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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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Anticipated treatment plan for third-line endocrine therapy. Patients must have responded and failed two successive antihormonal therapies to be eligible for a course of low-dose oestradiol therapy for 3 months. The anticipated response rate is 30% [44] and responding patients will be treated with anastrozole until relapse. Validation of the treatment plan via the Center of Excellence Grant (Figure 1) will establish a platform to enhance response rates with apoptotic oestrogen by integrating known inhibitors of tumour survival pathways into the 3-month low-dose oestrogen debulking treatment plan. The overall goal is to increase response rates and maintain patients for longer on antihormonal strategies before chemotherapy is required.
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Figure 2: Anticipated treatment plan for third-line endocrine therapy. Patients must have responded and failed two successive antihormonal therapies to be eligible for a course of low-dose oestradiol therapy for 3 months. The anticipated response rate is 30% [44] and responding patients will be treated with anastrozole until relapse. Validation of the treatment plan via the Center of Excellence Grant (Figure 1) will establish a platform to enhance response rates with apoptotic oestrogen by integrating known inhibitors of tumour survival pathways into the 3-month low-dose oestrogen debulking treatment plan. The overall goal is to increase response rates and maintain patients for longer on antihormonal strategies before chemotherapy is required.

Mentions: The ultimate goal of our clinical trial design is illustrated in Figure 2 and currently consists of two separate but interconnected therapeutic oestrogen studies, designed to determine the lowest dose of a 12-week course of oestrogen that causes a positive therapeutic effect.


Oestrogen is bad for patients with breast cancer?
Anticipated treatment plan for third-line endocrine therapy. Patients must have responded and failed two successive antihormonal therapies to be eligible for a course of low-dose oestradiol therapy for 3 months. The anticipated response rate is 30% [44] and responding patients will be treated with anastrozole until relapse. Validation of the treatment plan via the Center of Excellence Grant (Figure 1) will establish a platform to enhance response rates with apoptotic oestrogen by integrating known inhibitors of tumour survival pathways into the 3-month low-dose oestrogen debulking treatment plan. The overall goal is to increase response rates and maintain patients for longer on antihormonal strategies before chemotherapy is required.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 2: Anticipated treatment plan for third-line endocrine therapy. Patients must have responded and failed two successive antihormonal therapies to be eligible for a course of low-dose oestradiol therapy for 3 months. The anticipated response rate is 30% [44] and responding patients will be treated with anastrozole until relapse. Validation of the treatment plan via the Center of Excellence Grant (Figure 1) will establish a platform to enhance response rates with apoptotic oestrogen by integrating known inhibitors of tumour survival pathways into the 3-month low-dose oestrogen debulking treatment plan. The overall goal is to increase response rates and maintain patients for longer on antihormonal strategies before chemotherapy is required.
Mentions: The ultimate goal of our clinical trial design is illustrated in Figure 2 and currently consists of two separate but interconnected therapeutic oestrogen studies, designed to determine the lowest dose of a 12-week course of oestrogen that causes a positive therapeutic effect.

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