Training in oncoplastic surgery for mastologists.

OBJECTIVE: The radical change in the treatment of breast cancer has promoted the necessity for more comprehensive training of the professionals involved, ensuring the preservation of oncological safety while also allowing for cosmetic interventions to benefit breast cancer survivors. The aim of this study was to present the methods employed in the training of breast surgeons, highlighting the importance of oncoplasty and breast reconstruction. METHODS: A literature review was conducted in two databases, identifying articles related to medical education in the context of oncoplastic surgery and breast reconstruction. We also assessed the Brazilian experience in oncoplastic centers. RESULTS: The basis for educational discussions was derived from 16 articles. We observed approaches that included hands-on courses utilizing simulator models, porcine models, cadaver labs, and fellowship programs. Positive outcomes were observed in Brazil, a fact based on seven oncoplasty training centers for senior mastologists and five training centers for junior mastologists. From 2009 to 2023, an estimated 452 seniors and 42 juniors received training, representing approximately 30% of mastologists in Brazil who have acquired training and experience in oncoplasty. CONCLUSION: Despite the limited number of publications on training methods, oncoplastic centers have made significant progress in Brazil, establishing a successful model that can be replicated in other countries.

Outcomes after elevation of serratus anterior fascia flap versus serratus muscle flap in direct-to-implant breast reconstruction following mastectomy: a prospective study.

Objective: The purpose of this study was to compare postoperative pain between SF flap and serratus anterior muscle (SM) in direct-to-implant breast reconstruction. Methods: This is a prospective cohort study that included 53 women diagnosed with breast cancer who underwent mastectomy and one-stage implant-based breast reconstruction from January 2020 to March 2021. Twenty-nine patients (54.7%) had SF elevation, and 24 patients (45.3%) underwent SM elevation. We evaluated patient-reported early postoperative pain on the first day after surgery. Also, it was reported that all surgical complications in the first month and patient reported outcomes (PROs) were measured with the BRECON 23 questionnaire. Results: The serratus fascia group used implants with larger volumes, 407.6 ± 98.9 cc (p < 0.01). There was no significant difference between the fascial and muscular groups regarding the postoperative pain score reported by the patients (2 versus 3; p = 0.30). Also, there was no difference between the groups regarding early surgical complications and PROs after breast reconstruction. Conclusion: The use of SF seems to cause less morbidity, which makes the technique an alternative to be considered in breast reconstruction. Although there was no statistical difference in postoperative pain scores between the fascia and serratus muscle groups.

Training in oncoplastic surgery for mastologists

SUMMARY OBJECTIVE: The radical change in the treatment of breast cancer has promoted the necessity for more comprehensive training of the professionals involved, ensuring the preservation of oncological safety while also allowing for cosmetic interventions to benefit breast cancer survivors. The aim of this study was to present the methods employed in the training of breast surgeons, highlighting the importance of oncoplasty and breast reconstruction. METHODS: A literature review was conducted in two databases, identifying articles related to medical education in the context of oncoplastic surgery and breast reconstruction. We also assessed the Brazilian experience in oncoplastic centers. RESULTS: The basis for educational discussions was derived from 16 articles. We observed approaches that included hands-on courses utilizing simulator models, porcine models, cadaver labs, and fellowship programs. Positive outcomes were observed in Brazil, a fact based on seven oncoplasty training centers for senior mastologists and five training centers for junior mastologists. From 2009 to 2023, an estimated 452 seniors and 42 juniors received training, representing approximately 30% of mastologists in Brazil who have acquired training and experience in oncoplasty. CONCLUSION: Despite the limited number of publications on training methods, oncoplastic centers have made significant progress in Brazil, establishing a successful model that can be replicated in other countries.

