Genomic Profiling

BackgroundAccurate prognosis and identification of cancer subtypes at molecular level are important steps towards effective and personalised treatments of breast cancer. To this end, many computational methods have been developed to use gene (mRNA) expression data for breast cancer subtyping and prognosis. Meanwhile, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have been extensively studied in the last 2 decades and their associations with breast cancer subtypes and prognosis have been evidenced. However, it is not clear whether using miRNA and/or lncRNA expression data helps improve the performance of gene expression based subtyping and prognosis methods, and this raises challenges as to how and when to use these data and methods in practice.ResultsIn this paper, we conduct a comparative study of 35 methods, including 12 breast cancer subtyping methods and 23 breast cancer prognosis methods, on a collection of 19 independent breast cancer datasets. We aim to uncover the roles of miRNAs and lncRNAs in breast cancer subtyping and prognosis from the systematic comparison. In addition, we created an R package, CancerSubtypesPrognosis, including all the 35 methods to facilitate the reproducibility of the methods and streamline the evaluation.ConclusionsThe experimental results show that integrating miRNA expression data helps improve the performance of the mRNA-based cancer subtyping methods. However, miRNA signatures are not as good as mRNA signatures for breast cancer prognosis. In general, lncRNA expression data does not help improve the mRNA-based methods in both cancer subtyping and cancer prognosis. These results suggest that the prognostic roles of miRNA/lncRNA signatures in the improvement of breast cancer prognosis needs to be further verified.

In many Australian suburbs, rows of weather sealed brick and tiled boxes ‘stand to attention’ and could be seen to evoke a somewhat cold uniformity of taste. Contrary to the contemporary belief that our suburban architecture should respond to individual needs and desires by housing people in environments that enrich their lives, the majority of mass housing could be dubbed an “architecture of ignorance.”1 One badly designed project home after another, exhibits countless mistakes such as picture windows facing due west, bathrooms orientated toward the prime views and service facilities blocking the best sun. In recent years however, something notably new is beginning to occur. It is as if there is a new design consciousness circulating the mass market.2 Traces of the ‘contemporary Queensland style’, widely practiced by regional architects, could be seen to be slowly filtering down the line and appearing in the project home market. Several project companies now employ architects to lead their design teams and facades are springing up in the suburbs that leave one wondering, ‘is this architect designed or just another project home?’ This dissertation aims to examine; 1. The extent to which the principles of contemporary Queensland architectural design are being embraced by the project home market. 2. The extent to which buyers are exhibiting a new design consciousness and appreciation for well designed homes that are fitting for the Queensland lifestyle. The idea that there are various forms of capital; cultural, social and economic is used to examine the extent to which buyers are embracing the ‘contemporary Queensland style’ that may be encroaching upon the project market and also the extent to which the various capitals may influence home choice. The literature review then goes on to examine the principles of the contemporary Queensland style exhibited in the residential designs of Queensland’s widely recognised architects. Chapter 3 of this dissertation undertakes and reports on a case study of the Edenbrooke housing development in Brisbane’s Western suburbs to identify the extent to which the developers and project builders have embraced principles of good architectural design, suited to the Queensland lifestyle. The case study also examines the choices buyers have made with respect to their homes, with reference to the theory of taste and the acceptance of a contemporary Queensland style of domestic architecture. It is concluded that a portion of the project home market, through observation of some of the principles of Queensland architectural design, appear to be attempting to discover a style of home that reflects the overall preference for a relaxed, enjoyable family lifestyle and that the tag of ‘good design’ is becoming increasingly important to buyers, in the wake of a period of new Australian design awareness. However, it is suggested that no matter how ‘architecturally enlightened’ a project home might become, it may never be comparable to the quality offered by ‘one off’ architectural designs because the very factors that make a project home cheaper and more economical, are the very factors that are opposed to regional architectural principles. While mass production results in more economic but standardised outcomes, architectural design often involves individual detailing for unusual components of the building and the cost of contractors providing individual service can be high. It could thus be seen that the ‘means of production’ also sets the project home apart from the architectural dwelling. In this light, no matter how much cultural capital a buyer may possess, the expression of it may well be limited by access to economic capital. ____________________ 1 Peter Hyatt, Local Heroes: Architects of Australia’s Sunshine Coast (Sydney: Craftsman House, 2001): 16. 2 Davina Jackson and Chris Johnson, Australian Architecture Now (London: Thames and Hudson, 2000): 10.

