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Oestrogen is bad for patients with breast cancer?

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Breast cancer is a hormone-dependent disease, and a proportion of patients with oestrogen receptors (ERs) will respond to ovarian ablation... This proved to be a cheap source of new medicines... High-dose synthetic oestrogen administration was found to be effective in the treatment of breast and prostate cancer, but low-dose synthetic oestrogens never really became accepted as hormone replacement therapy in postmenopausal women... Based on the link identified between oestrogen and the development and growth of some breast cancers, the current strategy for the treatment and prevention of ER-positive breast cancer is the application of long-term antihormonal therapy... The use of long-term tamoxifen therapy has had a profound effect on survival, but in addition the wide distribution of tamoxifen has resulted in a declining death rate from breast cancer over the past few years... Furthermore, MCF7 cells kept for many years under oestrogen-depleted conditions using medium containing stripped foetal bovine serum produce rapid apoptosis via an intrinsic mechanism directed at the mitochondrion... However, both Lewis and coworkers and Song and Santen found that apoptosis is modulated through bcl-2 or bcl-2XL... Overall, the phenomenon observed with long term oestrogen withdrawal is similar to the phase II resistance of the model described for SERMs. Lonning and coworkers addressed the hypothesis that patients with ER-positive breast cancers who have been treated exhaustively with antihormonal therapy could potentially respond to high-dose oestrogen therapy... Overall, these extremely encouraging preliminary studies with high-dose oestrogen therapy are complemented by anecdotal reports of the effectiveness of low-dose oestrogen treatment for those women with endocrine refractory breast cancer after exhaustive antihormonal therapy (Ingle J, Dixon M, personal communication)... The recognition of the new biology of oestrogen action that causes apoptosis in sensitive breast tumours now opens an unanticipated door of opportunity to exploit the findings to aid patients... Although the actual clinical responses may not be profound in unselected patient populations or in populations whose tumours do not have the correct (stage II) form of breast cancer drug resistance, our ability to decipher apoptotic mechanisms from laboratory models, and eventually to target patients appropriately, may have profound and positive effects for some patients... Years later, after deciphering the target populations and translating the appropriate treatment strategies from the laboratory to the clinic, the drug became the 'gold standard' for endocrine therapy and was credited with improving the survival of hundreds of thousands of women... The challenge for the future is to exploit the profound apoptotic action of oestradiol as a lead to develop innovative new therapies for cancer.

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Organization of Department of Defense Center of Excellence Grant. Shown is the organization of our Department of Defense Center of Excellence Grant entitled 'A new therapeutic paradigm for breast cancer exploiting low-dose oestrogen-induced apoptosis'. The model systems to study the survival and apoptosis induced with oestrogen are being used in time course experiments at the Fox Chase Cancer Center. The materials are distributed to Translational Genomics for genomic analysis using comparative genomic hybridization, small interfering (si)RNA analysis or Agilent gene array analysis, and the Vincent T Lombardi Cancer Center is involved in conducting proteomics analysis. All results are uploaded into a shared secure web for data processing and target identification by our informatics and biostatistical group. Each laboratory is able to validate emerging pathways and study individual genes of interest. Our programme is integrated with a clinical trials programme that provides patient samples for validation of apoptotic or survival pathways. We are grateful to our external advisory board of patient advocates and professional colleagues for their continuing advice and support.
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Figure 1: Organization of Department of Defense Center of Excellence Grant. Shown is the organization of our Department of Defense Center of Excellence Grant entitled 'A new therapeutic paradigm for breast cancer exploiting low-dose oestrogen-induced apoptosis'. The model systems to study the survival and apoptosis induced with oestrogen are being used in time course experiments at the Fox Chase Cancer Center. The materials are distributed to Translational Genomics for genomic analysis using comparative genomic hybridization, small interfering (si)RNA analysis or Agilent gene array analysis, and the Vincent T Lombardi Cancer Center is involved in conducting proteomics analysis. All results are uploaded into a shared secure web for data processing and target identification by our informatics and biostatistical group. Each laboratory is able to validate emerging pathways and study individual genes of interest. Our programme is integrated with a clinical trials programme that provides patient samples for validation of apoptotic or survival pathways. We are grateful to our external advisory board of patient advocates and professional colleagues for their continuing advice and support.

Mentions: Based on preclinical laboratory modelling, we have translated the new biology of oestrogen action into a Department of Defense Center of Excellence grant with laboratory and clinical collaborators illustrated in Figure 1. Our goal is to define the pathways for oestrogen-induced survival and apoptosis in endocrine responsive breast and endometrial cancer, and to use the emerging database to guide the interpretation and development of a series of clinical trials.


