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BACKGROUND In human epidermal growth factor receptor 2 (HER2)-positive breast cancer, emerging evidence imply that clinical behaviors differ according to hormone receptor (HR) status. However, there is no conclusion about the relevance between estrogen receptor (ER) or progesterone receptor (PR) expression and clinical outcome of HER2+ breast cancer. Our study aimed to determine the influence of different ER/PR levels on survival outcome of HER2+ early breast cancer. PATIENTS AND METHODS Nine hundred and nineteen early HER2+ breast cancer patients treated between 2009 and 2016 were retrospectively reviewed and HR+/HER2+ patients were further divided based on ER level (Low/L: 1%-9%; Median/M: 10%-79%; High/H: 80%-100%) and PR level (Low/L: 0%-19%; High/H: 20%-100%) according to restricted cubic spline (RCS) smoothing curve. Disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier method and log rank test. RESULTS Four hundred and forty two HR+/HER2+ and 477 HR-/HER2+ breast cancer patients were included in our study and 73.2% received target therapy (HR+ 69.7%, HR- 76.5%). While HR+/HER2+ breast cancer showed better survival than HR-/HER2+ subtype in 5-year disease free survival (DFS, 93.0% vs. 86.8%, P < .001), no significant difference was observed between DFS in ER+/PR+ and ER+/PR- subgroup (94.4% vs. 90.4%, P = .22). However, a potential correlation was found between ER/PR levels and DFS in HR+/HER2+ (P = .074) tumors. In HR+/HER2+ breast cancer, all subgroups showed DFS improvement trend versus M-ER/L-PR. In all HER2+ patients, hazard ratio of H-ER/H-PR compared with HR- subtype was 0.10 (95%CI 0.01-0.74, P = .024) in all patients and 0.14 (95%CI, 0.02-1.02, P = .053) in patients receiving anti-HER2 therapy. CONCLUSION ER/PR expression may become a predictor of survival benefit in HER2+ early breast cancer and a higher ER/PR level might be associated with better DFS.

Organic field‐effect transistors (OFETs) are of great significance in next‐generation optoelectronics and have made remarkable advances during the last decade. For the commercialization of OFETs, power consumption is one of the main issues needed to be addressed. To this end, OFETs with low‐voltage operation are constructed, and several strategies have been successively developed, which have attracted intensive attention for researchers to achieve this goal. In this review, we summarized the recent progress of various approaches for realizing low‐voltage OFETs, including adopting high‐k dielectrics, ultra‐thin dielectric, electrolyte dielectric, and interface engineering. Besides, the potential applications of low‐voltage OFETs in organic electronics are introduced. Finally, we give a brief outlook of this area for the future direction.

Yujie Lu,1,&ast; Yiwei Tong,1,&ast; Jiahui Huang,1 Lin Lin,2 Jiayi Wu,1 Xiaochun Fei,3 Xiaosong Chen,1 Kunwei Shen1 1Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 2Department of Clinical Laboratory, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, People’s Republic of China; 3Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaosong Chen; Kunwei ShenDepartment of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of ChinaEmail chenxiaosong0156@hotmail.com; kwshen@medmail.com.cnBackground: It remains uncertain whether the 21-gene recurrence score (RS) of a primary tumor has selective prognostic value for locoregional recurrence (LRR) or distant metastasis (DM). The current study aimed to compare the distribution and single-gene expression on the RS panel in breast cancer patients with LRR versus DM.Methods: Consecutive early breast cancer patients who had been operated on at the Comprehensive Breast Health Center, Ruijin Hospital from January 2009 to December 2016 were retrospectively reviewed. Patients were divided into LRR, DM, and no-recurrence groups according to the first reported recurrent event. Comparison and subgroup analysis of 21-gene RS, RS category, and single-gene expression on the RS panel were conducted among patients with different recurrence status.Results: A total of 1,287 patients were included, with median follow-up of 61.5 months, and 27, 47, and 1,213 patients were classified as LRR, DM, and no recurrence groups, respectively. RS was significantly diversely distributed among the three groups (P< 0.001). No-recurrence patients (median 22) presented much lower RS than LRR (median 39, P< 0.001) and DM (median 30, P< 0.001) patients. LRR patients had lower PR (P< 0.001), BCL2 (P=0.010), and CEGP1 (P< 0.001) expression, and DM patients had higher STMY3 (P=0.019) expression than no-recurrence patients. Moreover, CEGP1 expression was significantly lower in the LRR group than the DM one (P=0.028).Conclusion: RS was differently distributed between recurrent and nonrecurrent patients. PR, BCL2, CEGP1, and STMY 3 expression was associated with LRR and DM, while CEGP1 was lower in the LRR group than DM patients, warranting further clinical evaluation.Keywords: breast cancer, 21-gene recurrence assay, gene expression, locoregional recurrence, distant metastasis

