Breast cancer: The translation of big genomic data to cancer precision medicine

Low, Siew‐Kee; Zembutsu, Hitoshi; Nakamura, Yusuke

doi:10.1111/cas.13463

Cited by 112 publications

(77 citation statements)

References 100 publications

(176 reference statements)

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“…The identification of genetic profiles related to the susceptibility, progression and prognosis of mammary neoplasia is of paramount importance in a clinical context. Recognizing high‐risk genetic profiles could allow the establishment of preventive and surveillance protocols, as well as the implementation of individualized therapeutic measures appropriated for a specific patient at a defined time, which constitutes the basis of personalized cancer medicine …”

Section: Discussionmentioning

confidence: 99%

Influence of E‐cadherin genetic variation in canine mammary tumour risk, clinicopathological features and prognosis

Canadas

Santos

Medeiros

et al. 2019

Vet Comparative Oncology

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E-cadherin is a cell adhesion molecule that participates in several cellular processes that guarantee the maintenance of structural and functional integrity of epithelial tissues. E-cadherin plays an important role in mammary carcinogenesis, and various studies have demonstrated the effect of CDH1 genetic variation in risk, progression and biological behaviour of human breast cancer. Although there are some recognized genetic variations in canine CDH1 gene, their influence in canine mammary tumour development and progression has not been previously evaluated. In this study, we aim to assess the influence of CDH1 SNPs rs850805755, rs852280880 and rs852639930 in the risk, clinicopathological features and clinical outcome of canine mammary tumours. A case-control study was conducted involving 206 bitches with mammary tumours and 161 bitches free of mammary neoplasia. CDH1 SNPs rs850805755 and rs852280880 were associated with a decreased risk and a later onset of mammary tumour development. Furthermore, these SNPs were related to the development of small size carcinomas, of low histological grade and low nuclear pleomorphism. SNP rs852639930 was associated with the development of small size tumours with a non-infiltrative, noninvasive growth pattern. Data from the present investigation demonstrate that these CDH1 genetic variants could have a protective role in canine mammary tumours, by being associated with low risk of tumour development, delayed onset of the disease and less aggressive clinicopathological features. K E Y W O R D S canine mammary tumour, CDH1 gene, E-cadherin, risk, SNP

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Section: Discussionmentioning

confidence: 99%

Influence of E‐cadherin genetic variation in canine mammary tumour risk, clinicopathological features and prognosis

Canadas

Santos

Medeiros

et al. 2019

Vet Comparative Oncology

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“…On the one hand, these features make it difficult to rule out familial inheritance, but on the other hand favor our hypothesis of using holistic germline information to characterize sporadic-like TNBC. Our approach assumes that rare non-synonymous germline mutations predispose individuals in a population to cancer, whereas somatic mutations initiated and triggered the progression of the cancer (55). Furthermore, we postulated that breast cancer is a 'bubbling' and persistent pathogenic stress on the female population, and that resistance against this stress is evolutionary selected.…”

Section: Discussionmentioning

confidence: 99%

Rare non-synonymous germline mutations systematically define the risk of triple negative breast cancer

Yang

Fan

et al. 2018

Preprint

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Early identification of the risk for triple-negative breast cancer (TNBC) at the asymptomatic phase could lead to better prognosis. Here we developed a machine learning method to quantify systematic impact of all rare germline mutations on each pathway. We collected 106 TNBC patients and 287 elder healthy women controls. The spectra of activity profiles in multiple pathways were mapped and most pathway activities exhibited globally suppressed by the portfolio of individual germline mutations in TNBC patients. Accordingly, all individuals were delineated into two types: A and B. Type A patients could be differentiated from controls (AUC = 0.89) and sensitive to BRCA1/2 damages; Type B patients can be also differentiated from controls (AUC = 0.69) but probably being protected from BRCA1/2 damages. Further we found that Individuals with the lowest activity of selected pathways had extreme high relative risk (up to 21.67 in type A) and increased lymph node metastasis in these patients. Our study showed that genomic DNA contains information of unimaginable pathogenic factors. And this information is in a distributed form that could be applied to risk assessment for more cancer types.Significance: We identified individuals who are more susceptible to triple negative breast cancer. Our method performs much better than previous assessments based on BRCA1/2 damages, even polygenic risk scores. We disclosed previously unimaginable pathogens in a distributed form on genome and extended risk prediction to scenarios for other cancers.

