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Deficits in plasma oestradiol measurement in studies and management of breast cancer.

Dowsett M, Folkerd E - Breast Cancer Res. (2004)

Bottom Line: Commercially available analytical methods, which measure the hormone levels without prior purification, have been successfully developed for measuring oestradiol in premenopausal women.The application of these methodologies to the quantification of the very low levels of oestradiol in postmenopausal women is more problematic in terms of accuracy and interpretation.The importance of using appropriate methodology is discussed and illustrated with data demonstrating the disparity in the results obtained when low levels of oestradiol were quantified using direct and indirect methods.

View Article: PubMed Central - HTML - PubMed

Affiliation: Academic Department of Biochemistry, The Royal Marsden Hospital, London, UK. mitch.dowsett@icr.ac.uk

ABSTRACT
The determination of plasma oestradiol has numerous applications in epidemiology, reproductive medicine and breast cancer management. Commercially available analytical methods, which measure the hormone levels without prior purification, have been successfully developed for measuring oestradiol in premenopausal women. The application of these methodologies to the quantification of the very low levels of oestradiol in postmenopausal women is more problematic in terms of accuracy and interpretation. The importance of using appropriate methodology is discussed and illustrated with data demonstrating the disparity in the results obtained when low levels of oestradiol were quantified using direct and indirect methods.

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Each panel shows the results of analysing pairs of samples from 10 postmenopausal breast cancer patients. Light column, measured serum oestradiol before treatment (Pre); dark column, result during the use of the aromatase inhibitor, anastrozole. (a), (b) Results obtained when the oestradiol was measured by direct assay: (a) Beckman Coulter Access Immumoassay system Estradiol 33540, and (b) DSL 3rd Generation Estradiol Radioimmunoassay DSL-39100. (c), (d) Results when the oestradiol is measured after a pre-extraction with an organic solvent: (c) extraction and radioimmunoassay (as used at the Royal Marsden [6]), and (d) the DSL-39100 kit after pre-extraction of serum samples with diethyl ether. Arrows indicate the detection limits for the assays; no arrow in (d) since this analysis was performed for the present study only and no detection limit was determined.
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Figure 2: Each panel shows the results of analysing pairs of samples from 10 postmenopausal breast cancer patients. Light column, measured serum oestradiol before treatment (Pre); dark column, result during the use of the aromatase inhibitor, anastrozole. (a), (b) Results obtained when the oestradiol was measured by direct assay: (a) Beckman Coulter Access Immumoassay system Estradiol 33540, and (b) DSL 3rd Generation Estradiol Radioimmunoassay DSL-39100. (c), (d) Results when the oestradiol is measured after a pre-extraction with an organic solvent: (c) extraction and radioimmunoassay (as used at the Royal Marsden [6]), and (d) the DSL-39100 kit after pre-extraction of serum samples with diethyl ether. Arrows indicate the detection limits for the assays; no arrow in (d) since this analysis was performed for the present study only and no detection limit was determined.

Mentions: The way in which the performance of most direct assays varies from the performance of an assay that uses organic extraction, and has been sensitised and validated for use in postmenopausal women, is vividly demonstrated by the comparisons made in Fig. 2. Each panel in Fig. 2 demonstrates the results obtained when pairs of samples taken from 10 postmenopausal breast cancer patients were analysed for oestradiol using four different methods. For each patient the first sample was taken before, and the second sample during, the use of anastrozole, an aromatase inhibitor. Anastrozole inhibits aromatase, the sole source of steroidal oestrogens, by a mean 97% [5]. However, in Fig. 2a (Estradiol 33540; Beckman Coulter Access Immunoassay system, Fullerton, CA, USA) and in Fig. 2b (3rd Generation Estradiol Radioimmunoassay, DSL-39100; Diagnostic Systems Laboratories Inc., Webster, TX, USA) the application of two types of direct assays gives values that fall by a mean 25% and 34%, respectively, and in some cases patients show no suppression in oestradiol levels at all. This observation contrasts markedly with the situation in Fig. 2c, which shows the results from applying a sensitive extraction assay [6]. All these patients show almost complete suppression of oestradiol levels, mostly to below the sensitivity limit of the assay (3 pmol/l). By designating samples with values below the detection limit as having values of 3 pmol/l a mean suppression of 88% may be calculated, but this is inevitably an underestimate. Revealingly, the application of an extraction step prior to use of the DSL-39100 kit (used in its normal direct fashion in Fig. 2b) leads to results that now resemble those derived from the extraction assay.