Oestrogen is bad for patients with breast cancer?
Organization of Department of Defense Center of Excellence Grant. Shown is the organization of our Department of Defense Center of Excellence Grant entitled 'A new therapeutic paradigm for breast cancer exploiting low-dose oestrogen-induced apoptosis'. The model systems to study the survival and apoptosis induced with oestrogen are being used in time course experiments at the Fox Chase Cancer Center. The materials are distributed to Translational Genomics for genomic analysis using comparative genomic hybridization, small interfering (si)RNA analysis or Agilent gene array analysis, and the Vincent T Lombardi Cancer Center is involved in conducting proteomics analysis. All results are uploaded into a shared secure web for data processing and target identification by our informatics and biostatistical group. Each laboratory is able to validate emerging pathways and study individual genes of interest. Our programme is integrated with a clinical trials programme that provides patient samples for validation of apoptotic or survival pathways. We are grateful to our external advisory board of patient advocates and professional colleagues for their continuing advice and support.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2230530&req=5

Figure 1: Organization of Department of Defense Center of Excellence Grant. Shown is the organization of our Department of Defense Center of Excellence Grant entitled 'A new therapeutic paradigm for breast cancer exploiting low-dose oestrogen-induced apoptosis'. The model systems to study the survival and apoptosis induced with oestrogen are being used in time course experiments at the Fox Chase Cancer Center. The materials are distributed to Translational Genomics for genomic analysis using comparative genomic hybridization, small interfering (si)RNA analysis or Agilent gene array analysis, and the Vincent T Lombardi Cancer Center is involved in conducting proteomics analysis. All results are uploaded into a shared secure web for data processing and target identification by our informatics and biostatistical group. Each laboratory is able to validate emerging pathways and study individual genes of interest. Our programme is integrated with a clinical trials programme that provides patient samples for validation of apoptotic or survival pathways. We are grateful to our external advisory board of patient advocates and professional colleagues for their continuing advice and support.
Mentions: Based on preclinical laboratory modelling, we have translated the new biology of oestrogen action into a Department of Defense Center of Excellence grant with laboratory and clinical collaborators illustrated in Figure 1. Our goal is to define the pathways for oestrogen-induced survival and apoptosis in endocrine responsive breast and endometrial cancer, and to use the emerging database to guide the interpretation and development of a series of clinical trials.

View Article: PubMed Central - HTML

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Breast cancer is a hormone-dependent disease, and a proportion of patients with oestrogen receptors (ERs) will respond to ovarian ablation... This proved to be a cheap source of new medicines... High-dose synthetic oestrogen administration was found to be effective in the treatment of breast and prostate cancer, but low-dose synthetic oestrogens never really became accepted as hormone replacement therapy in postmenopausal women... Based on the link identified between oestrogen and the development and growth of some breast cancers, the current strategy for the treatment and prevention of ER-positive breast cancer is the application of long-term antihormonal therapy... The use of long-term tamoxifen therapy has had a profound effect on survival, but in addition the wide distribution of tamoxifen has resulted in a declining death rate from breast cancer over the past few years... Furthermore, MCF7 cells kept for many years under oestrogen-depleted conditions using medium containing stripped foetal bovine serum produce rapid apoptosis via an intrinsic mechanism directed at the mitochondrion... However, both Lewis and coworkers and Song and Santen found that apoptosis is modulated through bcl-2 or bcl-2XL... Overall, the phenomenon observed with long term oestrogen withdrawal is similar to the phase II resistance of the model described for SERMs. Lonning and coworkers addressed the hypothesis that patients with ER-positive breast cancers who have been treated exhaustively with antihormonal therapy could potentially respond to high-dose oestrogen therapy... Overall, these extremely encouraging preliminary studies with high-dose oestrogen therapy are complemented by anecdotal reports of the effectiveness of low-dose oestrogen treatment for those women with endocrine refractory breast cancer after exhaustive antihormonal therapy (Ingle J, Dixon M, personal communication)... The recognition of the new biology of oestrogen action that causes apoptosis in sensitive breast tumours now opens an unanticipated door of opportunity to exploit the findings to aid patients... Although the actual clinical responses may not be profound in unselected patient populations or in populations whose tumours do not have the correct (stage II) form of breast cancer drug resistance, our ability to decipher apoptotic mechanisms from laboratory models, and eventually to target patients appropriately, may have profound and positive effects for some patients... Years later, after deciphering the target populations and translating the appropriate treatment strategies from the laboratory to the clinic, the drug became the 'gold standard' for endocrine therapy and was credited with improving the survival of hundreds of thousands of women... The challenge for the future is to exploit the profound apoptotic action of oestradiol as a lead to develop innovative new therapies for cancer.

No MeSH data available.


Related in: MedlinePlus