[64] Breast cancer after stopping estrogen plus progestin in postmenopausal women in the women's health initiative.

Chlebowski RT, Kuller L, Anderson G, Mason JA, Schenken R, Rajkovic A, Stefanick M, Sarto G, Ravdin P, Prentice R LABioMed, Torrance; University of Pittsburgh, Pittsburgh; Fred Hutchinson Cancer Research Center, Seattle; Brigham & Women's Hospital, Chestnut Hill; University of Texas Health Science Center, San Antonio; Baylor College of Medicine, Houston; Stanford University, San Jose; University of Wisconsin, Madison; University of Texas MD Anderson Cancer Center, Houston

Background
Following the Women's Health Initiative (WHI) estrogen plus progestin (E+P) trial report (JAMA 2002;288:321), menopausal hormone therapy use decreased dramatically in the United States. Subsequently, breast cancer incidence also dropped substantially, suggesting possible causality (NEJM 2007;16:1680); however, the etiology remains controversial.
Methods
To define effects of stopping E+P on breast cancer incidence more precisely, additional analyses were conducted in the WHI randomized trial of daily conjugated equine estrogens (CEE, 0.625 mg) plus medroxyprogesterone acetate (MPA, 2.5 mg) versus placebo. Furthermore, temporal trends for breast cancer diagnoses in the WHI observational study cohort were examined. Breast cancer risk factors, mammography utilization and calendar time-specific breast cancer incidence were assessed relative to E+P use.
Results: The time-specific linear hazard ratio (HR) curves examining E+P influence on breast cancer in the E+P clinical trial (CT), and in the observational study (OS, the later adjusted for E+P use during follow-up) are attached.



In the CT, breast cancer incidence, initially lower in the E+P group, increased with longer duration use but decreased postintervention despite closely comparable mammogram frequency between randomization groups. In the OS, breast cancer incidence was about two-fold higher in E+P users vs non-users (likely reflecting longer duration exposure) but decreased rapidly following year-to-year reductions in E+P use, while differences in mammogram frequency between E+P users and non-users were unchanged.
Conclusion: These findings suggest that cessation of E+P use is associated with a rapid reduction in breast cancer incidence which is not explained by mammography utilization change and support the hypothesis that the recent reduction in breast cancer incidence seen in certain age groups is predominantly related to a decrease in combined menopausal therapy use.

Saturday, December 13, 2008 4:15 PM

General Session 6 (3:30 PM-5:00 PM)