Switching to letrozole versus continued tamoxifen therapy in treatment of postmenopausal women with early breast cancer.

BACKGROUND: Tamoxifen has been the mainstay of breast cancer therapy. Over time, resistance to tamoxifen may develop. The aromatase inhibitors have proven to be a powerful drug for use in hormone-sensitive early breast cancer. The switching strategy was designed to combine the apparent superior efficacy of aromatase inhibitors with tamoxifen favourable effects. METHODS: This study was performed on 120 postmenopausal women with histologically confirmed, hormone receptor-positive, operable invasive breast carcinoma who remained free of disease after 2 years of adjuvant tamoxifen therapy. They were randomized to receive either letrozole 2.5mg/day (60 patients) or to continue 20mg/day tamoxifen for 5 years (60 patients). RESULTS: The treatment groups were well balanced in terms of age, tumor size, nodal status, oestrogen and progesterone receptor status, and previous surgery. The disease recurred in 10 patients in the group receiving tamoxifen and 3 patients in the same group switched to letrozole. There were 8 deaths in the group receiving tamoxifen and 3 deaths in the group of patients who switched to letrozole. Disease-free survival was higher in the group of patients who switched to letrozole compared to the group of patients who received tamoxifen (p=0.04), while the overall survival was not statistically significantly different in the two groups. Letrozole was associated with a significantly lower rate of vaginal bleeding and thromboembolic events. However, bone fractures and adverse cardiovascular events were more frequent in the arm receiving letrozole than in the arm receiving tamoxifen but these differences were not statistically significant. CONCLUSION: Switching to letrozole after 2 years of tamoxifen may be better than continuing five years of tamoxifen therapy as regard efficacy and tolerability. Further study is recomended on a larger group of patients to verify this finding. KEY WORDS: Breast cancer - Hormonal treatment - Letrozole - Tamoxifen.

Rapid diagnosis and follow up of bladder cancer patients using urinary high molecular weight cytokeratins.

We have developed an office-based dot-EIA for the detection of a urinary high molecular weight cytokeratin (CK). Immunohistochemical staining and western blot based on CK1K10 monoclonal antibody were used to identify the CK. Urine of 192 patients with different types, grades, and stages of bladder tumor and 72 controls were evaluated using dot-EIA. An intense and diffuse cytoplasmic reaction was shown in bladder squamous cell carcinoma. The target epitope was identified in urine at 65, 56, and 40-kDa. The CK purified from urine showed single polypeptide at 65-kDa using SDS-PAGE and single peak at 7.4 min using capillary zone electrophoresis. The dot-EIA detected the CK with high sensitivity (97%) and specificity (94%). The CK was not detected in urine of bladder cancer patients showing response to radiotherapy. The sensitive and specific office-based detection of urinary cytokeratin would be helpful in rapid diagnosis and follow up of bladder carcinoma.

An office-based immunodiagnostic assay for detecting urinary nuclear matrix protein 52 in patients with bladder cancer.

OBJECTIVE: To report the rapid (5 min) and simple detection of a nuclear matrix protein (NMP) in the urine of patients with bladder cancer, using a newly developed office-based dot-enzyme-linked immunosorbent assay (ELISA). PATIENTS AND METHODS: Western blot and specific immunoglobulin-G antibody were used to identify the urinary NMP marker. Urine samples from 149 patients with bladder cancer and 72 controls were evaluated using the developed dot-ELISA. The initial responses of 43 patients treated by irradiation were followed using the assay. RESULTS: The NMP marker was identified in the urine of patients with bladder cancer at 52 kDa (NMP-52) by Western blot. The dot-ELISA detected the urinary NMP-52 marker in 92% of patients with squamous cell carcinoma, 98% with transitional cell carcinoma, and all six of those with adenocarcinoma of the bladder, with a specificity of 94%. The positive and negative predictive values (97% and 94%, respectively) and efficiency (96%) of the dot-ELISA were high. In addition, the NMP-52 tumour marker was not detected in the urine of patients who showed a response after radiotherapy. CONCLUSION: Detecting the urinary NMP-52 marker using dot-ELISA would be helpful in the rapid diagnosis and follow-up of patients with bladder cancer.