Predictive factors of invasion in ductal carcinoma in situ diagnosed by core-needle biopsy.

OBJECTIVE: To identify clinical, radiological, and histopathological characteristics that could be predictive factors of microinvasive/invasive breast carcinoma in patients with diagnosis of ductal carcinoma in situ (DCIS) by core-needle biopsy. MATERIAL AND METHODS: This is a retrospective study conducted from 2006-2017, which included women ≥18 years of age with initial DCIS, and who were treated with surgery. Final diagnosis was divided in DCIS and microinvasive/invasive carcinoma. RESULTS: 334 patients were included: 193 (57.8%) with DCIS and 141 (42.2%) with microinvasive/invasive carcinoma (microinvasive 5.1%, invasive 37.1%). Lymph node metastasis occurred in 16.3%. Differences between DCIS and microinvasive/invasive groups included the presence of palpable nodule (36.7% vs. 63.2%), radiological nodule (29% vs. 51%), bigger radiological-tumor size (1.2 cm vs. 1.7 cm), and larger microcalcification extension (2.5 cm vs. 3.1 cm), all of these variables p ≤0.05. Hormonal receptors and HER2 expression were similar. After logistic regression analysis, predictive factor of invasion was the presence of palpable nodule (OR = 4.072, 95%CI = 2.520-6.582, p <0.001) and radiological multicentric disease (OR = 1.677, 95%CI = 1.036-2.716, p = 0.035). CONCLUSIONS: In patients with DCIS, palpable nodule, and radiological multicentric disease, upgrade to microinvasive/invasive is high, and sentinel lymph node is recommended.

OBJETIVO: Identificar características clínicas, radiológicas e histopatológicas como factores predictivos de carcinoma mamario microinvasor/invasor en pacientes con Carcinoma Ductal In Situ (CDIS) diagnosticado mediante aguja de corte. MATERIAL Y MÉTODOS: Estudio retrospectivo de 2006­2017, en mujeres ≥18 años con CDIS diagnosticado con aguja de corte y tratadas con cirugía. Los diagnósticos finales fueron CDIS y carcinoma microinvasor/invasor. RESULTADOS: Se incluyeron 334 pacientes, 193 (57.8%) con CDIS y 141 (42.2%) con carcinoma microinvasor/invasor (microinvasor 5.1%, invasor 37.1%). Hubo 16.3% casos con afección ganglionar. Las diferencias entre el grupo de CDIS y carcinoma microinvasor/invasor fue la presencia de tumor palpable (36.7% vs. 63.2%), nódulo visto por imagen (29% vs. 51%), tumores más grandes (1.2 cm vs. 1.7 cm), y mayor extensión de microcalcificaciones (2.5 cm vs. 3.1 cm), estas variables con p ≤0.05. Los receptores hormonales y HER2 fueron similares. En el análisis de regresión logística, los factores predictivos de invasión fueron tumor palpable (OR = 4.072, IC95% = 2.520­6.582, p <0.001) y multicentricidad radiológica (OR = 1.677, IC95% = 1.036­2.716, p = 0.035). CONCLUSIONES: En CDIS, tumor palpable y enfermedad multicéntrica radiológica, el escalamiento a carcinoma microinvasor/invasor es alto y es recomendable realizar ganglio centinela.

Comprehensive omic characterization of breast cancer in Mexican-Hispanic women.

Breast cancer is a heterogeneous pathology, but the genomic basis of its variability remains poorly understood in populations other than Caucasians. Here, through DNA and RNA portraits we explored the molecular features of breast cancers in a set of Hispanic-Mexican (HM) women and compared them to public multi-ancestry datasets. HM patients present an earlier onset of the disease, particularly in aggressive clinical subtypes, compared to non-Hispanic women. The age-related COSMIC signature 1 was more frequent in HM women than in those from other ancestries. We found the AKT1E17K hotspot mutation in 8% of the HM women and identify the AKT1/PIK3CA axis as a potentially druggable target. Also, HM luminal breast tumors present an enhanced immunogenic phenotype compared to Asiatic and Caucasian tumors. This study is an initial effort to include patients from Hispanic populations in the research of breast cancer etiology and biology to further understand breast cancer disparities.

