Vacuum state truncation via the quantum Zeno effect

In the context of quantum state engineering we analyze the effect of observation on nonlinear optical $n$-photon Fock state generation. We show that it is possible to truncate the vacuum component from an arbitrary photon number superposition without modifying its remaining parts. In the course of the full dynamical analysis of the effect of observation, it is also found that the Zeno and the anti-Zeno effects repeat periodically. We discuss the close relationship between vacuum state truncation and so-called "interaction-free" measurement.Comment: 4 pages, 2 figures, LaTeX; TeX errors fixe

Counterfactual Quantum Cryptography

Quantum cryptography allows one to distribute a secret key between two remote parties using the fundamental principles of quantum mechanics. The well-known established paradigm for the quantum key distribution relies on the actual transmission of signal particle through a quantum channel. This paper shows that the task of a secret key distribution can be accomplished even though a particle carrying secret information is not in fact transmitted through the quantum channel. The proposed protocols can be implemented with current technologies and provide practical security advantages by eliminating the possibility that an eavesdropper can directly access the entire quantum system of each signal particle.Comment: 19 pages, 1 figure; a little ambiguity in the version 1 removed; abstract, text, references, and appendix revised; suggestions and comments are highly appreciate

Factors associated with late recurrence after completion of 5-year adjuvant tamoxifen in estrogen receptor positive breast cancer

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Abstract Background Recent large trials have shown the survival benefits of 10-year use of tamoxifen by reducing late recurrence compared with 5-year therapy in estrogen receptor(ER)-positive breast cancer. We tried to identify clinical factors associated with the late recurrence. Methods We reviewed our database of ER-positive patients who had received operations between 1996 and 2006 in two institutions. We selected 444 who had completed 5-year tamoxifen and were disease-free up to 10 years after the operation. Patients who had received aromatase inhibitors with any regimens were excluded. As a late recurrence group, 139 patients were identified who had completed 5-year tamoxifen, but had recurrence afterwards. Among them, 61 had local/contralateral breast recurrence and 78 had distant metastasis. The median follow-up was 9.7 years. Clinicopathological factors at the time of initial operation, such as age, menopausal status, progesterone receptor expression, HER2 status, tumor grade and Ki-67, were compared between the disease-free group and the late recurrence group. Results In a univariate analysis, tumor size (>2 cm), lymph node metastasis and high histologic grade were significantly associated with late recurrences (p < 0.05). In a multivariate analysis, only axillary lymph node metastasis was significant (p < 0.001). Late distant metastasis was significantly associated with tumor size and axillary lymph node metastasis (p = 0.038, p < 0.001,respectively). Late local/contralateral breast recurrence was associated with axillary lymph node metastasis (p = 0.042). Conclusions Our data showed axillary lymph node metastasis at initial operation was the only risk factor of late recurrence after completion of tamoxifen for 5 years. Our results can be helpful in making decisions to use extended tamoxifen beyond 5 years

An integrative approach for exploring the nature of fibroepithelial neoplasms.

BACKGROUND: Malignant phyllodes tumour (MPT) is a rare breast malignancy with epithelial and mesenchymal features. Currently, there are no appropriate research models or effective targeted therapeutic approaches for MPT. METHODS: We collected fresh frozen tissues from nine patients with MPT and performed whole-exome and RNA sequencing. Additionally, we established patient-derived xenograft (PDX) models from patients with MPT and tested the efficacy of targeting dysregulated pathways in MPT using the PDX model from one MPT. RESULTS: MPT has unique molecular characteristics when compared to breast cancers of epithelial origin and can be classified into two groups. The PDX model derived from one patient with MPT showed that the mouse epithelial component increased during tumour growth. Moreover, targeted inhibition of platelet-derived growth factor receptor (PDGFR) and phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) by imatinib mesylate and PKI-587 showed in vivo tumour suppression effects. CONCLUSIONS: This study revealed the molecular profiles of MPT that can lead to molecular classification and potential targeted therapy, and suggested that the MPT PDX model can be a useful tool for studying the pathogenesis of fibroepithelial neoplasms and for preclinical drug screening to find new therapeutic strategies for MPT

