Background Breast cancer currently is the most frequently diagnosed neoplasm and the leading cause of death from cancer in women worldwide, which is mainly due to metastatic disease. Increasing our understanding of the molecular mechanisms leading to metastasis might thus improve the pharmacological management of the disease. Epithelial-mesenchymal transition (EMT) is a key factor that plays a major role in tumor metastasis. Some pro-inflammatory cytokines, like IL-6, have been shown to stimulate phenotypes consistent with EMT in transformed epithelial cells as well as in carcinoma cell lines. Since the EMT is one of the crucial steps for metastasis, we studied the effects of metformin (MTF) on EMT. Methods Cytotoxic effect of MTF was evaluated in eight primary breast cancer cell cultures by crystal violet assay. EMT markers and downstream signaling molecules were measured by Western blot. The effect of MTF on cell proliferation and cell migration were analyzed by MTT and Boyden chamber assays respectively. Results We observed that the response of cultured breast cancer primary cells to MTF varied; mesenchymal cells were resistant to 10 mM MTF and expressed Vimentin and SNAIL, which are associated with a mesenchymal phenotype, whereas epithelial cells were sensitive to this MTF dose, and expressed E-cadherin but not mesenchymal markers. Further, exposure of mesenchymal cells to MTF down-regulated both Vimentin and SNAIL as well as cell proliferation, but not cell migration. In an in vitro IL-6-induced EMT assay, primary breast cancer cells showing an epithelial phenotype underwent EMT upon exposure to IL-6, with concomitant activation of STAT3 and NF-κB; addition of MTF to IL-6-induced EMT reversed the expression of the mesenchymal markers Vimentin and SNAIL, decreased pSTAT3 Y705 and pNF-κB S536 and increased E-cadherin. In addition, downregulation of STAT3·activation was dependent on AMPK, but not NF-κB phosphorylation. Further, MTF inhibited cell proliferation and migration stimulated by IL-6. Conclusion These results suggest that MTF inhibits IL-6-induced EMT, cell proliferation, and migration of primary breast cancer cells by preventing the activation of STAT3 and NF-κB. STAT3 inactivation occurs through AMPK, but not NF-κB. Electronic supplementary material The online version of this article (10.1186/s12885-019-5945-1) contains supplementary material, which is available to authorized users.

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Background: Breast cancer is the frequent neoplasia in young women, which in developing countries is associated with more adverse outcomes. In Latin America, reports have shown an increased incidence of breast cancer in young women. No information exist regarding breast cancer characteristics in young Guatemalan women. We aimed to describe the clinical-pathological features among women aged 45 years or less treated in a tertiary-level hospital in Guatemala. Methods: We examined data from 119 women aged 45 years or less diagnosed with primary invasive breast cancer at the Oncology Unit Roosevelt Hospital in Guatemala between 2016 and 2020. Data were drawn from medical files on sociodemographic characteristics, histology, clinical stage, and breast cancer subtypes.Results: Of the total sample, breast cancer in women aged 45 years or less represented 31.2% of the cases. Of these, 24.36% is before 35 years, 28.57% between 35 to 39 years, and 47.05% between 39 to 45 years. Advanced clinical stages affected 66.6% of young women (48.33% for stages III and 18.33% stage IV). Data from specific breast cancer molecular subtype showed that 72.35% of cases in young women expressed an aggressive molecular subtype (Her-2 positive 27.06%, triple-negative 21.76%, and luminal/Her-2 positive 23.53%). Regarding treatment, most young patients received surgical treatment, as well as neoadjuvant or adjuvant chemotherapy. Only 24.37% received hormonal and 26.89% radiation therapy. Conclusions: Our finding suggested that young women treated for breast cancer at a tertiary-level hospital in Guatemala had a high proportion of aggressive molecular subtypes and a high rate of locally advanced disease. This aggressive cancer behavior among young women is consistent with findings in other Latin American countries. Evidence examining risk factors for aggressive cancer in young women, such as delay in diagnosis and treatment timing, is warranted. Table 1. Distributions of socio-demographic and cancer-related characteristics variables% (SE)n = 119ETHNIC GROUPMayan Indigenous12.61 (3.05)No-Mayan Indigenous87.39 (3.05)HISTOLOGYDuctal96.64 (1.66)Lobular1.68 (1.18)Other1.68 (1.18)CLINICAL STAGE*I1.67 (1.17)II31.67 (4.26)III48.33 (4.58)IV18.33 (3.54)BREAST CANCER SUBTYPELuminal27.65 (4.76)Her2 positive27.06 (5.11)Triple-negative21.76 (5.05)Luminal/Her223.53 (6.61)TREATMENTSurgery55.46 (4.58)Neoadjuvant Chemotherapy82.35 (3.51)Adjuvant Chemotherapy47.06 (4.59)Radiotherapy26.89 (4.08)Hormonotherapy24.37 (3.95) Citation Format: Juan F Alvarado-Muñoz, Agatha Reyes-Morales, Alba J Kihn-Alarcón, Marco Chivalan, Silvana Torselli, Victor Puac-Polanco. Breast cancer in young women in a tertiary-level hospital in Guatemala [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-64.