Outcomes after elevation of serratus anterior fascia flap versus serratus muscle flap in direct-to-implant breast reconstruction following mastectomy: a prospective study

Abstract Objective: The purpose of this study was to compare postoperative pain between SF flap and serratus anterior muscle (SM) in direct-to-implant breast reconstruction. Methods: This is a prospective cohort study that included 53 women diagnosed with breast cancer who underwent mastectomy and one-stage implant-based breast reconstruction from January 2020 to March 2021. Twenty-nine patients (54.7%) had SF elevation, and 24 patients (45.3%) underwent SM elevation. We evaluated patient-reported early postoperative pain on the first day after surgery. Also, it was reported that all surgical complications in the first month and patient reported outcomes (PROs) were measured with the BRECON 23 questionnaire. Results: The serratus fascia group used implants with larger volumes, 407.6 ± 98.9 cc (p < 0.01). There was no significant difference between the fascial and muscular groups regarding the postoperative pain score reported by the patients (2 versus 3; p = 0.30). Also, there was no difference between the groups regarding early surgical complications and PROs after breast reconstruction. Conclusion: The use of SF seems to cause less morbidity, which makes the technique an alternative to be considered in breast reconstruction. Although there was no statistical difference in postoperative pain scores between the fascia and serratus muscle groups.

Use of the serratus anterior fascia in immediate implant-based breast reconstruction

Using the serratus anterior fascia may be a safe and effective option to recreate the lateral breast profile during subpectoral breast reconstruction, with minimal functional impact on the donor site. However, the literature is scarce when it comes to studies on this fascia flap in implant-based reconstruction. This article aimed to review the use of the serratus anterior fascia in immediate implant-based breast reconstruction, searching the electronic databases PubMed, Embase, Lilacs, and SciELO. The search was carried out by combining the following keywords: 'breast reconstruction' and 'serratus anterior fascia'. In the Pubmed and Embase databases, the search yielded a total of 12 and 15 articles, respectively, of which seven were selected according to the scope of this article. We found no studies on serratus anterior fascia and breast reconstruction in the Lilacs and SciELO databases. All works have results favorable for the use of the serratus anterior fascia flap and agree that this technique can be considered in the algorithm for the coverage of the inferolateral portion during subpectoral breast reconstruction

Immunohistochemical and clinicopathologic features of estrogen receptor-negative, progesterone receptor-positive, HER-2 negative breast carcinomas.

OBJECTIVE: Currently, there is an ongoing debate whether progesterone receptor positive and estrogen receptor negative breast carcinomas represent a true distinct subtype of tumor or a mere immunohistochemical artifact. In this study, we conducted an immunohistochemistry panel with the antibodies TFF1, EGFR, and CK5 to reclassify this phenotype in a luminal or basal-like subtype. METHODS: Tumors estrogen receptor -/progesterone receptor +, Her-2 - from a large population of breast cancer patients were selected to be studied. Immunohistochemistry with the antibodies TFF1, EGFR, and CK5 was performed. Tumors showing positivity for TFF1, regardless of EGFR and CK5 results, were classified as luminal-like carcinomas. Those lesions that were negative for TFF1, but were positive for EGFR and/or CK5, were classified as basal-like triple-negative carcinomas. When the three markers were negative, tumors were classified as undetermined. Clinical pathologic characteristics of patients and tumor recurrence were evaluated. RESULTS: Out of 1188 breast carcinomas investigated, 30 cases (2.5%) presented the estrogen receptor -/progesterone receptor +/HER2- phenotype. Of them, 27 tumors (90%) were classified as basal-like triple-negative carcinomas, one as luminal-like (3.3%), and two as undetermined tumors (6.7%). The mean follow-up for the study group was 27.7 (2.7 to 50) months. Out of the 26 patients, 6 had cancer recurrence: 2 local and 4 systemic recurrences. The average time for recurrence was 17 (8 to 38) months. CONCLUSION: Estrogen receptor -/progesterone receptor +/tumors exhibit aggressive behavior, similar to triple-negative tumors. An appropriate categorization of these tumors should be made to improve their therapeutic management.

Immunohistochemical and clinicopathologic features of estrogen receptor-negative, progesterone receptor-positive, HER-2 negative breast carcinomas

