Obesity, non-protein-bound estradiol levels, and distribution of estradiol in the sera of breast cancer patients

Ota, David M.; Jones, Lovell A.; Jackson, Gilchrist L.; Jackson, Paige; Kemp, Katherine; Bauman, Donald H.

doi:10.1002/1097-0142(19860201)57:3<558::aid-cncr2820570326>3.0.co;2-1

Cited by 76 publications

(15 citation statements)

References 13 publications

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“…Several recent studies have found that breast cancer cases have higher percentages of free E2 or greater amounts of free E2 than controls (Moore et al, 1982(Moore et al, , 1986Reed et al, 1983Reed et al, , 1985Bruning et al, 1985;Langley et al, 1985;Ota et al, 1986;Siiteri et al, 1986;Jones et al, 1987). Because higher weight is associated with lower levels of SHBG and higher percentages of both free E2 and non-SHBG bound E2 (Siiteri et al, 1981), the reported higher weight of cases in several of these studies can account, at least in part, for the observed differences.…”

Section: Discussionmentioning

confidence: 95%

Hormone levels in older women: a study of post-menopausal breast cancer patients and healthy population controls

Bernstein

Ross²,

Pike³

et al. 1990

Br J Cancer

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Summary Hormone concentrations in blood and total 12 h urine values were compared between 40 postmenopausal women with breast cancer and 40 control women in a study which carefully controlled for the possible confounding effects of age, weight and pregnancy history by individually matching cases and controls on these factors. Breast cancer cases had received only surgical treatment for their localised disease, which was diagnosed from 1 to 9 years before hormonal evaluation. Cases had 15% higher serum oestradiol levels (P=0.02), 40% more urinary oestradiol (P=0.03) and 44% more urinary oestriol (P=0.04) than control women. Cases also had higher levels of serum and urinary oestrone, but these differences were not statistically significant. The percentages of serum oestradiol not bound to albumin or sex-hormone binding globulin did not differ between cases and controls, nor were there statistically significant differences in the serum levels of prolactin, sex-hormone binding globulin or dehydroepiandrosterone sulphate. These results provide further support for the hypothesis that breast cancer risk is determined in part by post-menopausal serum oestrogen concentration.There is a substantial body of epidemiological, experimental and clinical evidence for a role of oestrogens in the aetiology of female breast cancer (Henderson et al., 1988). In premenopausal women, the major source of endogenous oestrogens is the ovary. Menopause signals a marked decline in the amount of circulating oestrogens and this decline is at least part of the explanation for the decreased risk of breast cancer associated with early menopause (Trichopoulos et al., 1972). Although breast cancer incidence continues to rise after menopause in US and European women, the rate of increase in breast cancer incidence decreases substantially. In post-menopausal women, the major source of oestrogen is the peripheral conversion of androstenedione in fat tissue (Grodin et al., 1973). This offers the most probable explanation for the association of obesity with increased risk of breast cancer in post-menopausal women (Lubin et al., 1985).In women, 40-50% of plasma oestradiol (E2) is bound to sex hormone-binding globulin (SHBG) and all but 2-4% of the remainder is bound to albumin (Anderson, 1974). With the development of relevant laboratory technology, attention has focused on evaluating whether the free, non-protein bound fraction of plasma E2 is higher in women with breast cancer than in other women, as free E2 is considered to be freely diffusible into cells and biologically available to receptors in target tissues (Siiteri, 1980); this may also be true of the non-SHGB bound E2 (Pardridge, 1986). This would further explain the effect of body weight on breast cancer risk in older women as increased weight is not only associated with higher post-menopausal oestrogen levels but also with reduced levels of SHBG and, therefore, with greater 'tissue availability' of oestrogens (Siiteri et al., 1981).A number of studies have compared endogenous oestrogen and ...