Introduction The experiment was undertaken to estimate the effect of BMSC seeding in different scaffold incorporation with HBO on the repair of a seawater-immersed bone defect. And future compared n-HA/PLGA with β-TCP/PLGA as a scaffold in treatment effect of the seawater-immersed bone defect. Methods Sixty New Zealand White rabbits with standard seawater defect in radius were randomly divided into group A (implant with nothing), group B (implanted with autogenous bone), group C (implanted with n-HA/PLGA/BMSCs), and group D (implanted with β-TCP/PLGA/BMSCs). After the implant, each rabbit receives HBO treatment at 2.4 ATA 100% oxygen for 120 min/day for 2 weeks. Radiograph, histological, and biomechanical examinations were used to analyze osteogenesis. Result X-ray analysis shows that n-HA/PLGA/BMSCs and β-TCP/PLGA/BMSCs could accelerate the new bone formation, and the new bone formation in group C was larger than that in group D or group A and close to group B (P < 0.05). After 12 weeks, in group A, the defect without scaffold shows a loose connect tissue filled in the areas. The medullary canal in group B was recanalized. Defects in groups C and D show a larger number of woven bone formation. The new woven bone formation in defect areas in group C was larger than that in group D. The mechanical examination revealed ultimate strength at 12 weeks was group D > group C > group B > group A (P < 0.05). Conclusion Scaffolds of n-HA/PLGA and β-TCP/PLGA incorporation with HBO and BMSCs were effective to treat seawater-immersed bone defect, and n-HA/PLGA was more excellent than β-TCP/PLGA.

Radiation-induced skin injury (RISI) is one of the common serious side effects of radiotherapy (RT) for patients with malignant tumors. Mesenchymal stem cells (MSCs) are applied to RISI repair in some clinical cases series except some traditional options. Though direct replacement of damaged cells may be achieved through differentiation capacity of MSCs, more recent data indicate that various cytokines and chemokines secreted by MSCs are involved in synergetic therapy of RISI by anti-inflammatory, immunomodulation, antioxidant, revascularization, and anti-apoptotic activity. In this paper, we not only discussed different sources of MSCs on the treatment of RISI both in preclinical studies and clinical trials, but also summarized the applications and mechanisms of MSCs in other related regenerative fields.

Background The aim of this study was to analyze the association of molecular subtype concordance and disease outcome in patients with synchronous bilateral breast cancer (SBBC) and metachronous breast cancer (MBBC). Patients and methods Patients diagnosed with SBBC or MBBC in the Surveillance, Epidemiology, and End Results (SEER) database or Comprehensive Breast Health Center (CBHC) Ruijin Hospital, Shanghai were retrospectively reviewed and included. Clinicopathologic features, molecular subtype status concordance, and prognosis were compared in patients with SBBC and MBBC. Other prognostic factors for breast cancer-specific survival (BCSS) and overall survival (OS) were also identified for bilateral breast cancer patients. Results Totally, 3395 and 115 patients were included from the SEER and Ruijin CBHC cohorts. Molecular subtype concordance rate was higher in the SBBC group compared to MBBC in both SEER cohort (75.8% vs 57.7%, p, Highlights • SBBC was associated with higher concordance rates of ER, PR, HER2, and molecular subtype status compared to MBBC. • SBBC had worse BCSS than MBBC. • Molecular subtype discordance was independently related to worse prognosis in SBBC but has no impact on prognosis of MBBC.