SUMMARY OBJECTIVE: Currently, there is an ongoing debate whether progesterone receptor positive and estrogen receptor negative breast carcinomas represent a true distinct subtype of tumor or a mere immunohistochemical artifact. In this study, we conducted an immunohistochemistry panel with the antibodies TFF1, EGFR, and CK5 to reclassify this phenotype in a luminal or basal-like subtype. METHODS: Tumors estrogen receptor -/progesterone receptor +, Her-2 - from a large population of breast cancer patients were selected to be studied. Immunohistochemistry with the antibodies TFF1, EGFR, and CK5 was performed. Tumors showing positivity for TFF1, regardless of EGFR and CK5 results, were classified as luminal-like carcinomas. Those lesions that were negative for TFF1, but were positive for EGFR and/or CK5, were classified as basal-like triple-negative carcinomas. When the three markers were negative, tumors were classified as undetermined. Clinical pathologic characteristics of patients and tumor recurrence were evaluated. RESULTS: Out of 1188 breast carcinomas investigated, 30 cases (2.5%) presented the estrogen receptor -/progesterone receptor +/HER2- phenotype. Of them, 27 tumors (90%) were classified as basal-like triple-negative carcinomas, one as luminal-like (3.3%), and two as undetermined tumors (6.7%). The mean follow-up for the study group was 27.7 (2.7 to 50) months. Out of the 26 patients, 6 had cancer recurrence: 2 local and 4 systemic recurrences. The average time for recurrence was 17 (8 to 38) months. CONCLUSION: Estrogen receptor -/progesterone receptor +/tumors exhibit aggressive behavior, similar to triple-negative tumors. An appropriate categorization of these tumors should be made to improve their therapeutic management.

Clinical impact of melatonin on breast cancer patients undergoing chemotherapy; effects on cognition, sleep and depressive symptoms: A randomized, double-blind, placebo-controlled trial.

This randomized, double-blinded, placebo-controlled trial tested the hypothesis that 20mg of melatonin before and during the first cycle of adjuvant chemotherapy for breast cancer (ACBC) reduced the side effects associated with cognitive impairment. We evaluated the effects of melatonin on cognition, depressive symptoms and sleep quality, and whether these effects were related to serum levels of Brain Derived Neurotrophic Factor (BDNF) and its receptor, tropomyosin kinase B (TrkB). Thirty-six women were randomly assigned to receive melatonin or placebo for 10 days. To evaluate cognitive performance, we used the Trail-Making-Test Parts A and B (A-B), Rey Auditory-Verbal Learning Test (RAVLT), Controlled Oral Word Association Test (COWAT) and an inhibitory task type Go / No-Go. Our results revealed that melatonin improved executive function on TMT scores, enhanced episodic memory (immediate and delayed) and recognition on RAVLT, and increased verbal fluency in the orthographic COWAT. The TMT-A-B(A-B) were negatively correlated with baseline levels of TrkB and BDNF, respectively. At the end of treatment, changes in TrkB and BDNF were inversely associated with depressive symptoms and sleep quality, but not with the TMT scores. These results suggest a neuroprotective effect of melatonin to counteract the adverse effects of ACBC on cognitive function, sleep quality and depressive symptoms.

Oncologic safety of immediate autologous fat grafting for reconstruction in breast-conserving surgery.

IMPORTANCE: Autologous fat grafting (AFG), or lipofilling, has been used for immediate reconstruction at the time of breast-conserving surgery in order to achieve a satisfactory cosmetic outcome in patients with breast cancer and an unfavorable tumor-to-breast volume ratio or unfavorable tumor location. However, the oncologic safety of this technique is still unclear. OBJECTIVE: To determine whether AFG performed simultaneously with breast-conserving surgery is associated with differences in local relapse rates and disease-free survival. DESIGN: Matched retrospective cohort study. SETTING: Tertiary referral center. PARTICIPANTS: Patients undergoing breast-conserving surgery with or without AFG between 2004 and 2016 were retrospectively enrolled and matched for age, staging, grade, tumor histology, and tumor immunohistochemical profile. MAIN OUTCOME(S) AND MEASURE(S): The cumulative incidence of locoregional recurrence (LRR) and disease-free survival were the primary end points, while distant recurrence and overall survival were the secondary end points. RESULTS: A total of 320 patients were followed. Cases were matched with controls at a 1:4 ratio. There was no difference in LRR or distant recurrence of breast cancer between the two groups. The annual LRR rate was 0.86% in patients who received immediate AFG vs. 0.7% in patients undergoing breast-conserving surgery alone (p ≥ 0.05). Number of lymph nodes was the sole independent risk factor for local recurrence (p = 0.045). No significant differences in disease-free survival rates were found between the groups. CONCLUSIONS AND RELEVANCE: At a mean follow-up of 5 years, no significant differences in locoregional recurrence rates were found between patients who received immediate AFG and those who underwent breast-conserving surgery alone. These findings corroborate previous research demonstrating the oncological safety of immediate AFG reconstruction, further suggesting that this technique as a safe, effective way to achieve optimal cosmetic outcomes in primary breast cancer surgery without jeopardizing oncologic outcomes.