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Section: Discussionmentioning

confidence: 95%

Hormone levels in older women: a study of post-menopausal breast cancer patients and healthy population controls

Bernstein

Ross²,

Pike³

et al. 1990

Br J Cancer

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“…Current hypotheses about the mechanism underlying the associations between obesity and breast cancer include increased aromatisation of steroid precursors and reduced binding of oestrogens to sex hormone-binding globulin, resulting in increased levels of biological available oestrogens (Enriori & Reforzo-Membrives, 1984;Ota et al, 1986). A similar hypothesis has been proposed for the relationship between fat distribution and breast cancer.…”

Section: Discussionmentioning

confidence: 96%

A prospective study on obesity and subcutaneous fat patterning in relation to breast cancer in post-menopausal women participating in the DOM project

Tonkelaar

Seidell²,

Collette³

et al. 1994

Br J Cancer

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Summary The associations of body fat and body fat distribution with breast cancer risk were examined in a prospective study in 9,746 post-menopausal women with a natural menopause, aged [49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66] (Tornberg et al., 1988;Tretli, 1989).The relationship between body fat distribution and breast cancer has been studied in four American studies and three European studies (Lapidus et al., 1988; Ballard-Barbash et al., 1990;Folsom et al., 1990;Schapira et al., 1990;Soennichsen et al., 1990;Bruning et al., 1992;Petrek et al., 1993). The characteristics and results of these studies are summarised in Table I. The potential relationship between fat distribution and breast cancer is also currently debated. In most studies waist-hip ratio was used as an indicator of fat distribution. The ratio of triceps-subscapular skinfolds has also been used as an indicator of fat distribution and was found to be related to coronary heart disease and diabetes (Bj6rntorp, 1991).In a previous, cross-sectional study on obesity and subcutaneous fat patterning in relation to breast cancer we observed a significant association between overall fatness and breast cancer, whereas fat distribution, as measured by contrasting subscapular and triceps skinfold thickness, was not related to breast cancer (Tonkelaar et al., 1992).In

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“…Similarly, increased amounts of free E 2 have been found in women at risk of breast cancer (11) or in women who subsequently developed the disease (13,14). However, others have failed to find such a clear-cut association (16).…”

Section: Introductionmentioning

confidence: 92%

“…Armstrong and colleagues (9) have produced evidence that vegetarians do exhibit above-normal blood concentrations of SHBG. This might have implications for breast cancer risk, because it has been reported that the increased percentages and/or enhanced levels of unbound E 2 are present in women with breast cancer, when compared with controls (10)(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

The binding of blood‐borne estrogens in normal vegetarian and omnivorous women and the risk of breast cancer

Fentiman

Caleffi

Wang

et al. 1988

Nutrition and Cancer

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Serial blood samples were taken at two-hour intervals over a 24-hour period from 25 premenopausal vegetarians (12 vegans and 13 ovolactovegetarians) and from 21 omnivorous controls. All members of the former group had been on a vegetarian diet for a minimum of three years. The mean proportion of estradiol unbound to blood proteins was similar in both vegetarians (1.26%) and meat eaters (1.16%). However, the amount bound to albumin was significantly raised in vegetarians (50.1% vs. 43.1%, p less than 0.009), whereas that bound to sex hormone-binding globulin (SHBG) was correspondingly lower (48.7% vs. 55.8%, p = 0.01). Mean levels of SHBG were similar in vegetarians (59.9 nmole/l) and omnivores (62.0 nmole/l), as was the total amount of free fatty acid (0.42 mmole/l for both). Within the vegetarian group, no differences were detected between vegans and ovolactovegetarians.

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Obesity, non-protein-bound estradiol levels, and distribution of estradiol in the sera of breast cancer patients

Cited by 76 publications

References 13 publications

Hormone levels in older women: a study of post-menopausal breast cancer patients and healthy population controls

Hormone levels in older women: a study of post-menopausal breast cancer patients and healthy population controls

A prospective study on obesity and subcutaneous fat patterning in relation to breast cancer in post-menopausal women participating in the DOM project

The binding of blood‐borne estrogens in normal vegetarian and omnivorous women and the risk of breast cancer

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