Oncoplastic Breast Consortium consensus conference on nipple-sparing mastectomy

Purpose Indications for nipple-sparing mastectomy (NSM) have broadened to include the risk reducing setting and locally advanced tumors, which resulted in a dramatic increase in the use of NSM. The Oncoplastic Breast Consortium consensus conference on NSM and immediate reconstruction was held to address a variety of questions in clinical practice and research based on published evidence and expert panel opinion. Methods The panel consisted of 44 breast surgeons from 14 countries across four continents with a background in gynecology, general or reconstructive surgery and a practice dedicated to breast cancer, as well as a patient advocate. Panelists presented evidence summaries relating to each topic for debate during the in-person consensus conference. The iterative process in question development, voting, and wording of the recommendations followed the modified Delphi methodology. Results Consensus recommendations were reached in 35, majority recommendations in 24, and no recommendations in the remaining 12 questions. The panel acknowledged the need for standardization of various aspects of NSM and immediate reconstruction. It endorsed several oncological contraindications to the preservation of the skin and nipple. Furthermore, it recommended inclusion of patients in prospective registries and routine assessment of patient-reported outcomes. Considerable heterogeneity in breast reconstruction practice became obvious during the conference. Conclusions In case of conflicting or missing evidence to guide treatment, the consensus conference revealed substantial disagreement in expert panel opinion, which, among others, supports the need for a randomized trial to evaluate the safest and most efficacious reconstruction techniques

Retrospective, multicenter analysis comparing conventional with oncoplastic breast conserving surgery: oncological and surgical outcomes in women with high-risk breast cancer from the OPBC-01/iTOP2 study

Introduction: Recent data suggest that margins ≥2 mm after breast-conserving surgery may improve local control in invasive breast cancer (BC). By allowing large resection volumes, oncoplastic breast-conserving surgery (OBCII; Clough level II/Tübingen 5-6) may achieve better local control than conventional breast conserving surgery (BCS; Tübingen 1-2) or oncoplastic breast conservation with low resection volumes (OBCI; Clough level I/Tübingen 3-4). Methods: Data from consecutive high-risk BC patients treated in 15 centers from the Oncoplastic Breast Consortium (OPBC) network, between January 2010 and December 2013, were retrospectively reviewed. Results: A total of 3,177 women were included, 30% of whom were treated with OBC (OBCI n = 663; OBCII n = 297). The BCS/OBCI group had significantly smaller tumors and smaller resection margins compared with OBCII (pT1: 50% vs. 37%, p = 0.002; proportion with margin <1 mm: 17% vs. 6%, p < 0.001). There were significantly more re-excisions due to R1 (“ink on tumor”) in the BCS/OBCI compared with the OBCII group (11% vs. 7%, p = 0.049). Univariate and multivariable regression analysis adjusted for tumor biology, tumor size, radiotherapy, and systemic treatment demonstrated no differences in local, regional, or distant recurrence-free or overall survival between the two groups. Conclusions: Large resection volumes in oncoplastic surgery increases the distance from cancer cells to the margin of the specimen and reduces reexcision rates significantly. With OBCII larger tumors are resected with similar local, regional and distant recurrence-free as well as overall survival rates as BCS/OBCI

Oncoplastic Breast Consortium consensus conference on nipple-sparing mastectomy.

Purpose Indications for nipple-sparing mastectomy (NSM) have broadened to include the risk reducing setting and locally advanced tumors, which resulted in a dramatic increase in the use of NSM. The Oncoplastic Breast Consortium consensus conference on NSM and immediate reconstruction was held to address a variety of questions in clinical practice and research based on published evidence and expert panel opinion. Methods The panel consisted of 44 breast surgeons from 14 countries across four continents with a background in gynecology, general or reconstructive surgery and a practice dedicated to breast cancer, as well as a patient advocate. Panelists presented evidence summaries relating to each topic for debate during the in-person consensus conference. The iterative process in question development, voting, and wording of the recommendations followed the modified Delphi methodology. Results Consensus recommendations were reached in 35, majority recommendations in 24, and no recommendations in the remaining 12 questions. The panel acknowledged the need for standardization of various aspects of NSM and immediate reconstruction. It endorsed several oncological contraindications to the preservation of the skin and nipple. Furthermore, it recommended inclusion of patients in prospective registries and routine assessment of patient-reported outcomes. Considerable heterogeneity in breast reconstruction practice became obvious during the conference. Conclusions In case of conflicting or missing evidence to guide treatment, the consensus conference revealed substantial disagreement in expert panel opinion, which, among others, supports the need for a randomized trial to evaluate the safest and most efficacious reconstruction techniques

Bisfenol A, um dos fatores envolvidos na etiologia da Hipomineralização Incisivo-Molar? Uma revisão sistemática

