Clinical importance of estrogen receptor-beta evaluation in breast cancer patients treated with adjuvant tamoxifen therapy.
OBJECTIVE
The clinicopathologic importance of a second estrogen receptor (ER), ER-beta, in breast cancers has been intensely studied; however, there is still no real consensus regarding the clinical utility of an ER-beta assay, probably because of the lack of standardized methodology, the presence of several ER-beta isotypes (ER-beta1-5, and so on), and, more importantly, the lack of convincing data on whether the ER-beta status provides clinically useful information over what is already provided by the traditional ER-alpha/progesterone receptor (PR) assay. A large and systematic study is needed to address these important issues.


METHODS
Archival materials of 442 invasive breast cancers from women treated with adjuvant tamoxifen monotherapy and with a long follow-up period (median, 11.1 years) were subjected to immunohistochemical study using three commercially available anti-ER-beta antibodies that detect ER-beta1-3 (ER-betaN), ER-beta1, and ER-betacx (ER-beta2).


RESULTS
Positive staining for ER-betaN or ER-beta1 was associated with significantly better survival. By contrast, ER-betacx status did not influence survival. In multivariate analysis, ER-beta1 status emerged as an independent predictor of recurrence and mortality. ER-beta1 status was significantly associated with survival in postmenopausal, but not premenopausal, women. Importantly, ER-beta1 positivity was associated with significantly better survival in patients with ER-alpha-negative/PR-negative or ER-alpha-negative/PR-negative/human epidermal growth factor receptor 2-negative (triple-negative) tumors, which are widely believed to be hormone unresponsive, have poor prognosis, and require chemotherapy.


CONCLUSIONS
Immunohistochemical examination of ER-beta1 in addition to ER-alpha and PR is clinically important in patients with breast cancer treated with tamoxifen monotherapy. Further studies are needed to confirm our findings.
Honma
Naoko
N
Research Team for Geriatric Diseases, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan. nhonma@tmig.or.jp
Horii
Rie
R
Iwase
Takuji
T
Saji
Shigehira
S
Younes
Mamoun
M
Takubo
Kaiyo
K
Matsuura
Masaaki
M
Ito
Yoshinori
Y
Akiyama
Futoshi
F
Sakamoto
Goi
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D047629:Estrogen Receptor beta / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008593:Menopause; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D020033:Protein Isoforms; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*; D016019:Survival Analysis; D013629:Tamoxifen / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D047629:Estrogen Receptor beta; D020033:Protein Isoforms; D018719:Erb-b2 Receptor Tyrosine Kinases; D011980:Receptors, Progesterone; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; C508053:ERBB2 protein, human