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Objective: The objective of this work is to identify unmet information needs of long-term-survivors of breast cancer (BC) and future research needs from the perspectives of patients and health care professionals., Methods: Two online Delphi surveys were conducted. Participants in Survey 1 were patients. Participants in Survey 2 were health care professionals from both primary and secondary care involved in BC care. Both surveys included three successive rounds. The first round aimed to identify research and information needs; the second round aimed to rank the relative importance of those needs; the third round aimed to find consensus., Results: The most important information needs were self-management recommendations of common health problems after treatment and complications of breast reconstruction after 5 years. The most important research priorities were related to interventions and tools to increase information provision by professionals about certain tests, diet, and coordinated action between primary and specialised care during follow-up, and indications and safety issues of pregnancy in survivors., Conclusions: Two fundamental ideas were identified: (1) Patients request information about self-management common health problems after treatment and breast reconstruction complications. (2) Health care professionals emphasise the need for a standardised approach based on protocols, recommendations, and coordinated actions in the provision of information., Implications for Cancer Survivors: Given the increasing number of BC survivors, it is essential to identify information and research needs to improve their care and health outcomes., (© 2022 John Wiley & Sons Ltd.)

Breast cancer risk for carriers of BRCA1 pathological variants is modified by genetic factors. Genetic variation in HMMR may contribute to this effect. However, the impact of risk modifiers on cancer biology remains undetermined and the biological basis of increased risk is poorly understood. Here, we depict an interplay of molecular, cellular, and tissue microenvironment alterations that increase BRCA1-associated breast cancer risk. Analysis of genome-wide association results suggests that diverse biological processes, including links to BRCA1-HMMR profiles, influence risk. HMMR overexpression in mouse mammary epithelium increases Brca1-mutant tumorigenesis by modulating the cancer cell phenotype and tumor microenvironment. Elevated HMMR activates AURKA and reduces ARPC2 localization in the mitotic cell cortex, which is correlated with micronucleation and activation of cGAS-STING and non-canonical NF-κB signaling. The initial tumorigenic events are genomic instability, epithelial-to-mesenchymal transition, and tissue infiltration of tumor-associated macrophages. The findings reveal a biological foundation for increased risk of BRCA1-associated breast cancer., (© 2022. The Author(s).)

Advancements in genetic sequencing techniques along with the identification of specific mutations and structural changes in multiple cancer genes, make it possible to identify circulating tumor cells and cell free nucleic acids as blood-based biomarkers, serving as a liquid biopsy (LB) with great utility for the diagnosis, treatment and follow-up of patients with neoplasms. This systematic review focuses on the clinical utility of LB in patients with breast cancer (BC). Articles published between 1990 and 2021 were included. Databases searched: Trip Database, WoS, EMBASE, PubMed, SCOPUS, and Clinical Keys. Variables studied: Publication year, country, number of cases, primary study design, LB detection methods, genes found, overall survival, disease-free survival, stage, response to treatment, clinical utility, BC molecular type, systemic treatment and methodological quality of primary studies. Of 2619 articles, 74 were retained representing 12 658 patients, mainly cohort studies (66.2%), the majority were from China (15%) and Japan (12.2%). All primary studies described clinical stage and type of systemic treatment used. Most used biomarker detection method: DNA (52.7%) and type of analysis: quantification of total cfDNA (35.1%). PIK3CA mutation was most frequent (62.9%). Evidence suggests clinically useful applications of BC. Though heterogeneous, publications suggest that LB will constitute part of the standard diagnostic-therapeutic process of BC., (© 2021 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Germline pathogenic variants in BRCA1 confer a high risk of developing breast and ovarian cancer. The BRCA1 exon 11 (formally exon 10) is one of the largest exons and codes for the nuclear localization signals of the corresponding gene product. This exon can be partially or entirely skipped during pre-mRNA splicing, leading to three major in-frame isoforms that are detectable in most cell types and tissue, and in normal and cancer settings. However, it is unclear whether the splicing imbalance of this exon is associated with cancer risk. Here we identify a common genetic variant in intron 10, rs5820483 (NC_000017.11:g.43095106_43095108dup), which is associated with exon 11 isoform expression and alternative splicing, and with the risk of breast cancer, but not ovarian cancer, in BRCA1 pathogenic variant carriers. The identification of this genetic effect was confirmed by analogous observations in mouse cells and tissue in which a loxP sequence was inserted in the syntenic intronic region. The prediction that the rs5820483 minor allele variant would create a binding site for the splicing silencer hnRNP A1 was confirmed by pull-down assays. Our data suggest that perturbation of BRCA1 exon 11 splicing modifies the breast cancer risk conferred by pathogenic variants of this gene., (© 2021 Wiley Periodicals LLC.)