The Effects of Melatonin on the Descending Pain Inhibitory System and Neural Plasticity Markers in Breast Cancer Patients Receiving Chemotherapy: Randomized, Double-Blinded, Placebo-Controlled Trial.

Background: Adjuvant chemotherapy for breast cancer (ACBC) has been associated with fatigue, pain, depressive symptoms, and disturbed sleep. And, previous studies in non-cancer patients showed that melatonin could improve the descending pain modulatory system (DPMS). We tested the hypothesis that melatonin use before and during the first cycle of ACBC is better than placebo at improving the DPMS function assessed by changes in the 0-10 Numerical Pain Scale (NPS) during the conditioned pain modulating task (CPM-task) (primary outcome). The effects of melatonin were evaluated in the following secondary endpoints: heat pain threshold (HPT), heat pain tolerance (HPTo), and neuroplasticity state assessed by serum brain-derived neurotrophic factor (BDNF), tropomyosin kinase receptor B, and S100B-protein and whether melatonin's effects on pain and neuroplasticity state are due more so to its impact on sleep quality. Methods: Thirty-six women, ages 18 to 75 years old, scheduled for their first cycle of ACBC were randomized to receive 20mg of oral melatonin (n = 18) or placebo (n = 18). The effect of treatment on the outcomes was analyzed by delta (Δ)-values (from pre to treatment end). Results: Multivariate analyses of covariance revealed that melatonin improved the function of the DPMS. The Δ-mean (SD) on the NPS (0-10) during the CPM-task in the placebo group was -1.91 [-1.81 (1.67) vs. -0.1 (1.61)], and in the melatonin group was -3.5 [-0.94 (1.61) vs. -2.29 (1.61)], and the mean difference (md) between treatment groups was 1.59 [(95% CI, 0.50 to 2.68). Melatonin's effect increased the HPTo and HPT while reducing the (Δ)-means of the serum neuroplasticity marker in placebo vs. melatonin. The Δ-BDNF is 1.87 (7.17) vs. -20.44 (17.17), respectively, and the md = 22.31 [(95% CI = 13.40 to 31.22)]; TrKB md = 0.61 [0.46 (0.17) vs. -0.15 (0.18); 95% CI = 0.49 to 0.73)] and S00B-protein md = -8.27[(2.89 (11.18) vs. -11.16 (9.75); 95% CI = -15.38 to -1.16)]. However, melatonin's effect on pain and the neuroplastic state are not due to its effect on sleep quality. Conclusions: These results suggest that oral melatonin, together with the first ACBC counteracts the dysfunction in the inhibitory DPMS and improves pain perception measures. Also, it shows that changes in the neuroplasticity state mediate the impact of melatonin on pain. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03205033.

Breast-Conserving Surgery with Immediate Autologous Fat Grafting Reconstruction: Oncologic Outcomes.

INTRODUCTION: Autologous fat grafting (AFG; lipofilling, lipografting) has been used in delayed breast reconstruction. Recently, it has also been investigated as an alternative for immediate reconstruction in patients submitted to breast-conserving surgery (BCS). Although good aesthetic results have been reported, the oncologic safety of the procedure remains under investigation. This article aims to assess oncologic outcomes of patients submitted to BCS with immediate AFG reconstruction. METHODS: This study consisted of 65 patients undergoing BCS with AFG between January 2010 and January 2017. They were closely followed after surgery for a median period of 40.8 months. Locoregional and systemic recurrences were the primary endpoints of this study. RESULTS: Ten patients developed cancer recurrence (15.4%). The median time for recurrence was 58.9 months. Only two patients presented locoregional recurrence (LRR) (3.07%). Five patients had systemic recurrence (7.69%), and three had both systemic and LRR (4.61%). Median disease-free survival (DFS) was 42.2 months, and overall survival (OV) was 44.3 months. Recurrences were significantly associated with the number of metastatic axillary lymph nodes detected. CONCLUSION: Oncologic outcomes of immediate AFG are similar to the results previously reported in BCS without AFG. Locoregional and systemic recurrences are associated with the presence of axillary metastases. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

TP53 p.Arg337His germline mutation prevalence in Southern Brazil: Further evidence for mutation testing in young breast cancer patients.

