Biology, prognosis and response to therapy of breast carcinomas according to HER2 score.

BACKGROUND: The standardization of the HER2 score and recent changes in therapeutic modalities points to the need for a reevaluation of the role of HER2 in recently diagnosed breast carcinoma. PATIENTS AND METHODS: A multicenter, retrospective study of 1794 primary breast carcinomas diagnosed in Italy in 2000/2001 and scored in HER2 four categories according to immunohistochemistry was conducted. RESULTS: Ductal histotype, vascular invasion, grade, MIB1 positivity, estrogen and progesterone receptor expression differed significantly in HER2 3+ tumors compared with the other categories. HER2 2+ tumors almost showed values intermediate between those of the negative and the 3+ subgroups. The characteristics of HER2 1+ tumors were found to be in between those of HER2 0 and 2+ tumors. With a median follow-up of 54 months, HER2 3+ status was associated with higher relapse rates in node-positive and node-negative subgroups, while HER2 2+ only in node positive. Analysis of relapses according to type of therapy provided evidence of responsiveness of HER2-positive tumors to chemotherapy, especially taxanes. CONCLUSIONS: The present prognostic significance of HER2 is correlated to receptor expression level and points to the need to consider HER2 2+ and HER2 3+ tumors as distinct diseases with different outcomes and specific features.

Metastasis to the thyroid gland: a case report and review of the literature.

Metastatic cancer to the thyroid is uncommon. Although the thyroid is richly supplied with blood, there are a few reports of metastatic cancer spreading to this gland. The overall incidence in autopsy series has been quite varied, with rates from 1.2 to 24% of malignant tumors. Most of this metastases are not detected in clinical practice. The majority of these patients had widespread metastases and, as a result, had very short survival times. Although detection of metastases to the thyroid gland often indicates poor prognosis, aggressive surgical and medical treatment may be effective, especially for renal carcinoma. In this report, we present a case of renal carcinoma with thyroid metastases and a review of the literature.

[Anaplastic carcinoma of the thyroid: diagnosis and treatment]. / Il carcinoma anaplastico della tiroide: inquadramento diagnostico e attuali possibilità terapeutiche.

Anaplastic thyroid carcinoma (ATC), accounting for 5% to 15% of primary malignant thyroid neoplasm, is one of the most aggressive solid tumors in humans. It is rapidly fatal, with a mean survival of 6 months after diagnosis. Multimodality treatment with surgery and/or external beam radiotherapy and chemotherapy are of fundamental importance for local control of disease and to enhance survival. Molecular biology studies have shown that ATC is associated with a p 53 mutation. ATC usually does not concentrate radioiodine or express thyroglobulin. It is essential to verify the diagnosis histologically because insular thyroid cancer, lymphomas, and medullary thyroid cancer are occasionally confused with undifferentiated neoplasms. Immunohistochemical study is helpful in establishing the diagnosis. Multimodal therapy and development of effective systemic chemotherapy agents would provide to result in improvements in survival although no single agent has yet been identified. Aggressive multimodality treatment regimens show promise in improving local control in patients with ATC. Survival rates however remain low. Despite intense applications of such integrated therapy, no standardized successful treatment protocol has yet been established.

[Medullary carcinoma of the thyroid: diagnosis and therapy]. / Il carcinoma midollare della tiroide: diagnosi e terapia.

Medullary thyroid carcinoma (MTC) originates in the thyroid C cells, or parafollicular cells, secreting calcitonin. It may be either sporadic or familial. Familial form can be isolated or expression of a multiple endocrine neoplasia type II. Mutations of the RET proto-oncogene have been identified in the germline DNA of patients with familial MTC syndromes. Genetic testing can identify patients affected by multiple endocrine neoplasia and familial MTC, allowing early diagnosis and possible cure. The initial treatment is surgical and the adequate surgery consists of total thyroidectomy. The treatment of occult or minimal disease can be curative. Plasma calcitonin measurements are excellent markers for post-operative follow-up. Imaging study can help to discover recurrent or metastatic disease. Adjunctive therapy includes radiotherapy and chemotherapy. Radiotherapy is reserved for bone metastases or for non resectable neck recurrences. Chemotherapy is reserved for patients with progressive MTC. Many chemotherapeutic regimens have been tried, results are controversial.

[Evaluation of acute cardiotoxicity from the combination cyclophosphamide-mitoxantrone-5-fluorouracil (CMF) with Holter ECG]. / Valutazione della cardiotossicità in acuto dell'associazione ciclofosfamide-novantrone-5-fluorouracile (CNF) mediante ecg di Holter.

By making use of a twenty-four hour Holter monitoring, it as been possible to compute the acute cardiotoxicity of the cyclophosphamide + mitoxantrone + 5-fluorouracil (CNF) association in twenty oncologic patients (pts) each of whom being immune from organic cardiopathy emerging clinically and at their first cycle of chemotherapy. The following parameters have been computed: meaningful changes in the heart frequency; premature atrial and ventricular depolarizations, both as a first appearance and as a clear growth in the number; the ST dislocation entity; malignant ventricular arrhythmias. The administration of CNF at the doses of: 600 mg/m2 of cyclophosphamide, 12 mg/m2 of mitoxantrone and 600 mg/m2 of 5-fluorouracil , has caused a meaningful increase in the heart frequency on 6 pts (30%), an increase of premature atrial depolarization on 4 pts (20%) with an appearance ex novo on 2 pts (10%), an increase of premature ventricular depolarization, without any passing to superior Lown classes, on 2 pts (10%) with an appearance ex novo on 3 pts (15%). Although the results in the study point out a frequency percentage of simple hyperkinetic arrhythmias equal to the 55%, the lack of more serious hyperkinetic arrhythmias and of intense disorders of ventricular repolarization testified to a synergic effect as a determining factor on the acute cardiotoxicity of the previously discussed association, in our opinion.