Despite the great and continuing interest in methods of effective teaching of computer science concepts, especially programming, there is little hard data to back up the opinions that are so vigorously expressed. Moreover, most of those studies that have attempted to investigate programming instruction have been sufficiently flawed so as to render them of little use. The first section of this paper deals with many of the flaws commonly found in studies of instruction in programming. These include non-random assignment of subjects, assuming identical instruction to different groups, experimenter bias, use of "available resources", short experimental treatments, home grown tests, and questionable analysis techniques. The second section contains a description of the principles of good experimental design, using the concepts of internal and external validity. An experiment usually requires a compromise between the internal validity, which relates to control of experimental conditions, and the external validity, which has to do with the generalizability of the results. The final section contains conclusions concerning initial steps that might be taken to rectify the problem caused by a lack of valid data. These steps include better and more objective quantification of the attributes of good programs and more integrative techniques for analyzing the results of multiple studies.

Summary: Evidence-based medicine is a strong movement in this century, and randomized clinical trials continue to be the best level of evidence for establishing cause-effect relationships between treatment interventions and outcomes. The field of physical medicine and rehabilitation has many excellent research questions on the effects of treatment but seems to rely mostly on weak observational methods (eg, chart review, case series, and single-group designs) for answers. This paper highlights 3 basic and relatively simple principles of good experimental design: control, randomization, and replication that were developed by R. A. Fisher for large, complex, agricultural field trials. The principles diffused readily into many scientific arenas, and Fisher even applied the principles in his backyard studies into Mendelian genetics. The thoughts of R. A. Fisher, arguably the most influential statistician of the 20th century, on the promise and challenges of randomized clinical trials in medicine should motivate rehabilitation clinicians to do their own small-scale controlled trials, with Institutional Review Board approval, when faced with equally realistic and plausible treatment options for their patients.

Radical innovations are designs that alter the meaning of our life experiences. In order to realize such innovation, a designer needs a vision, a strong personal view on the world. The identity and values of designers however, are often denied in modern design processes. onsequently, (junior) designers have difficulties in connecting with their values and standing for their ideals, especially when designing within a corporate setting. We report a case study that demonstrates how nurturing a designer’s personal understanding of ‘good design’ and integration of this understanding in his work, influences a design-driven innovation project and outcome. Our findings suggest that a designer’s principles for good design, enable him to design more in tune with his identity and related ideals. Personal principles for good design empowered the designer’s creativity, decision making, process planning, and drive to design and promote the acceptance of a radical idea within a corporate setting. We hope to inspire designers to use personal values and identity for design-driven innovation, and would like to start a discussion with design research and education communities to ponder on how designers can be supported in this journey.

The Internet has stimulated enormous expectation in many fields of learning, including language acquisitiori. From a position in which technology enhanccd language learning was at the forefront of pedagogic development, we now see a situation in which good design - both pedagogic and instructional - is all too often sacrificed for the sake of technological convenience. Some of the techniques which were possible using multimedia on a CD-ROM platform have all but disappeased as end users expect to find good learning experiences from the Web. One major reason why good design principles are often ignored in web-based learning design is the lack insuficient. easy-to-use authoring tools, leading to an over-reliance on simple Iiypcstext routines (though even with tliese there is no excuse for the woeful neglect of feedback techniques so ol'ten encouiiiered). or the need to rely on technically trained personnel with an insuficiciit understanding of clear instructional design principles. I Iclp is bEginning to arrive with sonlc good authoring systems, and this work looks at Hot Potatoes and MALTEB, whilst at the same time postulating that a clear approach to pedagogic issues and. above all. instructional design work, cari still create sound learning programs with even simple hypertext tools. l'he work concludes with a practical check-list of advice for the would-be author o l language learning programs.

