Polymorphisms in the gene regions of the adaptor complex LAMTOR2/LAMTOR3 and their association with breast cancer risk.

Background: The late endosomal LAMTOR complex serves as a convergence point for both the RAF/MEK/ERK and the PI3K/AKT/mTOR pathways. Interestingly, both of these signalling cascades play a significant role in the aetiology of breast cancer. Our aim was to address the possible role of genetic polymorphisms in LAMTOR2 and LAMTOR3 as genetic risk factors for breast cancer. Methodology/Results: We sequenced the exons and exon-intron boundaries of LAMTOR2 (p14) and LAMTOR3 (MP1) in 50 prospectively collected pairs of cancerous tissue and blood samples from breast cancer patients and compared their genetic variability. We found one single nucleotide polymorphism (SNP) in LAMTOR2 (rs7541) and two SNPs in LAMTOR3 (rs2298735 and rs148972953) in both tumour and blood samples, but no somatic mutations in cancerous tissues. In addition, we genotyped all three SNPs in 296 samples from the Risk Prediction of Breast Cancer Metastasis Study and found evidence of a genetic association between rs148972953 and oestrogen (ER) and progesterone receptor negative status (PR) (ER: OR = 3.60 (1.15-11.28); PR: OR = 4.27 (1.43-12.72)). However, when we additionally genotyped rs148972953 in the MARIE study including 2,715 breast cancer cases and 5,216 controls, we observed neither a difference in genotype frequencies between patients and controls nor was the SNP associated with ER or PR. Finally, all three SNPs were equally frequent in breast cancer samples and female participants (n = 640) of the population-based SAPHIR Study. Conclusions: The identified polymorphisms in LAMTOR2 and LAMTOR3 do not seem to play a relevant role in breast cancer. Our work does not exclude a role of other not yet identified SNPs or that the here annotated polymorphism may in fact play a relevant role in other diseases. Our results underscore the importance of replication in association studies

Obtaining Adequate Surgical Margins in Breast-Conserving Therapy for Patients with Early-Stage Breast Cancer: Current Modalities and Future Directions

Inadequate surgical margins represent a high risk for adverse clinical outcome in breast-conserving therapy (BCT) for early-stage breast cancer. The majority of studies report positive resection margins in 20% to 40% of the patients who underwent BCT. This may result in an increased local recurrence (LR) rate or additional surgery and, consequently, adverse affects on cosmesis, psychological distress, and health costs. In the literature, various risk factors are reported to be associated with positive margin status after lumpectomy, which may allow the surgeon to distinguish those patients with a higher a priori risk for re-excision. However, most risk factors are related to tumor biology and patient characteristics, which cannot be modified as such. Therefore, efforts to reduce the number of positive margins should focus on optimizing the surgical procedure itself, because the surgeon lacks real-time intraoperative information on the presence of positive resection margins during breast-conserving surgery. This review presents the status of pre- and intraoperative modalities currently used in BCT. Furthermore, innovative intraoperative approaches, such as positron emission tomography, radioguided occult lesion localization, and near-infrared fluorescence optical imaging, are addressed, which have to prove their potential value in improving surgical outcome and reducing the need for re-excision in BCT

Clinicopathologic Features Associated With Having Four or More Metastatic Axillary Nodes in Breast Cancer Patients With a Positive Sentinel Lymph Node

The survival benefit of a completion axillary lymph node dissection (ALND) in patients after removal of a metastatic sentinel lymph node (SLN) is uncertain and is under study in ongoing clinical trials. The completion ALND remains necessary, however, for the identification of cases with at least four metastatic lymph nodes, in which extended-field locoregional and/or postmastectomy radiation will be recommended. Our goal was evaluate clinicopathologic features that might serve as surrogates for determining which patients with a positive SLN are likely or unlikely to belong to this high-risk subset.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41409/1/10434_2006_Article_9251.pd

