Smoking is associated with postmenopausal breast cancer in women with high levels of estrogens.

We investigated the association between smoking and risk of postmenopausal breast cancer in groups defined by high levels of estrogens, a factor known to enhance tumour progression. Two prospective cohorts of Swedish women provided 260 postmenopausal breast cancer cases and 514 controls. Blood samples were collected at baseline, and anthropometry, life-style factors and reproductive history had been assessed. Subjects were classified into quartiles with regard to the level of estrone, and into three categories with regard to estradiol. All analyses of the relation between smoking and breast cancer were repeated in different categories of these hormones. Logistic regression analysis, adjusted for matching factors, i.e., age at baseline, storage time and sub-cohort, yielded odds ratios (OR) with 95% confidence intervals (CI). Ever-smoking was associated with breast cancer in the top category of estrone, 2.02 (1.17-3.49). The highest risk was seen among ex-smokers, 2.96 (1.53-5.75). The pattern was similar for estradiol. Recent smoking cessation was associated with a high OR in top categories of estrone, 4.38 (1.27-15.2) and estradiol 10.0 (1.14-88.7). Smoking initiation before the age of 20 was associated with breast cancer in the top category of estrone, 2.73 (1.27-5.91). Several potential confounders were introduced into the statistical model, but none remained using backward selection. We conclude that ever-smoking was associated with the risk of breast cancer in women with high levels of estrone, and that ex-smoking was associated with breast cancer in women with high levels of estrone or estradiol. Copyright 2004 Wiley-Liss, Inc.