Reproductive breast cancer risk factors are hypothesized to act by increasi
ng exposure of the breast to endogenous estrogens, but few studies have qua
ntitatively examined the association of these risk factors with breast tiss
ue composition. This study is part of a case-control study of breast histol
ogical characteristics and breast cancer risk, nested within the Nurses' He
alth Study, a prospective study of 121,700 registered nurses. We studied 30
0 women who had not been diagnosed with breast cancer, but for whom we obta
ined slides from a prior benign breast biopsy. We used a computer-assisted
image analysis technique to assess the proportion of epithelial and fibrous
stromal tissue on benign breast biopsy slides, excluding obvious mass lesi
ons, Mean epithelial proportion was 5.3% (0.1-23%), and mean stromal propor
tion,vas 58.7% (3-93%), Women with proliferative breast disease without aty
pia had higher epithelial and stromal proportions than women with nonprolif
erative breast disease (P < 0.001). Postmenopausal women had a lower epithe
lial proportion (P = 0.01), and increasing age at biopsy was associated wit
h decreasing stromal proportion among postmenopausal parous women (P = 0.00
4). Among premenopausal women, increasing years since last birth was associ
ated with lower epithelial proportion (P < 0.001). Other reproductive risk
factors were not independently associated with epithelial or stromal propor
tion. Epithelial and stromal breast tissue were associated with different f
actors with the exception of proliferative breast disease, which was associ
ated with an increase in both epithelial and stromal proportion. The quanti
tative measurement of epithelial and stromal proportion may be useful for m
easuring changes in breast composition.