Background We evaluated the outcome of liver transplantation (LT) in neonatal-onset citrullinemia type I patients, especially its impact on neurological deficits and developmental retardation. Methods From October 2006 to October 2019, 5 of the 2003 children who received LT at Ren Ji Hospital had been diagnosed with citrullinemia type I. The primary indication for transplantation was repeated metabolic compensation and developmental retardation in 4 patients and prophylactic transplantation in the other. Among them, 3 patients received living donor LT and 2 received orthotopic LT. Results All recipients had successfully recovered within the median follow-up period of 32 months (range, 6-54 mo). Transplantation restored citrulline metabolism and liver function. Plasma ammonia and citrulline concentration decreased to normal levels with no further hyperammonemic episodes being reported, even after normal diet intake began. Meanwhile, uracil-2 and orotic acid were not detected in urinary excretion. Strikingly, patients suffered developmental retardation before LT showed improved psychomotor ability and significant catch-up growth during the follow-up period. Cognitive ability, including language skills and academic performance, also greatly improved. Three patients had sustained brain injuries and exhibited severe neurological deficits before transplantation, especially repeated generalized tonic-clonic seizures. LT halted neurological deterioration and controlled seizure episodes, which further facilitated the intellectual development and improvement of life quality. Conclusions LT is an effective treatment for neonatal-onset citrullinemia type I patients, which reverses metabolism decompensation and improves quality of life. For patients who have suffered severe hyperammonemic insults, LT should be conducted at an early age to avoid further neurological or developmental deficits.

Purpose: The ACOSOG Z0011 study demonstrated that axillary lymph node dissection (ALND) can be safely omitted in patients with one to two positive sentinel lymph node (SLN) who underwent breast-conserving surgery (BCS) with planned whole-breast irradiation. This study aimed to analysis the surgical management in patients with one to two positive SLNs, and further evaluate the rates of non-sentinel lymph node (non-SLN) metastasis between patients receiving BCS or total mastectomy (TM). Methods: We performed a retrospective analysis of patients with early breast carcinoma from the Shanghai Jiao Tong University-Breast Cancer Database (SJTU-BCDB) between 2011 to 2018. The inclusion criteria were (1) cT1-2N0M0 invasive breast cancer, (2) aged ≥18 years at diagnosis, (3) received surgical treatment for the primary tumor and the axilla, (4) had one to two positive SLNs, (5) no history of previous or concurrent malignant disease, and (6) no neoadjuvant therapy. Patients were classified into the BCS and TM groups. Time trends of ALND rates were analyzed with Chi-square tests. And the rates of non-SLN metastasis between BCS and TM groups were also analyzed with Chi-square tests. Multivariable logistic regression was used to determine factors influencing the completion of ALND and non-SLN metastasis. And Kaplan-Meier estimator and log-rank tests were used to analysis the recurrence-free survival (RFS) between SLNB alone and SLNB+ALND arms. Results: Of the 891 patients enrolled, 586 (65.8%) received TM and 305 (34.2%) received BCS. Between 2011 and 2018, the completion of ALND for 1-2 positive SLN decreased from 100% to 72.7% (P 50% (P =0.001), and SLN macro-metastasis (P 50% (OR=3.43, 95%CI 2.28-5.17; P Citation Format: Weiqi Gao, Xiaosong Chen, Kunwei Shen. Does the axilla surgical management for limited sentinel lymph nodes involvement vary between total mastectomy and breast-conserving surgery [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-53.