G protein-coupled estrogen receptor (GPER), or GPR30, is a membrane receptor reported to mediate non-genomic estrogen responses. Tamoxifen is a partial agonist at GPER in vitro. Here, we investigated if GPER expression is prognostic in primary breast cancer, if the receptor is treatment-predictive for adjuvant tamoxifen, and if receptor subcellular localization has any impact on the prognostic value. Total and plasma membrane (PM) GPER expression was analyzed by immunohistochemistry in breast tumors from 742 postmenopausal lymph node-negative patients subsequently randomized for tamoxifen treatment for 2-5 years versus no systemic treatment, regardless of estrogen receptor (ER) status, and with a median follow-up of 17 years for patients free of event. PM GPER expression was a strong independent prognostic factor for poor prognosis in breast cancer without treatment-predictive information for tamoxifen. In the tamoxifen-treated ER-positive and progesterone receptor (PgR)-positive patient subgroup, the absence of PM GPER (53 % of all ER-positive tumors) predicted 91 % 20-year distant disease-free survival, compared to 73 % in the presence of GPER (p = 0.001). Total GPER expression showed positive correlations with ER and PgR and negative correlation with histological grade, but the correlations were biphasic. On the other hand, PM GPER expression showed strong negative correlations with ER and PgR, and strong positive correlation with HER2 overexpression and high histological grade. GPER overexpression and PM localization are critical events in breast cancer progression, and lack of GPER in the PM is associated with excellent long-term prognosis in ER-positive and PgR-positive tamoxifen-treated primary breast cancer.

Background:Breast cancer is the most commonly diagnosed malignancy and a major cause of cancer-related deaths in women globally. Identification of novel prognostic and pathogenesis biomarkers play a pivotal role in the management of the disease.Methods:Three data sets from the GEO database were used to identify differentially expressed genes (DEGs) in breast cancer. Gene Ontology (GO) enrichment and Kyoto Encyclopaedia of Genes and Genomes pathway analyses were performed to elucidate the functional roles of the DEGs. Besides, we investigated the translational and protein expression levels and survival data of the DEGs in patients with breast cancer from the Gene Expression Profiling Interactive Analysis (GEPIA), Oncomine, Human Protein Atlas, and Kaplan Meier plotter tool databases. The corresponding change in the expression level of microRNAs in the DEGs was also predicted using miRWalk and TargetScan, and the expression profiles were analyzed using OncomiR. Finally, the expression of novel DEGs were validated in Chinese breast cancer tissues by RT-qPCR.Results:A total of 46 DEGs were identified, and GO analysis revealed that these genes were mainly associated with biological processes involved in fatty acid, lipid localization, and regulation of lipid metabolism. Two novel biomarkers, ADH1A and IGSF10, and 4 other genes (APOD, KIT, RBP4, and SFRP1) that were implicated in the prognosis and pathogenesis of breast cancer, exhibited low expression levels in breast cancer tissues. Besides, 14/25 microRNAs targeting 6 genes were first predicted to be associated with breast cancer prognosis. RT-qPCR results of ADH1A and IGSF10 expression in Chinese breast cancer tissues were consistent with the database analysis and showed significant down-regulation.Conclusion: ADH1A, IGSF10, and the 14 microRNAs were found to be potential novel biomarkers for the diagnosis, treatment, and prognosis of breast cancer.

BackgroundTransforming growth factor β (TGFβ) is a critical regulator of lung metastasis of breast cancer and is correlated with the prognosis of breast cancer. However, not all TGFβ stimulated genes were functional and prognostic in breast cancer lung metastatic progress. In this study, we tried to determine the prognosis of TGFβ stimulated genes in breast cancer.MethodsTGFβ stimulated genes in MDA-MB-231 cells and lung metastasis-associated genes in LM2-4175 cells were identified through gene expression microarray. The prognosis of the induced gene (TGFBI) in breast cancer was determined through bioinformatics analysis and validated using tissue microarray. The immune infiltrations of breast cancer were determined through “ESTIMATE” and “TIMER”.ResultsTGFBI was up-regulated by TGFβ treatment and over-expressed in LM2-4175 cells. Through bioinformatics analysis, we found that higher expression of TGFBI was associated with shorted lung metastasis-free survival, relapse-free survival, disease-free survival, and overall survival of breast cancer. Moreover, the prognosis of TGFBI was validated in 139 Chinese breast cancer patients. Chinese breast cancer patients with higher TGFBI expression had lower overall survival. Correspondingly, breast cancer patients with higher TGFBI methylation had higher overall survival. TGFBI was correlated with the score of the TGFβ signaling pathway and multiple immune-related signaling pathways in breast cancer. The stromal score, immune score, and the infiltrations of immune cells were also correlated with TGFBI expression in breast cancer.ConclusionsTGFβ-induced gene TGFBI was correlated with the prognosis and immune infiltrations of breast cancer.

