatic site of colon cancer is the liver, lung, and bone. In this article, we report a rare case of breast metastasis of signet ring cell carcinoma from the colon.Case presentationA 44-year-old woman was diagnosed with colon cancer and received a radical surgery of colon cancer in 2019. Combined with postoperative pathological and computed tomography (CT) images, a diagnosis of cT3N2M0 mucinous adenocarcinoma of colon (according to AJCC cancer staging manual, Version 8) was established. Adjuvant chemotherapy (XELOX: oxaliplatin 130 mg/m2 on day 1 plus capecitabine 1000 mg/m2 twice daily on days 1 to 14 every 3 weeks for 18 weeks) was performed followed by surgical resection. Fourteen months later, the patient underwent mastectomy for breast mass, which was diagnosed pathologically as metastasis of signet ring cell carcinoma from the colon. XELOX chemotherapy regimen (oxaliplatin 130 mg/m2 on day 1 plus capecitabine 1000 mg/m2 twice daily on days 1 to 14 every 3 weeks for 24 weeks) combined with bevacizumab (7.5 mg/kg on day 1) was used after the mastectomy. The patient had stable disease according to her last examination (RECIST criteria).ConclusionIt is rare to find a report of a patient of colon cancer that metastasizes to breast. We hope to increase treatment experience for patients with this rare metastasis.

Three Cases of Atypical Breast Metastasis from Lung Adenocarcinoma

Metastatic disease to the breast is rare. Melanoma and lymphoma are the most common primary tumors metastasizing to the breast, and breast metastasis from a primary lung neoplasm is uncommon. It can be difficult to distinguish metastatic disease from primary breast cancer clinically. Immunohistochemistry, combined with further diagnostic imaging, play important roles in identifying the primary origin of the malignancy. An accurate diagnosis is imperative for therapeutic planning, and further workup should be considered for unusual cytological patterns. In this report, three cases of pulmonary metastasis to the breast with atypical clinical presentations are presented and discussed.

Abstract 12697: Pharmacological Inhibition of BAG3-HSP70 With the Proposed Breast Cancer Therapeutic JG-98: In-vivo Mice Study

Introduction: The co-chaperone Bcl2-associated athanogene-3 (BAG3), along with its cofactor heat shock protein 70 (HSP70), is fundamental for protein quality control and cell survival in a healthy heart. However, elevated expression of BAG3 is also associated with metastasis in breast and other cancers, and small molecules such as JG-98 that disrupt BAG3-HSP70 binding have been shown to reduce cancer cell proliferation. We previously showed JG-98 is cardiotoxic in neonatal rat ventricular myocytes. Hypothesis: As BAG3-HSP70 is fundamental for autophagic protein turnover, JG-98 will reduce tumor size but have cardiotoxic effects. Methods: BT474 Resistant breast cancer cells were injected bilaterally into mammary fat pads of female athymic nude mice. When tumors reached 25 mm 2 , mice received a baseline echocardiography and were randomized to intraperitoneal injections of either PBS/DMSO vehicle or 3 mg/kg JG-98 twice weekly for 3 weeks (n = 4/group) or 6 weeks (n=10/group). Tumor growth was monitored using calipers and echocardiography was performed prior to sacrifice. Results: After 3 weeks, tumor volume increased by ~44% in Vehicle treated mice but decreased by 17% in JG-98 treated mice, effectively halting tumor growth. However, cardiac echocardiography did not reveal any functional or structural differences between the vehicle and JG-98 treated mice after either 3 or 6 weeks. JG-98 did result in dysregulation of BAG3 and its interactome in the LV. JG-98 slightly increased BAG3 levels in the LV at 3 weeks, but slightly decreased levels at 6 weeks. This agrees with data showing acute stress upregulates BAG3, but chronic stress downregulates it. Similarly, we found altered protein expression of the BAG3 binding partners HSBP8, HSPB5, and HSP70. Conclusions: JG-98 had no overt cardiotoxic effects, suggesting the adult heart may be resistant to disrupted BAG3-HSP70. However, we also observed dysregulated protein levels in the BAG3-mediated autophagy pathways that could precede dysfunction with more chronic treatment. Furthermore, mutations in BAG3 or altered expression levels could sensitize individuals to JG-98 treatment. Further work is necessary to understand the cardiac impact of cancer therapeutics that target BAG3.