Prognostic impact of AJCC response criteria for neoadjuvant chemotherapy in stage II/III breast cancer patients: breast cancer subtype analyses

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Background Neoadjuvant chemotherapy (NAC) is a standard treatment for stage II/III breast cancer patients, and response to NAC is a useful prognostic marker. Since its introduction, 6–8 cycles of NAC has become the standard regimen to improve the outcome of these patients. The purpose of this study is to evaluate the prognostic impact of the American Joint Committee on Cancer (AJCC) response criteria and this tools usefulness in four different breast cancer subtypes. Methods We conducted a retrospective cohort study of clinical stage II/III breast cancer patients who received NAC of more than 6 cycles. Response after NAC and the clinicopathological factors were reviewed. AJCC response criteria for NAC were adopted from the AJCC Manual, 7th edition: complete response (CR), partial response (PR), and no response (NR). Results A total of 183 patients were enrolled; 22 (12.0 %), 123 (67.2 %), and 38 (20.8 %) patients showed CR, PR, and NR, respectively. The AJCC response was significantly associated with relapse-free survival (RFS) (P < 0.001), whereas pathologic CR (pCR), the current gold standard for response evaluation for NAC, was not (P = 0.140). AJCC response was a significant prognostic factor for RFS in all four breast cancer subtypes, namely luminal A (P = 0.006), luminal B (P = 0.001), HER-2 enriched (P = 0.039), and triple-negative breast cancer (P = 0.035). Conclusions The AJCC response criteria represent a simple and easily reproducible tool for response evaluation of NAC patients and a useful clinical prognostic marker for RFS. These criteria also have a prognostic impact in all four breast cancer subtypes, including luminal A in which pCR has a limited role

Limitations of Conventional Contrast-enhanced MRI in Selecting Sentinel Node Biopsy Candidates among DCIS Patients

