Schizophrenia has been associated with increased risk of breast cancer, yet the risk of schizophrenia following breast cancer is unclear. Here, the authors show a bidirectional association between breast cancer and schizophrenia in Sweden and a shared genetic contribution to both diseases.
Breast Cancer Awareness Month
Breast cancer is the most common cancer in women worldwide. It is a heterogeneous disease and molecular features include activation of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and/or BRCA mutations. The most critical point for the best prognosis is to identify the disease at an early-stage. Several diagnostic approaches are currently available including mammography, magnetic resonance imaging, ultrasound, computerized tomography, positron emission tomography and biopsy. Treatment strategies include surgery and radiation as well as systemic therapy approaches such as endocrine therapy for ER+ disease, chemotherapy, anti-HER2 therapy, poly(ADP-ribose) polymerase inhibitors and, more recently, immunotherapy. Adjuvant chemotherapy is also often used to prevent recurrence of the disease.
This collection, curated by the cancer team at Nature Communications on occasion of the Breast Cancer Awareness Month in October, includes a variety of both translational and clinical research articles that shed light on the complex biology of the disease and on novel diagnostic and therapeutic approaches.
The emergence of tumour adaptive radioresistance can limit the success of radiation therapy and immunotherapy in breast cancer. In this study, the authors demonstrate that CD47 and HER2 are coordinating in tumor response to radiation and that co-blockage of both receptors can eliminate radiorestistant breast cancer cells.
European polygenic risk score for prediction of breast cancer shows similar performance in Asian women
Polygenic risk scores predict the likelihood that an individual will develop a certain cancer, however these are often specific for a given population. Here, the authors show that a risk score developed to assess the risk of breast cancer in European women can also predict risk in Asian populations.
TET2 loss is associated with human cancers but its role in the mammary gland development and tumorigenesis is unclear. Here, the authors show that TET2–FOXP1 complex mediates demethylation of genes involved in luminal lineage commitment and endocrine response, underlying a role of TET2 loss in endocrine resistant breast cancer.
Breast cancer colonization by Fusobacterium nucleatum accelerates tumor growth and metastatic progression
High levels of Fusobacterium nucleatum have been associated with poor overall survival in patients with colorectal and esophageal cancer. Here, the authors show that F. nucleatum is abundant in breast cancer samples and that the colonization by F. nucleatum accelerates tumor growth and metastasis in preclinical breast cancer models.
Comparison of spontaneous canine cancers and human cancers may illuminate future therapeutic avenues. Here, genomic analyses of these tumors highlights a convergence on PI3K-Akt oncogenic pathways.
Metastasis-initiating cells induce and exploit a fibroblast niche to fuel malignant colonization of the lungs
How cancer cells engage the microenvironment to establish metastasis is poorly understood. Here, the authors show that CXCR3-expressing breast cancer cells secrete IL-1 to induce a paracrine crosstalk with fibroblasts in the lung, which involves CXCL9/10 production and results in colonization of the lung.
Therapeutic paradigm of dual targeting VEGF and PDGF for effectively treating FGF-2 off-target tumors
Anti-VEGF therapy has many limitations that might be resolved by using combination treatment approaches. Here, the authors demonstrate that the dual-targeting of VEGF and PDGF is required for targeting resistant FGF2+ tumors which depend on the recruitment of pericytes on tumor microvessels.
Triple negative breast cancer is a deadly form of breast cancer with limited therapeutic options. Here the authors show the efficacy of GLUT1 pharmacological inhibition against a subset of tumors expressing RB1, thereby identifying RB1 protein level as a biomarker of sensitivity to anti-GLUT1 therapy.
Cancer stem-like cells are the culprits of tumour recurrence and metastasis, but their regulatory mechanisms are not fully understood. Here, the authors show that the scaffold protein SH3RF3 enhances the stem-like properties of breast cancer by facilitating activation of the JNK-JUN pathway and PTX3 expression.
Comprehensive characterization of claudin-low breast tumors reflects the impact of the cell-of-origin on cancer evolution
Claudin-low tumors are a rare aggressive subtype of breast cancers. In this study, the authors use a multiomics approach to demonstrate that these tumors are heterogeneous and comprise three main subgroups that emerge from different evolutionary processes.
Acquired resistance to chemotherapy can lead to multi-drug resistance and poor prognosis in cancer. Here, the authors show that Rac1 increases glycolysis and non-oxidative pentose phosphate pathway activity leading to neoadjuvant chemotherapy (NAC) resistance, thus its inhibition sensitizes resistant breast cancer PDXs to NAC.