A hipomineralização incisivo-molar (MIH) é uma patologia caracterizada pela diminuição da mineralização dos primeiros molares permanentes frequentemente associada aos incisivos permanentes. Clinicamente, apresenta como opacidades demarcadas do esmalte (mole e poroso) de cor diferente nos dentes afetados, que ocasionalmente sofrem uma quebra pós eruptiva. Embora a etiologia desta doença, que afeta cerca de 18% das crianças, seja incerta, existem algumas dúvidas sobre o bisfenol A (BPA). Esta molécula exibe efeitos que mimetizam o estrogênio (E2), poderá ter um papel na perturbação da amelogénese. O objetivo deste estudo consiste em avaliar o conhecimento que a literatura científica atual nos traz sobre a possível influência do BPA na etiologia da MIH. Formulou-se uma questão segundo a estratégica PICOS e como orientação o PRISMA. Uma pesquisa bibliográfica foi realizada na base de dados: PubMed, Cochrane Library e ScienceDirect utilizando combinações das palavras-chave e abrangendo artigos entre 2010 e 2021 de idioma inglês. Mais de 83% da população apresenta concentração superior ao LOD nas suas urinas. A mediana das concentrações de BPA observadas é inferior à TDI. Correlação com: idade, inter-familiar, sócio-económico e localização. A hipomineralização do esmalte por BPA deve-se à perturbação de um pequeno número de genes que controlam a qualidade do esmalte, por EMPs, proteases e reguladores de homeostasia. A contaminação por BPA é principalmente oral. A exposição ao BPA durante o período crítico da mineralização dentária, enfraquece o esmalte, tornando-o mais propenso a gerar defeitos de mineralização frequentes, tais como MIH. Palavras-chave: Hipoplasia do Esmalte Dentário, Hipomineralização Incisivo-Molar, Amelogénese, Desreguladores Endócrinos, Bisfenol A, Factor(es) Perinatal

Identification of Somatic Mutations in Thirty-year-old Serum Cell-free DNA From Patients With Breast Cancer: A Feasibility Study.

INTRODUCTION The aim of this study was to assess the feasibility of cell-free DNA (cfDNA) extraction and circulating tumor DNA sequencing in 30-year-old serum samples. MATERIALS AND METHODS We evaluated serum samples from 52 patients with breast cancer, which were collected between 1983 and 1991, with correlating clinicopathologic data. cfDNA was extracted by using the QIAamp Circulating Nucleic Acid Extraction Kit (Qiagen). Of these 52 cfDNA samples, 10 were randomly selected and sequenced with the Oncomine Breast cfDNA Assay (A31183). In a second step, high-depth targeted sequencing of 15 additional cfDNA samples was performed using a custom Ampliseq Ion Torrent panel targeting breast cancer-related genes. RESULTS cfDNA extraction was successful in 52 (100%) of 52 patients with a total concentration of 0.2 to 54 ng/uL. A total of 24 cancer-specific mutations were found in 22 (88%) of the 25 samples undergoing sequencing. Of the 52 patients, 32 (62%) had died from breast cancer after a median follow-up of 7.9 years (interquartile range, 3.7-15.5 years). CONCLUSION The present study shows that current next generation sequencing technology is sufficiently robust and specific to analyze 30-year-old serum. Therefore, longitudinal studies can be designed with storage of serum samples over many years, thereby obviating the need for timely and continuous cfDNA extraction and sequencing. The samples can be pooled and processed at once with the most modern technology available at the end of the study, when accumulation of events allows correlation of clinical outcomes with adequate power

Predictors of Nodal Pathological Complete Response in Asian Women with Stage II–III Node-Positive Breast Cancer

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Neoadjuvant chemotherapy (NAC) is increasingly used to treat node-positive (N+) breast cancer. Predictors of nodal pathological complete response (pCR) in Asian women are poorly described and there is variety in the management of the axilla after NAC. We evaluated predictors of nodal pCR and axillary management in a cohort of Asian N+ patients. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Consecutive biopsy-proven N+ breast cancer patients treated with NAC were identified from the Shanghai Ruijin Hospital in China. Axillary lymph node dissection was performed on all patients, irrespective of the nodal response to NAC. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; A total of 323 patients were included. Nodal pCR was achieved in 105 patients (33%), 15% of HR+/HER2– tumors, 38% of HR+/HER2+ tumors, 49% of HR–/HER2+ tumors, and 42% of HR–/HER2–tumors (&lt;i&gt;p&lt;/i&gt; &amp;#x3c; 0.001). Factors associated with nodal pCR were (1) receptor status (HR+/HER2– [referent]: OR 3.42, 95% CI 1.43–8.16, &lt;i&gt;p&lt;/i&gt; = 0.006 for HR+/HER2+; OR 4.19, 95% CI 1.85–9.50, &lt;i&gt;p&lt;/i&gt; = 0.001 for HR–/HER2+; and OR 2.94, 95% CI 1.11–7.74, &lt;i&gt;p&lt;/i&gt; = 0.029 for HR–/HER2–), (2) breast pCR (no pCR [referent]: OR 15.22, 95% CI 6.29–36.79, &lt;i&gt;p&lt;/i&gt; &amp;#x3c; 0.001), and (3) absence of lymphovascular invasion (LVI [referent]: OR 9.04, 95% CI 2.09–39.18, &lt;i&gt;p&lt;/i&gt; = 0.003). &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; This study confirmed expected predictors of nodal pCR in Asian women and the benefit of NAC in downstaging the axilla independently of ethnicity. </jats:p

Interplay between Rab35 and Arf6 controls cargo recycling to coordinate cell adhesion and recycling

Cells inversely adjust the plasma membrane levels of integrins and cadherins during cell migration and cell-cell adhesion but the regulatory mechanisms that coordinate these trafficking events remain unknown. Here, we demonstrate that the small GTPase Rab35 maintains cadherins at the cell surface to promote cell-cell adhesion. Simultaneously, Rab35 supresses the activity of the GTPase Arf6 to down regulate an Arf6-dependent recycling pathway for β1-integrin and EGF receptors, resulting in inhibition of cell migration and attenuation of signaling downstream of these receptors. Importantly, the phenotypes observed following Rab35 knock down are consistent with the epithelial-mesenchymal transition, a feature of invasive cancer cells, and we show that Rab35 expression is suppressed in a subset of cancers characterized by Arf6 hyperactivity. Our data thus identify a key molecular mechanism that efficiently coordinates the inverse intracellular sorting and cell surface levels of cadherin and integrin receptors for cell migration and differentiation.</jats:p

Knowledge Gaps in Oncoplastic Breast Surgery

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