Loss of estrogen receptor in recurrent breast cancer is associated with poor response to endocrine therapy.

Kuukasjärvi, Tuula; Kononen, Juha; Helin, Heikki; Holli, Kaija; Isola, Jorma

doi:10.1200/jco.1996.14.9.2584

Cited by 309 publications

(219 citation statements)

References 18 publications

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“…Metastases from ER? tumors may be ER- [7] supporting the hypothesis that ER-expressing and ER-negative breast cancers represent different disease entities [8]. In contrast, a large proportion of the patients with ER?…”

Section: Introductionmentioning

confidence: 76%

Meta-analysis of gene expression profiles related to relapse-free survival in 1,079 breast cancer patients

Győrffy

Schäfer

2008

Breast Cancer Res Treat

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The transcriptome of breast cancers have been extensively screened with microarrays and large sets of genes associated with clinical features have been established. The aim of this study was to validate original gene sets on a large cohort of raw breast cancer microarray data with known clinical follow-up. We recovered 20 publications and matched them to Affymetrix HGU133A annotations. Raw Affymetrix HGU133A microarray data were extracted from GEO and MAS5 normalized. For classifying patients using the selected gene sets, we applied prediction analysis of microarrays and constructed KaplanMeier plots. A new classification including all patients was generated using supervised principal components analysis. Seven studies including 1,470 patients were downloaded from GEO. Notably, we uncovered 641 microarrays representing 251 individual tumor specimens among them, which were repeatedly described under independent GEO identifiers. We excluded all redundant data and used the remaining 1,079 samples. Eight of the 20 gene sets were able to predict response at a significance of P \ 0.05. The discrimination of good and poor prognosis groups exclusively relying on gene expression data resulted in high significance (P = 1.8E-12). A model including genes fitted by both gene expression and clinical covariates (lymph node status and grade) contains 44 genes and can predict response at P = 9.5E-7. The outcome provides a ranking of the gene lists regarding applicability on an independent dataset. We established a consensus predictor combining the available clinical and gene expression data. The database comprising expression profiles of 1,079 breast cancers can be used to classify individual patients.

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Section: Introductionmentioning

confidence: 76%

Meta-analysis of gene expression profiles related to relapse-free survival in 1,079 breast cancer patients

Győrffy

Schäfer

2008

Breast Cancer Res Treat

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“…Although the analysis was based on the tumour characteristics at presentation rather than at relapse, evidence suggests that c-erbB2 overexpression is similar in primary and metastatic disease (Niehans et al, 1993). Although ER loss has been reported, in most patients with ER-positive primary tumours the recurrent disease is also ER-positive (Kuukasjarvi et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of c-erbB2 is an independent marker of resistance to endocrine therapy in advanced breast cancer

et al. 1999

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The present study investigated the interaction between c-erbB2 overexpression and the response to first-line endocrine therapy in patients with advanced breast cancer. The primary tumours of 241 patients who were treated at first relapse with endocrine therapy were assessed for overexpression of c-erbB2 by immunohistochemistry. c-erbB2 was overexpressed in 76 (32%) of primary breast cancers and did not correlate with any other prognostic factor. The overall response to treatment and time to progression were significantly lower in patients with c-erbB2-positive tumours compared to those that were c-erbB2-negative (38% vs 56%, P = 0.02; and 4.1 months vs 8.7 months, P < 0.001, respectively). In multivariate analysis, c-erbB2 status was the most significant predictive factor for a short time to progression ( P = 0.0009). In patients with ER-positive primary tumours treated at relapse with tamoxifen ( n = 170), overexpression of c-erbB2 was associated with a significantly shorter time to progression (5.5 months vs 11.2 months, P < 0.001). In conclusion, overexpression of c-erbB2 in the primary tumour is an independent marker of relative resistance to first-line endocrine therapy in patients with advanced breast cancer. In patients with ER-positive primary tumours, the overexpression of c-erbB2 defines a subgroup less likely to respond to endocrine therapy. © 1999 Cancer Research Campaign

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“…In a proportion of cases, patients who initially present with ERα-positive breast cancer, become ERα-negative [5]. The mechanisms by which ERα expression is lost are unclear, although epigenetic silencing of the ERα gene may be involved [6].…”

Section: Introductionmentioning

confidence: 99%

Transient over-expression of estrogen receptor-α in breast cancer cells promotes cell survival and estrogen-independent growth

Tolhurst

Thomas

Kyle

et al. 2010

Breast Cancer Res Treat

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Loss of estrogen receptor in recurrent breast cancer is associated with poor response to endocrine therapy.

Abstract: Loss of ER expression in recurrent breast cancer should be considered as a cause for poor response to endocrine therapy in primarily ER-positive patients. We conclude that analysis of recurrent tumor samples may improve the predictive value of ER and PR assays.

Cited by 309 publications

References 18 publications

Meta-analysis of gene expression profiles related to relapse-free survival in 1,079 breast cancer patients

Meta-analysis of gene expression profiles related to relapse-free survival in 1,079 breast cancer patients

Overexpression of c-erbB2 is an independent marker of resistance to endocrine therapy in advanced breast cancer

Transient over-expression of estrogen receptor-α in breast cancer cells promotes cell survival and estrogen-independent growth

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