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November 6, 1996, Vol 276, No. 17 >
ARTICLE | November 6, 1996

Bone Mineral Density and Risk of Breast Cancer in Older Women: Title and subTitle BreakThe Study of Osteoporotic Fractures FREE

Jane A. Cauley, DrPH; Frances Leslie Lucas, RN, PhD; Lewis H. Kuller, MD, DrPH; Molly T. Vogt, PhD; Warren S. Browner, MD, MPH; Steven R. Cummings, MD
[+] Author Affiliations

A complete list of the Study of Osteoporotic Fractures Research Group appears at the end of this article.

Reprints: Jane A. Cauley, DrPH, University of Pittsburgh, Department of Epidemiology, 130 DeSoto St, Crabtree Hall A524, Pittsburgh, PA 15261.


JAMA. 1996;276(17):1404-1408. doi:10.1001/jama.1996.03540170048031
Text Size: A A A
Published online
Article
References

Objective.  —To test the hypothesis that bone mineral density (BMD) is associated with the risk of developing breast cancer in older women.

Design.  —Prospective cohort study with mean (SD) follow-up of 3.2 (1.6) years.

Setting.  —Four clinical centers, one each located in the following areas: Baltimore, Md; Minneapolis, Minn; Portland, Ore; and the Monongahela Valley in Pennsylvania.

Participants.  —A total of 6854 nonblack women who were 65 years of age or older and enrolled in the Study of Osteoporotic Fractures.

Measurements.  —Radius and calcaneus BMD by single photon absorptiometry at baseline; hip and spine BMD by dual-energy x-ray absorptiometry 2 years later.

Main Outcome Measure.  —Breast cancer confirmed by medical record review.

Results.  —A total of 97 women developed breast cancer. In the multivariate model, adjusting for age, the degree of obesity, and other important covariates, the risk of breast cancer was about 30% to 50% higher per 1 SD increase in BMD (relative risk, distal radius BMD=1.50; 95% confidence interval, 1.16-1.95). The age-adjusted incidence rate of breast cancer per 1000 person-years among women in the lowest quartile of distal radius BMD was 2.46, compared with 5.99 among women with the highest BMD. Women with BMD above the 25th percentile were at 2.0 to 2.5 times increased risk of breast cancer compared with women below the 25th percentile. Results were consistent across all BMD sites.

Conclusions.  —Bone mineral density predicts the risk of breast cancer in older women. The magnitude of the association is similar to that observed between BMD and all fractures. Our findings suggest a link between 2 of the most common conditions affecting a woman's health. Identifying a common denominator for these conditions should substantially improve our understanding of their etiology and prevention.

