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April 28, 1993, Vol 269, No. 16 >
ARTICLE | April 28, 1993

Breast Cancer in Mothers Prescribed Diethylstilbestrol in Pregnancy: Title and subTitle BreakFurther Follow-up FREE

Theodore Colton, ScD; E. Robert Greenberg, MD; Kenneth Noller, MD; Laurence Resseguie, PhD; Carla Van Bennekom, MPH; Timothy Heeren, PhD; Yuqing Zhang, MB, MPH
[+] Author Affiliations

Reprint requests to Boston University School of Public Health, 80 E Concord St, Boston, MA 02118 (Dr Colton).


JAMA. 1993;269(16):2096-2100. doi:10.1001/jama.1993.03500160066033
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Objective.  —Further assessment of the long-term risk of breast cancer associated with diethylstilbestrol (DES) during pregnancy.

Design.  —Follow-up continuation through June 1, 1989, of a historical cohort of DES-exposed and unexposed mothers ascertained by review of obstetric records.

Participants.  —Totals of 3029 each of DES-exposed and unexposed mothers who had delivered live babies at four centers in the United States during 1940 through 1960. Questionnaires were returned for 92.6% of the DES-exposed and 88.8% of the unexposed women.

Main Outcome Measures.  —Breast cancer incidence and mortality assessed from returned questionnaires and review of medical records and death certificates.

Main Results.  —The relative rate of breast cancer associated with DES exposure, after adjustment for demographic and reproductive variables, was 1.35 (95% confidence interval, 1.05 to 1.74). For 30 years or more following exposure, the relative rate was not appreciably higher (relative rate, 1.33; 95% confidence interval, 0.95 to 1.87) than that in earlier periods. Surveillance and increased detection seemed unlikely explanations for the increased risk, since DES-exposed women had excesses of both large and small breast cancers and the two cohorts reported similar breast cancer detection practices. A history of miscarriage before first term delivery was not associated with breast cancer occurrence.

Conclusion.  —Exposure to DES during pregnancy is associated with a modest but statistically significant increased risk of breast cancer. Contrary to prior indications, the risk does not appear to increase greatly over time. The findings are sufficient to exclude the possibility of a doubling of risk for the period of 30 or more years following exposure.(JAMA. 1993;269:2096-2100)

REFERENCES

1 +
Greenberg ER, Barnes AB, Resseguie L, et al.  Breast cancer in mothers given diethylstilbestrol in pregnancy. N Engl J Med . 1984;;311:1393-1398.
2 +
Ross RK, Krailo M, Pike MC, Henderson BE.  Breast cancer in mothers given diethylstilbestrol in pregnancy. N Engl J Med . 1985;;312:1059.
3 +
Stevens M, Smith B, Greenberg ER.  Costs and problems of finding women exposed to a hazardous drug. Am J Prev Med . 1985;;1:11-14.
4 +
Kaplan EL, Meier P.  Nonparametric estimation from incomplete observations. J Am Stat Assoc . 1958;;53:457-481.
5 +
Cox DR.  Regression models and life-tables. J R Stat Soc (B) . 1972;;34:187-202.
6 +
Pike MC, Henderson BE, Casagrande JT, Rosario I, Gray GE.  Oral contraceptive use and early abortion as risk factors for breast cancer in young women. Br J Cancer . 1981;;43:72-76.
7 +
Brinton LA, Hoover R, Fraumeni JF Jr.  Reproductive factors in the aetiology of breast cancer. Br J Cancer . 1983;;47:757-762.
8 +
Hadjimichael OC, Boyle CA, Meigs JW.  Abortion before first livebirth and risk of breast cancer. Br J Cancer . 1986;;53:281-284.
9 +
Howe HL, Senie RT, Bzduch H, Herzfeld P.  Early abortion and breast cancer risk among women under age 40. Int J Epidemiol . 1989;;18:300-304.
10 +
Rosenberg L, Palmer JR, Kaufman DW, Strong BL, Schottenfeld D, Shapiro S.  Breast cancer in relation to the occurrence and time of induced and spontaneous abortion. Am J Epidemiol . 1988;;127:981-989.
11 +
Adami H-O, Bergstrom R, Lund E, Meirik O.  Absence of association between reproductive variables and the risk of breast cancer in young women in Sweden and Norway. Br J Cancer . 1990;;62:122-126.
12 +
Kvale G, Heuch I, Eide GE.  A prospective study of reproductive factors and breast cancer, I: parity. Am J Epidemiol . 1987;;126:831-841.
13 +
Bibbo M, Haenszel WM, Wied GL, Hubby M, Herbst AL.  A twenty-five year follow-up study of women exposed to diethylstilbestrol during pregnancy. N Engl J Med . 1978;;298:763-767.
14 +
Beral V, Colwell L.  Randomized trial of high doses of stilbestrol and ethisterone in pregnancy: long-term follow-up of mothers. BMJ . 1980;;281:1098-1101.
15 +
Vessey MP, Fairweather DVI, Norman-Snith B, Buckley J.  A randomized double-blind controlled trial of the value of stilboestrol therapy in pregnancy: long-term follow-up of mothers and their offspring. Br J Obstet Gynaecol . 1983;;90:1007-1017.
16 +
Hadjimichael OC, Meigs JW, Falcier FW, Thompson WD, Flannery JT.  Cancer risk among women exposed to exogenous estrogens during pregnancy. J Natl Cancer Inst . 1984;;73:831-834.
17 +
Brian DD, Tilley BC, Labarthe DR, O'Fallon WM, Noller KL, Kurland LT.  Breast cancer in DES-exposed mothers: absence of association. Mayo Clin Proc . 1980;;55:89-93.
18 +
Evaluation of Carcinogenic Risks to Humans— Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs Vol 1-42 . Lyon, France: International Agency for Research on Cancer; 1987;: 273-278. IARC monographs supplement 7.
19 +
Willett W.  The search for the causes of breast and colon cancer. Nature . 1989;;338:389-394.
20 +
Kelsey JL, Gammon MD.  Epidemiology of breast cancer. Epidemiol Rev . 1990;;12:228-240.
21 +
Adami H-O, Adams G, Boyle P, et al.  Chapter II: breast-cancer etiology. Int J Cancer . 1990;;5 ( (suppl) ):22-39.

