In utero exposure to diethylstilbestrol (DES) does not increase genomic instability in normal or neoplastic breast epithelium.
BACKGROUND
In 1992, the National Cancer Institute (NCI) established the Continuation of Follow-Up of DES-Exposed Cohorts to study the long-term health effects of exposure to diethylstilbestrol (DES). Genetic effects on human breast tissue have not been examined. The authors investigated whether breast tissue of women exposed in utero to DES might exhibit the genetic abnormalities that characterize other DES-associated tumors.


METHODS
Subjects enrolled in the NCI Cohort were queried about breast biopsies or breast cancer diagnoses. Available tissue blocks were obtained for invasive cancers (IC), in situ cancers (CIS), or atypical hyperplasia (AH). Exposure status was blinded, lesions were microdissected, and their DNA was analyzed for microsatellite instability (MI) and loss of heterozygosity (LOH), or allele imbalance (AI), at 20 markers on 9 chromosome arms.


RESULTS
From 31 subjects (22 exposed, 9 unexposed), 273 samples were analyzed (167 normal epithelium, 16 AH, 30 CIS, 60 IC). Exposed and unexposed subjects exhibited no differences in breast cancer risk factors or demographic characteristics, except for age at diagnosis (exposed vs. unexposed: 43.2 vs. 48.8 years of age, P = .02). The authors found that MI was rare and that AI was common, with frequencies consistent with previous reports. The global age-adjusted relative rate (RR) of AI was 1.3, 95% CI = 0.8-2.4. No statistically significant associations were observed after adjustment for risk factors or after stratification by histology or by chromosome arm.


CONCLUSIONS
In utero DES exposure does not appear to significantly increase genomic instability in breast epithelium, as measured by MI and AI. Breast tissue may respond differently from that of the reproductive tract to in utero DES exposure. Consequences of in utero DES exposure on the breast may be mediated by proliferative effects of estrogen.
Larson
Pamela S
PS
Department of Pathology and Laboratory Medicine, Boston University Medical Center, Boston, Massachusetts 02118, USA.
Ungarelli
Rosemarie A
RA
de Las Morenas
Antonio
A
Cupples
L Adrienne
LA
Rowlings
Kathleen
K
Palmer
Julie R
JR
Rosenberg
Carol L
CL
D000328:Adult; D017668:Age of Onset; D022981:Allelic Imbalance; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D004054:Diethylstilbestrol / Q000009:adverse effects*; D004968:Estrogens, Non-Steroidal / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019656:Loss of Heterozygosity; D042361:Mammary Glands, Human / Q000473:pathology; D018811:Maternal Exposure; D053842:Microsatellite Instability; D008875:Middle Aged; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012016:Reference Values
D004968:Estrogens, Non-Steroidal; D004054:Diethylstilbestrol