REFERENCES

1 +
Kvale G, Heuch I.  Menstrual factors and breast cancer risk . Cancer . 1988;;62:1625-1631.
2 +
Brinton LA, Schairer C, Hoover RN, Fraumeni JF.  Menstrual factors and risk of breast cancer . Cancer Invest . 1988;;6:245-254.
3 +
De Stavola BL, Wang DY, Allen DS, et al.  The association of height, weight, menstrual and reproductive events with breast cancer: results from two prospective studies on the island of Guernsey (United Kingdom) . Cancer Causes Control . 1993;;4:331-340.
4 +
Negri E, LaVecchia C, Bruzzi P, et al.  Risk factors for breast cancer: pooled results from three Italian case-control studies . Am J Epidemiol . 1988;;128:1207-1215.
5 +
Rautalahti M, Albanes D, Virtamo J, Palmeren J, Haukka J, Heinonen OP.  Lifetime menstrual activity: indicator of breast cancer risk . Eur J Epidemiol . 1993;;9:17-25.
6 +
Bergkvist L, Adami H, Persson I, Hoover R, Schairer C.  The risk of breast cancer after estrogen and estrogen-progestin replacement . N Engl J Med . 1989;;321:293-297.
7 +
Colditz GA, Hankinson SE, Hunter DJ, et al.  The use of estrogens and progestins and the risk of breast cancer in postmenopausal women . N Engl J Med . 1995;;332:1589-1593.
8 +
Ewertz M.  Influence of non-contraceptive exogenous and endogenous hormones on breast cancer risk in Denmark . Int J Cancer . 1988;;42:832-838.
9 +
Kaufman DW, Palmer JR, de Mouzon J, et al.  Estrogen replacement therapy and the risk of breast cancer: results from the case-control surveillance study . Am J Epidemiol . 1991;;134:1375-1385.
10 +
Wingo PA, Layde PM, Lee NC, Rubin G, Ory HW.  The risk of breast cancer in postmenopausal women who have used estrogen replacement therapy . JAMA . 1987;;257:209-215.
11 +
Bulbrook RD, Moore JW, Clark GMG, Wang DY.  Relation between risk of breast cancer and biological availability of estradiol in the blood: prospective study in Guernsey . Ann N Y Acad Sci . 1986;;464:378-388.
12 +
Moore JW, Clark GMG, Hoare SA, et al.  Binding of oestradiol to blood proteins and aetiology of breast cancer . Int J Cancer . 1986;;38:625-630.
13 +
Wysowski DK, Comstock GW, Helsing KN, Lau HL.  Sex hormone levels in serum in relation to the development of breast cancer . Am J Epidemiol . 1987;;125:791-799.
14 +
Helzlsouer KJ, Alberg AJ, Bush TL, Longcope C, Gordon GB, Comstock GW.  A prospective study of endogenous hormones and breast cancer . Cancer Detect Prev . 1994;;18:79-85.
15 +
Garland CF, Friedlander NJ, Barrett-Connor E, Khaw K.  Sex hormones and postmenopausal breast cancer: a prospective study in an adult community . Am J Epidemiol . 1992;;135:1220-1230.
16 +
Toniolo PG, Levitz M, Zelenvich-Jacquotte A, et al.  A prospective study of endogenous estrogens and breast cancer in post-menopausal women . J Natl Cancer Inst . 1995;;87:190-197.
17 +
Cauley JA, Gutai JP, Kuller LH, Powell JG.  Reliability and interrelations among serum sex hormones in postmenopausal women . Am J Epidemiol . 1991;;133:50-57.
18 +
Eriksen EF, Colvard DS, Berg NJ, et al.  Evidence of estrogen receptors in normal human osteoblast-like cells . Science . 1988;;241:84-86.
19 +
Fox KM, Magaziner J, Sherwin R, et al.  Reproductive correlates of bone mass in elderly women . J Bone Miner Res . 1993;;8:901-908.
20 +
Bauer DC, Browner WS, Cauley JA, et al.  Factors associated with appendicular bone mass in older women . Ann Intern Med . 1993;;118:657-665.
21 +
Jonnavithula S, Warren MP, Fox RP, Lazaro MI.  Bone density is compromised in amenorrheic women despite return of menses: a 2-year study . Obstet Gynecol . 1993;;81:669-673.
22 +
Nilas L, Christiansen C.  Bone mass and its relationship to age and the menopause . J Clin Endocrinol Metabol . 1987;;65:697-702.
23 +
Longcope C, Baker RS, Hui SL, Johnston CC.  Androgen and estrogen dynamics in women with vertebral crush fractures . Maturitas . 1984;;6:309-318.
24 +
Cauley JA, Seeley DG, Ensrud K, Ettinger B, Black D, Cummings SR.  Estrogen replacement therapy and fractures in older women . Ann Intern Med . 1995;;122:9-16.
25 +
