Content of epidermal growth factor receptor in metastatic breast cancer: its role in endocrine sensitivity prediction.

Epidermal growth factor receptor (EGF-R) is known as an indicator of endocrine independence of breast cancer. However, a small proportion of EGF-R expressing tumors was found to respond to endocrine treatments. On the other side, a cut-off point of EGF-R positivity is not yet defined. In the aim to find out whether there exists a cut-off value that sharply discriminate the endocrine sensitive and endocrine insensitive breast cancers, the quantitative EGF-R content was analyzed in a group of 42 female patients with metastatic disease, being routinely treated with chemo-, chemo-endocrine, or endocrine therapy alone. Steroid receptors (SR) and EGF-R were determined by biochemical methods in tissue samples of an unselected group of patients. Patients with metastatic disease, either at diagnosis, or developed after the treatment of operable or locally advanced breast cancer, were included in the present analysis. According to the treatments used, and their therapeutic response, all patients were divided in endocrine sensitive or resistant, and chemo-sensitive or resistant. The SR and EGF-R status and content was analyzed in relation to the sensitivity to both systemic treatments. The EGF-R content was significantly lower in responders to endocrine treatments, compared to non-responders, while there was no difference in EGF-R level, in relation to the sensitivity to chemotherapy. In addition, the EGF-R content was significantly higher in chemo-sensitive tumors, than in endocrine sensitive. On the contrary, ER content was significantly higher in endocrine sensitive, than in endocrine resistant, and in chemo sensitive patients, as well. Similar differences were found in PR content, but they were less pronounced. While the individual ER contents in endocrine sensitive and endocrine resistant tumors overlapped, the EGF-R ranges were different: no one endocrine sensitive tumor exceeded the EGF-R content of 26 fmol/mg, thus suggesting the EGF-R cut-off point of endocrine sensitivity. The clinical use of EGF-R, with the cut-off point of 26 fmol/mg, in addition to clinical criteria of endocrine sensitivity and SRs, would significantly improve the correct endocrine sensitivity prediction (from 52 to 78%). In conclusion, in a group of metastatic breast cancer patients, treated routinely by systemic therapies it was found, that the use of higher cut-off point for EGF-R positivity can improve the prediction of endocrine sensitivity. The prognostic relevance of this cut-off value remains to be analyzed.

Single 8 mg dose of oral ondansetron failed to prevent FAC chemotherapy-induced acute nausea and vomiting.

The aim of this open, nonrandomized, monocentric study was to evaluate the efficacy of a single daily dose of 8 mg oral ondansetron in the prophylaxis of acute nausea and vomiting in chemotherapy-naive breast cancer patients receiving their first cycle of chemotherapy with 5-fluorouracil, doxorubicin and cyclophosphamide (FAC). Forty-five female patients were recruited, median age 42 years. The number of emetic episodes and the grade of nausea were recorded. 51% of patients achieved complete, and 9% major control of acute emesis. 33% of patients experienced no acute nausea, and in 18% nausea was mild. Complete protection from nausea and vomiting (complete prophylaxis) was obtained in 12/45 (27%) of patients. Treatment success (no vomiting with no more than mild nausea) was achieved in 18/45 (40%) of patients. We conclude that the efficacy of a single dose of 8 mg oral ondansetron in controlling acute nausea and vomiting induced by FAC chemotherapy is not high enough to justify its use as a sole antiemetic agent in outpatients.

Daily oral etoposide in metastatic breast cancer.

Etoposide, administered i.v. or orally, as a single agent, in 1- to 5-day courses, was found to be minimally effective in pretreated advanced breast cancer patients. Clinical data suggested an effectiveness of a chronic low-dose oral etoposide schedule, in refractory and those malignancies otherwise unresponsive to the drug. Therefore, the aim of our open-labeled, non-randomized, phase II clinical study was to investigate the efficacy and toxicity of chronic daily etoposide (50 mg/m2 daily, for 21 consecutive days, every 28 days) as a first-line chemotherapy for metastatic breast cancer. Twenty-one advanced breast cancer patients, with or without previous adjuvant CMF chemotherapy, were included. One complete (CR) and five partial remissions (PR) were obtained in 18 patients evaluable for response. Disease stabilization was obtained in 10 patients (55%), while two patients (11%) failed to respond. Grade 3-4 hematological toxicity developed in seven out of 21 patients evaluable for toxicity or in 15 out of 96 cycles. Nonhematological toxicity was moderate. Our results showed the efficacy and relative low toxicity of a chronic oral etoposide regimen in advanced breast cancer patients. Adjuvant CMF chemotherapy did not influence the therapeutic response. Previous irradiation of the breast tended to increase the etoposide hematological toxicity.