The molecular portrait of triple-negative breast cancer: the LAG3 gene single nucleotide polymorphism rs2365094 has no impact on the clinical picture

Introduction. Triple-negative breast cancer (TNBC) is characterized by a lack of oestrogen, progesterone and human epidermal growth factor receptors. It is the one of most heterogeneous and highly-aggressive breast cancers, resulting in fast progression. In humans, the lymphocyte activation gene 3 (LAG3) is located on chromosome 12p13 and encodes an immune-regulatory molecule. The aim of the study was to perform a molecular analysis of LAG3 gene polymorphisms.  Material and method. The presence of single-nucleotide polymorphisms (SNPs) at rs2365094 was determined in 30 TNBC patients and 30 healthy controls using a polymerase chain reaction (PCR) and commercially-available TaqMan SNP Genotyping Assays. SNP status was then compared with the clinical outcome.  Results. The allelic alterations in LAG3 gene SNP in rs2365094 appear to have no influence on the clinicopathological picture among TNBC patients. The carriage rate for a single allele did not differ significantly between patients and controls.  Conclusions. No significant relationship was observed between the rs2365094 SNP status and clinicopathological determinants.

The molecular portrait of triple-negative breast cancer: the LAG3 gene single nucleotide polymorphism rs2365094 has no impact on the clinical picture

Introduction. Triple-negative breast cancer (TNBC) is characterized by a lack of estrogen, progesterone and human epidermal growth factor receptors. It is the one of most heterogeneous and highly-aggressive breast cancers, resulting in fast progression. In humans, the lymphocyte activation gene 3 (LAG3) is located on chromosome 12p13 and encodes an immune-regulatory molecule. The aim of the study was to perform a molecular analysis of LAG3 gene polymorphisms. Material and method. The presence of single-nucleotide polymorphisms (SNPs) at rs2365094 was determined in 30 TNBC patients and 30 healthy controls using polymerase chain reaction (PCR) and commercially-available TaqMan SNP Genotyping Assays. SNP status was the compared with clinical outcome. Results. The allelic alterations in LAG3 gene SNP in rs2365094 appear to have no influence on the clinicopathological picture among TNBC patients. The carriage rate for a single allele did not differ significantly between patients and controls. Conclusions. No significant relationship was observed between rs2365094 SNP status and clinicopathological determinants

Association of microRNAs and pathologic response to preoperative chemotherapy in triple negative breast cancer: preliminary report

Triple negative breast cancer (TNBC) has caught the attention of oncologists worldwide because of poor prognosis and paucity of targeted therapies. Gene pathways have been widely studied, but less is known about epigenetic factors such as microRNAs (miRNAs) and their role in tailoring an individual systemic and surgical approach for breast cancer patients. The aim of the study was to examine selected miRNAs in TNBC core biopsies sampled before preoperative chemotherapy and the subsequent pathologic response in mastectomy or breast conservation specimens. Prior to treatment, core needle biopsies were collected from 11 female patients with inoperable locally advanced TNBC or large resectable tumors suitable for down-staging. In all 11 TNBC core biopsies we analyzed 19 miRNAs per sample: 512, 190, 200, 346, 148, 449, 203, 577, 93, 126, 423, 129, 193, 182, 136, 135, 191, 122 and 222 (miRCURY LNA™ Universal RT microRNA polymerase chain reaction Custom Pick & Mixpanels). The Wilcoxon signed-rank test was used to compare related samples. Ingenuity pathway analysis was used to evaluate potential functional significance of differentially expressed miRNAs. Statistical analysis showed that 3 of 19 miRNAs differed in relation to pathologic response i.e. good versus poor. These differences failed to reach statistical significance, although a trend was observed (p = 0.06). Among these miRNAs, we identified—miR-200b-3p, miR-190a and miR-512-5p. In summary, our results indicate that higher miR-200b-3p, higher miR-190a and lower miR-512-5p expression levels in core biopsies sampled from TNBC patients may be associated with better pathologic response to chemotherapy and the increased feasibility of breast conserving surgery in these patients. Although these results were from a small cohort, they provide an important basis for larger, prospective, multicenter studies to investigate the potential role of miRNAs in neoadjuvant setting

ECCO Essential Requirements for Quality Cancer Care: Primary care.

