Basal-like immunophenotype markers and prognosis in early breast cancer.

AIMS AND BACKGROUND: Basal-like breast cancer is a distinct group of tumors with heterogeneous behavior, and not all have a poor prognosis. The present study analyzed the prevalence and prognosis of early basal-like breast cancer. METHODS AND STUDY DESIGN: A total of 112 patients with stage I and II breast cancer were retrospectively analyzed using immunohistochemical stains for estrogen receptor, progesterone receptor, HER2, cytokeratin 5/6 and epidermal growth factor receptor. Basal-like tumors were defined as being estrogen receptor, progesterone receptor and HER2 negative and cytokeratin 5/6 and/or epidermal growth factor receptor positive. RESULTS: Of the 112 cases, respectively 13 (11.6%) were basal-like, 77 (68.8%) luminal A or B, 13 (11.6%) HER2 positive and 9 (8%) undefined. In basal-like tumors, epidermal growth factor receptor and cytokeratin 5/6 expression was positive in 5 patients (38.5%) and 12 patients (92%), respectively. There was no significant correlation between basal-like breast cancer and age (P = 0.207), lymph node status (P = 1.0) or clinical stage (P = 0.53). Among all tested biomarkers, positivity was found in 81 (72.3%) for estrogen receptor, 13 (11.6%) for HER2, 11 (9.8%) for epidermal growth factor receptor and 36 (32.1%) for cytokeratin 5/6. Epidermal growth factor receptor expression was significantly correlated with estrogen receptor-negative (P = 0.01) and HER2-positive (P = 0.02) tumors. During a median follow-up of 81 months, there were 26 (23%) disease relapses and 12 (10.7%) deaths. No significant difference relating to disease-free survival and overall survival was noted between basal-like breast cancer and subtypes luminal A and B, HER2 positive and undefined. CONCLUSIONS: The addition of cytokeratin 5/6 and epidermal growth factor receptor defines a small subgroup of patients with basal-like tumors. In a population with early breast cancer, basal-like tumors did not have a prognosis different from the other subtypes. Neither was there a significant association with clinicopathological features. The high frequency of epidermal growth factor receptor positivity in estrogen receptor-negative and HER2-positive tumors represents a potential target in clinical trials.

Phase II study of thalidomide in patients with metastatic malignant melanoma.

Thalidomide has anti-angiogenic and immunomodulatory activity, exhibiting antitumour effects in patients with multiple myeloma and, more rarely, in several other solid tumours. We evaluated the single-agent antitumour activity and toxicity profile of thalidomide in patients with metastatic malignant melanoma, as well as its plasma pharmacokinetics and pharmacodynamic effects [vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF) levels]. A two-stage Gehan method was used with a stopping rule after 14 consecutive non-responding patients. Thalidomide was given orally at a daily dose of 200 mg/day, which was then escalated every 2 weeks by 200 mg/day as tolerated to a maximum of 800 mg/day. Patients were evaluated every 8 weeks for response using the World Health Organization (WHO)-27 criteria. Fourteen patients were enrolled and no objective responses were observed, with one stable disease and one mixed response. The dose-limiting toxicities were constipation, dizziness and somnolence. Other toxicities were oedema, neuropathy, dry skin, dry mouth, tremor and fatigue. The plasma pharmacokinetics of thalidomide were comparable with those of previous studies in normal volunteers and in patients with advanced prostate cancer. Serum levels of b-FGF and VEGF did not change significantly following drug administration. In conclusion, thalidomide showed poor activity, but acceptable toxicity, in patients with metastatic melanoma. Future studies should explore this agent in combination with other biological agents or cytotoxic agents, such as temozolomide.

Phase II trial and pharmacokinetic study of thalidomide in patients with metastatic colorectal cancer.

INTRODUCTION: This study was designed to estimate the percentage of objective tumor responses, toxicity profile, and obtain additional information about the plasma pharmacokinetics of thalidomide in patients with refractory and progressing metastatic colorectal cancer. STUDY DESIGN: This phase II clinical trial was conducted according to the two-stage Simon method with the inclusion of consecutive patients. The study protocol was approved by the Institutional Review Board (IRB) of the Academic Hospital (HCPA) of the Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. PATIENTS AND METHODS: Seventeen patients with previously treated, refractory progressive metastatic colorectal cancer were eligible. Six patients had prior radiotherapy. The patients had a median of one previous chemotherapy regimen. Patients were initially treated with 200 mg/day of thalidomide with an increase in dose by 200 mg/day every 2 weeks until a final daily dose of 800 mg/day was achieved. Patients were evaluated every 8 weeks for response by radiographic criteria. Plasma pharmacokinetics studies were performed in four patients at 200 mg level and in one patient at 600 mg during the first 24 h. MAIN OUTCOME MEASURES AND RESULTS: A total of 17 patients were accrued, all of them being evaluable for toxicity and 14 for response. Thalidomide was well tolerated, with constipation, somnolence, dizziness, and dry mouth being the major toxicities. There were no objective response or stable disease. The median survival was 3.6 months. Single-agent thalidomide is a generally well-tolerated drug that showed no antitumor activity in patients with advanced pretreated metastatic colorectal cancer. Although thalidomide did not show antitumor activity in this patient population, future studies of this agent in patients at initial stages of the disease (when its antiangiogenic properties may be more relevant to disease progression) could be considered.