BRCA1 is a tumor suppressor that regulates DNA repair by homologous recombination. Germline mutations in BRCA1 are associated with increased risk of breast and ovarian cancer and BRCA1 deficient tumors are exquisitely sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors. Therefore, uncovering additional components of this DNA repair pathway is of extreme importance for further understanding cancer development and therapeutic vulnerabilities. Here, we identify EDC4, a known component of processing-bodies and regulator of mRNA decapping, as a member of the BRCA1-BRIP1-TOPBP1 complex. EDC4 plays a key role in homologous recombination by stimulating end resection at double-strand breaks. EDC4 deficiency leads to genome instability and hypersensitivity to DNA interstrand cross-linking drugs and PARP inhibitors. Lack-of-function mutations in EDC4 were detected in BRCA1/2-mutation-negative breast cancer cases, suggesting a role in breast cancer susceptibility. Collectively, this study recognizes EDC4 with a dual role in decapping and DNA repair whose inactivation phenocopies BRCA1 deficiency.

Inhibitors of the mechanistic target of rapamycin (mTOR) are currently used to treat advanced metastatic breast cancer. However, whether an aggressive phenotype is sustained through adaptation or resistance to mTOR inhibition remains unknown. Here, complementary studies in human tumors, cancer models and cell lines reveal transcriptional reprogramming that supports metastasis in response to mTOR inhibition. This cancer feature is driven by EVI1 and SOX9. EVI1 functionally cooperates with and positively regulates SOX9, and promotes the transcriptional upregulation of key mTOR pathway components (REHB and RAPTOR) and of lung metastasis mediators (FSCN1 and SPARC). The expression of EVI1 and SOX9 is associated with stem cell-like and metastasis signatures, and their depletion impairs the metastatic potential of breast cancer cells. These results establish the mechanistic link between resistance to mTOR inhibition and cancer metastatic potential, thus enhancing our understanding of mTOR targeting failure.

Molecular evidence has linked the pathophysiology of lymphangioleiomyomatosis (LAM) to that of metastatic breast cancer. Following on this observation, we assessed the association between LAM and subsequent breast cancer. An epidemiological study was carried out using three LAM country cohorts, from Japan, Spain, and the United Kingdom. The number of incident breast cancer cases observed in these cohorts was compared with the number expected on the basis of the country-specific incidence rates for the period 2000-2014. Immunohistochemical studies and exome sequence analysis were performed in two and one tumors, respectively. All cohorts revealed breast cancer standardized incidence ratios (SIRs) ≥ 2.25. The combined analysis of all cases or restricted to pre-menopausal age groups revealed significantly higher incidence of breast cancer: SIR = 2.81, 95 % confidence interval (CI) = 1.32-5.57, P = 0.009; and SIR = 4.88, 95 % CI = 2.29-9.99, P = 0.0007, respectively. Immunohistochemical analyses showed positivity for known markers of lung metastatic potential. This study suggests the existence of increased breast cancer risk among LAM patients. Prospective studies may be warranted to corroborate this result, which may be particularly relevant for pre-menopausal women with LAM.

