Figure 2.

Invasive breast cancer incidence by estrogen plus progestin use at baseline modified by time-from-menopause to hormone therapy initiation (gap time). Nonparametric spline fit for the hazard ratio (HR) (95% confidence interval [CI] in shaded region) of the effect of estrogen plus progestin by gap time. The smoothness of the fit was chosen objectively by generalized cross-validation. P values corresponds to a test of whether the effect of estrogen plus progestin changes with gap time. Analyses were adjusted for age, race or ethnic group, body mass index, education, smoking status, alcohol use, self-reported health, level of physical activity, presence or absence of a family history of breast cancer, estimated breast-cancer risk based on the Gail model, and bilateral oophorectomy and stratified by baseline age group. All statistical tests were two-sided.