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1 +
Greenberg ER, Barnes AB, Resseguie L, et al.  Breast cancer in mothers given diethylstilbestrol in pregnancy. N Engl J Med . 1984;;311:1393-1398.
2 +
Ross RK, Krailo M, Pike MC, Henderson BE.  Breast cancer in mothers given diethylstilbestrol in pregnancy. N Engl J Med . 1985;;312:1059.
3 +
Stevens M, Smith B, Greenberg ER.  Costs and problems of finding women exposed to a hazardous drug. Am J Prev Med . 1985;;1:11-14.
4 +
Kaplan EL, Meier P.  Nonparametric estimation from incomplete observations. J Am Stat Assoc . 1958;;53:457-481.
5 +
Cox DR.  Regression models and life-tables. J R Stat Soc (B) . 1972;;34:187-202.
6 +
Pike MC, Henderson BE, Casagrande JT, Rosario I, Gray GE.  Oral contraceptive use and early abortion as risk factors for breast cancer in young women. Br J Cancer . 1981;;43:72-76.
7 +
Brinton LA, Hoover R, Fraumeni JF Jr.  Reproductive factors in the aetiology of breast cancer. Br J Cancer . 1983;;47:757-762.
8 +
Hadjimichael OC, Boyle CA, Meigs JW.  Abortion before first livebirth and risk of breast cancer. Br J Cancer . 1986;;53:281-284.
9 +
Howe HL, Senie RT, Bzduch H, Herzfeld P.  Early abortion and breast cancer risk among women under age 40. Int J Epidemiol . 1989;;18:300-304.
10 +
Rosenberg L, Palmer JR, Kaufman DW, Strong BL, Schottenfeld D, Shapiro S.  Breast cancer in relation to the occurrence and time of induced and spontaneous abortion. Am J Epidemiol . 1988;;127:981-989.
11 +
Adami H-O, Bergstrom R, Lund E, Meirik O.  Absence of association between reproductive variables and the risk of breast cancer in young women in Sweden and Norway. Br J Cancer . 1990;;62:122-126.
12 +
Kvale G, Heuch I, Eide GE.  A prospective study of reproductive factors and breast cancer, I: parity. Am J Epidemiol . 1987;;126:831-841.
13 +
Bibbo M, Haenszel WM, Wied GL, Hubby M, Herbst AL.  A twenty-five year follow-up study of women exposed to diethylstilbestrol during pregnancy. N Engl J Med . 1978;;298:763-767.
14 +
Beral V, Colwell L.  Randomized trial of high doses of stilbestrol and ethisterone in pregnancy: long-term follow-up of mothers. BMJ . 1980;;281:1098-1101.
15 +
Vessey MP, Fairweather DVI, Norman-Snith B, Buckley J.  A randomized double-blind controlled trial of the value of stilboestrol therapy in pregnancy: long-term follow-up of mothers and their offspring. Br J Obstet Gynaecol . 1983;;90:1007-1017.
16 +
Hadjimichael OC, Meigs JW, Falcier FW, Thompson WD, Flannery JT.  Cancer risk among women exposed to exogenous estrogens during pregnancy. J Natl Cancer Inst . 1984;;73:831-834.
17 +
Brian DD, Tilley BC, Labarthe DR, O'Fallon WM, Noller KL, Kurland LT.  Breast cancer in DES-exposed mothers: absence of association. Mayo Clin Proc . 1980;;55:89-93.
18 +
Evaluation of Carcinogenic Risks to Humans— Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs Vol 1-42 . Lyon, France: International Agency for Research on Cancer; 1987;: 273-278. IARC monographs supplement 7.
19 +
Willett W.  The search for the causes of breast and colon cancer. Nature . 1989;;338:389-394.
20 +
Kelsey JL, Gammon MD.  Epidemiology of breast cancer. Epidemiol Rev . 1990;;12:228-240.
21 +
Adami H-O, Adams G, Boyle P, et al.  Chapter II: breast-cancer etiology. Int J Cancer . 1990;;5 ( (suppl) ):22-39.

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