Premenopausal breast cancer (BC) is a core tumor of Li-Fraumeni (LFS) and Li-Fraumeni-like (LFL) Syndromes, predisposition disorders caused by germline mutations in TP53 gene. In the Southern and Southeastern regions of Brazil, a specific TP53 germline mutation, c.1010G>A (p.Arg337His), was identified at a population frequency of 0.3%, the highest value ever described for a TP53 germline variation. In Brazilian BC patients, carrier frequency can vary from 0.5% to 8.7%. The current study assessed carrier frequency by genotyping TP53 c.1010G>A in 2 BC groups: 1) 315 patients unselected for age of diagnosis and family history (FH) and 2) 239 patients diagnosed before 46 years and without Chompret criteria for LFS or LFL. One carrier was identified in group 1 (0.3%; CI 95% 0.1-1.76%) and six carriers in group 2 (2.5%; CI 95% 0.93-5.39%). The frequencies differed significantly between groups (p = 0.04). The mutation carrier frequency observed in group 2 could justify mutation testing in BC patients diagnosed before 46 years and without Chompret criteria for LFS or LFL. Further studies in larger samples of BC patients of different ages and regions of the country are necessary to provide more definitive TP53 p.Arg337His carrier frequencies in different scenarios.

Immediate reconstruction with autologous fat grafting: influence in breast cancerregional recurrence.

Objective: to evaluate local and systemic recurrence of breast cancer in patients submitted to autologous fat grafting in the immediate reconstruction after conservative surgery for breast cancer. Methods: this is a historical cohort study comparing 167 patients submitted to conservative surgery without reconstruction (conservative surgery group) with 27 patients submitted to conservative treatment with immediate graft reconstruction, following the Coleman's technique (lipofilling group). All patients had invasive carcinoma and were operated by a single surgeon from 2004 to 2011. The postoperative follow-up time was 36 months. Results: the overall incidence of local recurrence was 2.4%. No patient in the lipofilling group had local recurrence during the study period. For systemic recurrence, the rates obtained were 3.7% (one patient) for the fat grafting group and 1.8% (three patients) for the conservative surgery group without reconstruction. Conclusion: there was no significant difference for local or systemic recurrence in the groups studied. Immediate autologous fat grafting appears to be a safe procedure.

Objtivo: avaliar recorrência local e sistêmica do câncer de mama em pacientes submetidas ao enxerto autólogo de gordura na reconstrução imediata após cirurgia conservadora para o câncer de mama. Métodos: estudo de coorte histórica em que foram comparadas 167 pacientes submetidas à cirurgia conservadora sem reconstrução com 27 pacientes submetidas ao tratamento conservador com reconstrução imediata do enxerto, seguindo técnica de Coleman. Todas as pacientes eram portadoras de carcinoma invasor e foram operadas por um único cirurgião, no período de 2004 a 2011. O tempo de acompanhamento pós-operatório foi 36 meses. Resultados: a incidência global de recidiva local foi 2,4%. Nenhuma paciente do grupo de lipoenxertia apresentou recorrência local durante o período do estudo. Para recorrência sistêmica, as taxas obtidas foram de 3,7% (uma paciente) para o grupo lipoenxertia e 1,8% (três pacientes) para grupo da cirurgia conservadora sem reconstrução. Conclusão: não houve diferença significativa para recorrência local ou sistêmica nos grupos estudados. O enxerto autólogo imediato de gordura parece ser um procedimento seguro.

Immediate reconstruction with autologous fat grafting: influence in breast cancerregional recurrence / Reconstrução imediata com enxerto autólogo de gordura: influência na recorrência local de câncer de mama

ABSTRACT Objective: to evaluate local and systemic recurrence of breast cancer in patients submitted to autologous fat grafting in the immediate reconstruction after conservative surgery for breast cancer. Methods: this is a historical cohort study comparing 167 patients submitted to conservative surgery without reconstruction (conservative surgery group) with 27 patients submitted to conservative treatment with immediate graft reconstruction, following the Coleman's technique (lipofilling group). All patients had invasive carcinoma and were operated by a single surgeon from 2004 to 2011. The postoperative follow-up time was 36 months. Results: the overall incidence of local recurrence was 2.4%. No patient in the lipofilling group had local recurrence during the study period. For systemic recurrence, the rates obtained were 3.7% (one patient) for the fat grafting group and 1.8% (three patients) for the conservative surgery group without reconstruction. Conclusion: there was no significant difference for local or systemic recurrence in the groups studied. Immediate autologous fat grafting appears to be a safe procedure.