Local mechanical properties are important to cellular function; but conventional measurement techniques are limited in intact, living, 3D tissues. Here, the authors report on swellable hydrogel microparticles to monitor mechanical properties in situ via a temperature change.
In breast cancer the contribution of different genetic variants to disease heritability is complex and not fully understood. Here, the authors present a network-based analysis in 84,567 patients studying ~7.3 million variants, identifying gene modules associated with breast cancer survival.
PLK1 inhibition exhibits strong anti-tumoral activity in CCND1-driven breast cancer metastases with acquired palbociclib resistance
Identifying novel therapies for the treatment of CDK4/6 inhibitor-resistant patients is of great importance. Here, the authors demonstrate that PLK1 inhibition is a potential therapeutic target in CCND1-driven and in RB-positive Palbociclib-resistant breast cancers.
ABL1-dependent OTULIN phosphorylation promotes genotoxic Wnt/β-catenin activation to enhance drug resistance in breast cancers
Genotoxic agents have been shown to activate the Wnt/β-catenin signaling but the underlying mechanism remains unclear. Here, the authors show that upon DNA damage, the deubiquitinase OTULIN activates Wnt/β-catenin signaling by inhibiting linear ubiquitination, K48-linked polyubiquitination, and proteasomal degradation of β-catenin.
Identification of novel breast cancer susceptibility loci in meta-analyses conducted among Asian and European descendants
In breast cancer, genome-wide associations studies (GWAS) have highlighted loci associated with disease risk. Here, the authors perform a meta-analysis of GWAS data from Asian populations, discovering 31 potential new risk loci, 10 of which are validated in an independent disease cohort.
Predicting an individual's response to therapy is an important goal for precision medicine. Here, the authors use an algorithm that takes into account the interaction type and directionality of signalling pathways in protein–protein interactions and find that their pathway analysis can predict essential genes, which may be a target for therapy.
Targeting mitochondrial metabolism in cancer cells has shown promising therapeutic potential. Here, the authors screen FDA-approved compound library and show that the β1-blocker nebivolol inhibits oxidative phosphorylation and angiogenesis in cancer cells and can be re-purposed for cancer therapy.
Homologous recombination DNA repair deficiency and PARP inhibition activity in primary triple negative breast cancer
Defects in homologous recombination (HR) are found in some triple negative breast cancers, suggesting they may be sensitive to PARP inhibitors. In this phase II clinical trial of the PARP inhibitor rucaparib, changes in Ki67 levels did not correlate with markers of HR deficiency but HR deficiency was detected in 69% of tumours, indicating that PARP inhibitors may be a useful treatment.
TMBIM6, a member of the transmembrane BI-1 motif-containing family of proteins, is overexpressed in many cancer types. Here, the authors show that TMBIM6 regulates AKT activation through mTORC2 assembly and ribosome association and identify an antagonist of TMBIM6 with anti-tumor properties.
Cancer associated fibroblasts (CAFs) have been suggested to regulate cancer cell metabolism, but the mechanisms are not completely elucidated. Here, the authors show that low FAK expression in stromal cells correlates with poor prognosis in breast and pancreatic cancer patients and that FAK-silencing in CAFs promotes tumourigenesis by the paracrine regulation of cancer cell metabolism.
Autophagy deficiency promotes triple-negative breast cancer resistance to T cell-mediated cytotoxicity by blocking tenascin-C degradation
T cell mediated therapies have proven largely unsuccessful in triple-negative breast cancer (TNBC). Here, the authors show that autophagy is reduced in TNBC, which results in an increase in Tenascin C and reduced activation of tumour infiltrating lymphocytes.
Mechanisms governing adaptation of breast cancer to the brain metastatic microenvironment are unclear. Here, the authors use RNA-sequencing and Drosophila screening to identify Rab11b-mediated endosomal recycling as a unique mechanism for adaptation to a challenging metastatic microenvironment, which can be exploited by repurposing statins.
BRCA1 mutation carriers have higher chances of developing triple-negative breast cancer (TNBC). Here, the authors use the Sleeping Beauty mutagenesis system in Brca1 deficient mice and identify 169 putative driver genes, of which NOTCH1 accelerates TNBC formation through promoting epithelial-mesenchymal transition and cell cycle progression.
