Differential Profile of BRCA1 vs. BRCA2 Mutated Families: A Characterization of the Main Differences and Similarities in Patients.

The identification of families at-risk for hereditary breast cancer (BC) is important because affected individuals present a much higher cancer risk than the general population. The aim of this study was to identify the most important factors associated with the presence of a pathogenic BRCA1/BRCA2 mutation. Family history (FH), histopathological and immunohistochemical characteristics were compared among BC women with pathogenic BRCA1/BRCA2 variants; VUSs in BRCA1/BRCA2; BRCA1/BRCA2 WT and sporadic BC. The most significative differences observed concerned the molecular subtype of the tumors, age at cancer diagnosis and FH of cancer. The presence of bilateral breast cancer (BBC), number of BC cases and the presence of ovarian cancer (OC) increased (respectively) 5.797, 5.033 and 4.412 times the risk of being a BRCA1/BRCA2 mutation carrier. Besides, women with BRCA1 or BRCA2 mutations presented different tumor and FH profiles. The main characteristics associated with a BRCA1 mutation were triple negativity (OR: 17.31), BBC history (OR: 4.96) and occurrence of OC (OR: 4.32). There were no major discerning components associated with BRCA2 mutations. Thus, we conclude that tumor pathology and FH of cancer might be considered together at the time of genetic testing mainly in countries where access to genetic testing is still restricted.

The breast cancer immunophenotype of TP53-p.R337H carriers is different from that observed among other pathogenic TP53 mutation carriers.

Germline TP53 mutations are associated with Li-Fraumeni syndrome, an autosomal dominant disorder characterized by a predisposition to multiple early-onset cancers including breast cancer (BC), the most prevalent tumor among women. The majority of germline TP53 mutations are clustered within the DNA-binding domain of the gene, disrupting the structure and function of the protein. A specific germline mutation in the tetramerization domain of p53, p.R337H, was reported at a high frequency in Southern and Southeastern Brazil. This mutation appears to result in a more subtle defect in the protein, which becomes functionally deficient only under particular conditions. Recent studies show that the BC phenotype in TP53 mutation carriers is often HER2 positive (63-83%). Considering that the immunophenotype of BC among p.R337H carriers has not been reported, we reviewed immunohistochemistry data of 66 p.R337H carriers in comparison with 12 patients with other non-functional TP53 germline mutation. Although 75% of carriers of these mutations showed significant HER2 overexpression (3+), corroborating previous studies, only 22.7% of p.R337H patients had BC overexpressing HER2. These results reinforce the notion that different germline mutations in TP53 may predispose to BC via different mechanisms.

Câncer de mama hereditário e rastreamento em população de alto risco / Hereditary breast cancer and screening in high-risk population

Estima-se que para o câncer de mama, assim como para grande parte dos tumores malignos conhecidos, 5 a 10% sejam de caráter hereditário. A história de câncer em familiares de primeiro grau e a presença de alguns fatores específicos de risco, como câncer de mama bilateral, história familiar de câncer de mama e ovário, e câncer de mama em indivíduo do sexo masculino, são indicadores importantes de risco de câncer de mama hereditário. Os avanços em técnicas de biologia molecular nas últimas décadas resultaram na identificação de genes que, quando alterados, aumentam significativamente o risco de desenvolver câncer de mama, de ovário e outros tumores. Destacam-se os genes supressores tumorais BRCA1 e BRCA2, além de outros genes de predisposição ao câncer de mama identificados, que são igualmente importantes no risco da doença, embora correspondam a uma parcela menor dos casos hereditários. A possibilidade de identificar pacientes e familiares com elevado risco de desenvolvimento de câncer torna possível o emprego de uma abordagem preventiva e de detecção precoce do câncer. Além disso, a identificação de um indivíduo não portador de uma alteração genética em uma família de risco permite a tranquilização dele e elimina gastos/complicações com intervenções preventivas desnecessárias. Famílias de alto risco de desenvolvimento de câncer hereditário apresentam alta prevalência de câncer de mama, além de neoplasia com instalação precoce e com maior agressividade. Dessa forma, o rastreamento nesses casos deve ser diferente, objetivando alcançar a redução da morbidade e mortalidade associadas ao câncer nessa população.

It is estimated that for breast cancer, as well as for the great majority of malignant tumors, 5 to 10% are due to an inherited predisposition. Family history of cancer in first degree relatives and the presence of some specific risk factors, such as bilateral breast cancer, family history of breast and ovarian cancer, and breast cancer in a male person, are important indicators of risk for hereditary breast cancer. Advances in molecular biology in recent decades have resulted in the identification of genes that, when altered, increase significantly the risk of developing breast cancer, ovarian cancer and other tumors, for example, the tumor suppressor genes BRCA1 and BRCA2, as well as other genes predisposing to breast cancer identified, which are equally important in the risk for the disease, although a smaller portion of match cases hereditary. The ability to identify patients and relatives with high risk for developing cancer makes possible the use of a preventive approach and an early detection of cancer. In addition, the identification of a non-carrier individual in a family of high risk allows him to reassures the modification individual and eliminates expenses/complications with unnecessary preventive interventions. The typical profile of a patient with higher risk is high prevalence of breast cancer, earlier ages at cancer diagnosis and the worst prognosis and evolution of the tumor. In this way, follow up for these patients must be different in order to achieve the reduction of morbidity and mortality associated with cancer in this population.