RESUMO Objetivo: avaliar recorrência local e sistêmica do câncer de mama em pacientes submetidas ao enxerto autólogo de gordura na reconstrução imediata após cirurgia conservadora para o câncer de mama. Métodos: estudo de coorte histórica em que foram comparadas 167 pacientes submetidas à cirurgia conservadora sem reconstrução com 27 pacientes submetidas ao tratamento conservador com reconstrução imediata do enxerto, seguindo técnica de Coleman. Todas as pacientes eram portadoras de carcinoma invasor e foram operadas por um único cirurgião, no período de 2004 a 2011. O tempo de acompanhamento pós-operatório foi 36 meses. Resultados: a incidência global de recidiva local foi 2,4%. Nenhuma paciente do grupo de lipoenxertia apresentou recorrência local durante o período do estudo. Para recorrência sistêmica, as taxas obtidas foram de 3,7% (uma paciente) para o grupo lipoenxertia e 1,8% (três pacientes) para grupo da cirurgia conservadora sem reconstrução. Conclusão: não houve diferença significativa para recorrência local ou sistêmica nos grupos estudados. O enxerto autólogo imediato de gordura parece ser um procedimento seguro.

Cirurgia oncoplástica e reconstrutiva da mama: Reunião de Consenso da Sociedade Brasileira de Mastologia / Oncoplastic and reconstructive surgery of the breast: Consensus Meeting of the Brazilian Society of Mastology

Objetivo: Apesar do grande número de publicações em cirurgia oncoplástica e reconstrutiva da mama, diversas questões permanecem controversas. Assim, o objetivo desta Reunião de Consenso, foi desenvolver um guia prático de recomendações baseadas nas melhores evidências disponíveis na literatura. Método: Os painelistas foram os membros da Comissão de Cirurgia Oncoplástica e Reconstrutiva da Sociedade Brasileira de Mastologia. A reunião foi realizada em agosto de 2015 em Bento Gonçalves (RS). Cada painelista recebeu e respondeu previamente um questionário com 46 itens, com base na melhor evidencia cientifica e em sua experiência. Foi considerado consenso a concordância de 75% entre painelistas. Resultados: Houve consenso em 25 itens, dos quais para oito houve concordância de 100%. O mais importantes foram: comprometimento das margens em cirurgia oncoplástica pode ser resolvido com ampliação de margens na maioria dos casos; tumores multifocais não são contraindicação para cirurgia oncoplástica; idade >70 anos não representa contraindicação para uso de técnicas oncoplásticas; reconstrução imediata pode ser indicada com segurança para a maioria das candidatas à mastectomia; pacientes com indicação de radioterapia pós-mastectomia podem ser submetidas à reconstrução imediata, devendo ter ciência dos riscos maiores para mau resultado estético; mastectomia com preservação do complexo areolopapilar é segura nos casos de câncer; radioterapia após a mastectomia com preservação do complexo areolopapilar não está indicada fora dos critérios clássicos de irradiação do plastrão; tela abdominal reduz chances de hernia no caso de reconstrução com TRAM. Conclusão: através desta reunião foi possível estabelecer importantes pontos consensuais de acordo com a opinião dos especialistas, que poderão auxiliar os mastologistas na tomada de decisões em cirurgias oncoplásticas e reconstrutivas da mama.

Objective: Despite the large number of publications in oncoplastic and breast reconstructive surgery, several issues remain controversial. The aim of this Consensus Meeting was to develop a practical guide of recommendations based on the best evidence in the literature. Method: All panelists were members of the Oncoplastic Commission of the Brazilian Society of Mastology. The Consensus Meeting was held in Bento Gonçalves (RS), in August 2015. Each panelist received and answered a questionnaire with 46 items, based on the best evidence in the literature and in their expertise. It was considered consensus the agreement of 75% between panelists. Results: There was consensus on 25 items, of which eight were for 100% agreement. The most important of these topics were: involvement of the margins in oncoplastic surgery can be solved by resection of margins in most cases; multifocal tumors is not a contraindication for oncoplastic surgery; age >70 years is not a contraindication for use of oncoplastic techniques; immediate reconstruction can be performed safely to most candidates for mastectomy; patients for post-mastectomy radiotherapy may be subject to immediate reconstruction and should be aware of the risks for poor aesthetic result; mastectomy with preservation of the nipple and areola complex is safe in cancer; radiotherapy after mastectomy with preservation of the nipple and areola complex is not indicated outside the classical criteria of irradiation chest wall; abdominal mash reduces chances of hernia in TRAM flaps. Conclusion: In this meeting it was possible to establish important consensus points according to the opinion of experts, which can help breast surgeons in their decision-making in oncoplastic and reconstructive surgery of the breast.

