Risk of breast cancer in women exposed to diethylstilbestrol in utero: prelimiinary results (United States).
BACKGROUND
A synthetic estrogen, diethylstilbestrol (DES), was widely prescribed to pregnant women during the 1950s and 1960s but was later discovered to be associated with an increased risk of clear-cell carcinoma of the vagina and cervix in female offspring. DES has not been linked to other cancers in female offspring, but studies of other prenatal factors such as twin gestation and pre-eclampsia have indicated that in-utero estrogen levels may influence breast cancer risk. We evaluated the relation of in-utero DES exposure to the risk of adult breast cancer.


METHODS
A cohort of 4821 exposed women and 2095 unexposed women, most of whom were first identified in the mid-1970s, were followed by mailed questionnaires for an average of 19 years. Reported cancer outcomes were validated by medical record review. Breast cancer incidence in DES-exposed daughters was compared with cancer incidence in unexposed daughters with use of Poisson regression analysis, adjusting for year of birth, age at menarche, age at first birth, and number of births.


RESULTS
The rate ratio for incidence of invasive breast cancer in exposed versus unexposed women was 1.4 (95% confidence interval (CI) = 0.7-2.6). DES exposure was not associated with an increased risk of breast cancer in women under 40 years, but among women aged 40 and older the rate ratio was 2.5 (95% CI = 1.0-6.3). The rate ratio for the association of DES exposure with estrogen receptor-positive tumors was 1.9 (95% CI = 0.8-4.5).


CONCLUSIONS
While not statistically significant, the overall 40% excess risk, arising exclusively from the subset of estrogen receptor-positive cases, raises a concern calling for continued investigation.
Palmer
Julie R
JR
Slone Epidemiology Unit, Boston University School of Medicine, MA 02215, USA. jpalmer@slone.bu.edu
Hatch
Elizabeth E
EE
Rosenberg
Carol L
CL
Hartge
Patricia
P
Kaufman
Raymond H
RH
Titus-Ernstoff
Linda
L
Noller
Kenneth L
KL
Herbst
Arthur L
AL
Rao
R Sowmya
RS
Troisi
Rebecca
R
Colton
Theodore
T
Hoover
Robert N
RN
D000328:Adult; D001943:Breast Neoplasms / Q000139:chemically induced*; D015331:Cohort Studies; D004054:Diethylstilbestrol / Q000009:adverse effects*; D004968:Estrogens, Non-Steroidal / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017584:Reproductive History; D012306:Risk; D012307:Risk Factors
D004968:Estrogens, Non-Steroidal; D004054:Diethylstilbestrol