Prospective study: Impact of breast magnetic resonance imaging on oncoplastic surgery and on indications of mastectomy in patients who were previously candidates to breast conserving surgery.

Background: Routine use of magnetic resonance imaging (MRI) in the staging of patients with early breast cancer is still controversial. Oncoplastic surgery (OP) allows for wider resections without compromising the aesthetic results. This study aimed to assess the impact of preoperative MRI on surgical planning and on indications of mastectomy. Methods: Prospective study including T1-T2 breast cancer patients treated between January 2019 and December 2020 in the Breast Unit of the Hospital Nossa Senhora das Graças in Curitiba, Brazil. All patients had indication for breast conserving surgery (BCS) with OP and did a breast MRI after conventional imaging. Results: 131 patients were selected. Indication for BCS was based on clinical examination and conventional imaging (mammography and ultrasound) findings. After undergoing breast MRI, 110 patients (84.0%) underwent BCS with OP and 21 (16.0%) had their surgical procedure changed to mastectomy. Breast MRI revealed additional findings in 52 of 131 patients (38%). Of these additional findings, 47 (90.4%) were confirmed as invasive carcinoma. Of the 21 patients who underwent mastectomies, the mean tumor size was 2.9 cm (± 1,7cm), with all having additional findings on breast MRI (100% of the mastectomies group vs 28.2% of the OP, p<0.01). Of the 110 patients submitted to OP, the mean tumor size was 1,6cm (± 0,8cm), with only 6 (5.4%) presenting positive margins at the final pathology assessment. Conclusion: Preoperative breast MRI has an impact on the OP scenario, bringing additional information that may help surgical planning. It allowed selecting the group with additional tumor foci or greater extension to convert to mastectomy, with a consequent low reoperation rate of 5.4% in the BCS group. This is the first study to assess the impact of breast MRI in the preoperative planning of patients undergoing OP for the treatment of breast cancer.

MicroRNAs miR-142-5p, miR-150-5p, miR-320a-3p, and miR-4433b-5p in Serum and Tissue: Potential Biomarkers in Sporadic Breast Cancer.

Breast cancer (BC) is a heterogeneous disease, and establishing biomarkers is essential to patient management. We previously described that extracellular vesicle-derived miRNAs (EV-miRNAs) miR-142-5p, miR-150-5p, miR-320a, and miR-4433b-5p in serum discriminated BC from control samples, either alone or combined in a panel. Using these previously described markers, we intend to evaluate whether the same markers identified in EVs are also potential biomarkers in tissue and serum. Expression analysis using RT-qPCR was performed using serum of 67 breast cancer patients (BC-S), 19 serum controls (CT), 83 fresh tumor tissues (BC-T), and 29 adjacent nontumor tissue samples (NT). In addition, analysis from The Cancer Genome Atlas (TCGA) data (832 BC-T and 136 NT) was performed. In all comparisons, we found concordant high expression levels of miR-320a and miR-4433b-5p in BC-S compared to CT in both EVs and cell-free miRNAs (cf-miRNAs). Although miR-150-5p and miR-142-5p were not found to be differentially expressed in serum, panels including these miRNAs improved sensitivity and specificity, supporting our previous findings in EVs. Fresh tissue and data from the TCGA database had, in most comparisons, an opposite behavior when compared to serum and EVs: lower levels of all miRNAs in BC-T than those in NT samples. TCGA analyses revealed reduced expression levels of miR-150-5p and miR-320a-3p in BC-T than those in NT samples and the overexpression of miR-142-5p in BC-T, unlike our RT-qPCR results from tissue in the Brazilian cohort. The fresh tissue analysis showed that all miRNAs individually could discriminate between BC-T and NT in the Brazilian cohort, with high sensitivity and sensibility. Furthermore, combining panels showed higher AUC values and improved sensitivity and specificity. In addition, lower levels of miR-320a-3p in serum were associated with poor overall survival in BC Brazilian patients. In summary, we observed that miR-320a and miR-4433b-5p distinguished BC from controls with high specificity and sensibility, regardless of the sample source. In addition, lower levels of miR-150-5p and higher levels of miR-142-5p were statistically significant biomarkers in tissue, according to TCGA. When combined in panels, all combinations could distinguish BC patients from controls. These results highlight a potential application of these miRNAs as BC biomarkers.

