Limits...
Do classical oestrogen markers predict for clinical response to endocrine therapy?

View Article: PubMed Central - HTML

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Oestrogen may maintain the growth of some breast cancers, and oestrogen deprivation therapy can cause tumour regression... However, even in breast cancers that possess oestrogen receptors (the key transcription factor in oestrogen signalling), response rates to endocrine therapy are only 50% to 60%, hence the interest in identifying additional factors that might predict response/resistance to hormone therapy... Evidence is based on correlating oestrogen regulated markers (identified on account of having an oestrogen response element [ERE] in the promoter region of their genes and being classically oestrogen regulated in many hormone-sensitive tissues [the example used is the progesterone receptor (PR)], expression being regulated by oestrogen in breast cancer cell lines, and expression being regulated by oestrogen deprivation therapy in primary breast cancers) with clinical response to endocrine therapy either in patients with advanced breast cancer or in the neoadjuvant setting... It could be argued that rather than measure pretreatment PR expression, it might be more informative to relate change in PR level with clinical response... Treatment with aromatase inhibitors is associated with a reduction in immunohistochemical staining for PR... However, such a comparison is based upon change in expression for the cell line gene set and pretreatment expression for the clinical response signature... To avoid this confounder, the 141 gene list has been compared with genes that most significantly changed on letrozole neoadjuvant treatment but differentially expressed between responders and nonresponders... No correlation was found between the two sets of genes... Although the identity of these genes remains unreported, none were found among the 141 regulated by oestrogen in the MCF7 cell line... Other genes such as AURKA, IGFBP4, SLC7A5 and TPD52-1 are relatively unaffected by treatment in both responders and nonresponders... A list of genes most significantly influenced by neoadjuvant treatment (at 14 days) with letrozole has been published... Accurate prediction of clinical response requires a novel gene discovery programme to identify markers that are regulated by oestrogen in clinically responding tumours alone (or conversely in clinically resistant tumours alone)... It is concluded that oestrogen-regulated genes are molecular markers of oestrogen sensitivity (not dependence); that expression profiles and molecular responses to endocrine therapy in clinically resistant tumours may be similar to clinical responders; and, therefore, that most oestrogen-regulated genes are unlikely to be robust markers of clinical response to endocrine therapy.

No MeSH data available.


Related in: MedlinePlus

Changes in tumour expression of oestrogen-regulated genes after 14 days' neoadjuvant treatment with letrozole.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2230527&req=5

Figure 1: Changes in tumour expression of oestrogen-regulated genes after 14 days' neoadjuvant treatment with letrozole.

Mentions: To avoid this confounder, the 141 gene list has been compared with genes that most significantly changed on letrozole neoadjuvant treatment but differentially expressed between responders and nonresponders [10]. No correlation was found between the two sets of genes. Although the identity of these genes remains unreported, none were found among the 141 regulated by oestrogen in the MCF7 cell line. There are two major reasons for this. First, some genes change in both nonresponding and responding cases. Second, some genes change in culture following oestrogen exposure/withdrawal but are relatively unaffected by letrozole treatment in primary tumours. This can be illustrated, as is shown in Figure 1, by comparing the change in expression of the nine most commonly quoted oestrogen-regulated genes in MCF7 in responding and nonresponding tumours. It can be seen that genes such as NRIP1, STC2, CCND1, MYB and TFF1 are frequently downregulated by letrozole treatment in clinically responding tumours, but this also occurs in many of the nonresponding cases. Other genes such as AURKA, IGFBP4, SLC7A5 and TPD52-1 are relatively unaffected by treatment in both responders and nonresponders.


Do classical oestrogen markers predict for clinical response to endocrine therapy?
Changes in tumour expression of oestrogen-regulated genes after 14 days' neoadjuvant treatment with letrozole.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2230527&req=5

Figure 1: Changes in tumour expression of oestrogen-regulated genes after 14 days' neoadjuvant treatment with letrozole.
Mentions: To avoid this confounder, the 141 gene list has been compared with genes that most significantly changed on letrozole neoadjuvant treatment but differentially expressed between responders and nonresponders [10]. No correlation was found between the two sets of genes. Although the identity of these genes remains unreported, none were found among the 141 regulated by oestrogen in the MCF7 cell line. There are two major reasons for this. First, some genes change in both nonresponding and responding cases. Second, some genes change in culture following oestrogen exposure/withdrawal but are relatively unaffected by letrozole treatment in primary tumours. This can be illustrated, as is shown in Figure 1, by comparing the change in expression of the nine most commonly quoted oestrogen-regulated genes in MCF7 in responding and nonresponding tumours. It can be seen that genes such as NRIP1, STC2, CCND1, MYB and TFF1 are frequently downregulated by letrozole treatment in clinically responding tumours, but this also occurs in many of the nonresponding cases. Other genes such as AURKA, IGFBP4, SLC7A5 and TPD52-1 are relatively unaffected by treatment in both responders and nonresponders.

View Article: PubMed Central - HTML

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Oestrogen may maintain the growth of some breast cancers, and oestrogen deprivation therapy can cause tumour regression... However, even in breast cancers that possess oestrogen receptors (the key transcription factor in oestrogen signalling), response rates to endocrine therapy are only 50% to 60%, hence the interest in identifying additional factors that might predict response/resistance to hormone therapy... Evidence is based on correlating oestrogen regulated markers (identified on account of having an oestrogen response element [ERE] in the promoter region of their genes and being classically oestrogen regulated in many hormone-sensitive tissues [the example used is the progesterone receptor (PR)], expression being regulated by oestrogen in breast cancer cell lines, and expression being regulated by oestrogen deprivation therapy in primary breast cancers) with clinical response to endocrine therapy either in patients with advanced breast cancer or in the neoadjuvant setting... It could be argued that rather than measure pretreatment PR expression, it might be more informative to relate change in PR level with clinical response... Treatment with aromatase inhibitors is associated with a reduction in immunohistochemical staining for PR... However, such a comparison is based upon change in expression for the cell line gene set and pretreatment expression for the clinical response signature... To avoid this confounder, the 141 gene list has been compared with genes that most significantly changed on letrozole neoadjuvant treatment but differentially expressed between responders and nonresponders... No correlation was found between the two sets of genes... Although the identity of these genes remains unreported, none were found among the 141 regulated by oestrogen in the MCF7 cell line... Other genes such as AURKA, IGFBP4, SLC7A5 and TPD52-1 are relatively unaffected by treatment in both responders and nonresponders... A list of genes most significantly influenced by neoadjuvant treatment (at 14 days) with letrozole has been published... Accurate prediction of clinical response requires a novel gene discovery programme to identify markers that are regulated by oestrogen in clinically responding tumours alone (or conversely in clinically resistant tumours alone)... It is concluded that oestrogen-regulated genes are molecular markers of oestrogen sensitivity (not dependence); that expression profiles and molecular responses to endocrine therapy in clinically resistant tumours may be similar to clinical responders; and, therefore, that most oestrogen-regulated genes are unlikely to be robust markers of clinical response to endocrine therapy.

No MeSH data available.


Related in: MedlinePlus