Lindsay R.  Hormone replacement therapy for prevention and treatment of osteoporosis . Am J Med . 1993;;95:375-395.
26 +
Cauley JA, Gutai JP, Kuller LH, Scott J, Nevitt MC.  Black-white differences in serum sex hormones and bone mineral density . Am J Epidemiol . 1994;;139:1035-1046.
27 +
Cummings SR, Black DM, Nevitt MC, et al.  Appendicular bone density and age predict hip Fracture in women . JAMA . 1990;;263:665-668.
28 +
Steiger P, Cummings SR, Black DM, Spencer NE, Genant HK.  Age-related decrements in bone mineral density in women over 65 . J Bone Miner Res . 1992;;7:625-632.
29 +
Lohman TG, Martorell R. Anthropometric Standardization Reference Manual . Champaign, Ill: Human Kinetics Books; 1988;.
30 +
Black D, Cummings SR, Genant HK, Nevitt MC, Palermo L, Browner W.  Axial and appendicular bone density predict fractures in older women . J Bone Miner Res . 1992;;7:633-638.
31 +
Kelsey JL.  Breast cancer epidemiology: summary and future directions . Epidemiol Rev . 1993;;15:256-263.
32 +
Looker AC, Johnston CC, Wahner HW, et al.  Prevalence of low femoral bone density in older US women from NHANES III . J Bone Miner Res . 1995;;10:796-802.
33 +
Berg RL, Cassells JS. The Second Fifty Years: Promoting Health and Preventing Disability . Washington, DC: National Academy Press; 1990;:76-100.
34 +
Muir C, Waterhouse J, Mack T, Powell J, Whelan S. Cancer Incidence in 5 Continents . Lyon, France: International Agency for Research on Cancer; 1987;.
35 +
Salamone LM, Pressman AR, Seeley DG, Cauley JA.  Estrogen replacement therapy: a survey of older women's attitudes . Arch Intern Med . 1996;;156:1293-1297.
36 +
Cauley JA, Cummings SR, Black DM, Mascioli SR, Seeley DG.  Prevalence and determinants of estrogen replacement therapy in elderly women . Am J Obstet Gynecol . 1990;;163:1438-1444.
37 +
Schmid C.  IGF's—function and clinical importance: the regulation of osteoblast function by hormones and cytokines with special reference to insulin-like growth factors and their binding proteins . J Intern Med . 1993;;234:535-542.
38 +
Murphy LC.  Antiestrogen action and growth factor regulation . Breast Cancer Res Treat . 1994;;31:61-71.
39 +
van Daele PL, Stolk RP, Burger H, et al.  Bone density in non-insulin-dependent diabetes mellitus . Ann Intern Med . 1995;;122:409-414.
40 +
Cullen KJ, Smith HS, Hill S, Rosen N, Lippman ME.  Growth factor messenger RNA expressing by human breast fibroblasts from benign and malignant lesions . Cancer Res . 1991;;51:4978-4985.
41 +
Ellis MJC, Singer C, Hornby A, Rasmussen A, Cullen KJ.  Insulin-like growth factor mediated stromal-epithelial interactions in human breast cancer . Breast Cancer Res Treat . 1994;;31:249-261.
42 +
Persson I, Naessen T, Adami HO, et al.  Reduced risk of hip fracture in women with endometrial cancer . Int J Epidemiol . 1992;;21:636-642.
43 +
Olsson H, Hagglund G.  Reduced risk of morbidity and mortality in a prospective cohort of women with distal forearm fractures . Am J Epidemiol . 1992;;136:422-427.
44 +
Persson I, Adami HO, McLaughlin JK, Narssen T, Fraumeni JF.  Reduced risk of breast and endometrial cancer among women with hip fractures (Sweden) . Cancer Causes Control . 1994;;5:523-528.
45 +
Utz JP, Melton LJ III, Kan SH, Riggs BL.  Risk of osteoporotic fractures in women with breast cancer: a population-based cohort study . J Chronic Dis . 1987;;2:105-113.
46 +
Adami H, Zack M, Kressner U, et al.  Hip fractures in women with breast cancer . Am J Epidemiol . 1990;;132:877-883.
47 +
Nielsen HE, Sasko P, Poulsen HS, Godeberg CC.  Bone mineral content and estrogen receptors in women with breast tumors . Acta Radiol . 1985;;24:247-251.
48 +
Miller BA, Gloeckler LA, Hankey BF, et al. SEER Cancer Statistics Review, 1973-1990 . Bethesda, Md: US Dept of Health and Human Services; 1993;. National Institutes of Health publication 93-2789.
49 +
Strewler GJ, Nissenson RA.  Hypercalcemia in malignancy . West J Med . 1990;;153:635-640.
50 +
Browner WS, Seeley DG, Vogt TM, Cummings SR.  Non-trauma mortality in elderly women with low bone mineral density . Lancet . 1991;;338:355-358.