Comprehensive analysis of BRCA1, BRCA2 and TP53 germline mutation and tumor characterization: a portrait of early-onset breast cancer in Brazil.

Germline mutations in BRCA1, BRCA2 and TP53 genes have been identified as one of the most important disease-causing issues in young breast cancer patients worldwide. The specific defective biological processes that trigger germline mutation-associated and -negative tumors remain unclear. To delineate an initial portrait of Brazilian early-onset breast cancer, we performed an investigation combining both germline and tumor analysis. Germline screening of the BRCA1, BRCA2, CHEK2 (c.1100delC) and TP53 genes was performed in 54 unrelated patients <35 y; their tumors were investigated with respect to transcriptional and genomic profiles as well as hormonal receptors and HER2 expression/amplification. Germline mutations were detected in 12 out of 54 patients (22%) [7 in BRCA1 (13%), 4 in BRCA2 (7%) and one in TP53 (2%) gene]. A cancer familial history was present in 31.4% of the unrelated patients, from them 43.7% were carriers for germline mutation (37.5% in BRCA1 and in 6.2% in the BRCA2 genes). Fifty percent of the unrelated patients with hormone receptor-negative tumors carried BRCA1 mutations, percentage increasing to 83% in cases with familial history of cancer. Over-representation of DNA damage-, cellular and cell cycle-related processes was detected in the up-regulated genes of BRCA1/2-associated tumors, whereas cell and embryo development-related processes were over-represented in the up-regulated genes of BRCA1/2-negative tumors, suggesting distinct mechanisms driving the tumorigenesis. An initial portrait of the early-onset breast cancer patients in Brazil was generated pointing out that hormone receptor-negative tumors and positive familial history are two major risk factors for detection of a BRCA1 germline mutation. Additionally, the data revealed molecular factors that potentially trigger the tumor development in young patients.

The evolution of mastectomies in the oncoplastic breast surgery era.

Over time, surgical techniques have advanced to the point where oncological safety and aesthetic outcomes are the pillars of contemporary breast surgery. Variations of mastectomy came up and started allowing the oncological safety and the possibility of an immediate breast reconstruction. Nowadays the association between plastic surgical techniques and mastectomy with immediate breast reconstruction is one of the best alternatives to treat breast cancer and also improved overall aesthetic outcomes and favors the achievement of contralateral breast symmetry. "Oncoplastic mastectomy" is a feasible term and can be routinely used.

Necrotizing soft tissue infection of the breast: case report and literature review.

BACKGROUND: Necrotizing soft tissue infection (NSTI) is characterized by progressive infectious gangrene of the skin and subcutaneous tissue. Its treatment involves intensive care, broad-spectrum antibiotic therapy, and full debridement. METHODS: We present two cases of NSTI of the breast, adding these cases to the 14 described in the literature, reviewing the characteristics and evolution of all cases. CASE REPORT: On the fourth day after mastectomy, a 59-year-old woman with ulcerated breast cancer developed Type I NSTI caused by Pseudomonas aeruginosa, which had a favorable evolution after debridement and broad-spectrum antibiotics. The second patient was a 57-year-old woman submitted to a mastectomy and axillary dissection, who had recurrent seromas. On the 32nd post-operative day, after a seroma puncture, she developed Type II NSTI caused by ß-hemolytic streptococci. She developed sepsis and died on the tenth day after debridement, intensive care, and broad-spectrum antibiotics. The cases are the first description of breast NSTI after mammary seroma aspiration and the first report of this condition caused by P. aeruginosa. CONCLUSION: Necrotizing soft tissue infection is rare in breast tissue. It frequently is of Type II, occurring mainly after procedures in patients with breast cancer. The surgeon's participation in controlling the focus of the infection is of fundamental importance, and just as important are broad-spectrum antibiotic therapy and support measures, such as maintenance of volume, correction of electrolytic disorders, and treatment of sepsis and septic shock. Once the infection has been brought under control, skin grafting or soft tissue flaps can be considered. The mortality rate in breast NSTI is 18.7%, all deaths being in patients with the fulminant Type II form. Surgical oncologists need to be alert to the possibility of this rare condition.

The development of an Oncoplastic Training Center - OTC.