Background: Vitamin D may be protective against breast cancer (BC), yet current evidence from epidemiologic studies is inconsistent. We previously reported lowest serum 25-hydyroxyvitamin D (25OHD) levels in premenopausal women with the triple-negative (TN) subtype. We aimed to validate our findings in an independent cohort and to further investigate 25OHD levels in association with breast cancer prognosis. Methods: Using a case-cohort design, 1664 invasive breast cancer patients were selected from the Pathways Study, a prospective cohort at Kaiser Permanente Northern California (KPNC). 25OHD levels were measured by immunochemiluminometric assay in blood samples collected close to diagnosis. Demographic and lifestyle information at baseline came from in-person interviews, and information on cancer characteristics, treatment, recurrence and death were obtained from KPNC cancer registries and clinical databases. We examined quartiles of 25OHD in association with BC characteristics (stage, grade, estrogen receptor status, TN subtype) using logistic regression, and with disease-free survival (DFS) and overall survival (OS) using Cox proportional hazards regression with covariate adjustment. Pending analyses will account for sampling in which biospecimens from all minorities, all non-Lum A subtypes (Lum B/TN/HER2-overexpressing), and a subset (30%) of white Lum A subtypes were selected. Results: Blood collection in winter-spring, younger age, obesity, black or Hispanic race/ethnicity, current smoking, low moderate-vigorous physical activity, no vitamin D supplement use, and low dietary vitamin D intake were associated with low serum 25OHD levels. In premenopausal women, 25OHD levels were associated inversely with cancer stage and grade, and those with the TN subtype had the lowest levels (Q4: adjusted OR vs. Lum A=0.41, 95% CI=0.19-0.86). Among white women after a median follow-up time of 5.9 y (range 2.5-7.8 y), high 25OHD levels were associated with longer DFS (Q4: adjusted HR=0.67, 95% CI=0.45-0.98), as well as OS (Q4: adjusted HR=0.58, 95% CI=0.36-0.92). Additional adjustment for stage, grade, subtype and treatment received had minimal effects on the above associations. The associations with DFS and OS appeared stronger in premenopausal women than in postmenopausal women. Conclusion: In a large prospective cohort of breast cancer patients, we validated our previous findings of 25OHD levels being associated with lower odds of TN tumor subtype in premenopausal patients. Moreover, preliminary results indicate that high 25OHD levels at the time of diagnosis were associated with longer DFS and OS, the relationships were independent of cancer characteristics and treatment, and may be stronger in premenopausal women. These findings support potential benefits of maintaining sufficient vitamin D levels for improved breast cancer prognosis. Citation Format: Song Yao, Chi-Chen Hong, Marilyn L. Kwan, Ting-Yuan Cheng, Li Tang, Susan E. McCann, Isaac J. Ergas, Janise M. Roh, Warren Davis, Christine B. Ambrosone, Lawrence H. Kushi. The association of serum 25-hydroxyvitamin D with breast cancer characteristics and prognosis in the Pathways Study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4126. doi:10.1158/1538-7445.AM2014-4126

Trans people face uncertain risk for breast cancer and barriers to accessing breast screening. Our objectives were to identify and synthesize primary research evidence on the effect of cross-sex hormones (CSHs) on breast cancer risk, prognosis and mortality among trans people, the benefits and harms of breast screening in this population, and existing clinical practice recommendations on breast screening for trans people. We conducted 2 systematic reviews of primary research, 1 on the effect of CSHs on breast cancer risk, prognosis and mortality, and the other on the benefits and harms of breast screening, and a third systematic review of guidelines on existing screening recommendations for trans people. We searched PubMed, MEDLINE, Embase, CINAHL, the Cochrane Database of Systematic Reviews and grey literature sources for primary research, guidelines and position statements published in English between 1997 and 2017. Citations were screened by 2 independent reviewers. One reviewer extracted data and assessed methodological quality of included articles; a second reviewer verified these in full. The results were synthesized narratively. Four observational studies, 6 guidelines and 5 position statements were included. Observational evidence of very low certainty did not show an effect of CSHs on breast cancer risk in trans men or trans women. Among trans women, painfulness of mammography and ultrasonography was low. There was no evidence on the effect of CSHs on breast cancer prognosis and mortality, or on benefits and other harms of screening. Existing clinical practice documents recommended screening for distinct trans subpopulations; however, recommendations varied. The limited evidence does not show an effect of CSHs on breast cancer risk. Although there is insufficient evidence to determine the potential benefits and harms of breast screening, existing clinical practice documents generally recommend screening for trans people; further large-scale prospective comparative research is needed.