Figures

Tables

Interactive Graphics

Video

Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Kvale G, Heuch I.  Menstrual factors and breast cancer risk . Cancer . 1988;;62:1625-1631.
2 +
Brinton LA, Schairer C, Hoover RN, Fraumeni JF.  Menstrual factors and risk of breast cancer . Cancer Invest . 1988;;6:245-254.
3 +
De Stavola BL, Wang DY, Allen DS, et al.  The association of height, weight, menstrual and reproductive events with breast cancer: results from two prospective studies on the island of Guernsey (United Kingdom) . Cancer Causes Control . 1993;;4:331-340.
4 +
Negri E, LaVecchia C, Bruzzi P, et al.  Risk factors for breast cancer: pooled results from three Italian case-control studies . Am J Epidemiol . 1988;;128:1207-1215.
5 +
Rautalahti M, Albanes D, Virtamo J, Palmeren J, Haukka J, Heinonen OP.  Lifetime menstrual activity: indicator of breast cancer risk . Eur J Epidemiol . 1993;;9:17-25.
6 +
Bergkvist L, Adami H, Persson I, Hoover R, Schairer C.  The risk of breast cancer after estrogen and estrogen-progestin replacement . N Engl J Med . 1989;;321:293-297.
7 +
Colditz GA, Hankinson SE, Hunter DJ, et al.  The use of estrogens and progestins and the risk of breast cancer in postmenopausal women . N Engl J Med . 1995;;332:1589-1593.
8 +
Ewertz M.  Influence of non-contraceptive exogenous and endogenous hormones on breast cancer risk in Denmark . Int J Cancer . 1988;;42:832-838.
9 +
Kaufman DW, Palmer JR, de Mouzon J, et al.  Estrogen replacement therapy and the risk of breast cancer: results from the case-control surveillance study . Am J Epidemiol . 1991;;134:1375-1385.
10 +
Wingo PA, Layde PM, Lee NC, Rubin G, Ory HW.  The risk of breast cancer in postmenopausal women who have used estrogen replacement therapy . JAMA . 1987;;257:209-215.
11 +
Bulbrook RD, Moore JW, Clark GMG, Wang DY.  Relation between risk of breast cancer and biological availability of estradiol in the blood: prospective study in Guernsey . Ann N Y Acad Sci . 1986;;464:378-388.
12 +
Moore JW, Clark GMG, Hoare SA, et al.  Binding of oestradiol to blood proteins and aetiology of breast cancer . Int J Cancer . 1986;;38:625-630.
13 +
Wysowski DK, Comstock GW, Helsing KN, Lau HL.  Sex hormone levels in serum in relation to the development of breast cancer . Am J Epidemiol . 1987;;125:791-799.
14 +
Helzlsouer KJ, Alberg AJ, Bush TL, Longcope C, Gordon GB, Comstock GW.  A prospective study of endogenous hormones and breast cancer . Cancer Detect Prev . 1994;;18:79-85.
15 +
Garland CF, Friedlander NJ, Barrett-Connor E, Khaw K.  Sex hormones and postmenopausal breast cancer: a prospective study in an adult community . Am J Epidemiol . 1992;;135:1220-1230.
16 +
Toniolo PG, Levitz M, Zelenvich-Jacquotte A, et al.  A prospective study of endogenous estrogens and breast cancer in post-menopausal women . J Natl Cancer Inst . 1995;;87:190-197.
17 +
Cauley JA, Gutai JP, Kuller LH, Powell JG.  Reliability and interrelations among serum sex hormones in postmenopausal women . Am J Epidemiol . 1991;;133:50-57.
18 +
Eriksen EF, Colvard DS, Berg NJ, et al.  Evidence of estrogen receptors in normal human osteoblast-like cells . Science . 1988;;241:84-86.
19 +
Fox KM, Magaziner J, Sherwin R, et al.  Reproductive correlates of bone mass in elderly women . J Bone Miner Res . 1993;;8:901-908.
20 +
Bauer DC, Browner WS, Cauley JA, et al.  Factors associated with appendicular bone mass in older women . Ann Intern Med . 1993;;118:657-665.
21 +
Jonnavithula S, Warren MP, Fox RP, Lazaro MI.  Bone density is compromised in amenorrheic women despite return of menses: a 2-year study . Obstet Gynecol . 1993;;81:669-673.
22 +
Nilas L, Christiansen C.  Bone mass and its relationship to age and the menopause . J Clin Endocrinol Metabol . 1987;;65:697-702.
23 +
Longcope C, Baker RS, Hui SL, Johnston CC.  Androgen and estrogen dynamics in women with vertebral crush fractures . Maturitas . 1984;;6:309-318.
24 +
Cauley JA, Seeley DG, Ensrud K, Ettinger B, Black D, Cummings SR.  Estrogen replacement therapy and fractures in older women . Ann Intern Med . 1995;;122:9-16.
25 +
