Abstract
Aim
To determine the contribution of bone mineral density (BMD) to breast cancer risk relative to other established breast cancer risk factors in postmenopausal women with osteoporosis.
Methods
Data for this analysis comprised those collected from women randomized to placebo in the MORE and CORE trials (N = 2,576). Risk factors measured at baseline included age, family history of breast cancer, estradiol level, body mass index, prior hormone therapy, BMD and vertebral fracture status. Cox proportional hazards regression models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs).
Results
Over a total of 13,698 woman-years of follow-up, 65 incident breast cancers occurred. In univariate analyses, older age and family history of breast cancer were the strongest predictors of breast cancer risk, associated with a 2.4- and 2.6-fold increase in breast cancer incidence. A higher estradiol level was associated with a 1.9-fold increase in breast cancer incidence. The association between femoral neck BMD and breast cancer incidence was only significant after adjustment for age (P = 0.03). The final multivariable model included age, family history, estradiol, BMD, and the BMD-estradiol interaction since the effect of BMD on breast cancer varied by estradiol level (interaction P-value, 0.04); in those with a lower estradiol level, a higher BMD was associated with a 2.6-fold increased in breast cancer.
Conclusion
Overall, BMD is a relatively weak predictor of breast cancer risk in these postmenopausal women with osteoporosis, after taking into consideration age, family history and endogenous estradiol level.
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References
Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ (2005) Cancer statistics. CA Cancer J Clin 55:10–30
American Cancer Society. Breast Cancer Facts & Figures 2005–2006. Atlanta: American Cancer Society, Inc
Hulka BS (1997) Epidemiologic analysis of breast and glynecological cancers. Prog Clin Biol Res 396:17–29
Writing Group for the Women’s Health Initiative Investigators (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women. Principal results from the Women’s Health Initiative randomized controlled trial. JAMA 288:321–333
Key T, Appleby P, Barnes I, Reeves G (2002) Endogenous Hormones, Breast Cancer Collaborative Group: Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst 94:606–616
Key TJ, Appleby PN, Reeves GK, Roddam A, Dorgan JF, Longcope C, Stanczyk FZ, Stephenson HE Jr, Falk RT, Miller R, Schatzkin A, Allen DS, Fentiman IS, Key TJ, Wang DY, Dowsett M, Thomas HV, Hankinson SE, Toniolo P, Akhmedkhanov A, Koenig K, Shore RE, Zeleniuch-Jacquotte A, Berrino F, Muti P, Micheli A, Krogh V, Sieri S, Pala V, Venturelli E, Secreto G, Barrett-Connor E, Laughlin GA, Kabuto M, Akiba S, Stevens RG, Neriishi K, Land CE, Cauley JA, Kuller LH, Cummings SR, Helzlsouer KJ, Alberg AJ, Bush TL, Comstock GW, Gordon GB, Miller SR, Longcope C (2003) Endogenous Hormones Breast Cancer Collaborative Group: body mass index, serum sex hormones, and breast cancer risk in postmenopausal women. J Natl Cancer Inst 95:1218–1226
Zmuda JM, Cauley J, Ljung BM, Bauer DC, Cummings SR, Kuller LH (2001) The Study of Osteoporotic Fractures Research Group: bone mass and breast cancer risk in older women: differences by stage at diagnosis. J Natl Cancer Inst 93: 930–936
Nguyen TV, Center JR, Eisman JA (2000) Association between breast cancer and bone mineral density: the Dubbo Osteoporosis Epidemiology Study. Maturitas 36:27–34
Ganry O, Baudoin C, Fardellone P, Peng J, Raverdy N (2004) Bone mass density and risk of breast cancer and survival in older women. Eur J Epidemiol 19:785–792
Zhang Y, Kiel DP, Kreger BE, Cupples LA, Ellison RC, Dorgan JF, Schatzkin A, Levy D, Felson DT (1997) Bone mass and the risk of breast cancer among postmenopausal women. N Engl J Med 336:611–617
