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Estrogen Receptor β (ERβ) Level but Not Its ERβcx Variant Helps to Predict Tamoxifen Resistance in Breast Cancer
Ist Teil von
Clinical cancer research, 2004-09, Vol.10 (17), p.5769-5776
Ort / Verlag
Philadelphia, PA: American Association for Cancer Research
Erscheinungsjahr
2004
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
The antiestrogen tamoxifen, a major endocrine therapy of estrogen receptor (ER)-positive breast cancer, is nevertheless inefficient
in 30 to 40% of cases for unknown reasons. We retrospectively studied 50 ER-positive primary breast carcinomas. All of the
patients had received tamoxifen as the only adjuvant therapy. They were divided into two groups depending on whether they
relapsed within 5 years (16 tamoxifen-resistant cases) or did not relapse within 5 years (34 tamoxifen-sensitive cases). The
expression of total ERβ protein, and of ERβcx protein, was estimated anonymously in formalin-fixed, paraffin-embedded tumor
sections, by using specific antibodies and quantifiying nuclear immunostaining with a computer image analyzer. All of the
tumors were found to be HER-2/neu-negative by immunohistochemistry.
Univariate analysis showed that Scarff-Bloom-Richardsson grade modified by Elston (SBR grade; P < 0.001), tumor size ( P = 0.042), and MIB-1 proliferation index ( P = 0.02) were significantly higher in tamoxifen-resistant tumors. A low level of total ERβ, whether in percentage of positive
cells or in quantitative immunocytochemical (QIC) score, was also associated with tamoxifen resistance ( P = 0.004). ERβcx expression and lymph node status were similar between the two groups. The expression of ERβ in the total
population was positively correlated with ERβcx ( r = 0.63, P < 0.001), and was independent of the other parameters. In a multivariate analysis, ERβ expression was the most important
variable ( P = 0.001), followed by SBR grade (I+II versus III; P = 0.008), and MIB-1 ( P = 0.016).
To conclude, tamoxifen resistance is associated with classical variables of aggressive tumors (high SBR grade, proliferation
index, and tumor size) but not with node invasiveness. Low ERβ level is an additional independent marker, better than ERα
level, to predict tamoxifen resistance.