Effect of neoadjuvant chemotherapy on low-density lipoprotein (LDL) receptor and LDL receptor-related protein 1 (LRP-1) receptor in locally advanced breast cancer

Low-density lipoprotein (LDL) receptors are overexpressed in most neoplastic cell lines and provide a mechanism for the internalization and concentration of drug-laden nanoemulsions that bind to these receptors. The aim of the present study was to determine whether the administration of standard chemotherapeutic schemes can alter the expression of LDL and LDL receptor-related protein 1 (LRP-1) receptors in breast carcinoma. Fragments of tumoral and normal breast tissue from 16 consecutive volunteer women with breast cancer in stage II or III were obtained from biopsies before the beginning of neoadjuvant chemotherapy and after chemotherapy, from fragments excised during mastectomy. Tissues were analyzed by immunohistochemistry for both receptors. Because complete response to treatment was achieved in 4 patients, only the tumors from 12 were analyzed. Before chemotherapy, there was overexpression of LDL receptor in the tumoral tissue compared to normal breast tissue in 8 of these patients. LRP-1 receptor overexpression was observed in tumors of 4 patients. After chemotherapy, expression of both receptors decreased in the tumors of 6 patients, increased in 4 and was unchanged in 2. Nonetheless, even when chemotherapy reduced receptors expression, the expression was still above normal. The fact that chemotherapy does not impair LDL receptors expression supports the use of drug carrier systems that target neoplastic cells by the LDL receptor endocytic pathway in patients on conventional chemotherapy.

Effect of neoadjuvant chemotherapy on low-density lipoprotein (LDL) receptor and LDL receptor-related protein 1 (LRP-1) receptor in locally advanced breast cancer.

Low-density lipoprotein (LDL) receptors are overexpressed in most neoplastic cell lines and provide a mechanism for the internalization and concentration of drug-laden nanoemulsions that bind to these receptors. The aim of the present study was to determine whether the administration of standard chemotherapeutic schemes can alter the expression of LDL and LDL receptor-related protein 1 (LRP-1) receptors in breast carcinoma. Fragments of tumoral and normal breast tissue from 16 consecutive volunteer women with breast cancer in stage II or III were obtained from biopsies before the beginning of neoadjuvant chemotherapy and after chemotherapy, from fragments excised during mastectomy. Tissues were analyzed by immunohistochemistry for both receptors. Because complete response to treatment was achieved in 4 patients, only the tumors from 12 were analyzed. Before chemotherapy, there was overexpression of LDL receptor in the tumoral tissue compared to normal breast tissue in 8 of these patients. LRP-1 receptor overexpression was observed in tumors of 4 patients. After chemotherapy, expression of both receptors decreased in the tumors of 6 patients, increased in 4 and was unchanged in 2. Nonetheless, even when chemotherapy reduced receptors expression, the expression was still above normal. The fact that chemotherapy does not impair LDL receptors expression supports the use of drug carrier systems that target neoplastic cells by the LDL receptor endocytic pathway in patients on conventional chemotherapy.

Uptake by breast carcinoma of a lipidic nanoemulsion after intralesional injection into the patients: a new strategy for neoadjuvant chemotherapy.

OBJECTIVE: Previously we showed that after intravenous injection a lipidic nanoemulsion concentrates in breast carcinoma tissue and other solid tumors and may carry drugs directed against neoplastic tissues. Use of the nanoemulsion decreases toxicity of the chemotherapeutic agents without decreasing the anticancer action. Currently, the hypothesis was tested whether the nanoemulsion concentrates in breast carcinoma tissue after locoregional injection. METHODS: Three different techniques of injection of the nanoemulsion were tested in patients scheduled for surgical treatment: G1 (n=4) into the mammary tissue 5 cm away from the tumor; G2 (n=4) into the peritumoral mammary tissue; G3 (n=6) into the tumoral tissue. The nanoemulsion labeled with radioactive cholesteryl oleate was injected 12 h before surgery; plasma decay of the label was determined from blood samples collected over 24 h and the tissue fragments excised during the surgery were analyzed for radioactivity uptake. RESULTS: Among the three nanoemulsion injection techniques, G3 showed the greatest uptake (data expressed in c.p.m/g of tissue) by the tumor (44,769+/-54,749) and by the lymph node (2356+/-2966), as well as the greatest concentration in tumor compared to normal tissue (844+/-1673). In G1 and G2, uptakes were, respectively, tumor: 60+/-71 and 843+/-1526; lymph node: 263+/-375 and 102+/-74; normal tissue: 139+/-102 and 217+/-413. CONCLUSIONS: Therefore, with intralesional injection of the nanoemulsion, a great concentration effect can be achieved. This injection technique may be thus a promising approach for drug-targeting in neoadjuvant chemotherapy in breast cancer treatment.

A phase II trial of fractionated vinorelbine/doxorubicin as first-line therapy for advanced breast cancer.