Histopathological grading of breast ductal carcinoma in situ: validation of a web-based survey through intra-observer reproducibility analysis.

BACKGROUND: Histopathological grading diagnosis of ductal carcinoma in situ (DCIS) of the breast may be very difficult even for experts, and it is important for therapeutic decisions. The challenge may be due to the inaccurate and/or subjective application of the diagnosis criteria. The aim of this study was to investigate the intra-observer agreement between a traditional method and a developed web-based questionnaire for scoring breast DCIS. METHODS: A cross-sectional study was carried out to evaluate the diagnostic agreement of an electronic questionnaire and its point scoring system with the subjective reading of digital images for 3 different DCIS grading systems: Holland, Van Nuys and modified Black nuclear grade system. Three pathologists analyzed the same set of digitized images from 43 DCIS cases using two different web-based programs. In the first phase, they accessed a website with a newly created questionnaire and scoring system developed to allow the determination of the histological grade of the cases. After at least 6 months, the pathologists read again the same images, but without the help of the questionnaire, indicating subjectively the diagnoses. The intra-observer agreement analysis was employed to validate this innovative web-based survey. RESULTS: Overall, diagnostic reproducibility was similar for all histologic grading classification systems, with kappa values of 0.57 ± 0.10, 0.67 ± 0.09 and 0.67 ± 0.09 for Holland, Van Nuys classification and modified Black nuclear grade system respectively. Only two 2-step diagnostic disagreements were found, one for Holland and another for Van Nuys. Both cases were superestimated by the web-based survey. CONCLUSION: The diagnostic agreement between the web-based questionnaire and a traditional method, both using digital images, is moderate to good for Holland, Van Nuys and modified Black nuclear grade system. The use of a scoring point system does not appear to pose a major risk of presenting large (2-step) diagnostic disagreements. These findings indicate that the use of this point scoring system in this web-based survey to grade objectively DCIS lesions is a useful diagnostic tool.

CYP3A4*22 is related to increased plasma levels of 4-hydroxytamoxifen and partially compensates for reduced CYP2D6 activation of tamoxifen.

AIM: To evaluate the impact of CYP3A4*22 in the formation of endoxifen (EDF) and hydroxytamoxifen (HTF), under different CYP2D6 genotypic backgrounds. MATERIALS & METHODS: 178 patients were enrolled in the study. CYP2D6 and CYP3A4 genotyping and tamoxifen (TAM) and metabolites quantification were performed. RESULTS: EDF concentrations were lower in poor (2.77 ng ml(-1)) and CYP2D6 intermediate metabolizers (5.84 ng ml(-1)), comparing to functional group (EM-F) (10.67 ng ml(-1), p < 0.001). HTF and TAM levels were respectively 47 and 53% higher in CYP3A4*22 carriers compared with *1/*1 patients in the whole group. Patients with impaired CYP2D6 metabolism and carriers of CYP3A4*22 had EDF levels comparable to CYP2D6 EM-F group (9.06 and 10.67 ng ml(-1), p = 0.247). CONCLUSION: The presence of CYP3A4*22 might compensate the reduction of EDF concentrations related to CYP2D6 inactivity, especially due to increased HTF concentrations.

Immediate Reconstruction with Autologous fat Transfer Following Breast-Conserving Surgery.