LINC00460 Is a Dual Biomarker That Acts as a Predictor for Increased Prognosis in Basal-Like Breast Cancer and Potentially Regulates Immunogenic and Differentiation-Related Genes.

Breast cancer (BRCA) is a serious public health problem, as it is the most frequent malignant tumor in women worldwide. BRCA is a molecularly heterogeneous disease, particularly at gene expression (mRNAs) level. Recent evidence shows that coding RNAs represent only 34% of the total transcriptome in a human cell. The rest of the 66% of RNAs are non-coding, so we might be missing relevant biological, clinical or regulatory information. In this report, we identified two novel tumor types from TCGA with LINC00460 deregulation. We used survival analysis to demonstrate that LINC00460 expression is a marker for poor overall (OS), relapse-free (RFS) and distant metastasis-free survival (DMFS) in basal-like BRCA patients. LINC00460 expression is a potential marker for aggressive phenotypes in distinct tumors, including HPV-negative HNSC, stage IV KIRC, locally advanced lung cancer and basal-like BRCA. We show that the LINC00460 prognostic expression effect is tissue-specific, since its upregulation can predict poor OS in some tumors, but also predicts an improved clinical course in BRCA patients. We found that the LINC00460 expression is significantly enriched in the Basal-like 2 (BL2) TNBC subtype and potentially regulates the WNT differentiation pathway. LINC00460 can also modulate a plethora of immunogenic related genes in BRCA, such as SFRP5, FOSL1, IFNK, CSF2, DUSP7 and IL1A and interacts with miR-103-a-1, in-silico, which, in turn, can no longer target WNT7A. Finally, LINC00460:WNT7A ratio constitutes a composite marker for decreased OS and DMFS in Basal-like BRCA, and can predict anthracycline therapy response in ER-BRCA patients. This evidence confirms that LINC00460 is a master regulator in BRCA molecular circuits and influences clinical outcome.

Mitochondrial DNA Mutation Analysis in Breast Cancer: Shifting From Germline Heteroplasmy Toward Homoplasmy in Tumors.

Studies have suggested a potential role of somatic mitochondrial mutations in cancer development. To analyze the landscape of somatic mitochondrial mutation in breast cancer and to determine whether mitochondrial DNA (mtDNA) mutational burden is correlated with overall survival (OS), we sequenced whole mtDNA from 92 matched-paired primary breast tumors and peripheral blood. A total of 324 germline variants and 173 somatic mutations were found in the tumors. The most common germline allele was 663G (12S), showing lower heteroplasmy levels in peripheral blood lymphocytes than in their matched tumors, even reaching homoplasmic status in several cases. The heteroplasmy load was higher in tumors than in their paired normal tissues. Somatic mtDNA mutations were found in 73.9% of breast tumors; 59% of these mutations were located in the coding region (66.7% non-synonymous and 33.3% synonymous). Although the CO1 gene presented the highest number of mutations, tRNA genes (T,C, and W), rRNA 12S, and CO1 and ATP6 exhibited the highest mutation rates. No specific mtDNA mutational profile was associated with molecular subtypes of breast cancer, and we found no correlation between mtDNA mutational burden and OS. Future investigations will provide insight into the molecular mechanisms through which mtDNA mutations and heteroplasmy shifting contribute to breast cancer development.

FAM83H-AS1 is a potential modulator of cancer driver genes across different tumors and a prognostic marker for ER/PR + BRCA patients.

