Oestrogen receptors in primary and advanced breast cancer: An eight year review of 704 cases

Williams, Michael R.; Todd, John H.; Ellis, Ian O.; Dowle, C. S.; Haybittle, J. L.; Elston, C.W.; Nicholson, Robert Ian; Griffiths, K.; Blamey, R. W.

doi:10.1038/bjc.1987.14

Cited by 115 publications

(48 citation statements)

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“…Bone metastases are more likely to occur in ER-positive tumours. There is a strong correlation between ER positivity and well-differentiated tumours (Williams et al, 1987). Well-differentiated tumours are unlikely to metastasise unless lymph node positive, unlike poorly differentiated lymph node negative tumours which will still often metastasise.…”

Section: Discussionmentioning

confidence: 99%

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Bone metastases from breast carcinoma: histopathological – radiological correlations and prognostic features

et al. 2003

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The aim of this study was to identify factors that may be associated with the development of bone metastases in patients with metastatic breast carcinoma and to see if any of these factors had a bearing on subsequent survival. In total, 492 patients presented to the Nottingham City Hospital with metastatic breast carcinoma between July 1997 and December 2001. Of these, 267 patients had bone metastases at presentation with metastatic disease, 91 patients in this group had bone as their only site of metastatic disease. Sites of first presentation of metastatic disease were prospectively recorded, as were histological features of the primary tumour (tumour type, histological grade, lymph node stage, tumour size and oestrogen receptor (ER) status). The radiological features of the bone metastases, the metastasis-free interval and serological tumour marker levels at presentation with metastases were all recorded. There was a significant association between the development of bone metastases and lower grade tumours (P ¼ 0.019), ER-positive tumours (Po0.0001) and the lymph node stage of the primary tumour (P ¼ 0.047). A multivariate analysis found that metastasis-free interval, additional sites of metastatic disease other than bone, ER status and serological tumour marker levels all independently contributed to survival from time of presentation with bone metastases. British Journal of Cancer (2003) The survival of patients with metastases is variable ranging from a matter of months to many years. The ability to predict prognosis and response to treatment has a considerable impact on patient management. It is well established that oestrogen receptor (ER) status and site of presentation of metastatic disease have the greatest impact on patient survival, with additional contributions made by patient age, disease-free interval and histological grade.Bone is the most common site of metastases in patients with breast carcinoma and so patients with bone metastases make up the largest single group of patients presenting with metastatic disease. It has previously been reported that 20% of patients with bone metastases survive for more than 5 years, which emphasises the wide variation in survival seen in this group of patients (Coleman et al, 1987). The aim of this study was to identify factors that may be associated with the development of bone metastases and to see if any of these factors had any bearing on subsequent survival.We have assessed traditional factors such as ER status, histological grade, lymph node stage and size of the primary tumour, patient age, metastasis-free interval and the presence of metastases at sites other than bone. We have examined the radiological appearance of the bone metastases and looked for associations with the histological features of the tumour and patient survival. In common with other centres, we increasingly use serological tumour markers in the diagnosis and monitoring of patients with metastatic breast carcinoma. The prognostic significance of elevated tumour markers at presentation ...

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Section: Discussionmentioning

confidence: 99%

“…The close relationship between ER status and grade is well recognised with ER activity occurring more frequently in well-differentiated tumours (Williams et al, 1987). The reason ER status correlates better with survival is in large part due to the fact that ER status predicts for response to endocrine therapy.…”

Section: Discussionmentioning

confidence: 99%

Bone metastases from breast carcinoma: histopathological – radiological correlations and prognostic features

et al. 2003

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“…1 It is expressed in normal breast and 50-80% of breast cancers, depending on the assay used. [2][3][4] Estrogen receptor (ER) is a favorable prognostic factor and ER positive malignancies have a lower risk of relapse and a better overall survival. 5 However, ESR1 analysis is most useful in predicting response to endocrine therapies, although approximately half of all ER-positive cancers do not respond to antiestrogens or estrogen deprivation therapies.…”

Section: Introductionmentioning

confidence: 99%

Genes that co-cluster with estrogen receptor alpha in microarray analysis of breast biopsies