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Protein synthesis suppression protects breast cancer cells from clinically relevant stresses like hypoxia. Here, the authors show that unique mRNA isoforms that govern stem cell-like phenotypes escape translational repression to drive tumor progression and chemoresistance.
Tumor invasion in draining lymph nodes is associated with Treg accumulation in breast cancer patients
Tumor-draining lymph nodes are often the first site of metastasis in breast cancer patients. Here, the authors show that metastatic lymph nodes are characterized by the accumulation of suppressive regulatory T cells with a distinct phenotype compared to matched non-invaded lymph nodes and tumors.
Physical activity has been linked to lower risks of colorectal and breast cancer. Here, the authors present a Mendelian randomisation analysis supporting a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer.
Macropinocytosis allows cancer cells to cope with nutrient stress. Here, the authors use a selective, genetic approach to inhibit macropinocytosis and show that consuming necrotic cell debris via macropinocytosis—necrocytosis—affords resistance to many therapies that target biosynthesis.
The role of neutrophils in the regulation of tumour growth and metastasis remains controversial. Here, the authors demonstrate that neutrophils, by exerting inhibitory effects on cytotoxic NK cells, show a net pro-metastatic effect in immune-competent mice, while they are tumoricidal and anti-metastatic in NK cell-deficient hosts.
The RNA-binding protein AKAP8 suppresses tumor metastasis by antagonizing EMT-associated alternative splicing
Splice isoform switching regulated by the heterogeneous nuclear ribonucleoprotein M (hnRNPM) induces EMT and metastasis. Here, the authors report that AKAP8 is a metastasis suppressor that inhibits the splicing activity of hnRNPM and antagonizes genome-wide EMT-associated alternative splicing to maintain epithelial cell state.
ER-positive breast cancer patients do not usually respond to immunotherapy. In this phase II clinical trial, the authors report the safety and efficacy of combining vorinostat and pembrolizumab with tamoxifen in ER-positive breast cancers and provide evidence that T-cell exhaustion may serve as a potential signature for the response of this combination therapy.
Comprehensive molecular comparison of BRCA1 hypermethylated and BRCA1 mutated triple negative breast cancers
BRCA-deficient breast cancer is characterised by homologous recombination deficiency. Here, the authors show that hypermethylated BRCA1 phenotypically copies mutated BRCA1 in triple negative breast cancers.
STING-dependent paracriny shapes apoptotic priming of breast tumors in response to anti-mitotic treatment
Antimitotic compounds, such as paclitaxel, induce cell death in cycling cancer cells only. Here, the authors show that paclitaxel-targeted breast cancer cells prime neighboring cells to apoptosis through a STING-mediated paracrine signaling pathway.
A clinical trial published in Nature Communications examined the effect of fasting-mimicking diet (FMD) during chemotherapy in breast cancer patients. The overall negative study results highlight the need for ameliorating future trial design and investigating alternative FMD-based therapeutic combinations.
In breast cancer, the claudin-low breast cancer subtype is remarkably diverse. Here, the authors propose that claudin-low is not a classical intrinsic breast cancer subtype, but rather a complex additional phenotype that can occur across intrinsic subtypes.
ITGB3-mediated uptake of small extracellular vesicles facilitates intercellular communication in breast cancer cells
The integrin ITGB3 has been described to play an essential role in breast cancer metastasis, but the precise mechanisms remain undefined. Here the authors describe thus far unknown roles of ITGB3 in the uptake of extracellular vesicles, required for colony growth of breast cancer cells.
NPM1 upregulates the transcription of PD-L1 and suppresses T cell activity in triple-negative breast cancer
PD-L1 is highly expressed in triple-negative breast cancers (TNBC). Here, the authors show that nucleophosmin 1 (NPM1) transcriptionally activates PD-L1 expression and inhibits T cell activity in TNBC.
Breast cancer is frequently diagnosed using ultrasound. Here, the authors show that, in addition to ultrasound, shear wave elastography can be used to diagnose breast cancer and, in conjunction with deep learning and radiomics, can predict whether the disease has spread to axillary lymph nodes.
Elevated expression of ULK1 is known to be inversely correlated with breast cancer metastasis. Here, the authors report Exo70 as a substrate of ULK1 that suppresses cancer metastasis, and show that ERK1/2 mediated phosphorylation of Exo70 leads to opposing effects on tumour cell invasion.
