Antonio Maffuz-Aziz

Sequence analysis of mutations and translocations across breast cancer subtypes

Breast carcinoma is the leading cause of cancer-related mortality in women worldwide, with an estimated 1.38 million new cases and 458,000 deaths in 2008 alone. This malignancy represents a heterogeneous group of tumours with characteristic molecular features, prognosis and responses to available therapy. Recurrent somatic alterations in breast cancer have been described, including mutations and copy number alterations, notably ERBB2 amplifications, the first successful therapy target defined by a genomic aberration. Previous DNA sequencing studies of breast cancer genomes have revealed additional candidate mutations and gene rearrangements. Here we report the whole-exome sequences of DNA from 103 human breast cancers of diverse subtypes from patients in Mexico and Vietnam compared to matched-normal DNA, together with whole-genome sequences of 22 breast cancer/normal pairs. Beyond confirming recurrent somatic mutations in PIK3CA, TP53, AKT1, GATA3 and MAP3K1, we discovered recurrent mutations in the CBFB transcription factor gene and deletions of its partner RUNX1. Furthermore, we have identified a recurrent MAGI3–AKT3 fusion enriched in triple-negative breast cancer lacking oestrogen and progesterone receptors and ERBB2 expression. The MAGI3–AKT3 fusion leads to constitutive activation of AKT kinase, which is abolished by treatment with an ATP-competitive AKT small-molecule inhibitor.

Identification and pathway analysis of microRNAs with no previous involvement in breast cancer.

microRNA expression signatures can differentiate normal and breast cancer tissues and can define specific clinico-pathological phenotypes in breast tumors. In order to further evaluate the microRNA expression profile in breast cancer, we analyzed the expression of 667 microRNAs in 29 tumors and 21 adjacent normal tissues using TaqMan Low-density arrays. 130 miRNAs showed significant differential expression (adjusted P value = 0.05, Fold Change = 2) in breast tumors compared to the normal adjacent tissue. Importantly, the role of 43 of these microRNAs has not been previously reported in breast cancer, including several evolutionary conserved microRNA*, showing similar expression rates to that of their corresponding leading strand. The expression of 14 microRNAs was replicated in an independent set of 55 tumors. Bioinformatic analysis of mRNA targets of the altered miRNAs, identified oncogenes like ERBB2, YY1, several MAP kinases, and known tumor-suppressors like FOXA1 and SMAD4. Pathway analysis identified that some biological process which are important in breast carcinogenesis are affected by the altered microRNA expression, including signaling through MAP kinases and TP53 pathways, as well as biological processes like cell death and communication, focal adhesion and ERBB2-ERBB3 signaling. Our data identified the altered expression of several microRNAs whose aberrant expression might have an important impact on cancer-related cellular pathways and whose role in breast cancer has not been previously described.

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.

Abstract P2-07-15: Economic impact of breast cancer in Mexico

Background: Breast cancer is the most prevalent cancer in Mexico and is the leading oncologic death cause among women older than 25 years-old. Its incidence has steadily increased during the last decades. Unfortunately, most of the patients are diagnosed in advanced stages, increasing the cost of the treatment and mortality. Through this study, we analyse the annual economic impact of breast cancer in Mexico. Materials and methods: Data from Mexican official statistics from 2014 were obtained. The rate of population covered by the public health system, the mean income per capita , the age for retirement, the funds used in public hospitals according to clinical stages, the mean age for diagnosis and the mean age of death by breast cancer in Mexico and the mean cost of a funeral service were obtained. We calculate the direct costs including the funds used for diagnosis and treatment of the patients with breast cancer in the public hospitals. The indirect costs were obtained calculating the mean per capita income lost due to death by breast cancer, the number of deaths before 65 years-old (Age for retirement in Mexico) and the mean cost for funeral services. Costs for breast cancer treatment were also obtained according to the funds for early stages (0 – IIA), locally-advanced stages (IIB – IIIC) and metastatic stages (IV). Results were compared between groups. Results: In 2014, around 20,500 new cases of breast cancer were diagnosed in Mexico. Among them, 15,826 patients (77.2%) were treated in public health institutions. From these patients, 38.7% were diagnosed in early stages, 51% in locally-advanced stages and 9.6% in stage IV. Only 22% were diagnosed during screening mammography. In 2014, funds for early stages amounted to US

Salivary gland-like breast carcinomas: An infrequent disease.

44,077, 959; for locally-advanced stages to US

Primary Neuroendocrine Tumor of the Breast

120,727,505 and for metastatic stages to US

Loss of function of miR-342-3p results in MCT1 over-expression and contributes to oncogenic metabolic reprogramming in triple negative breast cancer

192,623,862. The total fund for breast cancer, including diagnosis and treatment, was US

Colgajo miocutáneo extendido de dorsal ancho en la reconstrucción de grandes defectos de la pared torácica posterior a resecciones extensas en enfermedad mamaria

304, 747,165. Treatments for locally advanced stages were 107.8% higher compared to early stages (US

Características clinicopatológicas del cáncer de mama en una población de mujeres en México

14,958 / 7,197). It has been demonstrated that the mean age of breast cancer diagnosis in Mexico is 53 years-old, while the mean age of death due to this disease is 58 years-old. Age for retirement is 65 years and 76% of the breast cancer patients appeared in this group of age or younger. The mean per capita income is US

Primary mucoepidermoid carcinoma of the breast

22 and the cost for funeral was US