Metastatic Invasive Lobular Carcinoma of Bilateral Breasts Presenting with an Abdominal Mass

Background: Breast cancer remains the most frequent malignancy in women, with the two most common histological subtypes of breast cancer being the invasive ductal carcinomas (IDC) and invasive lobular carcinomas (ILC). The most common sites of breast cancer metastases are the liver, lung, pleura, brain and bone. Gastrointestinal, peritoneal, gynaecological and renal metastases are less common, often masquerading as primary malignancies and causing diagnostic confusion, mostly occurring in ILC as compared to IDC. Case Presentation: We report a case of a young woman presenting with an enlarging abdominal mass which was suspicious of a primary abdominal malignancy. Endoscopy and gastric biopsy revealed poorly differentiated carcinoma. On the top-most slices of her abdominal CT, bilateral enhancing breast lesions were detected, suspicious of metastases. Ultrasound and biopsy done for the breast lesions showed bilateral ILCs. Further staining of the gastric biopsy specimen confirmed the final diagnosis of gastric metastases from bilateral breast ILCs rather than a primary gastric tumour with breast metastases. Conclusion: This case highlights how breast cancer metastases to the GI tract may mimic primary GI cancers as well as the importance of breast examination, family history, radiological and pathological examination in detecting the breast origin of advanced carcinomas. Awareness of the different patterns of metastatic spread of ILC and IDC is also important due to the infiltrating nature and non-specific imaging findings of these tumours, requiring a high index of suspicion from the surgeons, oncologists, radiologists and pathologists.

A nomogram based on radiomics signature and deep-learning signature for preoperative prediction of axillary lymph node metastasis in breast cancer.

To develop a nomogram based on radiomics signature and deep-learning signature for predicting the axillary lymph node (ALN) metastasis in breast cancer. A total of 151 patients were assigned to a training cohort (n = 106) and a test cohort (n = 45) in this study. Radiomics features were extracted from DCE-MRI images, and deep-learning features were extracted by VGG-16 algorithm. Seven machine learning models were built using the selected features to evaluate the predictive value of radiomics or deep-learning features for the ALN metastasis in breast cancer. A nomogram was then constructed based on the multivariate logistic regression model incorporating radiomics signature, deep-learning signature, and clinical risk factors. Five radiomics features and two deep-learning features were selected for machine learning model construction. In the test cohort, the AUC was above 0.80 for most of the radiomics models except DecisionTree and ExtraTrees. In addition, the K-nearest neighbor (KNN), XGBoost, and LightGBM models using deep-learning features had AUCs above 0.80 in the test cohort. The nomogram, which incorporated the radiomics signature, deep-learning signature, and MRI-reported LN status, showed good calibration and performance with the AUC of 0.90 (0.85-0.96) in the training cohort and 0.90 (0.80-0.99) in the test cohort. The DCA showed that the nomogram could offer more net benefit than radiomics signature or deep-learning signature. Both radiomics and deep-learning features are diagnostic for predicting ALN metastasis in breast cancer. The nomogram incorporating radiomics and deep-learning signatures can achieve better prediction performance than every signature used alone.

The Mechanistic Roles of Sirtuins in Breast and Prostate Cancer.