Breast cancer (BRCA) is a serious public health problem, as it is the most frequent malignant tumor in women worldwide. BRCA is a molecularly heterogenic disease, particularly at gene expression (mRNAs) level. Recent evidence shows that coding RNAs represent only 34% of the total transcriptome in a human cell. The rest of the 66% of RNAs are non-coding, so we might be missing relevant biological, clinical or regulatory information. In this report, we identified nine novel tumor types from TCGA with FAM83H-AS1 deregulation. We used survival analysis to demonstrate that FAM83H-AS1 expression is a marker for poor survival in IHC-detected ER and PR positive BRCA patients and found a significant correlation between FAM83H-AS1 overexpression and tamoxifen resistance. Estrogen and Progesterone receptor expression levels interact with FAM83H-AS1 to potentiate its effect in OS prediction. FAM83H-AS1 silencing impairs two important breast cancer related pathways: cell migration and cell death. Among the most relevant potential FAM83H-AS1 gene targets, we found p63 and claudin 1 (CLDN1) to be deregulated after FAM83H-AS1 knockdown. Using correlation analysis, we show that FAM83H-AS1 can regulate a plethora of cancer-related genes across multiple tumor types, including BRCA. This evidence suggests that FAM83H-AS1 is a master regulator in different cancer types, and BRCA in particular.

A lncRNA landscape in breast cancer reveals a potential role for AC009283.1 in proliferation and apoptosis in HER2-enriched subtype.

Breast cancer is the most commonly diagnosed neoplasm in women worldwide with a well-recognized heterogeneous pathology, classified into four molecular subtypes: Luminal A, Luminal B, HER2-enriched and Basal-like, each one with different biological and clinical characteristics. Long non-coding RNAs (lncRNAs) represent 33% of the human transcriptome and play critical roles in breast carcinogenesis, but most of their functions are still unknown. Therefore, cancer research could benefit from continued exploration into the biology of lncRNAs in this neoplasm. We characterized lncRNA expression portraits in 74 breast tumors belonging to the four molecular subtypes using transcriptome microarrays. To infer the biological role of the deregulated lncRNAs in the molecular subtypes, we performed co-expression analysis of lncRNA-mRNA and gene ontology analysis. We identified 307 deregulated lncRNAs in tumor compared to normal tissue and 354 deregulated lncRNAs among the different molecular subtypes. Through co-expression analysis between lncRNAs and protein-coding genes, along with gene enrichment analysis, we inferred the potential function of the most deregulated lncRNAs in each molecular subtype, and independently validated our results taking advantage of TCGA data. Overexpression of the AC009283.1 was observed in the HER2-enriched subtype and it is localized in an amplification zone at chromosome 17q12, suggesting it to be a potential tumorigenic lncRNA. The functional role of lncRNA AC009283.1 was examined through loss of function assays in vitro and determining its impact on global gene expression. These studies revealed that AC009283.1 regulates genes involved in proliferation, cell cycle and apoptosis in a HER2 cellular model. We further confirmed these findings through ssGSEA and CEMITool analysis in an independent HER2-amplified breast cancer cohort. Our findings suggest a wide range of biological functions for lncRNAs in each breast cancer molecular subtype and provide a basis for their biological and functional study, as was conducted for AC009283.1, showing it to be a potential regulator of proliferation and apoptosis in the HER2-enriched subtype.

Expression of long non-coding RNA ENSG00000226738 (LncKLHDC7B) is enriched in the immunomodulatory triple-negative breast cancer subtype and its alteration promotes cell migration, invasion, and resistance to cell death.

Triple negative breast cancer (TNBC) represents an aggressive phenotype with poor prognosis compared with ER, PR, and HER2-positive tumors. TNBC is a heterogeneous disease, and gene expression analysis has identified seven molecular subtypes. Accumulating evidence demonstrates that long non-coding RNA (lncRNA) are involved in regulation of gene expression and cancer biology, contributing to essential cancer cell functions. In this study, we analyzed the expression profile of lncRNA in TNBC subtypes from 156 TNBC samples, and then characterized the functional role of LncKLHDC7B (ENSG00000226738). A total of 710 lncRNA were found to be differentially expressed between TNBC subtypes, and a subset of these altered lncRNA were independently validated. We discovered that LncKLHDC7B (ENSG00000226738) acts as a transcriptional modulator of its neighboring coding gene KLHDC7B in the immunomodulatory subtype. Furthermore, LncKLHDC7B knockdown enhanced migration and invasion, and promoted resistance to cellular death. Our findings confirmed the contribution of LncKLHDC7B to induction of apoptosis and inhibition of cell migration and invasion, suggesting that TNBC tumors with enrichment of LncKLHDC7B may exhibit distinct regulatory activity, or that this may be a generalized process in breast cancer. Additionally, in silico analysis confirmed for the first time that the low expression of KLHDC7B and LncKLHDC7B is associated with poor prognosis in patients with breast cancer.

