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 mg ml À1 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 ¼ 0.008). Similarly, high levels of PR mRNA expression were associated with decreased paclitaxel chemosensitivity (P ¼ 0.007). Cells from carcinomas with T-stages 3 and 4 were less sensitive compared to stages 1 and 2 (P ¼ 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. Taxanes like paclitaxel play an important role in the adjuvant treatment of breast cancer (Henderson et al, 2003). The efficacy of paclitaxel containing treatment can be further improved by dose dense protocols in which the chemotherapy is administered every 2 weeks with G-CSF support. Arguably, sequential protocols in which paclitaxel is administered not only dose dense, but also dose intensified, might prove to be even more efficient. Despite the well-documented antitumour efficacy of paclitaxel, many tumours exhibit intrinsic resistance to paclitaxel. These patients will obviously not profit from addition of paclitaxel to an anthracycline-based adjuvant chemotherapy. Identifying these patients could not only spare them an ineffective treatment, but gives the opportunity to establish a more efficient protocol for this particular subgroup of paclitaxel-resistant patients. In the adjuvant setting, Henderson et al (2003) have shown that especially patients whose tumours were oestrogen receptor (ER) negative derived most of the benefit from adding paclitaxel to an anthracyclin-based regimen. However, it is not entirely clear whether in this setting the prognostic impact of the hormone receptor status and the effect of adjuvant treatment with tamoxifen might thus offset a potential predictive effect of the hormone receptor status for paclitaxel chemosensitivity.
No significant difference was detected between the treatment with mitoxantrone as a single agent and the combination of low-dose FEC in terms of response or survival; therefore, the imperative of the necessity of first-line combination chemotherapy for patients with high-risk metastatic breast cancer may be questioned. Since toxicity and quality of life score favored the single-agent mitoxantrone treatment arm, this treatment may be offered to patients preferring quality of life to a potential small prolongation of survival.
Purpose: Paclitaxel is an important agent in the pharmacological treatment of metastatic breast cancer. Despite its efficacy in selected patients, the majority of patients have a resistance against paclitaxel. The aim of this study was to identify the responding patients and hence prevent the other patients from ineffective treatment. Identifying these patients could spare them an ineffective treatment and could in turn characterize a subgroup of patients with a higher response rate. Material and methods: Thirty-three patients with metastatic breast cancer received paclitaxel 175 mg/m 2 either as first-(15 patients) or as second-line (18 patients) treatment. Immunohistochemistry was performed on the blocks of the primary tumors with monoclonal antibodies against p53, HER-2/neu, P-glycoprotein, Glutathione-S-Transferase-p, and b-tubulin II. The expression of those factors was then correlated with the objective response to paclitaxel. Results: Ten of 33 patients had an objective response to treatment. A significant correlation with the objective response was found for the expression of p53. None of the tumors with p53 expression (n=11) responded to paclitaxel. In contrast, 10 of the 22 patients without p53 expression showed an objective response (P=0.013). Expression of HER-2/ neu, P-glycoprotein, Glutathione-S-Transferase-p, and b-tubulin II did not show a correlation with the response to paclitaxel. Conclusion: The immunohistochemical detection of p53 characterizes patients with metastatic breast cancer unlikely to respond to paclitaxel.
Medroxyprogesterone acetate (MPA), a potent synthetic progestin, has been widely used in the hormonal treatment of advanced breast cancer, but presently with varying dose schedules. The availability of a sensitive RIA-method for determination of serum MPA has stimulated the research on MPA serum levels in patients after repeated MPA administration. The aim of this study was to assay blood level profiles of MPA as well as of Cortisol during repeated high-dose orally administered MPA. 34 patients with metastatic breast cancer were enrolled in this study. 12 patients died already within the first 4 weeks of MPA treatment due to multiple metastases. The dosage regimen based on the daily oral administration of 1,000 mg MPA suspension. During MPA treatment, a decrease of Cortisol serum levels was observed in nearly all patients. Within the observation time of 8 months out of 22 evaluable cases 18.2% responded to the therapy (complete and partial response). No change was observed in 36.4% and progression in 45.5% of the patients. Within the remission (complete and partial) group, a good correlation between constant MPA serum levels above 150 ng/ml and remission was observed. But in the groups with no change and progression no such correlation could be observed.
In recent years sufficient scientific and clinical data have become available to establish an individualized treatment plan for each patient suffering from vulvar carcinoma. Organ-preserving operations are strictly confined to "early cases" as described by a careful histopathology of the primary lesion. The high perioperative morbidity and the bad cosmetic results of extended radical vulvectomy are definitely improved by additional plastic reconstructive procedures. Neoadjuvant chemotherapy probably results in a better survival rate in lymph node positive patients.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.