ERβ expression and breast cancer risk prediction for women with atypias.
Estrogen receptor (ER) β is highly expressed in normal breast epithelium and a putative tumor suppressor. Atypical hyperplasia substantially increases breast cancer risk, but identification of biomarkers to further improve risk stratification is needed. We evaluated ERβ expression in breast tissues from women with atypical hyperplasia and association with subsequent breast cancer risk. ERβ expression was examined by immunohistochemistry in a well-characterized 171-women cohort with atypical hyperplasia diagnosed 1967-1991. Nuclear ERβ percent and intensity was scored in the atypia and adjacent normal lobules. An ERβ sum score (percent + intensity) was calculated and grouped as low, moderate, or high. Competing risks regression was used to assess associations of ERβ expression with breast cancer risk. After 15-year median follow-up, 36 women developed breast cancer. ERβ expression was lower in atypia lobules in than normal lobules, by percent staining and intensity (both P < 0.001). Higher ERβ expression in the atypia or normal lobules, evaluated by percent staining, intensity or sum score, decreased the risk of subsequent breast cancer by 2-fold (P = 0.04) and 2.5-fold (P = 0.006). High normal lobule ERβ expression conferred the strongest protective effect in premenopausal women: the 20-year cumulative incidence of breast cancer was 0% for women younger than 45 years with high versus 31% for low-moderate ERβ expression (P = 0.0008). High ERβ expression was associated with a significantly decreased risk of breast cancer in women with atypical hyperplasia. These data suggest that ERβ may be a useful biomarker for risk stratification and a novel therapeutic target for breast cancer risk reduction.
Department of Surgery, Mayo Clinic, Rochester, Minnesota. hieken.tina@mayo.edu.
Tina J
TJ
Hieken
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
Jodi M
JM
Carter
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota.
John R
JR
Hawse
Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Tanya L
TL
Hoskin
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
Melanie
M
Bois
Department of Oncology, Mayo Clinic, Rochester, Minnesota.
Marlene
M
Frost
Department of Oncology, Mayo Clinic, Rochester, Minnesota.
Lynn C
LC
Hartmann
Department of Biochemistry and Molecular Biology, Mayo Clinic, Jacksonville, Florida.
Derek C
DC
Radisky
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
Daniel W
DW
Visscher
Department of Surgery, Mayo Clinic, Rochester, Minnesota.
Amy C
AC
Degnim
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000473:pathology*; D015331:Cohort Studies; D047629:Estrogen Receptor beta / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006965:Hyperplasia / Q000473:pathology; D007150:Immunohistochemistry; D008875:Middle Aged; D015999:Multivariate Analysis; D012307:Risk Factors
D014408:Biomarkers, Tumor; C000600034:ESR2 protein, human; D047629:Estrogen Receptor beta