Kerlikowske K, Shepherd J, Creasman J, Tice JA, Ziv E, Cummings SR (2005) Are breast density and bone mineral density independent risk factors for breast cancer? J Natl Cancer Inst 97:368–374
Buist DS, LaCroix AZ, Barlow WE, White E, Weiss NS (2001) Bone mineral density and breast cancer risk in postmenopausal women. J Clin Epidemiol 54:417–422
van der Klift M, de Laet CE, Coebergh JW, Hofman A, Pols HA, Rotterdam S (2003) Bone mineral density and the risk of breast cancer: the Rotterdam Study. Bone 32:211–216
Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK, Christiansen C, Delmas PD, Zanchetta JR, Stakkestad J, Gluer CC, Krueger K, Cohen FJ, Eckert S, Ensrud K, Avioli LV, Lips P, Cummings SR (1999) Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. JAMA 282:637–645
Martino S, Cauley JA, Barrett-Connor E, Powles TJ, Mershon J, Disch D, Secrest RJ, Cummings S for the CORE Investigators (2004) Continuing Outcomes Relevant to Evista: breast cancer incidence in postmenopausal osteoporotic women in a randomized trial of raloxifene. J Natl Cancer Inst 96:1751–1761
Genant HK, Wu CY, van Kuijk C, Nevitt MC (1993) Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 8:1137–1148
Lu Y, Mathur AK, Blunt BA, Gluer CC, Will AS, Fuerst TP, Jergas MD, Andriano KN, Cummings SR, Genant HK (1996) Dual X-ray absorptiometry quality control: comparison of visual examination and process-control charts. J Bone Miner Res 11:626–637
Cummings SR, Duong T, Kenyon E, Cauley J, Whitehead M, Krueger KA (2002) Serum estradiol level and risk of breast cancer during treatment with raloxifene. JAMA 287:216–220
Rosner B (2000) Hypothesis test: person-time data. In: Duxbury (ed) Fundamentals of biostatistics. Pacific Grove, pp 677–741
Cauley J, Lucas FL, Kuller LH, Vogt MT, Browner WS, Cummings SR (1996) Bone mineral density and risk of breast cancer in older women: the study of osteoporotic fractures. Study of Osteoporotic Fractures Research Group. JAMA 276:1404–1408
Nelson RL, Turyk M, Kim J, Persky V (2002) Bone mineral density and the subsequent risk of cancer in the NHANES I follow-up cohort. BMC Cancer 2:22
Stewart A, Kumar V, Torgerson DJ, Fraser WD, Gilbert FJ, Reid DM (2005) Axial BMD, change in BMD and bone turnover do not predict breast cancer incidence in early postmenopausal women. Osteoporos Int 16:1627–1632
Cauley JA, Lucas FL, Kuller LH, Stone K, Browner W, Cummings SR (1999) Elevated serum estradiol and testosterone concentrations are associated with a high risk for breast cancer. Study of Osteoporotic Fractures Research Group. Ann Intern Med 130:270–277
Cummings SR, Lee JS, Lui LY, Stone K, Ljung BM, Cauleys JA (2005) Sex hormones, risk factors, and risk of estrogen receptor-positive breast cancer in older women: a long-term prospective study. Cancer Epidemiol Biomarkers Prev 14:1047–1051
Tok EC, Ertunc D, Oz U, Camdeviren H, Ozdemir G, Dilek S (2004) The effect of circulating androgens on bone mineral density in postmenopausal women. Maturitas 48: 235–242
Fuqua SA, Wiltschke C, Zhang QX, Borg A, Castles CG, Friedrichs WE, Hopp T, Hilsenbeck S, Mohsin S, O’Connell P, Allred DC (2000) A hypersensitive estrogen receptor-alpha mutation in premalignant breast lesions. Cancer Res 60:4026–4029
Costantino JP, Gail MH, Pee D, Anderson S, Redmond CK, Benichou J, Wieand HS (1999) Validation studies for models projecting the risk of invasive and total breast cancer incidence. J Natl Cancer Inst 91:1541–1548
Gail MH, Brinton LA, Byar DP, Corle DK, Green SB, Schairer C, Mulvihill JJ (1989) Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst 81:1879–1886
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Cauley, J.A., Song, J., Dowsett, S.A. et al. Risk factors for breast cancer in older women: the relative contribution of bone mineral density and other established risk factors. Breast Cancer Res Treat 102, 181–188 (2007). https://doi.org/10.1007/s10549-006-9326-5
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DOI: https://doi.org/10.1007/s10549-006-9326-5