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Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies.

Abstract

BACKGROUND

Reproductive and hormonal factors are involved in the etiology of breast cancer, but there are only a few prospective studies on endogenous sex hormone levels and breast cancer risk. We reanalyzed the worldwide data from prospective studies to examine the relationship between the levels of endogenous sex hormones and breast cancer risk in postmenopausal women.

METHODS

We analyzed the individual data from nine prospective studies on 663 women who developed breast cancer and 1765 women who did not. None of the women was taking exogenous sex hormones when their blood was collected to determine hormone levels. The relative risks (RRs) for breast cancer associated with increasing hormone concentrations were estimated by conditional logistic regression on case-control sets matched within each study. Linear trends and heterogeneity of RRs were assessed by two-sided tests or chi-square tests, as appropriate.

RESULTS

The risk for breast cancer increased statistically significantly with increasing concentrations of all sex hormones examined: total estradiol, free estradiol, non-sex hormone-binding globulin (SHBG)-bound estradiol (which comprises free and albumin-bound estradiol), estrone, estrone sulfate, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone. The RRs for women with increasing quintiles of estradiol concentrations, relative to the lowest quintile, were 1.42 (95% confidence interval [CI] = 1.04 to 1.95), 1.21 (95% CI = 0.89 to 1.66), 1.80 (95% CI = 1.33 to 2.43), and 2.00 (95% CI = 1.47 to 2.71; P(trend)<.001); the RRs for women with increasing quintiles of free estradiol were 1.38 (95% CI = 0.94 to 2.03), 1.84 (95% CI = 1.24 to 2.74), 2.24 (95% CI = 1.53 to 3.27), and 2.58 (95% CI = 1.76 to 3.78; P(trend)<.001). The magnitudes of risk associated with the other estrogens and with the androgens were similar. SHBG was associated with a decrease in breast cancer risk (P(trend) =.041). The increases in risk associated with increased levels of all sex hormones remained after subjects who were diagnosed with breast cancer within 2 years of blood collection were excluded from the analysis.

CONCLUSION

Levels of endogenous sex hormones are strongly associated with breast cancer risk in postmenopausal women.

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  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Cancer Research U.K. Epidemiology Unit, University of Oxford, Radcliffe Infirmary, Oxford, UK.

    , , ,

    Source

    Journal of the National Cancer Institute 94:8 2002 Apr 17 pg 606-16

    MeSH

    Aged
    Androstenedione
    Breast Neoplasms
    Case-Control Studies
    Dehydroepiandrosterone
    Dehydroepiandrosterone Sulfate
    Estradiol
    Estrone
    Female
    Hormone Replacement Therapy
    Humans
    Middle Aged
    Prospective Studies
    Risk
    Sex Hormone-Binding Globulin
    Testosterone
    Time Factors

    Pub Type(s)

    Journal Article
    Meta-Analysis
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    11959894

    Citation

    Key, T, et al. "Endogenous Sex Hormones and Breast Cancer in Postmenopausal Women: Reanalysis of Nine Prospective Studies." Journal of the National Cancer Institute, vol. 94, no. 8, 2002, pp. 606-16.
    Key T, Appleby P, Barnes I, et al. Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst. 2002;94(8):606-16.
    Key, T., Appleby, P., Barnes, I., & Reeves, G. (2002). Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. Journal of the National Cancer Institute, 94(8), pp. 606-16.
    Key T, et al. Endogenous Sex Hormones and Breast Cancer in Postmenopausal Women: Reanalysis of Nine Prospective Studies. J Natl Cancer Inst. 2002 Apr 17;94(8):606-16. PubMed PMID: 11959894.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. AU - Key,T, AU - Appleby,P, AU - Barnes,I, AU - Reeves,G, AU - ,, PY - 2002/4/18/pubmed PY - 2002/5/7/medline PY - 2002/4/18/entrez SP - 606 EP - 16 JF - Journal of the National Cancer Institute JO - J. Natl. Cancer Inst. VL - 94 IS - 8 N2 - BACKGROUND: Reproductive and hormonal factors are involved in the etiology of breast cancer, but there are only a few prospective studies on endogenous sex hormone levels and breast cancer risk. We reanalyzed the worldwide data from prospective studies to examine the relationship between the levels of endogenous sex hormones and breast cancer risk in postmenopausal women. METHODS: We analyzed the individual data from nine prospective studies on 663 women who developed breast cancer and 1765 women who did not. None of the women was taking exogenous sex hormones when their blood was collected to determine hormone levels. The relative risks (RRs) for breast cancer associated with increasing hormone concentrations were estimated by conditional logistic regression on case-control sets matched within each study. Linear trends and heterogeneity of RRs were assessed by two-sided tests or chi-square tests, as appropriate. RESULTS: The risk for breast cancer increased statistically significantly with increasing concentrations of all sex hormones examined: total estradiol, free estradiol, non-sex hormone-binding globulin (SHBG)-bound estradiol (which comprises free and albumin-bound estradiol), estrone, estrone sulfate, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone. The RRs for women with increasing quintiles of estradiol concentrations, relative to the lowest quintile, were 1.42 (95% confidence interval [CI] = 1.04 to 1.95), 1.21 (95% CI = 0.89 to 1.66), 1.80 (95% CI = 1.33 to 2.43), and 2.00 (95% CI = 1.47 to 2.71; P(trend)<.001); the RRs for women with increasing quintiles of free estradiol were 1.38 (95% CI = 0.94 to 2.03), 1.84 (95% CI = 1.24 to 2.74), 2.24 (95% CI = 1.53 to 3.27), and 2.58 (95% CI = 1.76 to 3.78; P(trend)<.001). The magnitudes of risk associated with the other estrogens and with the androgens were similar. SHBG was associated with a decrease in breast cancer risk (P(trend) =.041). The increases in risk associated with increased levels of all sex hormones remained after subjects who were diagnosed with breast cancer within 2 years of blood collection were excluded from the analysis. CONCLUSION: Levels of endogenous sex hormones are strongly associated with breast cancer risk in postmenopausal women. SN - 0027-8874 UR - https://www.unboundmedicine.com/medline/citation/11959894/full_citation L2 - https://academic.oup.com/jnci/article-lookup/doi/10.1093/jnci/94.8.606 DB - PRIME DP - Unbound Medicine ER -