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The oestrogen paradox: an hypothesis

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With these data as a background, it was quite surprising that recently published data suggested that women taking postmenopausal hormone therapy (MHT) with oestrogen alone for 5 to 9 years unexpectedly experienced a decrease in the risk for breast cancer... A second component of the oestrogen paradox is that high-dose oestrogen therapy in postmenopausal women with breast cancer causes tumour regression, whereas the anti-oestrogen tamoxifen is equally effective in causing remissions in similar patient groups... A recent exploratory analysis of updated data from this study examined subgroups to determine whether oestrogens might reduce the incidence of breast cancer significantly in women falling into certain categories... Notably, this analysis reported a statistically significant 33% reduction in invasive breast cancer incidence in patients who strictly adhered to their oestrogen therapy (HR 0.67, 95% CI 0.47 to 0.97)... In a concurrent report from the Nurses Health Study, a significant 26% decrease in risk for breast cancer was observed in obese women, and a nonsignificant 10% decrease in all study participants, taking oestrogen alone for 5 to 9 years... Other observational studies reported a reduction in risk with oestrogen alone but of lesser magnitude and not statistically significant... For example, Schairer and colleagues reported a 7% reduction in breast cancer risk at 6 years in women receiving oestrogen alone, and Lyytinen and coworkers identified a similar 7% reduction... These combined results, although not conclusive, are highly suggestive of a beneficial effect of oestrogen in reducing breast cancer risk... However, this conclusion must be considered provisional until rigorous confirmation in additional studies is reported... The postmenopausal women receiving MHT with oestrogen alone may be considered to be in a state of long-term oestradiol deprivation... We suggest that the increased risk for breast cancer results from long-term use of oestrogens alone because the risk from MHT may occur via different mechanisms : the genotoxic effects of oestradiol metabolites and the ER-mediated proliferative effects of oestradiol... If our hypothesis were correct, then exposure to oestrogen therapy as MHT would induce apoptosis and shrink or even eradicate the occult tumours, which would reduce the detection of a cancer by mammography or palpation over the next several years... These combined observations suggest that directly genotoxic as well as ER-mediated mechanisms may be responsible for the long-term carcinogenic effects of oestradiol... In time, the pro-carcinogenic effects of oestradiol would outweigh the pro-apoptotic effects.

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Hormonal risk factors associated with an increased risk of breast cancer and related to oestrogen exposure. For references supporting the validity of this figure, see Santen [1]. E, oestrogen; E2, oestradiol; HRT, hormone replacement therapy; OOX, oophorectomy; P, progesterone. Reproduced with permission from Santen RJ: Endocrine-responsive cancer. In Williams Textbook of Endocrinology. Edited by Larsen PR, Kronenberg HM, Melmed S, Polonsky KS. Philadelphia, PA: WB Saunders Company; 2007:1763–1801. © Elsevier 2007.
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Figure 1: Hormonal risk factors associated with an increased risk of breast cancer and related to oestrogen exposure. For references supporting the validity of this figure, see Santen [1]. E, oestrogen; E2, oestradiol; HRT, hormone replacement therapy; OOX, oophorectomy; P, progesterone. Reproduced with permission from Santen RJ: Endocrine-responsive cancer. In Williams Textbook of Endocrinology. Edited by Larsen PR, Kronenberg HM, Melmed S, Polonsky KS. Philadelphia, PA: WB Saunders Company; 2007:1763–1801. © Elsevier 2007.

Mentions: As shown in Figure 1, a wide range of epidemiologic and observational data suggest that oestrogens are associated with the development of breast cancer [1,2]. With these data as a background, it was quite surprising that recently published data suggested that women taking postmenopausal hormone therapy (MHT) with oestrogen alone for 5 to 9 years unexpectedly experienced a decrease in the risk for breast cancer [3,4]. However, when taken for more than 20 years, the risk appeared to increase [5,6]. We call this the 'oestrogen paradox' to highlight the fact that short-term oestrogen use decreases the risk for breast cancer whereas long-term use increases it. A second component of the oestrogen paradox is that high-dose oestrogen therapy in postmenopausal women with breast cancer causes tumour regression, whereas the anti-oestrogen tamoxifen is equally effective in causing remissions in similar patient groups [7-9]. It is paradoxical then that both oestrogens and anti-oestrogens cause tumour regressions.


