ENDOGENOUS ESTROGENS AND RISK OF BREAST-CANCER BY ESTROGEN-RECEPTOR STATUS - A PROSPECTIVE-STUDY IN POSTMENOPAUSAL WOMEN

A positive association between postmenopausal serum levels of total es tradiol, percentage of free estradiol, and percentage of estradiol not bound to sex hormone-binding globulin (SHBG) and breast cancer risk w as recently reported by the New York University Women's Health Study ( P. Toniolo et al., J. Natl. Cancer Inst., 87: 190-197, 1995). Data fro m this prospective study are used to assess whether the observed assoc iations differ according to estrogen receptor (ER) status of the tumor . Between 1985 and 1991, 7063 postmenopausal women donated blood and c ompleted questionnaires at a large breast cancer screening clinic in N ew York City. Before 1991, 130 eases of first primary breast cancer we re identified by active follow-up of the cohort. For each case, two co ntrols were selected, matching the case on age at first blood donation and length of storage of specimens. Biochemical analyses were perform ed on sera that had been stored at -80 degrees C since sampling. ER in formation was abstracted from pathology reports. Separate statistical analyses were conducted for ER-positive, ER-negative, and ER-unknown g roups (53, 23, and 54 matched sets, respectively). In each of the 3 gr oups, the mean estradiol and the mean percentage of free estradiol wer e greater (21-28% and 6-7%, respectively) in cases than in controls. C onversely, the mean percentage of estradiol bound to SHBG was 9-12% lo wer in cases than in controls. The logistic regression coefficients me asuring the strength of the association between estradiol and its free and SHBG-bound fractions and breast cancer risk were similar in the E R-positive, ER-negative, and ER-unknown groups. These data suggest tha t in postmenopausal women, the association of endogenous estrogens wit h breast cancer risk is independent of the ER status of the tumor. Thi s result is more compatible with the hypothesis of a progression from ER-positive to ER-negative tumors than with the hypothesis that ER sta tus identifies two distinct types of breast cancer.