Expression of estrogen receptor beta in the breast carcinoma of BRCA1 mutation carriers.
BACKGROUND
Breast cancers (BC) in women carrying mutations in BRCA1 gene are more frequently estrogen receptor negative than the nonhereditary BC. Nevertheless, tamoxifen has been found to have a protective effect in preventing contralateral tumors in BRCA1 mutation carriers. The identification of the second human estrogen receptor, ERbeta, raised a question of its role in hereditary breast cancer. The aim of this study was to assess the frequency of ERalpha, ERbeta, PgR (progesterone receptor) and HER-2 expression in breast cancer patients with mutated BRCA1 gene and in the control group.


METHODS
The study group consisted of 48 women with BRCA1 gene mutations confirmed by multiplex PCR assay. The patients were tested for three most common mutations of BRCA1 affecting the Polish population (5382insC, C61G, 4153delA). Immunostaining for ERalpha, ERbeta and PgR (progesterone receptor) was performed using monoclonal antibodies against ERalpha, PgR (DakoCytomation), and polyclonal antibody against ERbeta (Chemicon). The EnVision detection system was applied. The study population comprised a control group of 120 BC operated successively during the years 1998-99.


RESULTS
The results of our investigation showed that BRCA1 mutation carriers were more likely to have ERalpha-negative breast cancer than those in the control group. Only 14.5% of BRCA1-related cancers were ERalpha-positive compared with 57.5% in the control group (P < 0.0001). On the contrary, the expression of ERbeta protein was observed in 42% of BRCA1-related tumors and in 55% of the control group. An interesting finding was that most hereditary cancers (75% of the whole group) were triple-negative: ERalpha(-)/PgR(-)/HER-2(-) but almost half of this group (44.4%) showed the expression of ERbeta.


CONCLUSIONS
In the case of BRCA1-associated tumors the expression of ERbeta was significantly higher than the expression of ERalpha. This may explain the effectiveness of tamoxifen in preventing contralateral breast cancer development in BRCA1 mutation carriers.
Litwiniuk
Maria M
MM
Clinic of Oncology, Poznan University of Medical Sciences, Poznan, Poland. litwiniuk@skrzynka.pl
Roznowski
Krzysztof
K
Filas
Violetta
V
Godlewski
Dariusz D
DD
Stawicka
Małgorzata
M
Kaleta
Remigiusz
R
Breborowicz
Jan
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000096:biosynthesis* / Q000235:genetics; D047629:Estrogen Receptor beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D019398:Genes, BRCA1; D018734:Genes, erbB-2; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage; D013629:Tamoxifen / Q000008:administration & dosage
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen