Plasma sex steroid hormone levels and risk of breast cancer in postmenopausal women

Susan E. Hankinson, Walter C. Willett, Jo Ann E. Manson, Graham A. Colditz, David J. Hunter, Donna Spiegelman, Robert L. Barbieri, Frank E. Speizer

Research output: Contribution to journalArticlepeer-review

589 Scopus citations


Background: A positive relationship has generally been observed between plasma estrogen levels and breast cancer risk in postmenopausal women, but most of these studies have been small and few have evaluated specific estrogen fractions (such as percent bioavailable estradiol). In addition, few studies have evaluated plasma and androgen levels in relation to breast cancer risk, and their results have been inconsistent. We prospectively evaluated relationships between sex steroid hormone levels in plasma and risk of breast cancer in postmenopausal women by use of a case-control study nested within the Nurses' Health Study. Methods: Blood samples were collected during the period from 1989 through 1990. Among postmenopausal women not using hormone replacement therapy at blood collection (n = 11 169 women), 156 women were diagnosed with breast cancer after blood collection but before June 1, 1994. Two control subjects were selected per case subject and matched with respect to age, menopausal status, month and time of day of blood collection, and fasting status at the time of blood collection. Results: From comparisons of highest and lowest (reference) quartiles, we observed statistically significant positive associations with risk of breast cancer for circulating levels of estradiol (multivariate relative risk [RR] = 1.91; 95% confidence interval [CI] = 1.06-3.46), estrone (multivariate RR = 1.96; 95% CI = 1.05-3.65), estrone sulfate (multivariate RR = 2.25; 95% CI = 1.23- 4.12), and dehydroepiandrosterone sulfate (multivariate RR = 2.15; 95% CI = 1.11-4.17). We found no substantial associations with percent free or percent bioavailable estradiol, androstenedione, testosterone, or dehydroepiandrosterone. The positive relationships were substantially stronger among women with no previous hormone replacement therapy. Conclusion: Our data, in conjunction with past epidemiologic and animal studies, provide strong evidence for a causal relationship between postmenopausal estrogen levels and the risk of breast cancer.

Original languageEnglish
Pages (from-to)1292-1299
Number of pages8
JournalJournal of the National Cancer Institute
Issue number17
StatePublished - Sep 2 1998


Dive into the research topics of 'Plasma sex steroid hormone levels and risk of breast cancer in postmenopausal women'. Together they form a unique fingerprint.

Cite this