Breast Cancer Tissue Explants: An Approach to Develop Personalized Therapy in Public Health Services.

Breast cancer is one of the main causes of death worldwide. Lately, there is great interest in developing methods that assess individual sensitivity and/or resistance of tumors to antineoplastics to provide personalized therapy for patients. In this study we used organotypic culture of human breast tumor slices to predict the experimental effect of antineoplastics on the viability of tumoral tissue. Samples of breast tumor were taken from 27 patients with clinically advanced breast cancer; slices were obtained and incubated separately for 48 h with paclitaxel, docetaxel, epirubicin, 5-fluorouracil, cyclophosphamide, and cell culture media (control). We determined an experimental tumor sensitivity/resistance (S/R) profile by evaluating tissue viability using the Alamar Blue® metabolic test, and by structural viability (histopathological analyses, necrosis, and inflammation). These parameters were related to immunohistochemical expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. The predominant histological type found was infiltrating ductal carcinoma (85.2%), followed by lobular carcinoma (7.4%) and mixed carcinoma (7.4%). Experimental drug resistance was related to positive hormone receptor status in 83% of samples treated with cyclophosphamide (p = 0.027). Results suggest that the tumor S/R profile can help to predict personalized therapy or optimize chemotherapeutic treatments in breast cancer.

Antitumoral Effect of Laurinterol on 3D Culture of Breast Cancer Explants.

Macroalgae represent an important source of bioactive compounds with a wide range of biotechnological applications. Overall, the discovery of effective cytotoxic compounds with pharmaceutical potential is a significant challenge, mostly because they are scarce in nature or their total synthesis is not efficient, while the bioprospecting models currently used do not predict clinical responses. Given this context, we used three-dimensional (3D) cultures of human breast cancer explants to evaluate the antitumoral effect of laurinterol, the major compound of an ethanolic extract of Laurencia johnstonii. To this end, we evaluated the metabolic and histopathological effects of the crude extract of L. johnstonii and laurinterol on Vero and MCF-7 cells, in addition to breast cancer explants. We observed a dose-dependent inhibition of the metabolic activity, as well as morphologic and nuclear changes characteristic of apoptosis. On the other hand, a reduced metabolic viability and marked necrosis areas were observed in breast cancer explants incubated with the crude extract, while explants treated with laurinterol exhibited a heterogeneous response which was associated with the individual response of each human tumor sample. This study supports the cytotoxic and antitumoral effects of laurinterol in in vitro cell cultures and in ex vivo organotypic cultures of human breast cancer explants.