Circulating Hormone Concentrations in Women With Breast Cancer

I, McFadyen; Prescott, R.; Groom, G. V.; Forrest, A. P. M.; Golder, Meriel P.; Fahmy, D.R.; Griffiths, K.

doi:10.1016/s0140-6736(76)90064-7

Cited by 44 publications

(9 citation statements)

References 8 publications

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“…Several case-control studies (Grattarola et al, 1974;McFadyen et al, 1976;Adami et al, 1979;Secreto et al, 1983;Hill et al, 1985;Secreto et al, 1991) have reported that a significantly increased risk of breast cancer in post-menopausal women is associated with high levels of testosterone in serum and urine. The prospective studies of Berrino et al (1996) (24 cases) and Dorgan et al (1996) (71 cases) both reported a significant association between breast cancer risk and total testosterone concentration, quoting adjusted odds ratios of 7.0 and 6.2, respectively, for the top category of the concentration distribution.…”

Section: Discussionmentioning

confidence: 99%

A prospective study of endogenous serum hormone concentrations and breast cancer risk in post-menopausal women on the island of Guernsey

Thomas¹,

Key²,

Allen³

et al. 1997

Br J Cancer

202

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(SHBG) and risk of breast cancer in post-menopausal women were investigated in a prospective study on the island of Guernsey. Sixty-one women who developed breast cancer an average of 7.8 years after blood collection were matched for age, year of blood collection and number of years post-menopausal with 179 control subjects. Women using exogenous hormones at the time of blood collection were excluded from the study. Women who subsequently developed breast cancer had a 29% higher geometric mean oestradiol concentration than control women (P = 0.004). The odds ratio for breast cancer in the top third compared with the lowest third of the oestradiol concentration distribution was 5.03 (95% confidence interval 2.02-12.49, Pfor trend < 0.001). Adjusting for testosterone and SHBG concentrations did not substantially alter the odds ratio for oestradiol. Although testosterone and SHBG concentrations were associated with breast cancer risk, the concentrations of these hormones were correlated with those of oestradiol; the associations were not statistically significant after adjusting for oestradiol concentration. These data provide evidence that serum oestradiol concentrations in post-menopausal women may have a substantial effect on breast cancer risk.

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Section: Discussionmentioning

confidence: 99%

A prospective study of endogenous serum hormone concentrations and breast cancer risk in post-menopausal women on the island of Guernsey

Thomas¹,

Key²,

Allen³

et al. 1997

Br J Cancer

202

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“…Previous studies have evaluated either urinary oestrogen excretion (Persson & Risholm, 1964;Marmorston et al, 1965;Gronroos & Aho, 1968;Argeulles et al, 1973;Grattarola et , 1974;Thijssen et al, 1975;Morreal et al, 1979) or oestrogen concentrations in the blood (England et al, 1974;McFadyen et al, 1976;Malarkey et al, 1977;Adami et al, 1979;Drafta et al, 1980;Moore et al, 1982;Reed et al, 1983Reed et al, , 1985Secreto et al, 1983;Bruning et al, 1985;Siiteri et al, 1986;Wysowski et al, 1987) of breast cancer cases and controls. These studies have suggested that post-menopausal breast cancer cases have higher endogenous oestrogen levels than controls: five of the seven studies of urinary oestrogen levels found evidence of greater oestrogen excretion in cases (Persson & Risholm, 1964;Marmorston et al, 1965;Arguelles et al, 1973;Grattarola et al, 1974;Morreal et al,1979); of the studies comparing blood levels of E, and E2 in cases and controls, three of five found higher E, (Adami et al, 1979;Drafta et al, 1980;Reed et al, 1983) and eight of 11 found higher E2 levels in cases (England et al, 1974;McFadyen et al, 1976;Malarkey et al, 1977;Drafta et al, 1980;Moore et al, 1982;Reed et al, 1985;Bruning et al, 1985;Siiteri et al, 1986).…”

