No abstract

Lista de figurasEm trabalhos anteriores, mostrou-se que uma nanoemulsão lipídica denominada LDE após injeção endovenosa, em pacientes com carcinoma mamário e outros tumores sólidos concentra-se nos tecidos neoplásicos e pode direcionar especificamente agentes quimioterápicos ao tumor. Estudos clínicos mostraram que a LDE diminui acentuadamente os efeitos tóxicos desses agentes e em estudos com animais de experimentação não reduz seus efeitos antitumorais. No presente estudo, testamos a hipótese de a LDE injetada por via locorregional poderia concentrar-se no tumor de mama e nos linfonodos axilares da mama comprometida, visando futuras aplicações do sistema na quimioterapia neoadjuvante desse tumor. Três técnicas de injeção da LDE foram testadas em pacientes com carcinoma de mama avançado com tratamento cirúrgico pré-programado. A LDE marcada com colesterol radioativo foi injetada 12 horas antes da cirurgia, nas pacientes divididas em três grupos: Grupo 1 (G1, n=4): LDE injetada no parênquima mamário, a 5 cm da lesão ; Grupo 2 (G2, n=4): LDE injetada na região peritumoral; e Grupo 3 (G3 n=6): LDE injetada em região intratumoral. Este grupo foi subdividido em 2: em 2 pacientes realizaram cirurgia 2hs após a injeção da LDE e nas outras 4, 12hs após a injeção da LDE. Quantificou-se a captação da LDE nos fragmentos de tecido tumoral e mamário normal e do linfonodo axilar retirados durante a cirurgia por contagem de radioatividade após extração lipídica dos tecidos. Os resultados evidenciaram que, em G1, houve maior captação da LDE em tecido normal, sugerindo se tratar de metodologia inadequada. Em G2, a captação da LDE foi quatro vezes maior no tecido tumoral do que no tecido normal, próximo, portanto, dos valores encontrados em estudos anteriores que utilizaram a injeção da LDE por via hematológica. Em G3, o valor médio de captação da LDE foi 53 vezes maior no tecido tumoral (>75%), com mínima captação pelo tecido mamário normal (<8%). A injeção intratumoral da LDE mostrou-se, portanto, metodologia ainda superior à injeção da LDE por via endovenosa para a utilização efetiva dessa nanoemulsão como terapia-alvo em tumores primários de mama.Descritores: Neoplasia mamária; quimioterapia; nanoparticulas lipídicas; Lipoproteínas LDL. In previous work had showed that a lipidic nanoemulsion called LDE after intravenous injection in patients with breast carcinoma and others solid tumors focuses in the neoplasic tissue and can target especially chemotherapist agents to the tumors. Clinical studies showed that LDE decreases the toxic effects of those agents and in studies with experimental animals don't reduce yours antitumoral effects. In the present study, we had test the hypothesis of the LDE injected by locoregional could focuses in the breast tumor and in the axillary lymph node of the compromised breast, targeting future applications of the system in the neoadjuvant chemotherapy of this tumor. Three techniques of injection of the LDE had test in patients with advanced breast carcinoma with sirurgic treatment pre-programm...

e11555 Background: Previously we showed that after intravenous injection a lipidic nanoemulsion concentrates in breast carcinoma tissue and other solid tumors 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 hours 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 (44769±54749) 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. No significant financial relationships to disclose.

T or N stage, type of breast or axillary surgery, time from NACT end and surgery and time from surgery to radiation therapy were not predictive of relapse.Conclusions: Lack of pCR after NACT resulted in worse outcome. In patients with residual disease after NACT, presence of bilateral or multifocal/multicentric disease, pathologic residual tumor, pathologic nodal positivity and lymphovascular space invasion predicted worse RFS. These data can be used to stratify patients and potentially guide treatment decision-making identifying appropriate candidates for treatment intensification.