Inference of tamoxifen's effects on prevention of breast cancer from a randomized controlled trial

• 成果类型: Article
• 署名作者: Shen, Yu; Qin, Jing; Costantino, Joseph R.
• 署名单位: University of Texas System; UTMD Anderson Cancer Center; Howard Hughes Medical Institute; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh
• 刊物名称: JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION
• ISSN/ISSBN: 0162-1459
• DOI: 10.1198/016214506000001446
• 发表日期: 2007
• 页码: 1235-1244
• 关键词: surgical adjuvant breast; survival-data; long-term; Semiparametric models

摘要

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.