Abstract
Aromatase inhibitors, such as anastrozole, are established in the treatment of hormone-dependent breast cancer. However, approximately 20% of patients treated with anastrozole do not respond, and it remains impossible to accurately predict sensitivity. Thus, novel markers to predict response are required. The K303Restrogen receptor (ER)α mutation confers resistance to tamoxifen treatment. Moreover, K303R-expressing MCF-7 cells, transfected with an aromatase expression vector and stimulated with androstenedione (an aromatase substrate), were found to be resistant to the inhibitory effect of anastrozole. The aim of this study was to verify whether the presence of the K303R ERα mutation is associated with response to 3-month neoadjuvant treatment with anastrozole (Arimidex) in a cohort of post-menopausal breast cancer patients. Of 37 patients with ER+ tumors, 19 showed a clinical response to anastrozole and 18 were resistant. Biopsies were obtained from tumors responding to the therapy or from non-responding tumors. None carried the K303R ERα mutation. To our knowledge, this is the first study to search for K303R ERα mutations in tumors clinically responsive or resistant to an aromatase inhibitor. Lack of the mutation leads us to believe that this mutation has in vivo biological significance in only a subset of breast cancers.
| Original language | English |
|---|---|
| Pages (from-to) | 939-942 |
| Number of pages | 4 |
| Journal | Experimental and Therapeutic Medicine |
| Volume | 1 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Nov 2010 |
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Keywords
- Aromatase inhibitors
- Breast cancer
- Estrogen receptor mutation
ASJC Scopus subject areas
- Medicine(all)
- Cancer Research
- Immunology and Microbiology (miscellaneous)
Cite this
Absence of the K303R estrogen receptor α mutation in breast cancer patients exhibiting different responses to aromatase inhibitor anastrozole neoadjuvant treatment. / Ghimenti, Chiara; Mello-Grand, Maurizia; Regolo, Lea; Zambelli, Alberto; Chiorino, Giovanna.
In: Experimental and Therapeutic Medicine, Vol. 1, No. 6, 11.2010, p. 939-942.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Absence of the K303R estrogen receptor α mutation in breast cancer patients exhibiting different responses to aromatase inhibitor anastrozole neoadjuvant treatment
AU - Ghimenti, Chiara
AU - Mello-Grand, Maurizia
AU - Regolo, Lea
AU - Zambelli, Alberto
AU - Chiorino, Giovanna
PY - 2010/11
Y1 - 2010/11
N2 - Aromatase inhibitors, such as anastrozole, are established in the treatment of hormone-dependent breast cancer. However, approximately 20% of patients treated with anastrozole do not respond, and it remains impossible to accurately predict sensitivity. Thus, novel markers to predict response are required. The K303Restrogen receptor (ER)α mutation confers resistance to tamoxifen treatment. Moreover, K303R-expressing MCF-7 cells, transfected with an aromatase expression vector and stimulated with androstenedione (an aromatase substrate), were found to be resistant to the inhibitory effect of anastrozole. The aim of this study was to verify whether the presence of the K303R ERα mutation is associated with response to 3-month neoadjuvant treatment with anastrozole (Arimidex) in a cohort of post-menopausal breast cancer patients. Of 37 patients with ER+ tumors, 19 showed a clinical response to anastrozole and 18 were resistant. Biopsies were obtained from tumors responding to the therapy or from non-responding tumors. None carried the K303R ERα mutation. To our knowledge, this is the first study to search for K303R ERα mutations in tumors clinically responsive or resistant to an aromatase inhibitor. Lack of the mutation leads us to believe that this mutation has in vivo biological significance in only a subset of breast cancers.
AB - Aromatase inhibitors, such as anastrozole, are established in the treatment of hormone-dependent breast cancer. However, approximately 20% of patients treated with anastrozole do not respond, and it remains impossible to accurately predict sensitivity. Thus, novel markers to predict response are required. The K303Restrogen receptor (ER)α mutation confers resistance to tamoxifen treatment. Moreover, K303R-expressing MCF-7 cells, transfected with an aromatase expression vector and stimulated with androstenedione (an aromatase substrate), were found to be resistant to the inhibitory effect of anastrozole. The aim of this study was to verify whether the presence of the K303R ERα mutation is associated with response to 3-month neoadjuvant treatment with anastrozole (Arimidex) in a cohort of post-menopausal breast cancer patients. Of 37 patients with ER+ tumors, 19 showed a clinical response to anastrozole and 18 were resistant. Biopsies were obtained from tumors responding to the therapy or from non-responding tumors. None carried the K303R ERα mutation. To our knowledge, this is the first study to search for K303R ERα mutations in tumors clinically responsive or resistant to an aromatase inhibitor. Lack of the mutation leads us to believe that this mutation has in vivo biological significance in only a subset of breast cancers.
KW - Aromatase inhibitors
KW - Breast cancer
KW - Estrogen receptor mutation
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U2 - 10.3892/etm.2010.151
DO - 10.3892/etm.2010.151
M3 - Article
VL - 1
SP - 939
EP - 942
JO - Experimental and Therapeutic Medicine
JF - Experimental and Therapeutic Medicine
SN - 1792-0981
IS - 6
ER -