Lymphangioleiomyomatosis (LAM) is a rare lung-metastasizing neoplasm caused by the proliferation of smooth muscle-like cells that commonly carry loss-of-function mutations in either the tuberous sclerosis complex 1 or 2 (TSC1 or TSC2) genes. While allosteric inhibition of the mechanistic target of rapamycin (mTOR) has shown substantial clinical benefit, complementary therapies are required to improve response and/or to treat specific patients. However, there is a lack of LAM biomarkers that could potentially be used to monitor the disease and to develop other targeted therapies. We hypothesized that the mediators of cancer metastasis to lung, particularly in breast cancer, also play a relevant role in LAM. Analyses across independent breast cancer datasets revealed associations between low TSC1/2 expression, altered mTOR complex 1 (mTORC1) pathway signaling, and metastasis to lung. Subsequently, immunohistochemical analyses of 23 LAM lesions revealed positivity in all cases for the lung metastasis mediators fascin 1 (FSCN1) and inhibitor of DNA binding 1 (ID1). Moreover, assessment of breast cancer stem or luminal progenitor cell biomarkers showed positivity in most LAM tissue for the aldehyde dehydrogenase 1 (ALDH1), integrin-ß3 (ITGB3/CD61), and/or the sex-determining region Y-box 9 (SOX9) proteins. The immunohistochemical analyses also provided evidence of heterogeneity between and within LAM cases. The analysis of Tsc2-deficient cells revealed relative over-expression of FSCN1 and ID1; however, Tsc2-deficient cells did not show higher sensitivity to ID1-based cancer inhibitors. Collectively, the results of this study reveal novel LAM biomarkers linked to breast cancer metastasis to lung and to cell stemness, which in turn might guide the assessment of additional or complementary therapeutic opportunities for LAM.

Breast cancer is a prevalent disease affecting all areas of patients' lives. Therefore, family physicians ought to know thoroughly this pathology to optimize the health care services for these patients making the best use of available resources. A series of five articles on breast cancer is presented below. It is based on a review of the scientific literature over the last ten years. In this final section, the social, psychological, occupational and family issues related to the disease will be reviewed, as well as presenting some special situations of breast cancer, including breast cancer in men, during pregnancy and last stages of life. This summary report aims to provide a current and practical review about this disease, providing answers to family doctors and helping them to be by the patients for their benefit throughout their illness., (Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.)

Breast cancer is a prevalent disease affecting all areas of patients' lives. Therefore, family physicians must thoroughly understand this pathology in order to optimize the health care services and make the best use of available resources, for these patients. A series of 5 articles on breast cancer is presented below. It is based on a review of the scientific literature over the last 10 years. This fourth article deals with the treatment of the disease, the role of the primary care physician, and management of major complications. This summary report aims to provide a current and practical review about this problem, providing answers to family doctors and helping them to support their patients and care for them throughout their illness., (Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.)

Breast cancer is a prevalent disease with implications in all aspects of patientś life, therefore, family doctors must know this pathology in depth, in order to optimize the health care provided to these patients with the best available resources. This series of five articles on breast cancer is based on a review of the scientific literature of the last ten years. This third article will review the clinical context and the staging and prognostic factors of the disease. This summary report aims to provide a global, current and practical review about this problem, providing answers to family doctors and helping them to be by the patients for their benefit throughout their illness., (Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.)

Breast cancer is a prevalent disease affecting all areas of patients' lives. Therefore, family doctors need to thoroughly understand this disease in order to optimize the health care services for these patients, making the best use of available resources. A series of 5 articles on breast cancer is presented below. It is based on a review of the scientific literature over the last 10 years. The second one deals with population screening and its controversies, screening in high-risk women, and the current recommendations. This summary report aims to provide a current and practical review about this problem, providing answers to family doctors, and helping them to be able to care for their patients for their benefit throughout their illness., (Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.)

Breast cancer is a prevalent disease affecting all areas of the patients' lives. Therefore, family physicians should have a thorough knowledge of this disease in order to optimize the health care services for these patients, and making the best use of available resources. A series of 5 articles on breast cancer is presented below. It is based on a review of the scientific literature over the last 10 years. The first article reviews the epidemiology, risk factors, and protective factors in this disease This summary report aims to provide a current and practical review on breast cancer, providing answers to family doctors and helping them to support the patients for their benefit throughout their illness., (Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.)

Introduction: Endocrine therapies targeting cell proliferation and survival mediated by estrogen receptor α (ERα) are among the most effective systemic treatments for ERα-positive breast cancer. However, most tumors initially responsive to these therapies acquire resistance through mechanisms that involve ERα transcriptional regulatory plasticity. Herein we identify VAV3 as a critical component in this process., Methods: A cell-based chemical compound screen was carried out to identify therapeutic strategies against resistance to endocrine therapy. Binding to ERα was evaluated by molecular docking analyses, an agonist fluoligand assay and short hairpin (sh)RNA-mediated protein depletion. Microarray analyses were performed to identify altered gene expression. Western blot analysis of signaling and proliferation markers, and shRNA-mediated protein depletion in viability and clonogenic assays, were performed to delineate the role of VAV3. Genetic variation in VAV3 was assessed for association with the response to tamoxifen. Immunohistochemical analyses of VAV3 were carried out to determine its association with therapeutic response and different tumor markers. An analysis of gene expression association with drug sensitivity was carried out to identify a potential therapeutic approach based on differential VAV3 expression., Results: The compound YC-1 was found to comparatively reduce the viability of cell models of acquired resistance. This effect was probably not due to activation of its canonical target (soluble guanylyl cyclase), but instead was likely a result of binding to ERα. VAV3 was selectively reduced upon exposure to YC-1 or ERα depletion, and, accordingly, VAV3 depletion comparatively reduced the viability of cell models of acquired resistance. In the clinical scenario, germline variation in VAV3 was associated with the response to tamoxifen in Japanese breast cancer patients (rs10494071 combined P value = 8.4 × 10-4). The allele association combined with gene expression analyses indicated that low VAV3 expression predicts better clinical outcome. Conversely, high nuclear VAV3 expression in tumor cells was associated with poorer endocrine therapy response. Based on VAV3 expression levels and the response to erlotinib in cancer cell lines, targeting EGFR signaling may be a promising therapeutic strategy., Conclusions: This study proposes VAV3 as a biomarker and a rationale for its use as a signaling target to prevent and/or overcome resistance to endocrine therapy in breast cancer.

Purpose: Breast cancer is the most common malignant tumor among women worldwide. Breast cancer is one of the few cancers that can be early detected, and the survival rate of the women whose breast cancers are detected on their initial stage is virtually 100%. At the present time, ultrasound (US) is the most important imaging test together with the mammogram for the diagnostic evaluation of the breast. Recent studies have shown that ultrasound, in addition to mammography, helps doctors to spot significantly more cancers compared with mammograms alone. This work intends to standardize the process of the US breast examination, the storage and marking of the US images and their subsequent visualization and comparison., Methods: It presents an innovative technique for the intraglandular mapping of breast cancer in a 3D scene. An anatomical based model of the breast is used for storage of the US images. Hardware equipment needed for the breast examination is described. Soft application programmed on Apple tools is fully described. The database for the storage is presented., Results: First clinical applications of the presented tool are reported. Currently, the system is being distributed free of charge to clinical personal in order to evaluate its benefits., Conclusions: A first version of an application to standardize the process of the US breast examination is presented. First reports show the feasibility of the system to be applied on clinics., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Breast cancer is one of the most frequent causes of death in Mexican women over 35 years of age. At molecular level, changes in many genetic networks have been reported as associated with this neoplasia. To analyze these changes, we determined gene expression profiles of tumors from Mexican women with breast cancer at different stages and compared these with those of normal breast tissue samples., Methods: 32P-radiolabeled cDNA was synthesized by reverse transcription of mRNA from fresh sporadic breast tumor biopsies, as well as normal breast tissue. cDNA probes were hybridized to microarrays and expression levels registered using a phosphorimager. Expression levels of some genes were validated by real time RT-PCR and immunohistochemical assays., Results: We identified two subgroups of tumors according to their expression profiles, probably related with cancer progression. Ten genes, unexpressed in normal tissue, were turned on in some tumors. We found consistent high expression of Bik gene in 14/15 tumors with predominant cytoplasmic distribution., Conclusion: Recently, the product of the Bik gene has been associated with tumoral reversion in different neoplasic cell lines, and was proposed as therapy to induce apoptosis in cancers, including breast tumors. Even though a relationship among genes, for example those from a particular pathway, can be observed through microarrays, this relationship might not be sufficient to assign a definitive role to Bik in development and progression of the neoplasia. The findings herein reported deserve further investigation.

A simulation technique is employed to explore the possibility of locating millimeter-sized objects, immersed in turbid media, from time-gated measurements of the transmitted or reflected light. The simulation results for tissuelike phantoms are compared to experimental transillumination data and excellent agreement is found. Simulations of time-gated reflection experiments show that it is possible to detect objects of 1 mm diameter. This may open new possibilities for medical diagnosis of breast cancer in an early stage.