Section: Discussionmentioning

confidence: 99%

“…These studies have suggested that post-menopausal breast cancer cases have higher endogenous oestrogen levels than controls: five of the seven studies of urinary oestrogen levels found evidence of greater oestrogen excretion in cases (Persson & Risholm, 1964;Marmorston et al, 1965;Arguelles et al, 1973;Grattarola et al, 1974;Morreal et al,1979); of the studies comparing blood levels of E, and E2 in cases and controls, three of five found higher E, (Adami et al, 1979;Drafta et al, 1980;Reed et al, 1983) and eight of 11 found higher E2 levels in cases (England et al, 1974;McFadyen et al, 1976;Malarkey et al, 1977;Drafta et al, 1980;Moore et al, 1982;Reed et al, 1985;Bruning et al, 1985;Siiteri et al, 1986). The results of the present study provide evidence that the higher serum oestrogen concentrations of breast cancer cases are mirrored in the urine by higher urinary oestrogen excretion.…”

Section: Discussionmentioning

confidence: 99%

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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“…There are a large number of reports associating high androgen status in post-menopausal women with breast cancer (Grattarola et al, 1974;McFadyen et al, 1976;Adami et al, 1979;Secreto et al, 1983Secreto et al, , 1991Hill et al, 1985;Secreto and Zumoff, 1994;Dorgan et al, 1996;Thomas et al, 1997;Zeleniuch-Jacquotte et al, 1997). The post-menopausal type of disease could be influenced by oestrogens from the metabolism of adrenal androgens.…”

Section: Discussionmentioning

confidence: 99%

True

et al. 2000

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It would be very useful if it were possible to identify, within an apparently normal population, those who will develop breast cancer. Although this can be achieved by genetic testing for mutations of BRCA1 and BRCA2, such susceptibility genes are involved in the aetiology of only about 5% of breast cancer cases (Lynch and Lynch, 1986). By contrast, events related to a woman's menstrual and reproductive history, which have been widely recognized as determinants of breast cancer incidence, are not impressive predictors of individual risks. Such poor predictive performance could result from these epidemiological variables being only manifestations of other underlying factors. Indeed the size of the effects of the menstrual and reproductive variables and the observation that breast cancer rates change over a woman's life have stimulated investigation of endogenous sex hormones as potential causes underlying these observed effects (Key and Pike, 1988;Toniolo et al, 1995;Key et al, 1996). Methodological issues related to hormone measurements, however, complicate the study of their relationship with breast cancer. Furthermore, there is no general consensus regarding which biological forms of these hormones are actually associated with the observed changes in incidence rates.The role of steroids in the aetiology of breast cancer is uncertain. Extensive analysis of the scientific literature shows a highly significant increase in blood oestradiol levels in post-menopausal women with breast cancer (Thomas et al, 1997). The position of oestrogens and premenopausal women is uncertain (Key and Pike, 1988; Thomas et al, 1997). Androgens have been studied less extensively than oestrogens and no meta-analysis has yet been undertaken.The first prospective study in this field was performed by Bulbrook and Hayward who showed that levels of androsterone (A) and aetiocholanolone (E) were abnormally low in women who subsequently developed breast cancer (Bulbrook and Hayward, 1967;Bulbrook et al, 1971). Most of the cases were premenopausal and the abnormality was present up to 11 years before the clinical diagnosis of the disease, suggesting that high levels of androgen metabolites might have a protective effect, at least in younger women. However, other mainly retrospective casecontrol studies have claimed that high androgen excretion is positively associated with breast cancer risk (e.g. Secreto and Zumoff, 1994). Such contrasting results could be reconciled if the effects of androgens depended on menopausal status. This would occur if the androgens acted as oestrogen inhibitors in premenopausal women and as oestrogen enhancers (or even oestrogens) in the postmenopausal (Secreto and Zumoff, 1994;Adams, 1998 Summary Between 1961 and 1967 a cohort of over 5000 women volunteered for a prospective study to determine the relationship between the urinary androgen metabolites, androsterone (A) and aetiocholanolone (E), and risk of breast cancer. During the first 10 years of the study the concentration of urinary A and E was determined in 1...

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Circulating Hormone Concentrations in Women With Breast Cancer

Cited by 44 publications

References 8 publications

A prospective study of endogenous serum hormone concentrations and breast cancer risk in post-menopausal women on the island of Guernsey

A prospective study of endogenous serum hormone concentrations and breast cancer risk in post-menopausal women on the island of Guernsey

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

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