ECCO Essential Requirements for Quality Cancer Care (ERQCC) are checklists and explanations of organisation and actions that are necessary to give high-quality care to cancer patients. They are written by European experts representing all disciplines involved in cancer care. This paper concerns the integration of primary care into care for all cancers in Europe. Primary care integration

A Retrospective Study Assessing the Outcomes of Immediate Prepectoral and Subpectoral Implant and Mesh-Based Breast Reconstruction

(1) Introduction: In response to patient concerns about breast cancer recurrence, increased use of breast magnetic resonance imaging and genetic testing, and advancements in breast reconstruction techniques, mastectomy rates have been observed to rise over the last decade. The aim of the study is to compare the outcomes of prepectoral and subpectoral implants and long-term, dual-stage resorbable mesh-based breast reconstructions in mutation carriers (prophylactic surgery) and breast cancer patients. (2) Patients and methods: This retrospective, two-center study included 170 consecutive patients after 232 procedures: Prepectoral surgery was performed in 156 cases and subpectoral was performed in 76. (3) Results: Preoperative chemotherapy was associated with more frequent minor late complications (p p = 0.101), while postoperative chemotherapy was related to more frequent serious (p = 0.005) postoperative complications. Postoperative radiotherapy was associated with a higher rate of minor complications (31.03%) than no-radiotherapy (12.21%; p p p p = 0.915). (4) Conclusions: Implant-based breast reconstruction with the use of long-term, dual-stage resorbable, synthetic mesh is a safe and effective method of breast restoration, associated with low morbidity and good cosmesis. Nevertheless, prospective, multicenter, and long-term outcome data studies are needed to further evaluate the benefits of such treatments

Environmental exposure to cadmium in breast cancer – association with the Warburg effect and sensitivity to tamoxifen

The association between cadmium and breast cancer remains unexplained due to inconsistent epidemiological data and unknown underlying mechanisms. This study aimed to assess the relationship between environmental exposure to cadmium and the Warburg effect in breast cancer and, thus, its possible interference with breast cancer treatment. The observational study in two groups of breast cancer patients indicated a positive correlation between urinary cadmium concentration and tumor expression of HIF1A (a master regulator of the Warburg effect). Further explanatory research in MCF-7 cells showed no impact of cadmium exposure on molecular and biochemical markers of the Warburg effect. However, long-term exposure to a low and environmentally relevant concentration of cadmium led to the accumulation of the metal in MCF-7 cells and decreased their sensitivity to tamoxifen. To conclude, the association between cadmium and the Warburg effect was suggested in the observational study, although not confirmed in vitro. Nevertheless, cadmium seems to interfere with tamoxifen treatment which deserves further investigation in terms of its possible implication in intrinsic resistance to hormone therapy

Variation in treatment and survival of older patients with non-metastatic breast cancer in five European countries: A population-based cohort study from the EURECCA Breast Cancer Group

Background: Older patients are poorly represented in breast cancer research and guidelines do not provide evidence based recommendations for this specific group. We compared treatment strategies and survival outcomes between European countries and assessed whether variance in treatment patterns may be associated with variation in survival. Methods: Population-based study including patients aged ≥ 70 with non-metastatic BC from cancer registries from the Netherlands, Belgium, Ireland, England and Greater Poland. Proportions of local and systemic treatments, five-year relative survival and relative excess risks (RER) between countries were calculated. Results: In total, 236,015 patients were included. The proportion of stage I BC receiving endocrine therapy ranged from 19.6% (Netherlands) to 84.6% (Belgium). The proportion of stage III BC receiving no breast surgery varied between 22.0% (Belgium) and 50.8% (Ireland). For stage I BC, relative survival was lower in England compared with Belgium (RER 2.96, 95%CI 1.30-6.72, P <.001). For stage III BC, England, Ireland and Greater Poland showed significantly worse relative survival compared with Belgium. Conclusions: There is substantial variation in treatment strategies and survival outcomes in elderly with BC in Europe. For early-stage BC, we observed large variation in endocrine therapy but no variation in relative survival, suggesting potential overtreatment. For advanced BC, we observed higher survival in countries with lower proportions of omission of surgery, suggesting potential undertreatment