TY - JOUR
T1 - Intratumoral concentration of estrogens and clinicopathological changes in ductal carcinoma in situ following aromatase inhibitor letrozole treatment
AU - Takagi, K.
AU - Ishida, T.
AU - Miki, Y.
AU - Hirakawa, H.
AU - Kakugawa, Y.
AU - Amano, G.
AU - Ebata, A.
AU - Mori, N.
AU - Nakamura, Y.
AU - Watanabe, M.
AU - Amari, M.
AU - Ohuchi, N.
AU - Sasano, H.
AU - Suzuki, T.
N1 - Funding Information:
We appreciate the skillful technical assistance of Mr Katsuhiko Ono (Department of Anatomic Pathology, Tohoku University Graduate School of Medicine). This work was partly supported by Grant-in-Aid for Scientific Research (22590305) from the Japanese Ministry of Education, Culture, Sports, Science and Technology, and by an educational grant from Novartis Pharma (Tokyo, Japan).
PY - 2013/7/9
Y1 - 2013/7/9
N2 - Background:Estrogens have important roles in ductal carcinoma in situ (DCIS) of the breast. However, the significance of presurgical aromatase inhibitor treatment remains unclear. Therefore, we examined intratumoral concentration of estrogens and changes of clinicopathological factors in DCIS after letrozole treatment.Methods:Ten cases of postmenopausal oestrogen receptor (ER)-positive DCIS were examined. They received oral letrozole before the surgery, and the tumour size was evaluated by ultrasonography. Surgical specimens and corresponding biopsy samples were used for immunohistochemistry. Snap-frozen specimens were also available in a subset of cases, and used for hormone assays and microarray analysis.Results:Intratumoral oestrogen levels were significantly lower in DCIS treated with letrozole compared with that in those without the therapy. A great majority of oestrogen-induced genes showed low expression levels in DCIS treated with letrozole by microarray analysis. Moreover, letrozole treatment reduced the greatest dimension of DCIS, and significantly decreased Ki-67 and progesterone receptor immunoreactivity in DCIS tissues.Conclusion:These results suggest that estrogens are mainly produced by aromatase in DCIS tissues, and aromatase inhibitors potently inhibit oestrogen actions in postmenopausal ER-positive DCIS through rapid deprivation of intratumoral estrogens.
AB - Background:Estrogens have important roles in ductal carcinoma in situ (DCIS) of the breast. However, the significance of presurgical aromatase inhibitor treatment remains unclear. Therefore, we examined intratumoral concentration of estrogens and changes of clinicopathological factors in DCIS after letrozole treatment.Methods:Ten cases of postmenopausal oestrogen receptor (ER)-positive DCIS were examined. They received oral letrozole before the surgery, and the tumour size was evaluated by ultrasonography. Surgical specimens and corresponding biopsy samples were used for immunohistochemistry. Snap-frozen specimens were also available in a subset of cases, and used for hormone assays and microarray analysis.Results:Intratumoral oestrogen levels were significantly lower in DCIS treated with letrozole compared with that in those without the therapy. A great majority of oestrogen-induced genes showed low expression levels in DCIS treated with letrozole by microarray analysis. Moreover, letrozole treatment reduced the greatest dimension of DCIS, and significantly decreased Ki-67 and progesterone receptor immunoreactivity in DCIS tissues.Conclusion:These results suggest that estrogens are mainly produced by aromatase in DCIS tissues, and aromatase inhibitors potently inhibit oestrogen actions in postmenopausal ER-positive DCIS through rapid deprivation of intratumoral estrogens.
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U2 - 10.1038/bjc.2013.284
DO - 10.1038/bjc.2013.284
M3 - Article
C2 - 23756858
AN - SCOPUS:84880317683
SN - 0007-0920
VL - 109
SP - 100
EP - 108
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 1
ER -
