Establishment of triple-negative breast cancer cells based on BMI: A novel model in the correlation between obesity and breast cancer

IntroductionObesity has been associated with an increased risk of biologically aggressive variants in breast cancer. Women with obesity often have tumors diagnosed at later stages of the disease, associated with a poorer prognosis and a different response to treatment. Human cell lines have been derived from specific subtypes of breast cancer and have served to define the cell physiology of corresponding breast cancer subtypes. However, there are no current cell lines for breast cancer specifically derived from patients with different BMIs. The availability of those breast cancer cell lines should allow to describe and unravel functional alterations linked to these comorbidities. MethodsCell cultures were established from tumor explants. Once generated, the triple negative subtype in a patient with obesity and a patient with a normal BMI were chosen for comparison. For cellular characterization, the following assays were conducted: proliferation assays, chemo – sensitivity assays for doxorubicin and paclitaxel, wound healing motility assays, matrix invasion assays, breast cancer cell growth to estradiol by chronic exposure to leptin, induction of endothelial permeability and tumorigenic potential in athymic mice with normo - versus hypercaloric diets with an evaluation of the epithelium – mesenchymal transformation proteins.ResultsTwo different cell lines, were established from patients with breast cancer: DSG-BC1, with a BMI of 21.9 kg/m2 and DSG-BC2, with a BMI of 31.5 kg/m2. In vitro, these two cell lines show differential growth rates, motility, chemosensitivity, vascular permeability, response to leptin with an activation of the JAK2/STAT3/AKT signaling pathway. In vivo, they displayed distinct tumorigenic potential. In particular, DSG-BC2, presented higher tumorigenicity when implanted in mice fed with a hypercaloric diet.DiscussionTo our knowledge, these primary cultures are the first in vitro representation of both breast cancer and obesity. DSG – BC2 presented a more aggressive in vivo and in vitro phenotype. These results support the hypothesis that breast cancer generated in an obese metabolic state may represent a contrasting variant within the same disease. This new model will allow both further comprehension, functional studies and the analysis of altered molecular mechanisms under the comorbidity of obesity and breast cancer

Clinical and Epidemiological Profile of Breast Cancer in Mexico: Results of the Seguro Popular

Purpose: One half of the Mexican population lacks comprehensive health care coverage. In 2003, a reform to the General Health Law was approved that led to the creation of the System of Social Protection in Health and made universal health coverage mandatory. The main innovation of this reform was Seguro Popular, which provided coverage for breast cancer. Here we report the outcomes of women with breast cancer treated at a cancer center in Mexico under Seguro Popular. Materials and Methods: This was a retrospective cohort study that included all patients with breast cancer treated in the Instituto Nacional de Cancerología in Mexico City between January 2007 and December 2013 with Seguro Popular coverage. Demographic and clinical information were collected and survival outcomes were analyzed. Results: A total of 4,300 women with breast cancer were included in this analysis. Most patients had locally advanced disease at diagnosis (53%, n = 2,293), and 13% (n = 558) presented with stage IV disease. Neoadjuvant chemotherapy was administered to 1,834 patients (52%), with a pathologic complete response in 25.1% (n = 460). Median follow-up was 40.5 months. Five-year survival for the entire cohort was 82% (95% CI, 81% to 84%). Five-year survival was 97% for early-stage disease (95% CI, 95% to 98%), 82% for locally advanced disease (95% CI, 80% to 84%), and 36% for metastatic disease (95% CI, 30% to 42%). Conclusion: This represents the first description of a cohort of patients with breast cancer treated in Mexico under Seguro Popular. Seguro Popular has allowed our institution, and other Mexican centers, to establish efficient standardized mechanisms to treat patients with breast cancer

Mexican BRCA1 founder mutation: Shortening the gap in genetic assessment for hereditary breast and ovarian cancer patients.

The deletion of exons 9 to 12 of BRCA1 (9-12 del BRCA1) is considered a founder mutation in the Mexican population. We evaluate the usefulness of the target detection of 9-12 del BRCA1 as the first molecular diagnostic strategy in patients with Hereditary Breast and Ovarian Cancer (HBOC). We performed the genetic assessment of 637 patients with suspected HBOC. The region corresponding to the breakpoints for the 9-12 del BRCA1 was amplified by polymerase chain reaction (PCR). An analysis of the clinical data of the carriers and non-carriers was done, searching for characteristics that correlated with the deletion. The 9-12 del BRCA1 was detected in 5% of patients with suspected HBOC (30/637). In patients diagnosed with ovarian cancer, 13 of 30 were 9-12 del BRCA1 carriers, which represents 43%. We found a significant association between the 9-12 del BRCA1 carriers with triple negative breast cancer and high-grade papillary serous ovarian cancer. We concluded that the detection of the 9-12 del BRCA1 is useful as a first molecular diagnostic strategy in the Mexican population. In particular, it shortens the gap in genetic assessment in patients with triple negative breast cancer and ovarian cancer