The oestrogen paradox: an hypothesis
Hormonal risk factors associated with an increased risk of breast cancer and related to oestrogen exposure. For references supporting the validity of this figure, see Santen [1]. E, oestrogen; E2, oestradiol; HRT, hormone replacement therapy; OOX, oophorectomy; P, progesterone. Reproduced with permission from Santen RJ: Endocrine-responsive cancer. In Williams Textbook of Endocrinology. Edited by Larsen PR, Kronenberg HM, Melmed S, Polonsky KS. Philadelphia, PA: WB Saunders Company; 2007:1763–1801. © Elsevier 2007.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2230529&req=5

Figure 1: Hormonal risk factors associated with an increased risk of breast cancer and related to oestrogen exposure. For references supporting the validity of this figure, see Santen [1]. E, oestrogen; E2, oestradiol; HRT, hormone replacement therapy; OOX, oophorectomy; P, progesterone. Reproduced with permission from Santen RJ: Endocrine-responsive cancer. In Williams Textbook of Endocrinology. Edited by Larsen PR, Kronenberg HM, Melmed S, Polonsky KS. Philadelphia, PA: WB Saunders Company; 2007:1763–1801. © Elsevier 2007.
Mentions: As shown in Figure 1, a wide range of epidemiologic and observational data suggest that oestrogens are associated with the development of breast cancer [1,2]. With these data as a background, it was quite surprising that recently published data suggested that women taking postmenopausal hormone therapy (MHT) with oestrogen alone for 5 to 9 years unexpectedly experienced a decrease in the risk for breast cancer [3,4]. However, when taken for more than 20 years, the risk appeared to increase [5,6]. We call this the 'oestrogen paradox' to highlight the fact that short-term oestrogen use decreases the risk for breast cancer whereas long-term use increases it. A second component of the oestrogen paradox is that high-dose oestrogen therapy in postmenopausal women with breast cancer causes tumour regression, whereas the anti-oestrogen tamoxifen is equally effective in causing remissions in similar patient groups [7-9]. It is paradoxical then that both oestrogens and anti-oestrogens cause tumour regressions.

View Article: PubMed Central - HTML

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

With these data as a background, it was quite surprising that recently published data suggested that women taking postmenopausal hormone therapy (MHT) with oestrogen alone for 5 to 9 years unexpectedly experienced a decrease in the risk for breast cancer... A second component of the oestrogen paradox is that high-dose oestrogen therapy in postmenopausal women with breast cancer causes tumour regression, whereas the anti-oestrogen tamoxifen is equally effective in causing remissions in similar patient groups... A recent exploratory analysis of updated data from this study examined subgroups to determine whether oestrogens might reduce the incidence of breast cancer significantly in women falling into certain categories... Notably, this analysis reported a statistically significant 33% reduction in invasive breast cancer incidence in patients who strictly adhered to their oestrogen therapy (HR 0.67, 95% CI 0.47 to 0.97)... In a concurrent report from the Nurses Health Study, a significant 26% decrease in risk for breast cancer was observed in obese women, and a nonsignificant 10% decrease in all study participants, taking oestrogen alone for 5 to 9 years... Other observational studies reported a reduction in risk with oestrogen alone but of lesser magnitude and not statistically significant... For example, Schairer and colleagues reported a 7% reduction in breast cancer risk at 6 years in women receiving oestrogen alone, and Lyytinen and coworkers identified a similar 7% reduction... These combined results, although not conclusive, are highly suggestive of a beneficial effect of oestrogen in reducing breast cancer risk... However, this conclusion must be considered provisional until rigorous confirmation in additional studies is reported... The postmenopausal women receiving MHT with oestrogen alone may be considered to be in a state of long-term oestradiol deprivation... We suggest that the increased risk for breast cancer results from long-term use of oestrogens alone because the risk from MHT may occur via different mechanisms : the genotoxic effects of oestradiol metabolites and the ER-mediated proliferative effects of oestradiol... If our hypothesis were correct, then exposure to oestrogen therapy as MHT would induce apoptosis and shrink or even eradicate the occult tumours, which would reduce the detection of a cancer by mammography or palpation over the next several years... These combined observations suggest that directly genotoxic as well as ER-mediated mechanisms may be responsible for the long-term carcinogenic effects of oestradiol... In time, the pro-carcinogenic effects of oestradiol would outweigh the pro-apoptotic effects.

No MeSH data available.


Related in: MedlinePlus