et al. 2001

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The estrogen receptor plays a critical role in the pathogenesis and clinical behavior of breast cancer. To better understand the molecular basis of estrogen-dependent forms of this disease we studied gene expression profiles from 53 primary breast cancer biopsies. Gene expression data for more than 7000 genes were generated from each tumor sample with oligo microarrays. A standard correlation-clustering algorithm identified 18 genes that co-clustered with estrogen receptor alpha. Eleven of these genes had previously been associated with estrogen regulation or breast tumorigenesis including trefoil factor 1 and estrogen regulated LIV-1. Additional study of these 18 genes may further delineate the role of estrogen receptor in breast cancer, generate new predictive biomarkers for response to endocrine therapies and identify novel therapeutic targets. The Pharmacogenomics Journal ( BACKGROUNDThe estrogen receptor is a ligand-activated transcription factor containing hormone binding, DNA binding and transcription activation domains. 1 It is expressed in normal breast and 50-80% of breast cancers, depending on the assay used. 2-4 Estrogen receptor (ER) is a favorable prognostic factor and ER positive malignancies have a lower risk of relapse and a better overall survival. 5 However, ESR1 analysis is most useful in predicting response to endocrine therapies, although approximately half of all ER-positive cancers do not respond to antiestrogens or estrogen deprivation therapies. 6 The molecular basis for ESR1-positive, endocrine therapy-resistant disease is not well understood. Somatic mutations in ESR1 are rare, even in breast cancers that have acquired resistances to endocrine therapies. This finding has focused attention on other mechanisms, including the overexpression of tyrosone-kinase linked growth factor receptors, transcriptional coactivators such as AIB1 (amplified in breast cancer 1) or cell cycle regulators including Cyclin D1. Additional possibilities include mutations in other genes involved in the regulation of estrogen-dependent growth.Expression of the estrogen-regulated genes, progesterone receptor (PGR) and trefoil factor 1 (TFF1 or PS2) indicate the presence of a functional and activated ER. 7 Both of these proteins are predictive biomarkers for breast cancer endocrine therapy, although less valuable than ER in distinguishing estrogen-dependent from estrogen-independent breast cancer. The use of PGR improves upon the predictive value of ER alone, yet ෂ 40% of tumors that express both ER and PGR fail to respond to endocrine treatments in the metastatic setting. 8 Similarly, TFF1 is associated with a good prognosis and predicts a positive response to hormonal therapy, but it has not proved to be sufficient as a predictive biomarker for routine evaluation of breast cancer. 9 Thus, PGR and TFF1 may be modestly useful

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“…This has been interpreted to show that ER negativity correlates with more aggressive tumour biology and loss of cellular control. A second reason is the strong correlation between ER and therapeutic response to primary endocrine therapy (Samaan et al, 1981;Howell et al, 1984;Williams et al, 1987), which formed the basis for early hypotheses of endocrine sensitivity and resistance. Up to 60% of ER-positive tumours respond to hormone therapy (e.g.…”

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confidence: 99%

“…Up to 60% of ER-positive tumours respond to hormone therapy (e.g. Tamoxifen), while for ER-negative tumours the figure is around 10% Samaan et al, 1981;Williams et al, 1987). Therapeutic response to endocrine therapy is not permanent and eventually all such tumours progress.…”

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confidence: 99%

Oestrogen receptor: a stable phenotype in breast cancer

Robertson

1996

Br J Cancer

127

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Summary Oestrogen receptor (ER) expression in breast cancer is regarded as a phenotype that may change during the natural history of the disease or during endocrine therapy. It has been suggested that in up to 70% of tumours that show acquired resistance the mechanism may be changed in ER status from positive to negative. This paper proposes an alternative hypothesis that ER expression is a stable phenotype in breast cancer. The paper reviews the literature on ER expression during the natural history of breast cancer in patients and also presents data on the effect of endocrine therapy on ER expression. If the alternative hypothesis is true it has important implications for treatment from chemoprevention to acquired endocrine resistance in advanced disease. Equally, if the hypothesis is true, attempts to develop laboratory models of endocrine resistance where ER-positive tumours become ER negative need to be re-evaluated.Keywords: breast cancer; oestrogen receptor; stable phenotypeThe oestrogen receptor (ER) is a 65 kDa oestrogen-binding protein expressed by 46-77% of breast cancers (Walt et al., 1976;Knight et al., 1977; Maynard et al., 1978;Brooks et al., 1980;Osborne et al., 1980; Croton et al., 1981;Howell et al., 1984;Hawkins et al.,1987a;Williams et al., 1987;Clarke and McGuire, 1988). It is a generally held view that ER expression is not a permanent phenotype in breast cancer cells Moolgavakar et al., 1980; Encarnacion et al., 1993; Morrow and Jordon, 1993;Nomura et al., 1985;Jordan, 1994;Paik et al., 1994). One reason for this view is the belief that patients with ER-positive primary breast tumours often develop ER-negative metastases in regional lymph nodes or distant sites. This has been interpreted to show that ER negativity correlates with more aggressive tumour biology and loss of cellular control. A second reason is the strong correlation between ER and therapeutic response to primary endocrine therapy (Samaan et al., 1981;Howell et al., 1984;Williams et al., 1987), which formed the basis for early hypotheses of endocrine sensitivity and resistance. Up to 60% of ER-positive tumours respond to hormone therapy (e.g. Tamoxifen), while for ER-negative tumours the figure is around 10% Samaan et al., 1981;Williams et al., 1987). Therapeutic response to endocrine therapy is not permanent and eventually all such tumours progress. As ER negativity is strongly associated with primary resistance to endocrine therapy it is generally accepted that when responding tumours subsequently progress that in the majority of tumours this is due to loss of ER expression by the tumour Moolgavakar et al., 1980;Nomura et al., 1985; Encarnacion et al., 1993;Morrow and Jordan, 1993;Jordan, 1994;Paik et al., 1994). This paper proposes the alternative hypothesis that ER is a stable phenotype in breast cancer cells.The discovery of monoclonal antibodies (Kohler and Milstein, 1975) subsequently led to specific antibodies being raised to ER (Green and Jensen, 1982 . The ER-ICA allowed assessment of tumour tissue sections (King ...

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Oestrogen receptors in primary and advanced breast cancer: An eight year review of 704 cases

Cited by 115 publications

References 30 publications

Bone metastases from breast carcinoma: histopathological – radiological correlations and prognostic features

Bone metastases from breast carcinoma: histopathological – radiological correlations and prognostic features

Genes that co-cluster with estrogen receptor alpha in microarray analysis of breast biopsies

Oestrogen receptor: a stable phenotype in breast cancer

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