LOCAL RE-OPERATION AND RECURRENCE IN ONCOPLASTIC BREAST SURGERY / Reoperação e recidiva local em cirurgia oncoplástica mamária

Introduction: In addition to a surgical option, the oncoplastic surgery (OP) is a new philosophy in the mammary oncologic therapy, since it combines concepts of oncologic surgery and plastic surgery. There was a concern that plastic surgery techniques would compromise the oncologic radicalism, leading to an increased risk of tumor recurrence and damage to the patients' survival. The main purpose of the breast conservative surgery (BCS) is to obtain disease-free surgical margins, with a great esthetic-functional result. However, since the advent of this approach, the search for negative margins has been a problem. Despite the efforts to avoid compromised margins, they occur in 20 to 40% of the cases in the traditional BCS, and in many cases leading to the need of reexcision or even to mastectomy. Objective and method: In the analysis of recent studies, the OP role as a reduction factor of new surgeries and local recurrence is questioned. The aim of this paper is to analyze it based on literature review. Conclusion: According to recent studies, the OP became a safe oncological surgical technique that improves both the esthetic result and the disease local control, decreasing the compromised margins with impact on the mitigation of new surgeries rate.

Introdução: A cirurgia oncoplástica (OP) além de opção cirúrgica é uma nova filosofia no tratamento oncológico mamário, pois combina os princípios da cirurgia oncológica com os da cirurgia plástica. Existia um temor de que as técnicas de mamoplastias redutoras pudessem comprometer a radicalidade oncológica, levando a um risco aumentado para recidivas tumorais e prejuízo na sobrevida das pacientes. O objetivo primário da cirurgia conservadora de mama (CC) é obter margens cirúrgicas livres de doença, com bom resultado estético-funcional. Entretanto, desde o advento dessa abordagem, a busca por margens negativas tem sido problemática. Pois, apesar do esforço para se evitar margens comprometidas, elas ocorrem em 20 a 40% dos casos na CC tradicional, levando, em muitas situações, à necessidade de reexcisão ou até mesmo mastectomia. Objetivo e método: Analisando estudos recentes, questiona-se o papel da OP como um fator redutor de reoperações e recidiva local. O objetivo desse artigo é fazer uma discussão embasada em revisão da literatura. Conclusão: Conforme estudos recentes, a OP consagrou-se como técnica cirúrgica oncologicamente segura, com melhora tanto no resultado estético como no controle local da doença, diminuindo margens comprometidas e impactando na atenuação da taxa de reoperações.

Evaluation of Aesthetic and Quality-of-Life Results after Immediate Breast Reconstruction with Definitive Form-Stable Anatomical Implants.

BACKGROUND: Although there are many reports on different techniques in breast reconstruction, there are few data regarding immediate breast reconstruction with definitive form-stable anatomical implants in terms of aesthetics and quality-of-life outcomes. METHODS: Ninety-four patients underwent mastectomy with immediate breast reconstruction using anatomical implants and contralateral symmetrization. Aesthetic results were evaluated by three different methods: the patient's self-report, the assessment of four independent specialists (two breast surgeons and two plastic surgeons from different institutions), and the BCCT.core software. Quality of life was evaluated by means of the BREAST-Q instrument. RESULTS: Average age ± SD was 52.1 ± 11.6 years. Most of patients had medium size breasts and T1 tumors. Patients had evaluated their aesthetic results better than did software and specialists. There was no significant difference in the comparison between software and specialist's evaluation. Multifactorial analysis showed that age older than 70 years and radiotherapy were significant risk factors for poor aesthetic outcomes after immediate breast reconstruction with implants. Considering quality of life, most of the patients were satisfied with their outcome and psychosocial and sexual well-being. CONCLUSION: Immediate breast reconstruction with implants and contralateral symmetrization had a positive impact on the quality of life and showed satisfactory outcomes when evaluated by subjective and objective methods.