The development of chemoresistance is a major hurdle in triple negative breast cancer (TNBC). Here, the authors show that lysyl oxidase (LOX) is overexpressed in chemoresistant TNBCs, and when inhibited reduces collagen cross-linking, fibronectin fibril assembly, and downstream integrin signalling, overcoming resistance.
Mapping the breast cancer metastatic cascade onto ctDNA using genetic and epigenetic clonal tracking
Tracking tumour evolution in a patient via circulating tumour DNA (ctDNA) is complicated due to the unknown mix of fragmented alleles from different cancer lesions. Here, the authors make use of a rapid autopsy program to demonstrate how representative ctDNA profiling is of metastasis, as well as presenting methylation profiling method to track evolutionary change.
Cancer-associated fibroblast heterogeneity in axillary lymph nodes drives metastases in breast cancer through complementary mechanisms
Cancer associated fibroblasts are known to promote the progression of cancer. Here, the authors show that two particular subsets of cancer associated fibroblasts induce metastasis but work via distinct mechanisms including, chemokine signalling and Notch signalling.
Evaluating cell lines as models for metastatic breast cancer through integrative analysis of genomic data
While cell lines and organoids are extensively used to study cancer, how closely they resemble the disease in patients remains unclear. Here, Liu et al. shed light on this issue by comparing the genomic and transcriptomic profiles of different breast cancer cell lines and organoids to data from patient-derived breast cancer metastases.
Interval cancer patients are more likely to carry rare gene mutations than screen-detected breast cancer patients. Here, the authors report that interval cancer patients are more likely cancer survivors and are at a greater risk of developing other non-breast tumors.
Bone metastasis in breast cancer patients causes major skeletal-related complications. Here, the authors show that FOXF2/BMP/SMAD pathway plays a major role in bone metastasis and suggest targeting this axis to manage bone metastasis.
Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer
Over 170 susceptibility loci have been identified by genome-wide association studies in breast cancer. Here, the authors interrogated the role of risk-associated variants from non-breast tissue, and using expression quantitative trait loci, identify potential target genes of known breast cancer susceptibility variants, as well as 11 regions not previously known to be associated with breast cancer risk.
TRIB3 supports breast cancer stemness by suppressing FOXO1 degradation and enhancing SOX2 transcription
Cancer stem cells contribute to breast cancer metastasis and recurrence. Here the authors show that TRIB3 enhances breast cancer stemness through interaction with AKT to promote FOXO1 stability, which then increases SOX2 activity.
Microenvironmental IL1β promotes breast cancer metastatic colonisation in the bone via activation of Wnt signalling
In breast cancer, dormant cancer cells may develop into bone metastases. Here, the authors demonstrate that microenvironmental IL1β stimulates metastatic breast cancer cell colonisation in the bone via IL1β-NFKB/CREB-Wnt pathway activation and cancer stem cell colony formation
Oncogene induced senescence protects cells from unrestricted growth and cancer. Here, the authors show that PAK4 overrides this senescence in breast cancer cells through phosphorylation of RELB, thereby inhibiting transcription of the senescence regulator C/EBPβ.
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Breast cancer cells often invade the bone tissue and remain dormant until they are induced to colonize the metastatic site. Here the authors develop an ex vivo co-culture system consisting of bone and cancer cells from mice and show that CXCL5 has a role in metastatic colonization in the bone.
RNF208, an estrogen-inducible E3 ligase, targets soluble Vimentin to suppress metastasis in triple-negative breast cancers
Triple-negative breast cancer (TNBC) is an aggressive subtype lacking effective targeted therapies. Here, the authors show that RNF208, an estrogen-induced ubiquitin ligase, promotes the degradation of Vimentin, thereby suppressing lung metastasis of TNBC, and may serve as a biomarker for the disease.
Tetraspanin 8 (TSPAN8) has been implicated in a number of different tumours, but the underlying mechanisms remain unclear. Here, in breast cancer the authors highlight a role for TSPAN8 in promoting tumorigenesis through the activation of Hedgehog signalling.
Partially methylated domains are hypervariable in breast cancer and fuel widespread CpG island hypermethylation
In cancer, global DNA methylation loss and CpG island hypermethylation are commonly observed. Here, in breast cancer the authors find that hyper-variability of partially methylated domains is the prime source of DNA methylation variation and that these domains fuel CpG island hypermethylation.