[Feasibility and cosmetic outcome of oncoplastic surgery in breast cancer treatment]. / Factibilidad y resultado estético de la cirugía oncoplástica en el tratamiento de cáncer de mama.

BACKGROUND: Breast cancer is the leading oncological cause of death in Mexican women over 25 years old. Given the need to improve postoperative cosmetic results in patients with breast cancer, oncoplastic surgery has been developed, which allows larger tumour resections and minor cosmetic alterations. OBJECTIVE: To determine the oncological feasibility and cosmetic outcome of oncoplastic surgery at the Instituto de Enfermedades de la Mama, FUCAM, AC. MATERIAL AND METHODS: A review was conducted from January 2010 to July 2013, which included patients with breast cancer diagnosis treated with conventional breast-conserving surgery or with oncoplastic surgery in the Institute of Diseases of the Breast, FUCAM AC. Clinical and histopathological parameters were compared between the two groups, and a questionnaire of cosmetic satisfaction and quality of life was applied. RESULTS: Of the 171 patients included, 95 of them were treated with conventional breast-conserving surgery and 76 with oncoplastic surgery. Pathological tumour size was significantly larger in patients treated with oncoplastic surgery (p = 0.002). There were no differences found between the groups as regards the number of patients with positive surgical margin, the rate of complications, and cosmetic satisfaction. CONCLUSION: This study demonstrates the oncological feasibility and high cosmetic satisfaction of oncoplastic surgery with minimal psycho-social impact on patients.

[Impact on quality of life with breast reconstructive surgery after mastectomy for breast cancer]. / Impacto en la calidad de vida con cirugía reconstructiva posterior al tratamiento de cáncer de mama.

BACKGROUND: Breast cancer treatment leads mutilation and destruction of breast shape, with negative effects on body image and self-esteem. OBJECTIVES: Assessment on quality of life after breast reconstruction surgery, impact on sexuality, the cosmetic outcome experienced by the patient, and compare result with patients who refused breast reconstruction. MATERIAL AND METHODS: Retrospective, observational, descriptive, analytic study. We included breast cancer patients treated between April 15 2010 to April 15, 2011. Application of "The Survey Questionnaire short form Health 36" (SF-36) with valid use on Mexican population was conducted to measure quality of life, which uses 8 concepts: physical functioning, physical role, body pain, general health, vitality, social function, emotional role and mental health, the results are transferred to a scale 0 (worst health) to 100 (best health). RESULTS: 37 patients whit breast reconstruction had the inclusion criteria, mean age was 48.4 years. The score of SF-36 questionnaire in reconstructed patients was 76.8, in control group was 85.19 and mastectomy patients without reconstruction was 72.6. Among the items studied those with the greatest difference was the mental health, emotional role and social function, this means that patients with breast reconstruction are less affected in their social and sexual interaction. CONCLUSIONS: The reconstructed patients have a positive impact on quality of life slightly higher, sexuality is significantly worse in patients without breast reconstruction, it is important to inform and offer breast reconstruction because many do not require these procedures for fear or lack of information.

[Are antimicrobials useful in closed thoracostomy due to trauma?]. / Utilidad de los antimicrobianos en la toracostomía cerrada por trauma.