Simple SummaryThere are diverse reports of the dual role of sirtuin genes and proteins in breast and prostate cancers. This review discusses the current information on the tumor promotion or suppression roles of SIRT1–7 in breast and prostate cancers. Precisely, we highlight that sirtuins regulate various proteins implicated in proliferation, apoptosis, autophagy, chemoresistance, invasion, migration, and metastasis of both breast and prostate cancer. We also provide evidence of the direct regulation of sirtuins by miRNAs, highlighting the consequences of this regulation in breast and prostate cancer. Overall, this review reveals the potential value of sirtuins as biomarkers and/or targets for improved treatment of breast and prostate cancers.Mammalian sirtuins (SIRT1–7) are involved in a myriad of cellular processes, including apoptosis, proliferation, differentiation, epithelial-mesenchymal transition, aging, DNA repair, senescence, viability, survival, and stress response. In this review, we discuss the current information on the mechanistic roles of SIRT1–7 and their downstream effects (tumor promotion or suppression) in cancers of the breast and prostate. Specifically, we highlight the involvement of sirtuins in the regulation of various proteins implicated in proliferation, apoptosis, autophagy, chemoresistance, invasion, migration, and metastasis of breast and prostate cancer. Additionally, we highlight the available information regarding SIRT1–7 regulation by miRNAs, laying much emphasis on the consequences in the progression of breast and prostate cancer.

Hypoxia-driven metabolic reprogramming of adipocytes fuels cancer cell proliferation.

Obesity increases the risk of certain cancers, especially tumours that reside close to adipose tissue (breast and ovarian metastasis in the omentum). The obesogenic and tumour micro-environment share a common pathogenic feature, oxygen deprivation (hypoxia). Here we test how hypoxia changes the metabolome of adipocytes to assist cancer cell growth. Human and mouse breast and ovarian cancer cell lines were co-cultured with human and mouse adipocytes respectively under normoxia or hypoxia. Proliferation and lipid uptake in cancer cells were measured by commercial assays. Metabolite changes under normoxia or hypoxia were measured in the media of human adipocytes by targeted LC/MS. Hypoxic cancer-conditioned media increased lipolysis in both human and mouse adipocytes. This led to increased transfer of lipids to cancer cells and consequent increased proliferation under hypoxia. These effects were dependent on HIF1α expression in adipocytes, as mouse adipocytes lacking HIF1α showed blunted responses under hypoxic conditions. Targeted metabolomics of the human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes media revealed that culture with hypoxic-conditioned media from non-malignant mammary epithelial cells (MCF10A) can alter the adipocyte metabolome and drive proliferation of the non-malignant cells. Here, we show that hypoxia in the adipose-tumour microenvironment is the driving force of the lipid uptake in both mammary and ovarian cancer cells. Hypoxia can modify the adipocyte metabolome towards accelerated lipolysis, glucose deprivation and reduced ketosis. These metabolic shifts in adipocytes could assist both mammary epithelial and cancer cells to bypass the inhibitory effects of hypoxia on proliferation and thrive.

Overall survival of individuals with metastatic cancer in Sweden: a nationwide study

AimsConsistent improvements for overall survival (OS) have been reported for individuals with metastatic cancer. Swedish population-based registers allow national coverage and long follow-up time. The aim of this study was to estimate and explore long-term OS of individuals diagnosed with metastatic cancer using Swedish nationwide health registers.MethodsIndividuals with metastatic breast (MBC), non-small cell lung (MNSCLC), ovary (MOC) or colorectal cancer (MCRC) or metastatic malignant melanoma (MMM) were identified in the Swedish national cancer register and national patient registers. Survival was estimated and stratified by available variables. Potential cure fractions were estimated using mixture cure models.ResultsIn total, approximately 69,000 individuals were identified. The most common cancers were MCRC (36.2%) and MNSCLC (29.5%). Men were more frequently diagnosed with MNSCLC, MCRC, and MMM compared to women. Except for MOC, about 50% of individuals were 70 years or older at diagnosis. Throughout the study period survival differed across cancers. The longest median OS was observed for individuals with MOC and MBC. At 10 years of follow-up, the survival curves flatten at a survival rate of approximately 10% for all cancers except MNSCLC. The youngest age groups had the longest median OS. Increased survival was also observed for individuals diagnosed in 2015 and 2018 compared to individuals diagnosed during earlier years. The estimated cure fractions were 4% for MBC, 1.5% for MNSCLC, 6.8% for MCRC, 8.6% for MOC and MMM.ConclusionsLong-term survival has been assessed across all indications except for NSCLC.. The findings may be relevant for healthcare planning to meet the needs of future patients and potential long-term survivors.