Controversies in the Use of MIGS

Abstract Minimally invasive glaucoma surgery (MIGS) has fulfilled an unmet need in the management of glaucoma. This chapter highlights some controversial issues regarding the use of MIGS in clinical practice, including (1) whether there is sufficient evidence to advocate combining MIGS with cataract surgery over cataract surgery alone, (2) the merits and drawbacks of different approaches to trabecular bypass and canal-based MIGS procedures, (3) the effect of MIGS on endothelial cell loss, (4) suprachoroidal MIGS devices and whether there is still a role for these procedures, and (5) a comparison between subconjunctival MIGS and trabeculectomy. Several questions are still left unanswered and hopefully, further research and more clinical experience with these new technologies will help improve surgical outcomes for patients

Oncoplastic breast consortium recommendations for mastectomy and whole breast reconstruction in the setting of post-mastectomy radiation therapy

Aim Demand for nipple- and skin- sparing mastectomy (NSM/SSM) with immediate breast reconstruction (BR) has increased at the same time as indications for post-mastectomy radiation therapy (PMRT) have broadened. The aim of the Oncoplastic Breast Consortium initiative was to address relevant questions arising with this clinically challenging scenario. Methods A large global panel of oncologic, oncoplastic and reconstructive breast surgeons, patient advocates and radiation oncologists developed recommendations for clinical practice in an iterative process based on the principles of Delphi methodology. Results The panel agreed that surgical technique for NSM/SSM should not be formally modified when PMRT is planned with preference for autologous over implant-based BR due to lower risk of long-term complications and support for immediate and delayed-immediate reconstructive approaches. Nevertheless, it was strongly believed that PMRT is not an absolute contraindication for implant-based or other types of BR, but no specific recommendations regarding implant positioning, use of mesh or timing were made due to absence of high-quality evidence. The panel endorsed use of patient-reported outcomes in clinical practice. It was acknowledged that the shape and size of reconstructed breasts can hinder radiotherapy planning and attention to details of PMRT techniques is important in determining aesthetic outcomes after immediate BR. Conclusions The panel endorsed the need for prospective, ideally randomised phase III studies and for surgical and radiation oncology teams to work together for determination of optimal sequencing and techniques for PMRT for each patient in the context of BR

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

Eye-tracking-based visual field analysis (EFA): a reliable and precise perimetric methodology for the assessment of visual field defects

Objective Several studies report evidence for training-related neuroplasticity in the visual cortex, while other studies suggest that improvements simply reflect inadequate eye fixation control during perimetric prediagnostics and postdiagnostics.Methods and analysis To improve diagnostics, a new eye-tracking-based methodology for visual field analysis (eye-tracking-based visual field analysis (EFA)) was developed. The EFA is based on static automated perimetry and additionally takes individual eye movements in real time into account and compensates for them. In the present study, an evaluation of the EFA with the help of blind spots of 58 healthy participants and the individual visual field defects of 23 clinical patients is provided. With the help of the EFA, optical coherence tomography, Goldmann perimetry and a Humphrey field analyser, these natural and acquired scotomas were diagnosed and the results were compared accordingly.Results The EFA provides a SE of measurement of 0.38° for the right eye (OD) and 0.50° for the left eye (OS), leading to 0.44° of visual angle for both eyes (OU). Based on participants’ individual results, the EFA provides disattenuated correlation (validity) of 1.00 for both OD and OS. Results from patients suffering from cortical lesions and glaucoma further indicate that the EFA is capable of diagnosing acquired scotoma validly and is applicable for clinical use.Conclusion Outcomes indicate that the EFA is highly reliable and precise in diagnosing individual shape and location of scotoma and capable of recording changes of visual field defects (after intervention) with unprecedented precision. Test duration is comparable to established instruments and due to the high customisability of the EFA, assessment duration can be shortened by adapting the diagnostic procedure to the patients’ individual visual field characteristics. Therefore, the saccade-compensating methodology enables researchers and healthcare professionals to rule out eye movements as a source of inaccuracies in pre-, post-, and follow-up assessments