Purpose: A better predictive model for occult invasive disease in ductal carcinoma in situ (DCIS) patients is essential to guide the tailored use of sentinel node biopsies. We hypothesized that recent improvement of contrast-enhanced breast magnetic resonance imaging (MRI) could provide more accurate information on the presence of occult invasion in DCIS patients. Methods: From a prospectively maintained database, we identified 143 DCIS patients diagnosed with needle biopsies in whom MRI images were available. Results: Sixty-five patients (45.5%) were upstaged to invasive carcinoma after curative surgery. Ultrasonographic lesion size, mass-appearance on mammography, type of needle used, and the presence of suspicious microinvasive foci were associated with increased likelihood of upstaging. Among the features of MRI, only mass-appearance was significantly associated with the presence of invasive disease (p=0.002). However, up to 50% of masses in MRI cases had mass-appearance on mammography as well. Other morphologic and pharmacokinetic features of MRI, such as shape, margin, and patterns of enhancement and washout, did not have a significant association. Conclusion: Among various morphologic and pharmacokinetic parameters of contrast-enhanced MRI, only mass-appearance was associated with occult invasive disease. Our results show the limitations of current contrast-enhanced MRI in predicting invasive disease in patients with preoperative diagnoses of DCIS.Moon HG, 2009, ANN ONCOL, V20, P636, DOI 10.1093/annonc/mdn683Kuerer HM, 2009, J CLIN ONCOL, V27, P279, DOI 10.1200/JCO.2008.18.3103HU M, 2009, P NATL ACAD SCI USA, V106, P3372Gadre SA, 2008, HISTOPATHOLOGY, V53, P545, DOI 10.1111/j.1365-2559.2008.03152.xOkumura Y, 2008, BMC CANCER, V8, DOI 10.1186/1471-2407-8-287Sakorafas GH, 2008, CANCER TREAT REV, V34, P483, DOI 10.1016/j.ctrv.2008.03.001Morrow M, 2008, ANN SURG ONCOL, V15, P2641, DOI 10.1245/s10434-008-0083-zPorembka MR, 2008, ANN SURG ONCOL, V15, P2709, DOI 10.1245/s10434-008-9947-5Lee JW, 2008, J SURG ONCOL, V98, P15, DOI 10.1002/jso.21077Hu M, 2008, CANCER CELL, V13, P394, DOI 10.1016/j.ccr.2008.03.007Ansari B, 2008, BRIT J SURG, V95, P547, DOI 10.1002/bjs.6162Orel S, 2008, J CLIN ONCOL, V26, P703, DOI 10.1200/JCO.2007.14.3594Facius M, 2007, CLIN IMAG, V31, P394, DOI 10.1016/j.clinimag.2007.04.030Kuhl CK, 2007, LANCET, V370, P485Jung EJ, 2007, INT J CANCER, V120, P2331, DOI 10.1002/ijc.22434Nielsen BS, 2007, INT J CANCER, V120, P2086, DOI 10.1002/ijc.22340van der Velden APS, 2006, AM J SURG, V192, P172, DOI 10.1016/j.amjsurg.2006.02.026Goyal A, 2006, BREAST CANCER RES TR, V98, P311, DOI 10.1007/s10549-006-9167-2Mansel RE, 2006, J NATL CANCER I, V98, P599, DOI 10.1093/jnci/djj158Lyman GH, 2005, J CLIN ONCOL, V23, P7703, DOI 10.1200/JCO.2005.08.001Wilkie C, 2005, AM J SURG, V190, P563, DOI 10.1016/j.amjsurg.2005.06.011Groves AM, 2005, MAGN RESON IMAGING, V23, P733, DOI 10.1016/j.mri.2005.06.003Hylton N, 2005, J CLIN ONCOL, V23, P1678, DOI 10.1200/JCO.2005.12.002Leonard GD, 2004, J NATL CANCER I, V96, P906, DOI 10.1093/jnci/djh164Hata T, 2004, J AM COLL SURGEONS, V198, P190, DOI 10.1016/j.jamcollsurg.2003.10.008Hwang EW, 2003, ANN SURG ONCOL, V10, P381, DOI 10.1245/ASO.2003.03.085*AM COLL RAD, 2003, ACR BI RADS BREAST IMorrow M, 2002, CA-CANCER J CLIN, V52, P277Jackman RJ, 2001, RADIOLOGY, V218, P497Brown LF, 1999, CLIN CANCER RES, V5, P1041

Diagnostic accuracy of a three-protein signature in women with suspicious breast lesions: a multicenter prospective trial

Background Mammography screening has been proven to detect breast cancer at an early stage and reduce mortality; however, it has low accuracy in young women or women with dense breasts. Blood-based diagnostic tools may overcome the limitations of mammography. This study assessed the diagnostic performance of a three-protein signature in patients with suspicious breast lesions. Findings This trial (MAST; KCT0004847) was a prospective multicenter observational trial. Three-protein signature values were obtained using serum and plasma from women with suspicious lesions for breast malignancy before tumor biopsy. Additionally, blood samples from women who underwent clear or benign mammography were collected for the assays. Among 642 participants, the sensitivity, specificity, and overall accuracy values of the three-protein signature were 74.4%, 66.9%, and 70.6%, respectively, and the concordance index was 0.698 (95% CI 0.656, 0.739). The diagnostic performance was not affected by the demographic features, clinicopathologic characteristics, and co-morbidities of the participants. Conclusions The present trial showed an accuracy of 70.6% for the three-protein signature. Considering the value of blood-based biomarkers for the early detection of breast malignancies, further evaluation of this proteomic assay is warranted in larger, population-level trials. This Multi-protein Assessment using Serum to deTermine breast lesion malignancy (MAST) was registered at the Clinical Research Information Service of Korea with the identification number of KCT0004847 (https://cris.nih.go.kr).This study was supported by the Bertis Inc. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication

Phase II randomized trial of neoadjuvant metformin plus letrozole versus placebo plus letrozole for estrogen receptor positive postmenopausal breast cancer (METEOR)

