The expression of ER beta cx in human breast cancer and the relationship to endocrine therapy and survival.
OBJECTIVE
Estrogen receptor (ER) alpha-positive breast cancer is often treated with endocrine therapy using either antiestrogens or aromatase inhibitors. However, 30% of patients who receive endocrine therapy will derive no benefit from such treatments and may indeed suffer adverse effects. Currently, there are no ways to predict response to such treatments. ER beta cx, a variant of ER beta, has a dominant-negative effect over ER alpha, and its expression thought to modulate response to endocrine treatment may represent a predictor of response to endocrine therapy.


METHODS
We investigated the expression of the ER beta cx in 82 frozen breast samples (8 benign, 1 ductal carcinoma in situ, and 73 malignant) by Western blot analysis. The relationship between the expression of ER beta cx variants with prognosis and outcome of endocrine therapy was examined.


RESULTS
There was a statistically significant association between the presence of ER beta cx and the response to endocrine therapy (Fisher's exact test, P = 0.04). We also examined the influence of the ER beta cx status of a tumor on time to progression and death. There was a relationship between the presence of ER beta cx and survival, with patients whose tumors express ER beta cx having a longer survival rate (P = 0.05). Cell-type specificity of expression was assessed by immunohistochemistry on a selection of histological samples.


CONCLUSIONS
On the basis of this small group of patients, we conclude that the expression of ER beta cx correlated with favorable response to endocrine therapy. A larger study involving the staining of archival material is currently underway to confirm these preliminary results.
Palmieri
Carlo
C
Department of Cancer Medicine, Cancer Cell Biology Group, Cancer Research UK Laboratories, Imperial College-London, Hammersmith Hospital, London, United Kingdom.
Lam
Eric W-F
EW
Mansi
Janine
J
MacDonald
Claire
C
Shousha
Sami
S
Madden
Peter
P
Omoto
Yoko
Y
Sunters
Andrew
A
Warner
Margaret
M
Gustafsson
Jan-Ake
JA
Coombes
R Charles
RC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D015153:Blotting, Western; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D018450:Disease Progression; D004703:Endocrine System; D047629:Estrogen Receptor beta / Q000096:biosynthesis* / Q000737:chemistry; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D020033:Protein Isoforms; D013997:Time Factors; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D047629:Estrogen Receptor beta; D020033:Protein Isoforms