Hormone-replacement therapy influences gene expression profiles and is associated with breast-cancer prognosis: a cohort study.
BACKGROUND
Postmenopausal hormone-replacement therapy (HRT) increases breast-cancer risk. The influence of HRT on the biology of the primary tumor, however, is not well understood.


METHODS
We obtained breast-cancer gene expression profiles using Affymetrix human genome U133A arrays. We examined the relationship between HRT-regulated gene profiles, tumor characteristics, and recurrence-free survival in 72 postmenopausal women.


RESULTS
HRT use in patients with estrogen receptor (ER) protein positive tumors (n = 72) was associated with an altered regulation of 276 genes. Expression profiles based on these genes clustered ER-positive tumors into two molecular subclasses, one of which was associated with HRT use and had significantly better recurrence free survival despite lower ER levels. A comparison with external data suggested that gene regulation in tumors associated with HRT was negatively correlated with gene regulation induced by short-term estrogen exposure, but positively correlated with the effect of tamoxifen.


CONCLUSIONS
Our findings suggest that post-menopausal HRT use is associated with a distinct gene expression profile related to better recurrence-free survival and lower ER protein levels. Tentatively, HRT-associated gene expression in tumors resembles the effect of tamoxifen exposure on MCF-7 cells.
Hall
Per
P
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Per.Hall@ki.se
Ploner
Alexander
A
Bjöhle
Judith
J
Huang
Fei
F
Lin
Chin-Yo
CY
Liu
Edison T
ET
Miller
Lance D
LD
Nordgren
Hans
H
Pawitan
Yudi
Y
Shaw
Peter
P
Skoog
Lambert
L
Smeds
Johanna
J
Wedrén
Sara
S
Ohd
John
J
Bergh
Jonas
J
D001943:Breast Neoplasms / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D015331:Cohort Studies; D017931:DNA Primers; D018572:Disease-Free Survival; D015914:Estrogen Replacement Therapy; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D017698:Postmenopause; D017697:Premenopause; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis*; D016019:Survival Analysis; D014158:Transcription, Genetic
D017931:DNA Primers; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone