Role of the progesterone receptor for paclitaxel resistance in primary breast cancer.
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.
Schmidt
M
M
Department of Obstetrics & Gynecology, Medical School, University of Mainz, Mainz, Germany.
Bremer
E
E
Hasenclever
D
D
Victor
A
A
Gehrmann
M
M
Steiner
E
E
Schiffer
I B
IB
Gebhardt
S
S
Lehr
H-A
HA
Mahlke
M
M
Hermes
M
M
Mustea
A
A
Tanner
B
B
Koelbl
H
H
Pilch
H
H
Hengstler
J G
JG
D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000473:pathology*; D015342:DNA Probes; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007150:Immunohistochemistry; D017239:Paclitaxel / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics / Q000502:physiology*
D000972:Antineoplastic Agents, Phytogenic; D015342:DNA Probes; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D017239:Paclitaxel