RESUMEN
Fibroadenomas are the most common benign lump in females. The study of gene alterations and/or deregulation in reproductive years may help explain hormonal physiological processes involved in nodule development and evolution. The objective was to compare ER-alpha, c-myc, and bcl-2 gene expression in breast fibroadenomas and in normal tissue and evaluate menstrual cycle, parity, and oral contraceptive influences. Fifty-seven premenopausal women (14-49 years) undergoing surgical removal of fibroadenomas were selected. Samples from fibroadenomas and circumjacent normal tissue were obtained for RT-PCR paired analysis. Patients were divided in groups according to menstrual cycle, use of contraceptives and parity. Tissue from 32 patients was adequate for RT-PCR. Paired analysis showed higher expression of ER-alpha (P=0.012) and bcl-2 (P=0.001) in fibroadenomas than in normal breast, while c-myc presented a similar expression (P=0.655). ER-alpha was higher in fibroadenomas of patients in follicular phase versus contraceptive users and normal tissue (P=0.003); bcl-2 was higher in fibroadenomas of patients in luteal phase than in the normal samples from all groups (P=0.007). c-myc did not differ according to menstrual cycle, but was higher in fibroadenomas>3 cm versus<3 cm (P=0.015) and in nulliparous women (P=0.04). A positive correlation between c-myc levels and fibroadenoma diameter was demonstrated (r=0.536; P=0.007). Nulliparous mean nodule diameter was superior than parous women (P=0.008). In conclusion, the expression of ER-alpha, bcl-2 and c-myc depends on hormonal and reproductive factors, with a possible contribution to lump formation and evolution.
Asunto(s)
Neoplasias de la Mama/metabolismo , Mama/metabolismo , Receptor alfa de Estrógeno/química , Fibroadenoma/metabolismo , Regulación Neoplásica de la Expresión Génica , Proteínas Proto-Oncogénicas c-bcl-2/química , Proteínas Proto-Oncogénicas c-myc/metabolismo , Adolescente , Adulto , Apoptosis , ADN Complementario/metabolismo , Femenino , Humanos , Persona de Mediana Edad , Premenopausia , Progesterona/metabolismo , ARN/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
The status of the homolateral axillary lymph nodes is still the most important prognostic factor in early stage breast cancer. The information obtained from the pathological examination of the lymph nodes guides is of critical importance in the decision process regarding the use of postoperative adjuvant therapy. However, lymph node axillary dissection can be followed by significant locoregional morbidity. The sentinel lymph node (SLN) technique was developed as a means of avoiding the full exploration of the axilla and consists in the identification of the first lymph node in the lymphatic drainage system of the breast tumour in the homolateral axilla. It has been demonstrated that the status of the SLN is highly predictive for the presence or absence of tumour involvement in the remaining lymph nodes in the axilla. In this study we evaluated the SLN technique using both 99mTc labelled dextran 500 and patent blue V dye in relation to the classical lymph node resection a series of 56 women with early breast cancer who attended the Breast Unit of the Academic Hospital of the Federal University of Rio Grande do Sul, Brazil. To our knowledge this is the first report in the literature of the utilization of 99mTc dextran 500 for the SLN technique. As there are no similar commercially available dedicated radiopharmaceuticals labelled for use in lymphoscintigraphy studies, we report on an effective method to label dextran 500 with 99mTc which proved to be simple, inexpensive and yielded similar results for SLN identification compared with those given in the literature. The median age of the patients was 57 years (range 32-82 years). Seventeen patients were age 50 years or less, and 39 patients were older than 50 years. The median tumour size was 2.0 cm (range 0.8-7.0 cm). The mapping of the SLN was possible in all cases during the transoperative period by using a hand-guided gamma probe and a blue dye. A median of 2.0 (range 1-5) SLN were excised per patient. The median of axillary lymph nodes excised per patient was 21 (range 10-36). The calculated sensitivity and specificity of the method were 95.6% and 100%, respectively. The negative predictive value and overall accuracy were 97% and 98.2%, respectively. In conclusion, the SLN technique was feasible and produced similar positive results as previously reported in the literature.
Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Ganglios Linfáticos/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Colorantes , Dextranos , Femenino , Humanos , Persona de Mediana Edad , Compuestos de Organotecnecio , Valor Predictivo de las Pruebas , Estudios Prospectivos , Cintigrafía , Radiofármacos , Colorantes de RosanilinaRESUMEN
This phase II trial was conducted to evaluate the percentage of objective responses and the toxicity profile of combination doxorubicin (Adriamycin) and paclitaxel (Taxol) with granulocyte colony-stimulating factor as first-line therapy for patients with metastatic breast cancer (MBC) not previously exposed to anthracycline-containing regimens. Patients with measurable, visceral-dominant MBC and a performance status of 0 to 2 were included in the study. Doxorubicin 60 mg/m2 was administered as a short intravenous infusion, followed by paclitaxel 250 mg/m2 as a 3-hour intravenous infusion on day 1. Granulocyte colony-stimulating factor 5 micrograms/kg/d was given prophylactically as a subcutaneous injection from day 2 until granulocyte recovery to > or = 1,500/mm3. Treatment was repeated every 21 days for a maximum of six courses. Dose reductions (to doxorubicin 50 mg/m2 and paclitaxel 175 mg/m2) and/or treatment delay were applied in case of severe toxicity. All 25 women who entered were evaluable for response and toxicity. The main grade 3/4 toxicities observed were leukopenia, thrombocytopenia, and mucositis. Alopecia occurred in all patients. No clinically relevant cardiovascular toxicity was observed. Severe myelosuppression and/or mucositis necessitated dose reductions at courses 2 or 3 in all but one patient. The complete response rate was 28%, and the partial response rate was 52% for an overall objective response rate of 80%. Median progression-free survival for complete responders was 11 months (range, 3 to 24 months), while the progression-free survival was 7+ months (range 2 to 14+ months) for partial responders and 5 months (range, 3 to 9 months) for nonresponders. This combination produces a high objective response rate in women with MBC, but dose reductions were necessary in almost all cases. Toxicity was manageable after dose reduction, allowing patients to be re-treated for two to six courses without life-threatening toxicity or toxic deaths. Unfortunately, the duration of response was limited even among complete responders. Further trials of this combination in patients with MBC should explore improvements in this study regimen.