Characterization of MTAP Gene Expression in Breast Cancer Patients and Cell Lines.

MTAP is a ubiquitously expressed gene important for adenine and methionine salvage. The gene is located at 9p21, a chromosome region often deleted in breast carcinomas, similar to CDKN2A, a recognized tumor suppressor gene. Several research groups have shown that MTAP acts as a tumor suppressor, and some therapeutic approaches were proposed based on a tumors´ MTAP status. We analyzed MTAP and CDKN2A gene (RT-qPCR) and protein (western-blotting) expression in seven breast cancer cell lines and evaluated their promoter methylation patterns to better characterize the contribution of these genes to breast cancer. Cytotoxicity assays with inhibitors of de novo adenine synthesis (5-FU, AZA and MTX) after MTAP gene knockdown showed an increased sensitivity, mainly to 5-FU. MTAP expression was also evaluated in two groups of samples from breast cancer patients, fresh tumors and paired normal breast tissue, and from formalin-fixed paraffin embedded (FFPE) core breast cancer samples diagnosed as Luminal-A tumors and triple negative breast tumors (TNBC). The difference of MTAP expression between fresh tumors and normal tissues was not statistically significant. However, MTAP expression was significantly higher in Luminal-A breast tumors than in TNBC, suggesting the lack of expression in more aggressive breast tumors and the possibility of using the new approaches based on MTAP status in TNBC.

Comparative Proteomics of Tumor and Paired Normal Breast Tissue Highlights Potential Biomarkers in Breast Cancer.

BACKGROUND/AIM: Breast cancer is the most common type of cancer among women worldwide, and about 57,000 new cases are expected for the Brazilian population in 2015. Elucidation of protein expression and modification is essential for the biological understanding, early diagnosis and therapeutics of breast cancer. The main objectives of the study are comparison between the proteome of tumor and paired non-tumor breast cancer tissues, describing all identified proteins, highlighting the ones most differentially expressed and comparing the data with existing literature. MATERIALS AND METHODS: The five paired samples from patients with invasive ductal carcinoma were analyzed by 2-DE and MS. RESULTS: We collected 161 identified spots corresponding to 110 distinct proteins. Forty-three differentially-expressed spots were common to at least two samples, and the ten proteins with the highest-fold changes were CASPE, ENOG, TPM1, CAPG, VIME, TPM3, TRFE, PDIA6, WDR61 and PDIA3. Metabolic enzymes and proteins with binding functions were the most representative functional classes of proteins with increased and decreased expression in tumor tissue respectively. CONCLUSION: Taking the fold change as a parameter, we point to future targets to be studied by functional methods in a search for biomarkers for initiation and progress of breast cancer.

Comparative proteomics of primary breast carcinomas and lymph node metastases outlining markers of tumor invasion.

BACKGROUND: Lymph node metastasis is an important clinicopathological parameter for breast cancer prognostication and treatment. Although the development of metastasis is common in axillary lymph nodes, the mechanisms underlying the locoregional spread are yet poorly understood. In the present study, we outline the involvement of proteins in tumor invasion by comparing the proteome profile of primary breast tumors (PBT) against that of lymph node metastasis (LNM). PATIENTS AND METHODS: The comparative proteome analyses of seven paired samples were performed using two-dimensional gel electrophoresis (2DE) and mass spectrometry (MS). RESULTS: Recurrent proteins were differentially expressed in PBT and LNM across patients. Higher levels of 1433G, 1433T, K2C8, PSME2, SNAA, TPM4, TRFE and VIME were observed in primary tumors compared to the metastatic site. On the other hand, higher levels of ALDH2 and GDIR2 were identified in metastasis related to tumors. These proteins provide a new insight on breast cancer research. CONCLUSION: Our achievements strengthened previous omics-based studies and also support the validation of potential markers of tumor invasion and metastasis.