In western countries breast cancer is still the leading cause of death of women. Very promising results have been obtained by combining vinorelbine and doxorubicin, two of the most active drugs in metastatic breast cancer. However, despite the activity reported, this combination has shown a 10% rate of grade 2-4 cardiac toxicity, mainly due to the total cumulative doses of anthracycline delivered. The aim of this study was to divide the total dose of doxorubicin into two administrations on days 1 and 8, in order to cut down its toxicity while maintaining the same activity. Fifty-two chemotherapy naïve patients with metastatic breast cancer entered into the study and were treated with vinorelbine 25 mg/m2 plus doxorubicin 25 mg/m2 both on days 1 and 8 every three weeks. Fifty-one patients were eligible and evaluable for toxicity while 47 of them were evaluable for activity. Haematological toxicity was predominantly related to neutropenia, with grade 3/4 in 16% of cycles. Non-haematological toxicity was represented by alopecia grade 3 (which affected 65% of the patients), local phlebitis and severe constipation. No clinically significant cases of neuropathy or cardiac dysfunction were seen. With regard to activity, 38 out of 47 patients (80%) responded to therapy, nine of them achieving complete responses (19%). Median response duration was 16 months and the median overall survival was 22.7 months. We conclude that the fractionated administration of vinorelbine and doxorubicin is associated with excellent haematological and non-haematological tolerability (especially as regards cardiac toxicity), coupled with high levels of activity comparable to those observed using regimens based on unfractionated administration of treatment.

Tissue carcinoembryonic antigen in the prognosis of early invasive breast cancer.

Twenty-five patients with stage II ductal breast carcinoma followed up for ten years were studied for the presence of tissue carcinoembryonic antigen (CEA). Overall expression of CEA was 60%. The ten year survival rate was significantly higher for patients with CEA-negative tumours (70%) than for patients with CEA-positive tumours (27%), while the difference between the survival rate of patients with (30%) or without (53%) lymph node involvement did not reach significance. Among the 10 patients with lymph node involvement, CEA-negative patients had a better outcome. These results suggest that there is a correlation between the presence of tissue CEA and the prognosis of the disease, and that CEA status might possibly be more important than lymph node involvement, at least within stage II breast carcinomas.

Estudo clinico e laboratorial de pacientes climatericas (fase pos-menopausica) submetidas ao LIR-1660. / Clinical and laboratorial study of climacteric patients (post-menopausal phase) submitted to LIR 1660

Trinta pacientes na pos-menopausa fisiologica foram tratadas com LIR-1660 na dosagem de 100 mg/dia durante 20 dias. Atraves do indice menopausal de Kupperman, da dosagem de FSH, LH prolactina, estradiol e da colpocitologia hormonal observaram-se as modificacoes apos o tratamento. Pode-se concluir ser a droga eficaz no controle dos sintomas neurovegetativos, mas nao determina alteracoes nas concentracoes sanguineas dos hormonios estudados e na colpocitologia hormonal. Em nenhum caso foi observado efeitos colaterais e galactorreia

Estudo clinico de nova medicacao (LIR-1660) na sindrome climaterica (fase pos-menopausica) / Clinical study of a new drug (LTR-1660) in the climateric syndrome (post-menopausal phase)

Os autores estudaram 20 pacientes climatericas na fase pos-menopausica fisiologica, pertencentes a Secao de Climaterio da Clinica Ginecologica da FMUSP (Hospital das Clinicas - Servico do Prof. Carlos Alberto Salvatore), cujas idades oscilaram de 44 a 60 anos. A estas pacientes foi administrado LIR-1660 na dosagem de 100 mg por dia, via oral, por 20 dias consecutivos. Os resultados relacionados aos sintomas vasomotores foram satisfatorios em 80% dos casos e regulares em 20%; em nenhum caso observou-se efeito colateral a droga. Concluem os autores da eficacia desta substancia, e que a mesma representa uma boa alternativa terapeutica nas pacientes climatericas

Medida vascular no carcinoma da mama.Estudo mamografico quantitativo. / Vascular measurement in brest cancer Quantitative mammographic study

O padrao vascular das mamas apreciado pela mamografia foi estudado quantitativamente entre 1978 e 1982. Assim, a vascularizacao mamaria em 10 portadoras de carcinoma (Grupo A) foi comparada com a existente em 10 pacientes com displasia (Grupo B). A idade media foi de 47,1 e 45 anos para os grupos A e B, respectivamente. O total de mensuracoes nas 40 mamas foi de 4.000, escolhidas ao acaso. O diametro medio dos vasos nas mamas carcinomatosas foi de 1,60 +/- 0,11 milimetros, ao passo que o da glandula contralateral foi de 0,72 +/- 0, 12 milimetros, dados estatisticamente diferentes. O diametro medio dos vasos nas pacientes com displasia apresentou-se estatisticamente igual nas glandulas direita a esquerda, isto e, 0,71 +/- 0,08 e 0,68 +/- 0,10 milimetros, respectivamente. Comparou-se o diametro medio dos vasos nas mamas das enfermas com displasia (0,69 +/- 0,09 milimetros) com o correspondente das 10 glandulas normais em portadoras de carcinoma (0,73 +/- 0,11 milimetros).Nao houve diferenca estatistica nos dados encontrados, sugerindo que o aumento da vascularizacao em mamas carcinomatosas resulta de fator local

Nova medicacao nao estrogenica no tratamento da sindrome climaterica. / A new non-hormonal steroid drug in the treatment of climacteric syndrome

Os autores avaliaram, em 20 pacientes menopausadas, uma nova medicacao a base de ciclofenil e diazepam. O criterio de diagnostico da sindrome climaterica e do controle de eficacia foi feito atraves do indice de Kuppermann no pre e pos-tratamento. Devido aos excelentes resultados obtidos os autores concluem que a nova medicacao representa uma opcao eficaz para o adequado controle da sintomatologia climaterica