Epigenomic data on chromatin accessibility and transcription factor occupancy can reveal enhancer landscapes in cancer. Here, the authors develop a computational strategy called PSIONIC (patient-specific inference of networks informed by chromatin) to model the impact of enhancers on transcriptional programs in gynecologic and basal breast cancers.
In epithelial cells Zeb1 is involved in the epithelial to mesenchymal transition. In this study, the authors show in a mouse model of breast cancer, that Zeb1 expression in stromal cells is required for tumour formation and metastasis.
An independent poor-prognosis subtype of breast cancer defined by a distinct tumor immune microenvironment
In breast cancer, the immune infiltration of the tumour associates with clinical outcome. Here, the authors infer immune context based on gene expression data and identify a new independent subtype linked to pro-tumorigenic immune infiltration.
Mitochondrial supercomplex assembly promotes breast and endometrial tumorigenesis by metabolic alterations and enhanced hypoxia tolerance
Cancer cells rely on mitochondrial respiration to satisfy their metabolic demands. Here the authors show that the mitochondrial supercomplex assembly factor COX7RP is abundantly expressed in breast and endometrial cancer cells and promotes tumor growth and hypoxia tolerance partially by altering levels of the tricarboxylic acid cycle intermediates.
An ErbB2/c-Src axis links bioenergetics with PRC2 translation to drive epigenetic reprogramming and mammary tumorigenesis
Polycomb Repressor Complex 2 (PRC2) is frequently up-regulated in cancers. Here, the authors show that the tyrosine kinase c-Src stimulates mitochondrial function to signal energy sufficiency to mTORC1, increasing translation of the PRC2 subunits EZH2 and SUZ12 to support ErbB2-dependent tumours.
The HER2 monoclonal antibody, Trastuzumab, is the current standard treatment for HER2+ cancers but resistance to therapy occurs. Here, the authors show that activation of the PKR/eIF2α-P pathway exhibits anti-tumor effects in HER2+ cancer and is required for the response to Trastuzumab.
Effective precision medicine strategies rely on the ability to predict tumour behaviour based on molecular characteristics. Here, the authors build models to predict multiple distinct gene expression patterns using DNA copy number alterations
NLRP3 inflammasome in fibroblasts links tissue damage with inflammation in breast cancer progression and metastasis
Cancer associated fibroblasts (CAFs) are known to promote pro-tumorigenic inflammation. Here, the authors show that CAFs sense tissue damage and activate NLRP3 inflammasome and pro-inflammatory IL-1β secretion, and CAF-derived inflammasome signalling promotes breast tumour growth and metastasis.
Dickkopf-3 links HSF1 and YAP/TAZ signalling to control aggressive behaviours in cancer-associated fibroblasts
It is unclear how specific signalling pathways are coordinated to generate pathologically activated cancer associated fibroblasts (CAFs). Here, Ferrari et al show that stromal expression of Dickkopf-3 (DKK3) associates with aggressive tumours. DKK3 is a HSF-1 effector that activates β-catenin and YAP/TAZ, and DKK3-driven YAP/TAZ activation regulates the pro-tumorigenic behaviour of CAFs.
Tissue-specific microRNA expression alters cancer susceptibility conferred by a TP53 noncoding variant
TP53 mutations can cause increased risk for cancers. Here, the authors show a noncoding polymorphism in TP53 increases risk of some cancers but delays onset of others, and in a mouse model show this is via alteration of microRNA targeting sites that differ in impact depending on the tissue.
The transcriptomic profile of tumour-adjacent cells provides important information about tumour context but its clinical utility is unclear. Here, in breast cancer, Fox et al. show that the mRNA abundances of tumour and tumour-adjacent cells hold prognostic information.
Autophagy inhibition elicits emergence from metastatic dormancy by inducing and stabilizing Pfkfb3 expression
Cancer cells can use autophagy as a mechanism of surviving from external stresses. Here, the authors show that Pfkfb3, a glycolytic gene, is expressed in metastatic breast cancer cells but not in dormant cells that demonstrate features of autophagy.
Triple-negative breast cancer is an aggressive form of the disease. Here, the authors identify EGFL9 as a mediator of metastasis in TNBC through interactions with cMET.
Improved therapeutics are needed for treating breast cancer. Here they show the druggability of myoferlin with a small molecule inhibitor in breast cancer and demonstrate its anti-breast cancer effects in vitro and in vivo.
It is known that full-term pregnancies can reduce a woman’s breast cancer risk. Here, the authors interrogate data from 2.3 million Danish women, showing that this protective effect arises at precisely the 34th week of the pregnancy, and replicated this finding in 1.6 million women from Norway.