INTRODUCTION: Breast cancer now occurs worldwide and each country has its own approach to breast surgery, which is constantly evolving. A training program was established in Brazil to familiarize breast surgeons with basic oncoplastic techniques and recent developments. MATERIALS AND METHODS: The first 12 breast surgeons participating in the oncoplastic training program were surveyed regarding their experience of Urban's classification of oncoplastic procedures, and whether the training course met their expectations. RESULTS: The most part (11) of the breast surgeons surveyed had been breast specialists for more than five years. Just under one third (27.3%) wished to perform oncoplastic procedures in conjunction with a plastic surgeon. After the course the experience of the first group showed that just over half (seven) of the twelve specialists developed their skills sufficiently to perform Urban procedures at level III, and eleven others could perform until level II procedures. CONCLUSION: Organized oncoplastic training centers can enable breast surgeons to undertake reconstructive breast procedures without the assistance of a plastic surgeon.

A oncloplastia e o tempo de treinamento do cirurgião / Oncoplastic surgery and breast surgeon training

A cirurgia oncopIástica se tornou uma realidade em nosso meio, porém muitos mastologistas necessitam de habilitação nesse contexto. Atualmente, questiona-se quais profissionais podem realizar a oncoplastia e quando poderão realizar esse procedimento, sendo considerada a necessidade de um treinamento mínimo. Objetivo: Avaliar a taxa de realização de cirurgias oncoplásticas e a relação entre o tempo de treinamento do cirurgião em oncoplastia. Métodos: Estudo retrospectivo das 2.129 pacientes submetidas a cirurgia mamária no Serviço de Mastologia de Hospital de Câncer de Barretos, no período de Janeiro de 2006 a Junho de 2008. Todos os procedimentos cirúrgicos foram realizados por cirurgiões oncológicos ou mastologistas. O treinamento em oncoplastia dos profissionais variou de seis meses (cirurgião A) a dez anos (E), com mediana de três anos, sendo três profissionais com três anos de experiencia (B e C); porem, destes, um apresentou treinamento exclusivo em oncoplastia por um ano (D). Procurou-se avaliar o percentual de cirurgias oncoplásticas realizadas no serviço, bem como o risco relativo (RR) do cirurgião como fator de risco para indicação da cirurgia oncoplástica. Resultados: Das cirurgias realizadas, 275 (12,9%) foram catalogadas como cirurgias oncoplásticas. Avaliando os semestres, a taxa de cirurgias oncoplásticas variou de 10,9 a 15%. Em cirurgiões com ênfase exclusiva em cirurgia oncológica, não se observou a realização de cirurgia oncoplástica. Nos cirurgiões com treinamento em oncoplastia, a taxa de realização desse procedimento variou de 2,2 a 33,3%. As frequências das cirurgias oncoplásticas foram, para os cirurgiões A, B, C, D e E, respectivamente, 2,2, 12,2, 12,2, 17,5 e 33,3%. A indicação foi proporcional ao tempo de treinamento (p < 0,001). Considerando o risco de realização do procedimento, tendo como base o cirurgião de menor treinamento (A), observou-se para o cirurgião B um RR 12,3 (IC: 5,2-28,9); para o cirurgião C um RR de 12,5...

Introduction: Oncoplastic surgery became a reality, but many breast specialists need to be able in this context. Objective: To assess the rate of oncoplastic surgeries and the relationship between the breast surgeon training time. Methods: A retrospective study of 2,129 patients undergoing breast surgery at the Department of Mastology of Hospital de Cancer de Barretos (SP), from January, 2006 to June, 2008. All surgical procedures were performed by surgeons or breast cancer specialists. The oncoplastic surgeons training time ranged from six months (surgeon A) to ten years (E), with a median of three years; three professionals had three years of experience (B and C). The surgeon (D) had an exclusive training in oncoplastic by one year. This study evaluated the percentage of oncoplastic surgeries performed in the service, and the relative risk (RR) of the surgeon as a risk factor for oncoplastic surgical indication. Results: Of the surgeries performed, 275 (12.9%) were listed as oncoplastic surgeries. Assessing each six months, the rate of oncoplastic surgeries ranged from 10.9 to 15%. The oncoplastic procedure rate by surgeons with training ranged from 2.2 to 33.3%. The frequencies of oncoplastic procedures by surgeons A, B, C, D and E, respectively are 2.2, 12.2, 12.2, 115 and 33.3%. The statement was proportional to the training time (p < 0.001). Considering the risk of the procedure, based on the surgeon's training under “A”, RR 12.3 was observed for the surgeon B (CI: 5,2 -28,9); RR 12.5 for the surgeon C (C:. 5,3-29,4); RR 18.6 for the surgeon D (CI: 7,6-45,4); and RR of 41.1 for the surgeon E (CI: 119 -94.4) - P < 0.001. Conclusions: The breast surgeon training time influenced the indication of oncoplastic procedures. Oncoplastic training centers should be encouraged.