Prognostic evaluation of the B cell/IL-8 metagene in different intrinsic breast cancer subtypes

Hanker, Lars; Rody, Achim; Holtrich, Uwe; Pusztai, Lajos; Ruckhaeberle, Eugen; Liedtke, Cornelia; Ahr, A.; Heinrich, Tomas; Sänger, Nicole; Becker, Sven; Karn, Thomas

doi:10.1007/s10549-012-2356-2

Cited by 30 publications

(21 citation statements)

References 40 publications

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“…We compiled Affymetrix gene expression profiles of a total of 4467 breast cancer patients from 40 publicly available datasets as previously reported (Hanker et al., 2013) (see Methods section and Supplementary Table S1 and Figure 1). The clinical characteristics of all 4467 samples are given in Table 1.…”

Section: Resultsmentioning

confidence: 99%

OPG and PgR show similar cohort specific effects as prognostic factors in ER positive breast cancer

et al. 2014

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The RANK/RANKL/OPG pathway is well known for bone destruction in skeletal metastases but has also been implicated in osteoclast-independent roles in tumorigenesis and de novo metastasis. Experimental data suggest contribution of progesterone to tumorigenesis may be mediated by RANKL. Importantly, modulation of this pathway became possible through the availability of denosumab, an artificial counterpart of OPG, but significant gaps remain in the translation of preclinical findings on the pathway. We analyzed gene expression of RANK, RANKL and OPG from 40 Affymetrix datasets encompassing 4467 primary breast cancers and focused on ER positive disease. We did not observe a significant prognostic value of RANK and RANKL mRNA expression. In contrast, OPG was associated with a better prognosis among 1941 ER positive cancers (HR 0.64, 95% CI 0.53-0.77; P < 0.0001) using a cutoff from its highly bimodal expression. We detected considerable heterogeneity regarding the prognostic value of OPG between different datasets. This heterogeneity could neither be attributed to technical reasons nor to differences in standard clinical parameters or treatments of the cohorts. Interestingly, the prognostic value of the progesterone receptor and of OPG showed similar cohort specific effects. Still both factors were no surrogates for each other but contributed independent prognostic value in multivariate analyses. Thus, both OPG and PgR are independently associated with good prognosis in ER positive breast cancer. However both markers share common cohort specific differences in contrast to proliferation markers as Ki67 which may be based on the underlying biology.

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Section: Resultsmentioning

confidence: 99%

OPG and PgR show similar cohort specific effects as prognostic factors in ER positive breast cancer

et al. 2014

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“…For instance, a high B-cells and low IL-8 metagenes have been associated with good prognosis in this population, suggesting that IL-8 suppression may be a therapeutic approach 74. In another study, a group of 14 genes linked to immune/inflammatory cytokine regulation identified TNBC patients with a good outcome in the absence of aggressive adjuvant therapy 75.…”

Section: Gene Signatures In Er-negative Breast Cancermentioning

confidence: 94%

Role of inflammatory infiltrates in triple negative breast cancer

et al. 2015

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Triple negative breast cancer (TNBC) is a heterogenous disease often characterised by aggressive biology and poor prognosis. Efforts to precisely treat TNBC have been compounded by the lack of specific therapeutic molecular targets. Recent transcriptomic studies have revealed, among others, an immunomodulatory subtype of TNBC, whereby activated immune response genes are associated with good prognosis. Since then, a great deal of effort has been made to understand the immune microenvironment of some TNBC subtype, which comprises several immune cell populations including lymphocytes and macrophages. There is increasing evidence that the basal subtype may be significantly regulated by tumour-infiltrating T-cells and that high levels of tumour-infiltrating CD8+ T-cells may be a reflection of improved prognosis with chemotherapy sensitivity in TNBC. On the other hand, tumour-associated macrophages have been associated with a relatively poor outcome in TNBC. Comparison of the immune signatures in TNBC with non-TNBC may furthermore help us to understand these immune mechanisms potentially leading to new therapeutic approaches. Within this short review, we discuss the current scientific evidence regarding (a) the role of tumour-infiltrating lymphocytes in the clinical outcome in TNBC and (b) the newly discovered immunomodulatory genotype that may provide for a therapeutic target in TNBC.

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“…We compiled Affymetrix gene expression data (U133A or U133Plus2.0 arrays) of 4467 breast cancer patients from 40 publicly available datasets as previously described [17,33] (Supplementary Table 1). All analyses were performed according to the ''REporting recommendations for tumour MARKer prognostic studies'' (REMARK) [26,34] and the respective guidelines to microarray-based studies for clinical outcomes [12].…”

Section: Patientsmentioning

confidence: 99%

The prognostic impact of age in different molecular subtypes of breast cancer

Liedtke

Rody

Gluz

et al. 2015

Breast Cancer Res Treat

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Breast cancer is a heterogeneous entity composed of distinct molecular subgroups with different molecular and clinical features. We analyzed the association between molecular breast cancer subgroups, age at diagnosis, and prognosis in a compilation of publicly available gene expression datasets. Affymetrix gene expression data (U133A or U133Plus2.0 arrays) of 4467 breast cancers from 40 datasets were compiled and homogenized. Breast cancer subgroups were defined based on expression of ESR1, PR, HER2, and Ki67. Event-free survival was calculated as recurrence-free survival or distant metastasis-free survival if recurrence-free survival was not available. Young age at diagnosis is associated with higher frequency of triple negative and HER2 subtypes and lower frequency of luminal A breast cancers. The 5-year event-free survival rates of patients aged less than 40, between 40 and 50, and >50 years were 54.3 ± 3.5, 68.5 ± 1.9, and 70.4 ± 1.3 %, respectively. When controlling for breast cancer subtype, we found that age <40 years remained significantly associated with poor prognosis in triple negative breast cancer. The effect was modest in luminal tumors and not found in HER2 subtype. Both subtypes and age retained their significances in multivariate analysis. Association of age at diagnosis with molecular breast cancer subtype contributes to its important role as prognostic factor among patients with breast cancer. Still, within the group of triple negative breast cancer, young age <40 years has a significant prognostic value which was retained in multivariate analysis.

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Prognostic evaluation of the B cell/IL-8 metagene in different intrinsic breast cancer subtypes

Cited by 30 publications

References 40 publications

OPG and PgR show similar cohort specific effects as prognostic factors in ER positive breast cancer

OPG and PgR show similar cohort specific effects as prognostic factors in ER positive breast cancer

Role of inflammatory infiltrates in triple negative breast cancer

The prognostic impact of age in different molecular subtypes of breast cancer

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