The link between circulating lipids and breast cancer risk is complex. Here, the authors utilise data from more than 400,000 participants in two-sample Mendelian randomization to assess the link between blood lipids and breast cancer risk, and they find risk-promoting effects of raised LDL-cholesterol and CETP-mediated raised HDL-cholesterol.
p38-mediated phosphorylation at T367 induces EZH2 cytoplasmic localization to promote breast cancer metastasis
Polycomb group protein EZH2 is overexpressed in ER- breast cancer, promoting metastasis. Here, the authors show that independent of the polycomb group, phosphorylation of EZH2 at T367 by p38 promotes cytoplasmic localization of EZH2, binding to vinculin and other regulators of cell migration and invasion.
DNA methylation is associated with breast cancer risk. Here the authors measure DNA methylation in the blood of individuals from 25 Australian families with multiple cases of breast cancer but not known mutations associated with breast cancer risk to identify possible heritable methylation markers.
The 17q23 amplicon containing the WIP1 oncogene is frequently amplified in HER2+ breast cancer. Here they find MIR21 to be present in WIP1-containing amplicons, and report nanoparticle based co-delivery of WIP1 and miR-21 inhibitors to be effective in trastuzumab-resistant HER2+ breast cancer.
Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls
Association between variants in 11 different genes and breast cancer risk has been established and sequencing of these genes is recommended to provide personalized diagnosis, therapy, and surveillance for the high-risk patients and their relatives. Here the authors analyse the frequency of germline pathogenic mutations in these genes specifically in a Japanese population.
Risk loci for breast cancer have been identified by genome-wide association studies. Here, the authors use Capture Hi-C to identify 110 putative target genes at 33 loci and assessed associations of gene expression, SNP genotype, and survival, providing evidence of mechanisms that may influence the prognosis and risk of breast cancer.
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LEM4 confers tamoxifen resistance to breast cancer cells by activating cyclin D-CDK4/6-Rb and ERα pathway
Tamoxifen resistance is a major problem in the treatment of ERa positive breast cancer. Here, the authors show that LEM4 confers tamoxifen resistance by activating the cyclin D-CDK4/6-Rb axis and ERa signaling in endocrine-resistant breast cancer.
Histone modifications in cancer can contribute to pathogenesis. Here, the authors demonstrate that targeting epigenetic modifier Ezh2 hinders metastatic behaviour in Luminal B breast cancer models, and highlight a mechanism where Ezh2 contributes to metastatic behaviour by repression of FOXC1.
Hyperactivation of HIF-1α is crucial in progression of triple-negative breast cancer, but how HIF-1α stability is maintained in a hypoxia-independent manner is unclear. Here, the authors show collagen prolyl-4-hydroylase 1 stabilises HIF-1α and is involved in chemoresistance in TNBC.
The current standard for breast cancer diagnostic is a mammogram; however, the sensitivity of mammography can be low in radiographically dense breasts. Here the authors develop a single-breath-hold photoacoustic computed tomography (SBH-PACT) system to reveal detailed angiographic structures in human breasts allowing the detection of higher blood vessel densities associated with tumors.
Tamoxifen-resistant breast cancer cells are resistant to DNA-damaging chemotherapy because of upregulated BARD1 and BRCA1
Most breast cancer patients are estrogen receptor positive and thus benefit from treatments that inhibit estrogen production; however, one third of tamoxifen-treated patients develops resistance and relapse. Here the authors show that tamoxifen resistant cells are resistant to chemotherapy because of BARD1 and BRCA1 upregulation.
Recurrent hotspot mutations in HRAS Q61 and PI3K-AKT pathway genes as drivers of breast adenomyoepitheliomas
Adenomyoepithelioma is a rare tumor of the breast with an unknown genetic basis. Here the authors perform a genomic analysis of adenomyoepitheliomas revealing that their repertoire of somatic mutations vary according to the estrogen receptor (ER) status, and that ER-negative tumors harbor recurrent mutations in HRAS and PI3K pathway genes.
Fusions of the gene RET have been described in thyroid and lung cancers. Here, the AUs identify RET gene alterations, including known fusions, novel fusions, and rearrangements in breast cancer (BC) that are involved in the tumorigenic process and show the benefit of RET therapy in a recurrent BC patient carrying the NCOA4-RET fusion.