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Abstract Background Neoadjuvant endocrine therapy with an aromatase inhibitor has shown efficacy comparable to that of neoadjuvant chemotherapy in patients with postmenopausal breast cancer. Preclinical and clinical studies have shown that the antidiabetic drug metformin has anti-tumor activity. This prospective, multicenter, phase II randomized, placebo controlled trial was designed to evaluate the direct anti-tumor effect of metformin in non-diabetic postmenopausal women with estrogen-receptor (ER) positive breast cancer. Methods/Design Patients meeting the inclusion criteria and providing written informed consent will be randomized to 24 weeks of neoadjuvant treatment with letrozole (2.5 mg/day) and either metformin (2000 mg/day) or placebo. Target accrual number is 104 patients per arm. The primary endpoint will be clinical response rate, as measured by calipers. Secondary endpoints include pathologic complete response rate, breast conserving rate, change in Ki67 expression, breast density change, and toxicity profile. Molecular assays will be performed using samples obtained before treatment, at week 4, and postoperatively. Discussion This study will provide direct evidence of the anti-tumor effect of metformin in non-diabetic, postmenopausal patients with ER-positive breast cancer. Trial registration ClinicalTrials.gov Identifier NCT0158936

Phase II randomized trial of neoadjuvant metformin plus letrozole versus placebo plus letrozole for estrogen receptor positive postmenopausal breast cancer (METEOR)

This study is being supported by grant no 04-2012-0290 from the SNUH Research fund and by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIP)(No. 2013005540). Letrozole and metformin are being supplied by the pharmaceutical company, Shin Poong Pharm. Co., Ltd.Background : Neoadjuvant endocrine therapy with an aromatase inhibitor has shown efficacy comparable to that of neoadjuvant chemotherapy in patients with postmenopausal breast cancer. Preclinical and clinical studies have shown that the antidiabetic drug metformin has anti-tumor activity. This prospective, multicenter, phase II randomized, placebo controlled trial was designed to evaluate the direct anti-tumor effect of metformin in non-diabetic postmenopausal women with estrogen-receptor (ER) positive breast cancer. Methods/Design : Patients meeting the inclusion criteria and providing written informed consent will be randomized to 24 weeks of neoadjuvant treatment with letrozole (2.5 mg/day) and either metformin (2000 mg/day) or placebo. Target accrual number is 104 patients per arm. The primary endpoint will be clinical response rate, as measured by calipers. Secondary endpoints include pathologic complete response rate, breast conserving rate, change in Ki67 expression, breast density change, and toxicity profile. Molecular assays will be performed using samples obtained before treatment, at week 4, and postoperatively. Discussion : This study will provide direct evidence of the anti-tumor effect of metformin in non-diabetic, postmenopausal patients with ER-positive breast cancer. Trial registration : ClinicalTrials.gov Identifier NCT01589367Peer Reviewe

An objective nodal staging system for breast cancer patients undergoing neoadjuvant systemic treatment

Abstract Background In this study, we aimed to develop an objective staging system to determine the degree of nodal metastasis in breast cancer patients undergoing neoadjuvant systemic treatment (NST). Methods We reviewed the pretreatment computed tomography (CT) images of 392 breast cancer patients who received NST. The association between the patterns of the enlarged regional lymph nodes and treatment outcome was analyzed. Results In the development cohort of 260 patients, 88 (33.8%) patients experienced tumor recurrence and had a significantly higher number of enlarged lymph nodes on the pretreatment CT compared to patients with no recurrence. When patients were classified according to the numbers and locations of enlarged lymph nodes on pretreatment CT, the number of lymph nodes larger than 1 cm was most significantly associated with tumor recurrence. The accuracy of the CT-based nodal staging system was validated in an independent cohort of 132 patients. The presence of the enlarged supraclavicular nodes was associated with worse outcome, but the effect seemed to originate from the accompanied extensive axillary nodal burden. The prognostic effect of the objectively measured axillary nodal metastasis was more pronounced in hormone receptor-negative tumors. Conclusions We have developed and validated an objective method of nodal staging in breast cancer patients who undergo NST based on the number of enlarged axillary lymph nodes. Our system can improve the current subjective approach, which uses physical examination alone