Endogenous steroid hormone concentrations and risk of breast cancer among premenopausal women.
BACKGROUND
Higher levels of endogenous sex steroid hormones are associated with increased risks of breast cancer in postmenopausal women. Data for premenopausal women are sparse, in part because of the complexity of measuring hormone levels that vary cyclically. We prospectively evaluated associations between plasma sex hormone levels and breast cancer risk among premenopausal women in a case-control study nested within the Nurses' Health Study II.


METHODS
From 1996 to 1999, blood samples were collected from 18,521 premenopausal women during the early follicular and midluteal phases of their menstrual cycles. A total of 197 cases of breast cancer were diagnosed among these women after blood collection and before June 1, 2003; these case subjects were matched to 394 control subjects. Logistic regression models, controlling for breast cancer risk factors, were used to calculate relative risks (RRs) and 95% confidence intervals (CIs). All statistical tests were two-sided.


RESULTS
Women in the highest (versus the lowest) quartiles of follicular total and free estradiol levels had statistically significantly increased risks of breast cancer (RR = 2.1 [95% CI = 1.1 to 4.1], P(trend) = .08, and RR = 2.4 [95% CI = 1.3 to 4.5], P(trend) = .01, respectively); the associations were stronger for invasive breast cancer and for estrogen and progesterone receptor-positive (ER+/PR+) tumors. Luteal estradiol levels were not associated with breast cancer risk. Higher levels of total and free testosterone and androstenedione in both menstrual cycle phases were associated with modest, non-statistically significant increases in overall risk of breast cancer and with stronger, statistically significant increases in risks of invasive and ER+/PR+ cancers (e.g., RR of invasive cancers for the top [versus bottom] quartile of luteal total testosterone levels = 2.0 [95% CI = 1.1 to 3.6], P(trend) = .05, and RR of ER+/PR+ cancers = 2.9 [95% CI = 1.4 to 6.0], P(trend) = .02). Levels of estrone, estrone sulfate, progesterone, and sex hormone-binding globulin were not associated with breast cancer risk. The absolute number of cases observed over 3 years were 30 among women in the lowest 25% of follicular total estradiol levels and 50 among women in the highest 25%.


CONCLUSIONS
Levels of circulating estrogens and androgens may be important in the etiology of premenopausal breast cancer.
Eliassen
A Heather
AH
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Ave., Boston, MA 02115, USA. heather.eliassen@channing.harvard.edu
Missmer
Stacey A
SA
Tworoger
Shelley S
SS
Spiegelman
Donna
D
Barbieri
Robert L
RL
Dowsett
Mitch
M
Hankinson
Susan E
SE
D000328:Adult; D000728:Androgens / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood / Q000453:epidemiology* / Q000378:metabolism*; D016022:Case-Control Studies; D004958:Estradiol / Q000097:blood / Q000378:metabolism; D004967:Estrogens / Q000097:blood; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D016015:Logistic Models; D009726:Nurses / Q000706:statistics & numerical data; D016017:Odds Ratio; D006080:Ovarian Follicle / Q000378:metabolism; D017697:Premenopause; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D011795:Surveys and Questionnaires; D014481:United States / Q000453:epidemiology
D000728:Androgens; D004967:Estrogens; D012739:Gonadal Steroid Hormones; D012738:Sex Hormone-Binding Globulin; D004958:Estradiol