Detection of axillary lymph node metastasis in breast cancer using dual-layer spectral computed tomography.

PurposeTo investigate the value of contrast-enhanced dual-layer spectral computed tomography (DLCT) in the detection of axillary lymph node (ALN) metastasis in breast cancer.Materials and MethodsIn this prospective study, 31 females with breast cancer underwent contrast-enhanced DLCT from August 2019 to June 2020. All ALNs were confirmed by postoperative histology. Spectral quantitative parameters, including λ HU (in Hounsfield units per kiloelectron-volt), nIC (normalized iodine concentration), and Zeff (Z-effective value) in both arterial and delay phases, were calculated and contrasted between metastatic and nonmetastatic ALNs using the McNemar test. Discriminating performance from metastatic and nonmetastatic ALNs was analyzed using receiver operating characteristic curves.ResultsIn total, 132 ALNs (52 metastatic and 80 nonmetastatic) were successfully matched between surgical labels and preoperative labels on DLCT images. All spectral quantitative parameters (λHu , nIC, and Zeff) derived from both arterial and delayed phases were greater in metastatic ALNs than in nonmetastatic SLNs (all p < 0.001). Logistic regression analyses showed that λHu in the delayed phase was the best single parameter for the detection of metastatic ALNs on a per-lymph node basis, with an area under the curve of 0.93, accuracy of 86.4% (114/132), sensitivity of 92.3% (48/52), and specificity of 87.5% (70/80).ConclusionThe spectral quantitative parameters derived from contrast-enhanced DLCT, such as λHu , can be applied for the preoperative detection of ALN metastasis in breast cancer.

342 (PB122) - Neutralizing antibody for S100A8/A9 soil sensing signal to prevent metastatic disease

Organotropism of cancer metastasis is driven by the ‘seed and soil’ theory where the soil (metastatic microenvironment) provides signals to attract the seeds (cancer cells) to grow on a certain location. S100A8/A9 is a ‘soil sensing signal’ that binds to receptors expressed by many cancer types. We aimed to understand the role of S100A8/A9 in melanoma, breast and lung cancer, to develop a neutralizing antibody, and to provide a proof-of-concept for the antibody for inhibiting metastasis. Cell lines were obtained from ATCC. Overexpression of S100A8/A9 receptors MCAM and NPTNβ was induced by cDNA vector and MCAM expression was silenced by a siRNA. Recombinant S100A8/A9 protein was produced in-house. Migration/invasion assays were performing with Boyden Chamber method, colony formation assay with agarose gel cultures, and the results were quantitated by counting crystal violet stained cells/colonies. mRNA expression was analyzed by qPCR. In mouse lung metastasis models, cancer cells were injected into tail vein, and lung metastases were monitored by X-ray Computed Tomography and quantitated by counting metastatic foci at endpoint. A chimeric S100A8/A9 antibody was produced in CHO-S cells by incorporating genomic sequences of heavy and light chains of a mouse monoclonal S100A8/A9 antibody to the Fab domain of human cDNA-encoded IgG2-Fc part. S100A8/A9 was expressed in monocytes and attracted cancer cells expressing its receptors to immunosuppressed premetastatic niche. Of these receptors, MCAM was highly expressed in metastatic, but not in non-metastatic melanoma and breast cancer cells. Overexpression of MCAM in non-metastatic melanoma cells increased migration, and downregulation in metastatic cells eliminated migration, but also resulted in lost sensitivity to S100A8/A9 stimulation. In breast cancer cells, overexpression of MCAM in non-metastastic cells increased migration, which was abrogated by addition of S100A8/A9 decoy receptor to the cultures. Overexpression of MCAM induced EMT-like expression profile in the breast cancer cells. In lung cancer, overexpression of S100A8/A9 receptor NPTNβ induced anchorage independent growth, migration and invasion, which were further increased by addition of S100A8/A9 ligand to the cultures. From the produced antibodies, the clones that efficiently bound S100A8 and A9 heterodimer most effectively inhibited migration and cytokine production. The S100A8/A9 antibody effectively prevented formation of lung metastases in melanoma and breast cancer lung metastasis models. These results demonstrate a role for S100A8/A9 and its receptors in metastasis of melanoma, breast and lung cancer. A neutralizing antibody for S100A8/A9 prevented formation of lung metastases, suggesting pharmacological inhibition of S100A8/A9 as a potential option for preventing metastatic disease. No conflict of interest.