Deficits in plasma oestradiol measurement in studies and management of breast cancer.

Dowsett M, Folkerd E - Breast Cancer Res. (2004)

Each panel shows the results of analysing pairs of samples from 10 postmenopausal breast cancer patients. Light column, measured serum oestradiol before treatment (Pre); dark column, result during the use of the aromatase inhibitor, anastrozole. (a), (b) Results obtained when the oestradiol was measured by direct assay: (a) Beckman Coulter Access Immumoassay system Estradiol 33540, and (b) DSL 3rd Generation Estradiol Radioimmunoassay DSL-39100. (c), (d) Results when the oestradiol is measured after a pre-extraction with an organic solvent: (c) extraction and radioimmunoassay (as used at the Royal Marsden [6]), and (d) the DSL-39100 kit after pre-extraction of serum samples with diethyl ether. Arrows indicate the detection limits for the assays; no arrow in (d) since this analysis was performed for the present study only and no detection limit was determined.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1064106&req=5

Figure 2: Each panel shows the results of analysing pairs of samples from 10 postmenopausal breast cancer patients. Light column, measured serum oestradiol before treatment (Pre); dark column, result during the use of the aromatase inhibitor, anastrozole. (a), (b) Results obtained when the oestradiol was measured by direct assay: (a) Beckman Coulter Access Immumoassay system Estradiol 33540, and (b) DSL 3rd Generation Estradiol Radioimmunoassay DSL-39100. (c), (d) Results when the oestradiol is measured after a pre-extraction with an organic solvent: (c) extraction and radioimmunoassay (as used at the Royal Marsden [6]), and (d) the DSL-39100 kit after pre-extraction of serum samples with diethyl ether. Arrows indicate the detection limits for the assays; no arrow in (d) since this analysis was performed for the present study only and no detection limit was determined.
Mentions: The way in which the performance of most direct assays varies from the performance of an assay that uses organic extraction, and has been sensitised and validated for use in postmenopausal women, is vividly demonstrated by the comparisons made in Fig. 2. Each panel in Fig. 2 demonstrates the results obtained when pairs of samples taken from 10 postmenopausal breast cancer patients were analysed for oestradiol using four different methods. For each patient the first sample was taken before, and the second sample during, the use of anastrozole, an aromatase inhibitor. Anastrozole inhibits aromatase, the sole source of steroidal oestrogens, by a mean 97% [5]. However, in Fig. 2a (Estradiol 33540; Beckman Coulter Access Immunoassay system, Fullerton, CA, USA) and in Fig. 2b (3rd Generation Estradiol Radioimmunoassay, DSL-39100; Diagnostic Systems Laboratories Inc., Webster, TX, USA) the application of two types of direct assays gives values that fall by a mean 25% and 34%, respectively, and in some cases patients show no suppression in oestradiol levels at all. This observation contrasts markedly with the situation in Fig. 2c, which shows the results from applying a sensitive extraction assay [6]. All these patients show almost complete suppression of oestradiol levels, mostly to below the sensitivity limit of the assay (3 pmol/l). By designating samples with values below the detection limit as having values of 3 pmol/l a mean suppression of 88% may be calculated, but this is inevitably an underestimate. Revealingly, the application of an extraction step prior to use of the DSL-39100 kit (used in its normal direct fashion in Fig. 2b) leads to results that now resemble those derived from the extraction assay.

Bottom Line: Commercially available analytical methods, which measure the hormone levels without prior purification, have been successfully developed for measuring oestradiol in premenopausal women.The application of these methodologies to the quantification of the very low levels of oestradiol in postmenopausal women is more problematic in terms of accuracy and interpretation.The importance of using appropriate methodology is discussed and illustrated with data demonstrating the disparity in the results obtained when low levels of oestradiol were quantified using direct and indirect methods.

View Article: PubMed Central - HTML - PubMed

Affiliation: Academic Department of Biochemistry, The Royal Marsden Hospital, London, UK. mitch.dowsett@icr.ac.uk

ABSTRACT
The determination of plasma oestradiol has numerous applications in epidemiology, reproductive medicine and breast cancer management. Commercially available analytical methods, which measure the hormone levels without prior purification, have been successfully developed for measuring oestradiol in premenopausal women. The application of these methodologies to the quantification of the very low levels of oestradiol in postmenopausal women is more problematic in terms of accuracy and interpretation. The importance of using appropriate methodology is discussed and illustrated with data demonstrating the disparity in the results obtained when low levels of oestradiol were quantified using direct and indirect methods.

Show MeSH
Related in: MedlinePlus