Background: Tumor characteristics such as grade, stage and receptor status are associated with breast cancer (BC) prognosis. Less is known about modifiable factors and BC prognosis. Advanced glycation end-products (AGEs) are reactive metabolites produced as a by-product of sugar metabolism, generated in conditions of increased oxidative stress. AGEs irreversibly accumulate in our tissues over time with pathogenic effects on genetic fidelity, protein function, cell signaling pathways, and chronic inflammatory diseases. The total body AGE pool is composed of endogenous AGEs and exogenous AGEs (consumed mainly through processed foods and those cooked at high temperatures). Serum AGE (sAGE) levels, a reflection of total body AGE, are higher in people with poor diet quality, lower levels of physical activity, and in women with BC compared to healthy controls. AGEs promote growth, migration and invasion in BC cell lines and activate prognostic inflammatory mediators such as interleukin-6 and C-reactive protein. Dietary AGEs have been associated with increased BC risk and increased mortality after BC diagnosis whereas lifestyle interventions can lower dietary and sAGE levels. The impact of sAGE levels, a better estimate of total body AGE than dietary AGE, on BC prognosis has not been previously evaluated. Methods: The Women’s Healthy Eating and Living (WHEL) study randomized 3088 BC patients stage I-III who completed their primary therapy to a high-vegetable, low-fat diet or control and followed for a median of 7.3 years. Main outcomes were invasive BC events (recurrence or new primary N=518), death due to BC (N=262) and deaths from any cause (N=315). sAGE was measured as the AGE metabolite carboxymethyllysine (ug/ml) from WHEL fasting blood specimens at study entry. sAGE was logged and corrected for plate batch effect via linear regression and analyzed in continuous scale and in quintiles. The Kaplan-Meier method and Cox regression model were performed for risk impact of sAGE on overall survival (OS), recurrence free survival (RFS), breast cancer specific survival (BCSS) and distant metastasis free survival (DMFS). We additionally adjusted in Cox models for potential confounding variables (age, race, BMI, smoking, alcohol use, physical activity, tumor characteristics). Results: 2564 participants had sAGE available. After excluding samples for excessive variabilities, 2315 samples were analyzed. Raw corrected sAGE ranged from 0.0-48.15 ug/ml (median 7.39); logged and corrected range -5.04-1.67. sAGE was positively associated with BMI (p<.0001, rs 0.10) and negatively associated with physical activity (p< .001, rs.-0.06). sAGE was not significantly associated with tumor stage, grade, receptor status, or race or menopausal status. Comparing the highest quintile (logged and corrected range=0.33~1.67) to the lowest quintile (range=-5.04~-0.30), sAGE was significantly associated with all survival outcomes (Table 1). As a continuous variable, AGE was associated with worse OS (HR 1.38, P=.031, β .32) and RFS (HR 1.29, P=.028, β .25) with a trend towards worse DMFS (HR 1.28, P=.067, β .25) and BCSS (HR 1.36, P=.06, β .31). Conclusions: Higher sAGEs are associated with worse survival outcomes in BC and may represent a novel, lifestyle-linked, modifiable prognostic biomarker in BC. Interventions aimed at lowering sAGE levels should be tested for their impact on known prognostic biomarkers as well as clinical outcomes. Individualized cancer-specific lifestyle recommendations are a crucial but currently lacking component of personalized cancer medicine. Citation Format: Lindsay L. Peterson, Yu Tao, Jingqin Luo, Graham A. Colditz, Yikyung Park, Jennifer A. Ligibel, David Turner. PD12-09 Serum Advanced Glycation End-Products are Associated with Breast Cancer Prognosis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD12-09.