MicroRNA Expression of Primary and Metastatic Colorectal and Breast Carcinoma

Background: Colorectal and breast carcinoma are frequently diagnosed cancers. At advanced stages, cancers metastasize to certain organs resulting in loss of function of these organs, and eventually death. Therefore, there is a specific need for the prognosis of these cancers. Currently, microRNAs (miRNAs), have emerged as a new target of cancer-specific biomarker. Objective: To examine the expression of miRNA in primary and metastatic breast and colorectal cancers. Methods: This study investigated the expression of 6 miRNAs (miR-10b, miR-21, miR-145, miR-155, miR-200c, and miR-373) in formalin fixed paraffin embed tissues from pairs of normal tissues with primary and metastatic tumor samples of breast and colorectal carcinoma cases in Ramathibodi Hospital, Thailand by real-time RT-PCR. Results: Among 6 miRNAs, miR-145 decreased significantly in all samples of primary and metastatic colorectal and breast carcinoma. There was significantly decreased expression of miR-145 in metastatic colorectal carcinoma compared to their primary colorectal carcinoma (P &lt; .05). Whereas miR-10b, miR-155, and miR-200c showed a decreased expression; miR-21, and miR-373 showed an increased expression in the majority of cases. Unlike miR-145, other miRNAs showed no significant difference of expression (P &gt; .05). Conclusions: This finding indicates that miR-145 may be the potential metastatic biomarker. Decrease of miR-145 could be applied to the prognosis and target for therapy of breast and colorectal carcinoma.

Vitamin D and circulating tumor cells in primary breast cancer.

BackgroundCirculating tumor cells (CTCs) contribute to the metastatic cascade and represent an independent survival predictor in breast cancer (BC) patients. Vitamin D has pleiotropic effects, and its low concentrations are associated with breast cancer and metastasis. The aim of this study was to assess plasma vitamin D in primary BC patients in relation to CTCs.MethodsThis study included 91 non-metastatic BC patients (stage I–III) and 24 healthy donors. Blood samples for the analyses were drawn at the time of surgery. CTCs were assessed using a quantitative RT-PCR assay for expression of epithelial (CK19) or epithelial-to-mesenchymal transition (EMT) genes (TWIST1, SNAIL1, SLUG, and ZEB1). Total 25-OH vitamin D was measured in plasma using ELISA. Plasma cytokines and angiogenic factors were measured by enzyme-linked immunoassay.ResultsCTCs were detected in 30 (33%) patients. Patients with detectable CTCs in peripheral blood had significantly lower vitamin D concentrations in comparison to patients without detectable CTCs ((mean ± SD) 8.50 ± 3.89 µg/L for CTC-positive vs 9.69 ± 3.49 µg/L for CTC-negative patients, p = 0.03). The mean ( ± SD) vitamin D plasma level was 9.3 ± 3.65 µg/L for breast cancer patients compared to 18.6 ± 6.8 for healthy donors (p < 0.000001). There was no association between plasma vitamin D and other patient/tumor characteristics. Plasma vitamin D levels are inversely correlated with plasma TGF-β1, TGF-β2, IL β, IL-5, and eotaxin (all p < 0.05). Patients with vitamin D above the median had a better overall survival (hazard ratio (HR) = 0.36, 95% CI 0.16–0.80, p = 0.017), and combined analysis showed the best survival for CTC-negative patients with vitamin D levels above the median as compared to patients with opposite characteristics (HR = 0.18, 95% CI 0.05–0.63, p = 0.004).ConclusionsLow vitamin D could be a consequence and hence a biomarker of a more invasive disease. Alternatively, vitamin D could be associated with survival because of its role in tumor dissemination. Whether its supplementation affects the metastatic cascade should be tested in animal experiments and interventional studies.