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“…Their intrinsic physical properties are particularly interesting for simultaneous drug delivery, molecular imaging and applications such as localized hyperthermia (Bender et al 2018;Iv et al 2015). These technical features provide special perspectives for breast cancer treatment and diagnosis, which is especially important because of the high incidence, drug resistance and recurrence risk related to this disease (Low et al 2018;Harmon et al 2015;Karakatsanis et al 2016). Current studies with maghemite nanoparticles, an iron oxide compound, have demonstrated in vitro and in vivo specific cytotoxic action for target cells, and these results have indicated this nanoparticle as a promising option for drug delivery (Manikandan et al 2018;Chaves et al 2017;Magro et al 2018).…”

Section: Introductionmentioning

confidence: 99%

Comparison of the effect of rhodium citrate-associated iron oxide nanoparticles on metastatic and non-metastatic breast cancer cells

et al. 2019

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Background: Nanocarriers have the potential to improve the therapeutic index of currently available drugs by increasing drug efficacy, lowering drug toxicity and achieving steady-state therapeutic levels of drugs over an extended period. The association of maghemite nanoparticles (NPs) with rhodium citrate (forming the complex hereafter referred to as MRC) has the potential to increase the specificity of the cytotoxic action of the latter compound, since this nanocomposite can be guided or transported to a target by the use of an external magnetic field. However, the behavior of these nanoparticles for an extended time of exposure to breast cancer cells has not yet been explored, and nor has MRC cytotoxicity comparison in different cell lines been performed until now. In this work, the effects of MRC NPs on these cells were analyzed for up to 72 h of exposure, and we focused on comparing NPs' therapeutic effectiveness in different cell lines to elect the most responsive model, while elucidating the underlying action mechanism. Results: MRC complexes exhibited broad cytotoxicity on human tumor cells, mainly in the first 24 h. However, while MRC induced cytotoxicity in MDA-MB-231 in a time-dependent manner, progressively decreasing the required dose for significant reduction in cell viability at 48 and 72 h, MCF-7 appears to recover its viability after 48 h of exposure. The recovery of MCF-7 is possibly explained by a resistance mechanism mediated by PGP (P-glycoprotein) proteins, which increase in these cells after MRC treatment. Remaining viable tumor metastatic cells had the migration capacity reduced after treatment with MRC (24 h). Moreover, MRC treatment induced S phase arrest of the cell cycle. Conclusion: MRC act at the nucleus, inhibiting DNA synthesis and proliferation and inducing cell death. These effects were verified in both tumor lines, but MDA-MB-231 cells seem to be more responsive to the effects of NPs. In addition, NPs may also disrupt the metastatic activity of remaining cells, by reducing their migratory capacity. Our results suggest that MRC nanoparticles are a promising nanomaterial that can provide a convenient route for tumor targeting and treatment, mainly in metastatic cells.

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Breast cancer: The translation of big genomic data to cancer precision medicine

Cited by 112 publications

References 100 publications

Influence of E‐cadherin genetic variation in canine mammary tumour risk, clinicopathological features and prognosis

Influence of E‐cadherin genetic variation in canine mammary tumour risk, clinicopathological features and prognosis

Rare non-synonymous germline mutations systematically define the risk of triple negative breast cancer

Comparison of the effect of rhodium citrate-associated iron oxide nanoparticles on metastatic and non-metastatic breast cancer cells

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