BACKGROUND: Thoracic trauma accounts for 25% of deaths due to trauma. Chest trauma patients generally present to the emergency room with pneumo- or hemothorax. According to the majority of the studies, management of closed thoracostomy for trauma includes the use of antimicrobial drugs to prevent infectious complications, but this has not been proven to be beneficial. We undertook this study to evaluate antimicrobial use in thoracic trauma patients with closed thoracostomy and its impact on the development of infectious complications. METHODS: We carried out a prospective, randomized, double blind, comparative study. Patients with isolated chest trauma requiring closed thoracostomy were divided into two groups. Group A received cefalotin, and group B received placebo. Ages ranged from 15-65 years. Results were analyzed with chi(2) and Fisher exact test. RESULTS: One hundred twenty six patients were included in this study. There were 63 patients in each group with similar demographic characteristics. The mean length of hospital stay with the tube was 6.56 days, but the average stay was 11 days for patients who developed empyema. Eight patients developed empyema, three patients with empyema belonged to group A patients and five patients with empyema belonged to group B. For empyema management, five cases were resolved by chest drainage, two cases required thoracoscopic cleaning and drainage and one patient was resolved with thoracotomy and pleural decortication. Bivariate analysis comparing antimicrobial use vs. empyema and length of drainage vs. antimicrobials did not show a statistically significant difference. CONCLUSIONS: The present study did not demonstrate that antimicrobial use was beneficial in the prevention of pleural infections in the management of chest trauma patients requiring closed thoracostomy.

Utilidad de los antimicrobianos en la toracostomía cerrada por trauma / Are antimicrobials useful in closed thoracostomy due to trauma?

Introducción: Una cuarta parte de las muertes en trauma son por trauma torácico. El paciente con trauma torácico generalmente presenta neumotórax o hemotórax, los cuales predisponen a complicaciones infecciosas que dependen de múltiples factores. El manejo en muchas instituciones incluye antimicrobianos para prevenir complicaciones infecciosas, si bien no está demostrada la reducción de la incidencia de infecciones. El objetivo de nuestra investigación fue evaluar la utilidad de los antimicrobianos en trauma torácico. Material y métodos: Estudio clínico controlado, doble ciego, analítico, longitudinal, prospectivo, comparativo, de dos grupos: A recibió cefalotina y B, placebo. Rango de edad de 15 a 65 años. El análisis estadístico se llevó a cabo con χ2 o prueba exacta de Fisher. Resultados: 126 pacientes fueron incluidos en el estudio, 63 en cada grupo, con similares características demográficas. La media de días con pleurostomía fue de 6.56, pero en quienes desarrollaron empiema fue de 11; la incidencia del empiema fue de 6.4 % (n = 8). Tres pacientes con empiema fueron del grupo A y cinco del B; tres empiemas fueron complejos y cinco simples; dos requirieron toracoscopia y uno toracotomía; cinco curaron con sonda endopleural. Al relacionar en el análisis bivariado el uso de antimicrobiano versus empiema y días de estancia, no se identificó diferencia estadísticamente significativa. Conclusiones: Este estudio no demostró que los antimicrobianos sean útiles para prevenir infecciones pleurales en trauma torácico.

BACKGROUND: Thoracic trauma accounts for 25% of deaths due to trauma. Chest trauma patients generally present to the emergency room with pneumo- or hemothorax. According to the majority of the studies, management of closed thoracostomy for trauma includes the use of antimicrobial drugs to prevent infectious complications, but this has not been proven to be beneficial. We undertook this study to evaluate antimicrobial use in thoracic trauma patients with closed thoracostomy and its impact on the development of infectious complications. METHODS: We carried out a prospective, randomized, double blind, comparative study. Patients with isolated chest trauma requiring closed thoracostomy were divided into two groups. Group A received cefalotin, and group B received placebo. Ages ranged from 15-65 years. Results were analyzed with chi(2) and Fisher exact test. RESULTS: One hundred twenty six patients were included in this study. There were 63 patients in each group with similar demographic characteristics. The mean length of hospital stay with the tube was 6.56 days, but the average stay was 11 days for patients who developed empyema. Eight patients developed empyema, three patients with empyema belonged to group A patients and five patients with empyema belonged to group B. For empyema management, five cases were resolved by chest drainage, two cases required thoracoscopic cleaning and drainage and one patient was resolved with thoracotomy and pleural decortication. Bivariate analysis comparing antimicrobial use vs. empyema and length of drainage vs. antimicrobials did not show a statistically significant difference. CONCLUSIONS: The present study did not demonstrate that antimicrobial use was beneficial in the prevention of pleural infections in the management of chest trauma patients requiring closed thoracostomy.