The Influence of Basal Phenotype on the Metastatic Pattern of Breast Cancer

Lück, A.; Evans, Andy; Green, Andrew; Rakha, Emad A.; Paish, Claire E.; Ellis, Ian O.

doi:10.1016/j.clon.2007.10.002

Cited by 63 publications

(53 citation statements)

References 35 publications

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“…Basal-like breast cancers have been reported to show preferable metastatic dissemination to sites such as the brain and liver, and less to the bone. 5,49,50 These distinctive metastatic patterns have been interpreted as a distinctive ability of basal-like breast cancers for early blood-borne metastasis. It was assumed, from such observations, that the frequency of blood vascular invasion would be higher in basal-like than in the non-basal-like group.…”

Section: Discussionmentioning

confidence: 99%

“…The associations between the clinicopathological characteristics of the basal-like subtypes, prognosis and difference from luminal subtypes have been the subject of many studies and are reported and discussed in detail elsewhere. 3,5,7,[35][36][37] Lymph-vessel density in the total study population ranged between 0.00 and 10.57/mm 2 , with a mean of 2.2 ± 0.16 and a median of 1.43. The lymphvessel density in the basal group was 2.2±0.16 compared with 1.64±0.14 in the non-basal group with no significant difference (P ¼ 0.227).…”

Section: Vascular Characteristics In Basal Vs Non-basal Tumour Types mentioning

confidence: 99%

“…29 It has been previously reported that basal-like breast cancers are more likely to metastasise to the brain and lung (intra-pulmonary) and that this may be an indication for preferential haematogenous spreading. 5 Recent results by the current authors have suggested that breast cancer cells show an initial preference for lymphatic rather than for blood vessels. 29 Such work was conducted on a relatively small cohort of 177 patients, and hence it was not possible to examine whether different breast cancer subtypes showed different patterns of vascular invasion.…”

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confidence: 99%

“…4 Their mammographic appearance is also different from that of non-basal tumours; they are more likely to manifest as an ill-defined mass or with comedo calcification, whereas non-basalphenotype tumours are more likely to manifest as a spiculated mass. 5 There is no one 'gold' standard definition of basal-like breast cancer. It has been defined by negativity for ER, PR and HER2, with positive expression of either basal cytokeratins or EGFR.…”

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confidence: 99%

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Lymphatic and blood vessels in basal and triple-negative breast cancers: characteristics and prognostic significance

et al. 2011

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Basal and triple-negative breast cancer phenotypes are characterised by unfavourable biological behaviour and outcome. Although certain studies have examined their pathological and molecular profile, the vascular characteristics of lymphatic and blood vessels have not been examined. Immunohistochemical staining with podoplanin, CD34 and CD31 was used to examine lymphatic and microvessel density, as well as vascular invasion in 197 basal-like and in 99 triple-negative breast tumours and compared against 200 non-basal and 334 non-triple-negative cases. All specimens were lymph node negative. Vascular invasion was identified as blood or lymphatic vascular invasion by the differential expression of markers. All measurements were correlated with clinicopathological features and prognosis. No significant difference was detected between the basal and triplenegative groups in terms of lymphatic or microvessel density or vascular invasion. However, both the basal and the triple-negative groups showed significantly higher microvessel density than did the non-basal and non-triple-negative groups (P ¼ 0.017 and Po0.001, respectively). Unlike microvessel density, no significant difference was detected in lymphatic density between the basal or triple-negative groups compared with their respective controls. Interestingly, vascular invasion, almost entirely lymphatic invasion, was detected in 27% of the basal and in 26% of the triple-negative groups with no significant difference in comparison with control groups. In both basal and triple negatives, vascular invasion was associated with poorer survival by univariate and multivariate analyses. The 20-year overall survival rate in basal-like tumours was 55% in vascular invasionpositive cases compared with 73% in vascular invasion-negative tumours (P ¼ 0.012), and 46% in triple-negative vascular invasion-positive compared with 79% in vascular invasion-negative tumours (P ¼ 0.001). Basal-like vs non-basal-like and triple-negative vs non-triple-negative tumours have similar vascular characteristics in terms of lymphatic vessel density and vascular invasion but higher microvessel density, suggesting that such groups may preferentially benefit from anti-angiogenic therapy. Vascular invasion was, in all phenotypes, almost entirely lymphatic vessel invasion and could stratify basal-like and triple-negative phenotypes into distinct prognostic groups.

