Role of the progesterone receptor for paclitaxel resistance in primary breast cancer
Details
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State: Public
Version: Final published version
State: Public
Version: Final published version
Serval ID
serval:BIB_7C8C8C23B2EE
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Role of the progesterone receptor for paclitaxel resistance in primary breast cancer
Journal
British Journal of Cancer
ISSN
0007-0920 (Print)
Publication state
Published
Issued date
2007
Volume
96
Number
2
Pages
241-247
Language
english
Notes
PT - Journal Article PT - Research Support, Non-U.S. Gov't
Abstract
Paclitaxel plays an important role in the treatment of primary breast cancer. However, a substantial proportion of patients treated with paclitaxel does not appear to derive any benefit from this therapy. We performed a prospective study using tumour cells isolated from 50 primary breast carcinomas. Sensitivity of primary tumour cells to paclitaxel was determined in a clinically relevant range of concentrations (0.85-27.2 microg ml(-1) paclitaxel) using an ATP assay. Chemosensitivity data were used to study a possible association with immunohistochemically determined oestrogen and progesterone receptor (ER and PR) status, as well as histopathological parameters. Progesterone receptor (PR) mRNA expression was also determined by quantitative RT-PCR. We observed a clear association of the PR status with chemosensitivity to paclitaxel. Higher levels of immunohistochemically detected PR expression correlated with decreased chemosensitivity (P=0.008). Similarly, high levels of PR mRNA expression were associated with decreased paclitaxel chemosensitivity (P=0.007). Cells from carcinomas with T-stages 3 and 4 were less sensitive compared to stages 1 and 2 (P=0.013). Multiple regression analysis identified PR receptor status and T-stage as independent predictors of paclitaxel chemosensitivity, whereas the ER, N-stage, grading and age were not influential. In conclusion, in vitro sensitivity to paclitaxel was higher for PR-negative compared with PR-positive breast carcinoma cells. Thus, PR status should be considered as a possible factor of influence when designing new trials and chemotherapy protocols
Keywords
Antineoplastic Agents,Phytogenic/therapeutic use/Base Sequence/Breast Neoplasms/Pathology/DNA Probes/Dose-Response Relationship,Drug/Drug Resistance,Neoplasm/Humans/Immunohistochemistry/Paclitaxel/RNA,Messenger/genetics/Receptors,Progesterone/physiology
Pubmed
Web of science
Open Access
Yes
Create date
29/01/2008 19:36
Last modification date
20/08/2019 15:38