Inference of Tamoxifen's Effects on Prevention of Breast Cancer From a Randomized Controlled Trial

Abstract

The largest randomized, double-blind, placebo-controlled chemoprevention trial, the National Surgical Adjuvant Breast and Bowel Project's Breast Cancer Prevention Trial (NSABP–BCPT), evaluated the efficacy of tamoxifen in preventing breast cancer among women at high risk of developing the disease. The trial has reported a reduction of breast cancer incidence for the tamoxifen group; however, the effect of tamoxifen on the time to diagnosis of the disease over the 6-year follow-up of the trial has not been fully explored in the literature. We propose a flexible semiparametric model to assess the effects of tamoxifen on the incidence of breast cancer as well as time to diagnosis of the disease separately in the framework of a cure rate model. We used an estimating equation approach to estimating the unknown parameters and assessed the semiparametric model assumption with a test based on the area between two survival curves. In the NSABP–BCPT data, we found that tamoxifen has a substantial effect in reducing invasive breast cancer events in estrogen receptor (ER)-positive tumors, but has no effect on ER-negative tumors. Among women diagnosed with ER-positive breast cancer during study follow-up, there was little difference in terms of time to diagnosis between the two arms. However, tamoxifen may advance the time to breast cancer diagnosis for ER-negative breast cancer, whereas the incidence of ER-negative tumors is similar in the two treatment arms.