Background: Breast cancer is the leading cause of cancer-related death in Mexico, with most deaths being related to locally advanced or metastatic disease at diagnosis. Epithelial-mesenchymal transition (EMT) is one of the steps that are indispensable for metastasis. Different factors trigger EMT, like TGF-β, EGF and interleukin 6 (IL-6), among others. EMT is characterized by E-cadherin expression loss and N-cadherin and vimentin expression. In this study, we investigated the role of IL-6 on EMT induction. Methods: MBCDF and MBCD17 primary breast cancer cell cultures were used. E-cadherin expression was measured by Western Blot. Cells were stimulated with IL-6 to induce EMT. STAT3 activation was measured using phospho-specific antibodies, and E-cadherin expression was measured as EMT marker. Results: MBCDF and MBCD17 primary breast cancer cell cultures stimulation with IL-6 induced STAT3-Tyr705 phosphorylation without its total levels being altered; in addition, IL-6 cell-stimulation was shown to induce EMT, as evidenced by E-cadherin loss. Conclusions:The results of the present work suggest that IL-6 induces EMT in primary breast cancer cell cultures through STAT3 phosphorylation. (creativecommons.org/licenses/by-nc-nd/4.0/).

Objectives, to stablish the frequency of BRCA1/2 mutation rate in high-penetrance breast cancer susceptibility population Methods Based on NCCN guidelines for testing criteria for high-penetrance breast cancer susceptibility genes genetic counseling was offered to 140 breast cancer patients in the hemato-oncology unit of Roosevelt Hospital at Guatemala City performing test with NGS and MLPA technology from 2019 to 2021. Results The overall BRCA1/2 mutation rate high-risk patients were 23% (33/140). Of the patients with mutations, 66.6% (22/33) had BRCA1 mutation, 33.3% (11/33) had BRCA2 mutation, of the mutated population the median age was 45 years. Regarding the phenotype in the mutated population, 75% were triple negative, 16% luminal and 9% with Her2 overexpression. Of the patients carrying the BRCA1 mutation, we identified the c.212+1G>A mutation in 40% of the patients, possibly a founder mutation. In the triple negative population and under 45 years of age, the percentage of patients with BRCA 1/2 mutation is 40.9 (88.8% BRCA1 and 11.1% BRCA2). Conclusions: we found a percentage of BRCA 1/2 mutations in the selected population (NCCN criteria) similar to that reported in other Latin American countries, highlighting the high percentage of BRCA mutations in women under 45 years with triple negative phenotype, previous reports have highlighted the frequency of the c.212+1G>A mutation of BRCA1 in breats cancer patient in Guatemala, in this study 40% of the BRCA1 mutations correspond to said mutation, considering it as a probable founder mutation. Citation Format: Juan Alvarado-Muñoz, Agatha Reyes-Morales, Marco Chivalan, Silvana Torselli, Hector Valenzuela, Gozalo Yalibat, Mario Ordoñez, Rosa León, Egly Alvarez. BRCA1/2 gene mutations in patients with high-risk breast cancer in a tertiary-level hospital in Guatemala [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-03-17.