Background: The association between 21-gene recurrence score (RS) and host factors such as overweight remains unclear for breast cancer patients. The objectives of the current study are to comprehensively analyze the distribution, single gene expression, and prognostic predictive value of RS between overweight or non-overweight patients.Patients and methods: Luminal-like patients receiving surgery between January 2009 and December 2018 in the Comprehensive Breast Health Center, Shanghai Ruijin Hospital, with 21-gene RS results were retrospectively retrieved. Association and subgroup analysis between BMI and 21-gene RS were conducted. Single-gene expression in 21-gene RS panel was compared between overweight and non-overweight groups. Recurrence-free survival (RFS) and overall survival (OS) were calculated according to RS category and BMI status.Results: Among 1876 patients included, 442 (23.56%), 995 (53.04%) and 439 (23.40%) were classified into low, intermediate and high risk groups. RS category was significantly differently distributed between overweight and non-overweight patients (P=0.035). Overweight patients had a trend of lower RS score than patients with normal weight (25.13 vs 26.17, P=0.080). The effect of BMI on RS significantly varied according to age (P=0.012) and menstruation status (P Citation Format: Yiwei Tong, Weiqi Gao, Jiayi Wu, Siji Zhu, Ou Huang, Jianrong He, Li Zhu, Weiguo Chen, Yafen Li, Kunwei Shen, Xiaosong Chen. Comprehensive association analysis of 21-gene recurrence score and overweight in breast cancer patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS17-38.

Background: The 21-gene recurrence score (RS) can predict chemotherapy benefit in estrogen receptor (ER)-positive, human epidermal growth factor receptor-2 (HER2)-negative early breast cancer patients. The TAILORx showed that age would influence the interaction between RS and chemotherapy effect, and patients ≤50 years with RS >15 can benefit from chemotherapy. The current study aimed to determine the RS threshold that can predict chemotherapy benefit in both young and elder women. Methods: Patients diagnosed with pN0-1, ER+/HER2- breast cancer between 2009 and 2016 at Shanghai Ruijin hospital were retrospectively reviewed. A one-to-one propensity score matching (PSM) was performed between women receiving chemotherapy or not. Patients were then stratified by different cutoffs of age (range, 30-65 years). In each prespecified strata of age, cox proportional hazards models were used to determine the RS threshold which was predictive of chemotherapy benefit. Results: A total of 1227 patients were included. The median age was 58 years and the median RS was 24. After matching, the RS values that can manifest the chemotherapy benefit varied with age. For patients at 55 years of age or younger, apparent chemotherapy benefit was observed in those who had RS >25 (P = 0.03), with 4-year invasive disease-free survival (IDFS) rate of 97.0% and 89.3% in patients receiving chemotherapy or not. While patients derived no benefit from chemotherapy if they had RS ≤25 (P = 0.66, 4-year IDFS rate: 95.3% vs. 94.6%). However, for patients older than 55 years, adjuvant chemotherapy was associated with better prognosis in those with RS >36 (P = 0.014, 4-year IDFS rate: 94.7% vs. 76.2%), but not in those having RS ≤36 (P = 0.13, 4-year IDFS rate: 92.3% vs. 95.8%). Conclusions: The RS threshold to demonstrate the chemotherapy benefit differed with age. Young patients with RS >25 and old patients with RS >36 could benefit from adjuvant chemotherapy. Survival of breast cancer patients receiving adjuvant chemotherapy or not stratified by age and theChemoendocrine therapyEndocrine therapyP-value4-year IDFS rate (%)95% CI (%)4-year IDFS rate (%)95% CI (%)≤55 yearsRS ≤2595.390.7-100.094.689.6-100.00.66RS >2597.091.3-100.089.382.0-97.30.03>55 yearsRS ≤3692.387.7-97.295.892.1-99.60.13RS >3694.787.9-100.076.252.1-100.00.014 Citation Format: Jing Yu, Caijin Lin, Jiahui Huang, Jin Hong, Weiqi Gao, