Deleuranmohr3347

PURPOSE Many human breast tumors become resistant to endocrine therapies and recur due to estrogen receptor (ERα) mutations that convey constitutive activity and a more aggressive phenotype. Here, we examined the effectiveness of a novel adamantyl antiestrogen, K-07, in suppressing the growth of breast cancer metastases containing the two most frequent ER-activating mutations, Y537S and D538G, and in extending survival in a preclinical metastatic cancer model. METHODS MCF7 breast cancer cells expressing luciferase and Y537S or D538G ER were injected into NOD-SCID-gamma female mice, and animals were treated orally with the antiestrogen K-07 or control vehicle. Comparisons were also made with the antiestrogen Fulvestrant. The development of metastases was monitored by in vivo bioluminescence imaging with phenotypic characterization of the metastases in liver and lung by immunohistochemical and biochemical analyses. RESULTS These breast cancer cells established metastases in liver and lung, and K-07 treatment reduced the metastatic burden. Mice treated with K-07 also survived much longer. By day 70, only 28% of vehicle-treated mice with mutant ER metastases were alive, whereas all K-07-treated D538G and Y537S mice were still alive. K-07 also markedly reduced the level of metastatic cell ER and the expression of ER-regulated genes. CONCLUSION The antiestrogen K-07 can reduce in vivo metastasis of breast cancers and extend host survival in this preclinical model driven by constitutively active mutant ERs, suggesting that this compound may be suitable for further translational examination of its efficacy in suppression of metastasis in breast cancers containing constitutively active mutant ERs.INTRODUCTION Current guidelines for the treatment of phyllodes tumors recommend wide local excision for all histopathological subtypes. However, it is unknown which subtypes have tendency to recur after marginal or incomplete excision. This may lead to over-treatment by re-excision surgery for tumors with little or no potential to recur. MATERIALS AND METHODS All patients with benign, borderline or malignant phyllode tumors presenting at our institution between 2000 and 2016 were retrospectively analyzed. RESULTS A total of 57 patients could be included, of which 39 tumors were benign (60%), three were borderline (5%), and seven were malignant phyllodes tumors (12%). There were also eight phyllodes-like fibroadenomas (14%). Fifty-two patients (91%) underwent local excision as primary treatment, resulting in tumor-positive or close-resection margins in 32 patients (61.5%) of whom five patients (15.6%) had re-excision surgery. During a median follow-up of 5 years, local recurrence occurred in four patients (7.0%) with a median time-to-recurrence of 12 months. Borderline and malignant subtypes were associated with a significantly higher recurrence rate compared to other subtypes (p = 0.039). CONCLUSION Although an adequate tumor-negative resection margin should be obtained for borderline and malignant phyllodes tumors, this study confirms that wide local excision is the appropriate primary treatment for all histopathological subtypes. However, if tumor-negative margins were not obtained at first excision, a wait-and-see approach is justified for benign phyllodes tumors.BACKGROUND HER2-positive breast cancer is an aggressive subtype of breast cancer that overexpresses human epidermal growth factor receptor 2 promoting cancer cell growth. Monoclonal antibodies targeting the HER2 receptor have improved survival for this patient population. Achieving pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) has correlated with disease-free survival in multiple trials, but we do not know why some HER2-positive tumors respond better to these therapies. We evaluated the correlation between HER2/CEP17 ratio and partial versus complete response following NAC. We evaluated whether patients with higher HER2/CEP17 ratios would have higher rates of pCR after NAC. METHODS Using the National Cancer Database (NCDB), we performed a retrospective review comparing pCR rates after NAC based on HER2 ratio between 2005 and 2014. Patients were excluded if they were HER2 negative, did not undergo NAC, or if the HER2 ratio was not recorded. Trends in percentage of pCR versus partial response were analyzed using SPSS. RESULTS The NCDB included 237,118 patients with HER2 equivocal or HER2-positive breast tumors. 29,291 of these patients underwent NAC, and HER2/CEP17 ratios were recorded in 14,597 of the NAC cases. A pCR was noted in 9752 patients and 11,402 patients had a partial response. The ratios were significantly different between complete vs. partial response groups (include ratios), P  less then  0.001. Using linear regression analysis, we identified a direct relationship between increasing the ratio and response to NAC. CONCLUSION Our study demonstrates a linear relationship between HER2/CEP17 ratio and pCR to NAC in patients included in the NCDB. The NCDB reflects current clinical practices across the country, and in this patient population, higher HER2 ratio is predictive of pCR to NAC and thus may be used in guiding decisions regarding the therapies that a patient receives in order to enhance pCR.BACKGROUND Although bleeding events are the major concern when using oral anticoagulants, intrathoracic hemorrhages due to warfarin are rare. Most cases in the literature have been related to trauma and have manifested as a hemothorax. Here we report a case of a nontraumatic hemorrhage within a pre-existing pulmonary cyst that presented as a lung mass during warfarin therapy. CASE PRESENTATION A 75-year-old asymptomatic woman presented with a 10-cm-diameter mass on chest radiography that was not evident 6 months prior. She had been taking warfarin for paroxysmal atrial fibrillation and a transient ischemic attack. Elimusertib There was no history of chest trauma, warfarin overdosing, or any suspected interactions with other drugs such as nonsteroidal anti-inflammatory drugs or antibiotics. The prothrombin time/international normalized ratio(PT-INR) was prolonged at 4.73 and her hemoglobin level was 8.7 g/dl. Chest computed tomography(CT)revealed an air-fluid mass adjacent to the right upper and middle lobes with a pleural effusion.