Creativity is often associated with free expression, dynamic innovation, originality, and insightful, unconstrained genius. Nowhere is this more so than in the practice of design. The embodiment of this myth is the genius designer, from whom creative ideas spring forth naturally, effortlessly. A companion myth within the world of interface and interaction design is that design and user experience experimentation are not allies in creativity; rather, user experience research is in service of creativity, laying the foundations for design inspiration by identifying gaps and needs, or providing summative evaluations of designs.To the first myth, constraints are part of the creative process; creativity is enacted and accomplished in design practice through the judicious application and relaxation of understood and discovered constraints. Constraints help you ask better questions, not simply drive for solutions. Good examples are design systems and frameworks that codify carefully thought-out, and frequently observed constraints; they operate to inform, to codify best practices and principles for design, and to offer useful boundaries that provoke design exploration. To the second, experimentation is a creative act in itself; systematic experimentation can and should be intimately woven into iterative design processes. Experimentation allows options to be tested and explored. Experimentation enables thoughtful exploration of permutation.In this talk I will share stories of collaboration between my team, Material Experience Research, and the designers and developers of Material Design. I will talk about tools for creatives, and the ways in which such tools can enhance rather than constrain and restrict creative exploration. I will discuss research we have been conducting on how good design and user experience principles, codified within design frameworks and systems, spark creativity through provisional constraint.

Background Inflammatory breast cancer (IBC) is one of the most rare and aggressive subtypes of primary breast cancer (BC). Our study aimed to explore hub genes related to the pathogenesis of IBC, which could be considered as novel molecular biomarkers for IBC diagnosis and prognosis. Material and Methods. Two datasets from gene expression omnibus database (GEO) were selected. Enrichment analysis and protein-protein interaction (PPI) network for the DEGs were performed. We analyzed the prognostic values of hub genes in the Kaplan-Meier Plotter. Connectivity Map (CMap) and Comparative Toxicogenomics Database (CTD) was used to find candidate small molecules capable to reverse the gene status of IBC. Results 157 DEGs were selected in total. We constructed the PPI network with 154 nodes interconnected by 128 interactions. The KEGG pathway analysis indicated that the DEGs were enriched in apoptosis, pathways in cancer and insulin signaling pathway. PTEN, PSMF1, PSMC6, AURKB, FZR1, CASP9, CASP6, CASP8, BAD, AKR7A2, ZNF24, SSX2IP, SIGLEC1, MS4A4A, and VSIG4 were selected as hub genes based on the high degree of connectivity. Six hub genes (PSMC6, AURKB, CASP9, BAD, ZNF24, and SSX2IP) that were significantly associated with the prognosis of breast cancer. The expression of CASP9 protein was associated with prognosis and immune cells infiltration of breast cancer. CASP9- naringenin (NGE) is expected to be the most promising candidate gene-compound interaction for the treatment of IBC. Conclusion Taken together, CASP9 can be used as a prognostic biomarker and a novel therapeutic target in IBC.

MicroRNAs (miRNAs) are non-coding single-stranded RNAs in eukaryotes and are involved in the regulation of the post-transcriptional expression of specific genes. Studies have demonstrated that miRNAs play important roles in regulating diverse physiological events such as cell proliferation, differentiation and embryo development. In recent decades, considerable attention has been given to the relationship between miRNA and the pathology of cancers, particularly breast cancer. A large number of miRNAs have been shown to be involved in the pathophysiology of breast cancer. Studies have revealed that some miRNAs might regulate the oncogenesis and growth of breast cancer by acting on breast tumor-initiating cells or other downstream targets. Studies have also demonstrated that some miRNAs act as suppressors of metastasis or promoters of breast cancer. Additionally, certain miRNAs are involved in cancer tissue angiogenesis (one of the most important mechanisms of tumor growth and metastasis). Clinical evidence indicates that some miRNAs can be used as diagnostic and prognostic biomarkers for breast cancer due to their significantly increased or decreased expression in cancer tissue. Moreover, certain miRNAs may have therapeutic potential for targeting ER-α/HER, breast tumor-initiating cells and metastasis as well as multidrug resistance. In this review, we discuss the relationship between miRNAs and the pathogenesis of breast cancer as well as the progress of current research on the miRNA-specific diagnosis, prognosis and treatment of breast cancer.