Long-Term Comparison of Aesthetical Outcomes After Oncoplastic Surgery and Lumpectomy in Breast Cancer Patients.

BACKGROUND: Lumpectomy may result in major deformities and asymmetries in approximately one-third of patients. Although oncoplastic surgery (OP) could be a useful alternative to avoid them, lack of strong data is causing some debate. The purpose of this study was to compare aesthetic outcomes in patients undergoing OP versus lumpectomy using three different assessment methods. METHODS: A total of 122 patients were included in this cross-sectional multicentric study; 57 underwent OP (46.7 %), and 65 underwent lumpectomy (53.3 %). Two breast surgeons and two plastic surgeons from different institutions using the Garbay scale independently evaluated aesthetic outcomes. BCCT.core software was applied in both groups, and the patients evaluated their aesthetic outcomes answering a questionnaire about their satisfaction rate. RESULTS: OP group had a higher proportion of excellent aesthetic results according to the BCCT.core software analysis (p = 0.028) and the specialists (p = 0.002). Multifactorial analyses showed that age ≥70 years (RP = 6.02; 95 % confidence interval [CI] 1.73-21.0; p = 0.005), tumors in the medial, inferior, and central quadrants (RP = 4.21; 95 % CI 1.88-9.44; p < 0.001), and large breasts (RP = 7.55; 95 % CI 2.48-23.0; p < 0.001) were significant risk factors for poor aesthetic outcomes after lumpectomy. The patients classified their results as better than those by the specialists and by the software, with no statistical difference between the groups. CONCLUSIONS: Excellent aesthetic results were more frequent in the OP group according to BCCT.core software analysis and specialists. In addition, some clinical conditions and tumor locations in the breast can be considered risky factors for poor aesthetic outcomes in lumpectomy.

Lack of association between LOH in the 9p region and clinicopathologic parameters in primary breast cancer.

Previous studies have suggested the involvement of the 9p region in the genesis and progression of several types of cancer. To perform a more in-depth investigation of the 9p region in samples from breast carcinomas, we analyzed loss of heterozygosity (LOH) in 230 patients with primary breast cancer using five microsatellite markers spanning a genomic region of approximately 16.2 megabases. Genomic DNA was obtained from frozen tumor tissue, and peripheral blood was used as a normal reference. Among all samples, 171 (74%) were informative for at least 1 marker and 44 (25.73%) showed LOH. The LOH rates detected for all markers ranged from 10.29% (D9S169) to 15.97% (D9S1749). Among the informative cases for intragenic markers D9S1748 (CDKN2A) and D9S1749 (MTAP), we noticed a concordant loss of 90% (9/10). Associations between LOH frequencies and clinicopathologic parameters were found between marker D9S200 and tumor grade (P < 0.05), and between marker D9S1748 and estrogen receptor (ER) status (P < 0.05). In conclusion, our results agree with other data from the literature that point to LOH as a secondary mechanism of tumor suppressor inactivation on 9p in breast cancer, showing lower frequencies than those observed in other types of cancer. On the other hand, our results point to an interesting association between the concordant loss of genes CDKN2A and MTAP, which was not sufficiently explored in primary breast cancer.

Ethics in sentinel node biopsy in breast cancer: an open question.

The sentinel node concept agrees with the modern principles of surgical oncology in breast cancer, which are related to lymphatic dissection, accurate axillary study, and less traumatic surgery. After publication of many series, it has proven its capacity to correctly stage axilla and select patients who need axillary dissection. The Brazilian Society of Senology established the current norms for its practice. However, the transportation of new surgical techniques from research to practice always occurs with some ethical dilemmas related to its introduction in clinical practice. The aim of this study was to analyze the ethical challenges of the sentinel node technique and problems with its implementation.