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Background. Endoscopic mastectomy has been reportedly associated with smaller scars and greater patient satisfaction; however, few reports on this topic have been made. The purpose of this retrospective study was to examine the early results of endoscopic nipple-sparing mastectomy (E-NSM) and to investigate the safety of this procedure. Methods. Between January 2002 and December 2005, a total of 87 patients with breast cancer but without skin and nipple involvement, including two cases of bilateral breast cancer, underwent E-NSM. In case of bloody nipple discharge and suspicious extension near the nipple as assessed by magnetic resonance imaging, the major ducts within the nipple were cored (nipple coring). In other cases, nipple coring was not performed. Results. Of the 89 breasts in 87 patients, 42 had tumors of [2 cm and 80 were diagnosed as having invasive carcinoma. Lymph node involvement was observed in 36 procedures. The overall rate of nipple necrosis was 18% (16 of 89). The rate of nipple necrosis among the procedures with nipple coring was statistically higher than that among those without nipple coring (7 of 17, 41%, vs. 9 of 72, 13%) (P = .01). Nipple involvement was observed in 2.2% (2 of 89). After a median follow-up period of 52 months, distant metastasis was observed in nine cases; no local recurrences occurred in this series.Conclusions. E-NSM is an oncologically safe procedure and an acceptable method in selected patients requiring a mastectomy. The higher rate of nipple necrosis may have been the result of a technical problem, indicating the need for continued improvement in nipple coring procedures.The removal of the nipple as part of a mastectomy has been routinely performed on the basis of the presumed risk of occult nipple involvement, which reportedly occurs in 5.6% to 58% of cases.1-11 However, many patients are dissatisfied with the reconstructed nipple for various reasons, including nipple projection, color matching, shape, size, texture, and position.12 A nipple-sparing mastectomy (NSM) is a procedure that can be applied as part of a skinsparing mastectomy, in which the nipple-areola complex (NAC) is preserved for cosmetic reasons. 9,11,[13][14][15][16][17][18][19] For patients without skin and nipple involvement, NSM has evolved as an alternative to a mastectomy with a safe oncologic profile and a better cosmetic outcome. 9,11,[13][14][15][16][17][18][19][20][21] In the early 1990s, endoscopic surgery of the breast was first applied for the treatment of patients with capsular contracture after breast augmentation. 22 Since then, it has been used for aesthetic breast surgery, breast lump excision, and breast surgery for breast cancer. [23][24][25][26][27][28][29][30][31][32][33][34] The addition of endoscopy to NSM for patients with breast cancer has been reportedly associated with smaller scars and greater patient satisfaction.27-29 However, few reports on endoscopic nipple-sparing mastectomy (E-NSM) have been made, and most of these studies had relatively short followup peri...

Uveal melanoma (UM) patients with metastatic disease usually die within one year, emphasizing an urgent need to develop new treatment strategies for this cancer. MEK inhibitors improve survival in cutaneous melanoma patients but show only modest efficacy in metastatic UM patients. In this study, we screened for growth factors that elicited resistance in newly characterized metastatic UM cell lines to clinical grade MEK inhibitors, trametinib and selumetinib. We show that neuregulin 1 (NRG1) and hepatocyte growth factor (HGF) provide resistance to MEK inhibition. Mechanistically, trametinib enhances the responsiveness to NRG1, and sustained HGF mediated activation of AKT. Individually targeting ERBB3 and cMET, the receptors for NRG1 and HGF respectively, overcomes resistance to trametinib provided by these growth factors and by conditioned medium from fibroblasts that produce NRG1 and HGF. Inhibition of AKT also effectively reverses the protective effect of NRG1 and HGF in trametinib-treated cells. UM xenografts growing in the liver in vivo and a subset of liver metastases of UM patients express activated forms of ERBB2 (the co-receptor for ERBB3) and cMET. Together, these results provide preclinical evidence for the use of MEK inhibitors in combination with clinical-grade anti-ERBB3 or anti-cMET monoclonal antibodies in metastatic UM.

Non-mass-like breast lesions detected on MRI showing a clustered ring enhancement, a branching-ductal pattern, and clumped architecture should be evaluated further by biopsy (category 4), while lesions not showing these characteristics may be observed without unnecessary intervention (category 3a). Lesions showing a linear-ductal pattern may be followed carefully or evaluated by biopsy as needed (category 3b).

Both cyclin D1 and c-myc are key molecules in breast cancer carcinogenesis, and their transcriptional level and stability are regulated through several signaling pathways, including the Wnt signaling pathway. We performed immunohistochemical and mutational analyses of Wnt signaling components to investigate the association of Wnt signaling alterations with breast cancer carcinogenesis using 49 surgically resected primary breast cancer samples. Positive staining of cyclin D1 and c-myc was observed in 55.1% and 30.6% of the 49 breast cancer samples, respectively. Aberrant cytoplasmic expression of β-catenin, which indicates the existence of alterations in the Wnt signaling pathway, was observed in 38.8% of breast cancer samples, though no mutation was found in the β-catenin and Axin 1 genes. Reduced expression of APC was observed in 34.7% of samples. Statistical analysis revealed strong correlations between overexpression of βcatenin and that of cyclin D1 and c-myc (p=0.0001 and 0.0117, respectively). Furthermore, overexpression of β-catenin was significantly correlated with reduced expression of APC (p=0.0127). Wnt signaling alterations were frequently observed in breast cancer from the results of β-catenin immunohistochemistry, although no mutation in the components of the Wnt signaling pathway was found in the present study. Based on the statistical analyses, we speculated that reduced expression of APC leads to overexpression of β-catenin, and aberrant expression of cyclin D1 and cmyc mainly depends on alterations in the Wnt signaling pathway in breast cancer.

Purpose This randomized phase II study was conducted to investigate the efficacy of cryotherapy in preventing peripheral neuropathy and dermatological adverse events in breast cancer patients treated with weekly paclitaxel. Methods Patients treated with 12 weekly doses of paclitaxel for breast cancer were randomized (1:1) into a cryotherapy or control group. The primary endpoint was the percentage of patients with a marked decrease in the Functional Assessment of Cancer Therapy-Neurotoxicity (FACT-NTX) score. The secondary endpoints were Patient Neurotoxicity Questionnaire (PNQ), Common Terminology Criteria for Adverse Event (CTCAE) for peripheral neuropathy, and FACT-Taxane score. Results Forty-four patients were randomly assigned to the cryotherapy (n = 22) or control groups (n = 22). The percentage of patients with a marked decrease in FACT-NTX scores was significantly lower in the cryotherapy group than in the control group (41 vs. 73%, p = 0.03). The incidence of CTCAE grade ≥ 2 sensory (p = 0.001) and motor peripheral neuropathy (p = 0.01), and PNQ grade D or higher for sensory peripheral neuropathy (p = 0.02), and decrease in the FACT-Taxane score (p = 0.02) were also significantly lower in the cryotherapy group than in the control group. There were no serious side effects associated with cryotherapy. Conclusion Cryotherapy is an effective approach for prevention of peripheral neuropathy and dermatological adverse events in breast cancer patients treated with weekly paclitaxel.

BackgroundMetastatic uveal melanoma is a highly fatal disease; most patients die from their hepatic metastasis within 1 year. A major drawback in the development of new treatments for metastatic uveal melanoma is the difficulty in obtaining appropriate cell lines and the lack of appropriate animal models. Patient-derived xenograft (PDX) tumor models, bearing ectopically implanted tumors at a subcutaneous site, have been developed. However, these ectopically implanted PDX models have obstacles to translational research, including a low engraftment rate, slow tumor growth, and biological changes after multiple passages due to the different microenvironment. To overcome these limitations, we developed a new method to directly transplant biopsy specimens to the liver of immunocompromised mice.ResultsBy using two metastatic uveal melanoma cell lines, we demonstrated that the liver provides a more suitable microenvironment for tumor growth compared to subcutaneous sites and that surgical orthotopic implantation (SOI) of tumor pieces allows the creation of a liver tumor in immunocompromised mice. Subsequently, 10 of 12 hepatic metastasis specimens from patients were successfully xenografted into the immunocompromised mice (83.3% success rate) using SOI, including 8 of 10 needle biopsy specimens (80%). Additionally, four cryopreserved PDX tumors were re-implanted to new mice and re-establishment of PDX tumors was confirmed in all four mice. The serially passaged xenograft tumors as well as the re-implanted tumors after cryopreservation were similar to the original patient tumors in histologic, genomic, and proteomic expression profiles. CT imaging was effective for detecting and monitoring PDX tumors in the liver of living mice. The expression of Ki67 in original patient tumors was a predictive factor for implanted tumor growth and the success of serial passages in PDX mice.ConclusionsSurgical orthotopic implantation of hepatic metastasis from uveal melanoma is highly successful in the establishment of orthotopic PDX models, enhancing their practical utility for research applications. By using CT scan, tumor growth can be monitored, which is beneficial to evaluate treatment effects in interventional studies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-017-1247-z) contains supplementary material, which is available to authorized users.

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