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Section: Discussionmentioning

confidence: 99%

Section: Vascular Characteristics In Basal Vs Non-basal Tumour Types mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Lymphatic and blood vessels in basal and triple-negative breast cancers: characteristics and prognostic significance

et al. 2011

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“…Current therapy decision making is increasingly governed by the molecular classification of breast cancer (luminal A, luminal B, basal like, HER2 þ , hormone receptor status). Cancer subtypes have characteristic sites to which they metastasise (Luck et al, 2008). A very common metastatic site for human breast cancer is the bone.…”

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confidence: 99%

Prognostic value of Dicer expression in human breast cancers and association with the mesenchymal phenotype

et al. 2009

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BACKGROUND: Dicer, a ribonuclease, is the key enzyme required for the biogenesis of microRNAs and small interfering RNAs and is essential for both mammalian development and cell differentiation. Recent evidence indicates that Dicer may also be involved in tumourigenesis. However, no studies have examined the clinical significance of Dicer at both the RNA and the protein levels in breast cancer. METHODS: In this study, the biological and prognostic value of Dicer expression was assessed in breast cancer cell lines, breast cancer progression cellular models, and in two well-characterised sets of breast carcinoma samples obtained from patients with long-term follow-up using tissue microarrays and quantitative reverse transcription -PCR. RESULTS: We have found that Dicer protein expression is significantly associated with hormone receptor status and cancer subtype in breast tumours (ER P ¼ 0.008; PR P ¼ 0.019; cancer subtype P ¼ 0.023, luminal A P ¼ 0.0174). Dicer mRNA expression appeared to have an independent prognostic impact in metastatic disease (hazard ratio ¼ 3.36, P ¼ 0.0032). In the breast cancer cell lines, lower Dicer expression was found in cells harbouring a mesenchymal phenotype and in metastatic bone derivatives of a breast cancer cell line. These findings suggest that the downregulation of Dicer expression may be related to the metastatic spread of tumours. CONCLUSION: Assessment of Dicer expression may facilitate prediction of distant metastases for patients suffering from breast cancer.

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Migration of breast cancer cell lines in response to pulmonary laminin 332

et al. 2016

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Because tumor cell motility is a requirement for metastasis, we hypothesized that lung tissue harbors substances that induce tumor cell migration. MCF‐7 breast carcinoma cells exposed to small airway epithelial cells and conditioned medium exhibited dose‐dependent tumor cell migration. Among the extracellular matrix proteins in the conditioned medium identified by mass spectrometry, laminin 332 (LM332) had the greatest contribution to the migration of MCF‐7 cells. Immunoblotting and immunohistochemistry for LM332‐specific chains identified LM332 in the lung and in pulmonary epithelial cells. Antibodies to either LM332 or its integrin receptor inhibited MCF‐7 motility, and knockdown of LM332 chains also reduced its migration‐inducing activity. Taken together, these findings implicate LM332 as a component of lung tissue that can induce motility in breast carcinoma cells that have been transported to lung during metastasis. Earlier studies on LM332 in tumor progression have examined LM332 expression in tumor cells. This investigation, in comparison, provides evidence that the tumor promoting potential of LM332 may originate in the lung microenvironment rather than in tumor cells alone. Furthermore, this study provides evidence that the motility‐inducing properties of the microenvironment can reside in epithelial cells. The findings raise the possibility that LM332 plays a role in the pulmonary metastases of breast carcinoma and may provide a target for antimetastasis therapy.

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The Influence of Basal Phenotype on the Metastatic Pattern of Breast Cancer

Cited by 63 publications

References 35 publications

Lymphatic and blood vessels in basal and triple-negative breast cancers: characteristics and prognostic significance

Lymphatic and blood vessels in basal and triple-negative breast cancers: characteristics and prognostic significance

Prognostic value of Dicer expression in human breast cancers and association with the mesenchymal phenotype

Migration of breast cancer cell lines in response to pulmonary laminin 332

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