Lindsay R.  Hormone replacement therapy for prevention and treatment of osteoporosis . Am J Med . 1993;;95:375-395.
26 +
Cauley JA, Gutai JP, Kuller LH, Scott J, Nevitt MC.  Black-white differences in serum sex hormones and bone mineral density . Am J Epidemiol . 1994;;139:1035-1046.
27 +
Cummings SR, Black DM, Nevitt MC, et al.  Appendicular bone density and age predict hip Fracture in women . JAMA . 1990;;263:665-668.
28 +
Steiger P, Cummings SR, Black DM, Spencer NE, Genant HK.  Age-related decrements in bone mineral density in women over 65 . J Bone Miner Res . 1992;;7:625-632.
29 +
Lohman TG, Martorell R. Anthropometric Standardization Reference Manual . Champaign, Ill: Human Kinetics Books; 1988;.
30 +
Black D, Cummings SR, Genant HK, Nevitt MC, Palermo L, Browner W.  Axial and appendicular bone density predict fractures in older women . J Bone Miner Res . 1992;;7:633-638.
31 +
Kelsey JL.  Breast cancer epidemiology: summary and future directions . Epidemiol Rev . 1993;;15:256-263.
32 +
Looker AC, Johnston CC, Wahner HW, et al.  Prevalence of low femoral bone density in older US women from NHANES III . J Bone Miner Res . 1995;;10:796-802.
33 +
Berg RL, Cassells JS. The Second Fifty Years: Promoting Health and Preventing Disability . Washington, DC: National Academy Press; 1990;:76-100.
34 +
Muir C, Waterhouse J, Mack T, Powell J, Whelan S. Cancer Incidence in 5 Continents . Lyon, France: International Agency for Research on Cancer; 1987;.
35 +
Salamone LM, Pressman AR, Seeley DG, Cauley JA.  Estrogen replacement therapy: a survey of older women's attitudes . Arch Intern Med . 1996;;156:1293-1297.
36 +
Cauley JA, Cummings SR, Black DM, Mascioli SR, Seeley DG.  Prevalence and determinants of estrogen replacement therapy in elderly women . Am J Obstet Gynecol . 1990;;163:1438-1444.
37 +
Schmid C.  IGF's—function and clinical importance: the regulation of osteoblast function by hormones and cytokines with special reference to insulin-like growth factors and their binding proteins . J Intern Med . 1993;;234:535-542.
38 +
Murphy LC.  Antiestrogen action and growth factor regulation . Breast Cancer Res Treat . 1994;;31:61-71.
39 +
van Daele PL, Stolk RP, Burger H, et al.  Bone density in non-insulin-dependent diabetes mellitus . Ann Intern Med . 1995;;122:409-414.
40 +
Cullen KJ, Smith HS, Hill S, Rosen N, Lippman ME.  Growth factor messenger RNA expressing by human breast fibroblasts from benign and malignant lesions . Cancer Res . 1991;;51:4978-4985.
41 +
Ellis MJC, Singer C, Hornby A, Rasmussen A, Cullen KJ.  Insulin-like growth factor mediated stromal-epithelial interactions in human breast cancer . Breast Cancer Res Treat . 1994;;31:249-261.
42 +
Persson I, Naessen T, Adami HO, et al.  Reduced risk of hip fracture in women with endometrial cancer . Int J Epidemiol . 1992;;21:636-642.
43 +
Olsson H, Hagglund G.  Reduced risk of morbidity and mortality in a prospective cohort of women with distal forearm fractures . Am J Epidemiol . 1992;;136:422-427.
44 +
Persson I, Adami HO, McLaughlin JK, Narssen T, Fraumeni JF.  Reduced risk of breast and endometrial cancer among women with hip fractures (Sweden) . Cancer Causes Control . 1994;;5:523-528.
45 +
Utz JP, Melton LJ III, Kan SH, Riggs BL.  Risk of osteoporotic fractures in women with breast cancer: a population-based cohort study . J Chronic Dis . 1987;;2:105-113.
46 +
Adami H, Zack M, Kressner U, et al.  Hip fractures in women with breast cancer . Am J Epidemiol . 1990;;132:877-883.
47 +
Nielsen HE, Sasko P, Poulsen HS, Godeberg CC.  Bone mineral content and estrogen receptors in women with breast tumors . Acta Radiol . 1985;;24:247-251.
48 +
Miller BA, Gloeckler LA, Hankey BF, et al. SEER Cancer Statistics Review, 1973-1990 . Bethesda, Md: US Dept of Health and Human Services; 1993;. National Institutes of Health publication 93-2789.
49 +
Strewler GJ, Nissenson RA.  Hypercalcemia in malignancy . West J Med . 1990;;153:635-640.
50 +
Browner WS, Seeley DG, Vogt TM, Cummings SR.  Non-trauma mortality in elderly women with low bone mineral density . Lancet . 1991;;338:355-358.

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