This study explores the technical viability of autologous fat grafting for immediate partial breast reconstruction following the primary conservative surgery for breast cancer; restoring volume, shape, and symmetry to the treated breast. We analyze the impact in relation to mammographic follow-up and the subjective degree of satisfaction with esthetic results and although we didn't have any local failure during the observation period; we understand that is too early for any kind of conclusion. From June of 2010 to July of 2011, 20 patients were selected for breast-conserving surgery (BCS) with partial breast reconstruction with autologous fat grafting performed during the same operation by the same medical team. The fat graft was injected in the subcutaneous and intraglandular breast tissue around the resected area. We performed an overcorrection, predicting a resorbing of about 30-50% of the volume grafted. All patients received the literature-based recommendations for breast cancer treatment with complementary radiotherapy. The follow-up period after the completion of radiotherapy ranged from 13 to 29 months. The average volume grafted was 121 cc and it was 2.1 times larger than the resected volume. The esthetic scores were considered very good or good in the majority of cases. Mammograms were taken every 6 months after radiotherapy and only one patient had a mammogram classified as BI-RADS 3, suggesting fat necrosis. The remaining patients were classified as BI-RADS 2. Immediate autologous fat grafting is a promising technique for partial breast reconstruction after BCS. It is associated with high patient and physician satisfaction. It is an alternative for reconstruction of small- and medium-sized breasts. This technique has the advantage that enables the reconstruction of defects in areas difficult to repair, particularly in the upper inner quadrants. It also may reduce the need for major glandular or myocutaneous flaps mobilization.

Ultra-high performance liquid chromatography tandem mass spectrometric method for the determination of tamoxifen, N-desmethyltamoxifen, 4-hydroxytamoxifen and endoxifen in dried blood spots--development, validation and clinical application during breast cancer adjuvant therapy.

A LC-MSMS method for the simultaneous determination of tamoxifen, N-desmethyltamoxifen, 4-hydroxytamoxifen and endoxifen in dried blood spots samples was developed and validated. The method employs an ultrasound-assisted liquid extraction and a reversed phase separation in an Acquity(®) C18 column (150×2.1 mm, 1.7 µm). Mobile phase was a mixture of formic acid 0.1% (v/v) pH 2.7 and acetonitrile (gradient from 60:40 to 50:50, v/v). Total analytical run time was 8 min. Precision assays showed CV % lower than 10.75% and accuracy in the range 94.5 to 110.3%. Mean analytes recoveries from DBS ranged from 40% to 92%. The method was successfully applied to 91 paired clinical DBS and plasma samples. Dried blood spots concentrations were highly correlated to plasma, with rs>0.83 (P<0.01). Median estimated plasma concentrations after hematocrit and partition factor adjustment were: TAM 123.3 ng mL(-1); NDT 267.9 ng mL(-1), EDF 10.0 ng mL(-1) and HTF 1.3 ng mL(-1,) representing in average 98 to 104% of the actually measured concentrations. The DBS method was able to identify 96% of patients with plasma EDF concentrations below the clinical threshold related to better prognosis (5.9 ng mL(-1)). The procedure has adequate analytical performance and can be an efficient tool to optimize adjuvant breast cancer treatment, especially in resource limited settings.

Development, validation and clinical application of a HPLC-FL method for CYP2D6 phenotyping in South Brazilian breast cancer patients.

OBJECTIVE: To develop and validate a method for determination of dextromethorphan (DMT) and dextrorphan (DTP) in plasma samples using HPLC-FL and to apply it to CYP2D6 phenotyping of a population from the South of Brazil. METHODS: Samples were prepared by hydrolysis and liquid-liquid extraction. Analysis was conducted in a reversed phase column, with isocratic elution and fluorescence detection. One hundred and forty patients being treated with tamoxifen were given 30 mg of dextromethorphan and their CYP2D6 phenotypes were determined on the basis of [DMT]/[DTP] metabolic ratios in plasma samples collected after 3h. RESULTS: Total chromatography running time was 12 min. Precision (CV%) was below 9.7% and accuracy was between 92.1 and 106.9%. The lower limits of quantification were 1 ng mL(-1) for DMT and 10 ng mL(-1) for DTP. Mean extraction yield of analytes was 86.6%. Mean age of patients was 55.7 years. Phenotype frequencies were as follows: 7.1% poor metabolizers, 13.6% intermediate metabolizers, 77.1% extensive metabolizers and 2.1 ultra-rapid metabolizers. Metabolic ratios for patients on strong (n=11) and weak (n=16) CYP2D6 activity inhibitors were different from each other and also different from ratios for patients not taking enzyme inhibitors (n=113). CONCLUSIONS: A sensitive method for determination of dextromethorphan and its metabolite in plasma samples was developed and successfully applied, providing evidence of the impact that CYP2D6 inhibitors have on the enzyme's metabolic capacity.