Lewis H. Kuller,1 Jane A. Cauley,1 Lee Lucas,1 Steve Cummings,2 and Warren S. Browner3
1University of Pittsburgh, Department of Epidemiology, Pittsburgh, Pennsylvania; 2University of California, San Francisco, California; 3VA Medical Center, San Francisco, California
Increased bone mineral density (BMD), as a marker of higher integrated estrogen exposure over time, could be an important risk factor for postmenopausal breast cancer. In the Study of Osteoporotic Fractures 8065 non-black women age 65 years and older were followed for an average of 3.2 years. There were 121 incident breast cancer cases. The age adjusted incidence rate/1000 person years of breast cancer was substantially higher among women with high BMD at several measured bone sites. There was approximately a 2-fold higher risk of breast cancer for women in the upper as compared to the lower 25th percentile of BMD. Considerable controversy exists about the association of hormone replacement therapy (HRT) and increased risk of breast cancer. In this paper we modeled the effects of selection for HRT, presuming that women with lower BMD would be more likely to be on HRT, then estimated the observed versus potential risk of breast cancer among HRT users as compared to nonusers. The model suggests that the potential risk of breast cancer associated with HRT could be greatly underestimated and that postmenopausal women with high BMD who are placed on HRT could have a substantially increased risk of breast cancer. This model of increased risk of breast cancer associated with BMD and HRT needs to be evaluated within clinical trials and larger observational studies that include measures of BMD. -- Environ Health Perspect 105(Suppl 3):593-599 (1997)
Key words: bone mineral density, estrogen, hormone replacement therapy, breast cancer
This paper was presented in part at the Workshop on Hormones, Hormone Metabolism, Environment, and Breast Cancer held 28-29 September 1995 in New Orleans, Louisiana. Manuscript received at EHP 6 June 1996; manuscript accepted 8 October 1996.
This work was supported by National Institute of Arthritis and Musculoskeletal and Skin Diseases grant 5 R01 AR35582-09 and Cancer Center Support grant CA47904.
Address correspondence to Dr. L.H. Kuller, University of Pittsburgh, GSPH Department of Epidemiology, 130 DeSoto Street, Pittsburgh, PA 15261. Telephone: (412) 624-3054. Fax (412) 624-7397. E-mail:kuller+@pitt.edu
Abbreviations used: BMD, bone mineral density; BMI, body mass index; BRCA, breast cancer associated; HDLc, high-density lipoprotein cholesterol; HRT, hormone replacement therapy; IGF, insulinlike growth factor; LDLc, low-density lipoprotein cholesterol; PEPI, Perimenopausal Estrogen/Progesterone Intervention; RR, relative risk; SOF, Study of Osteoporotic Fractures.
Last Update: April 10, 1997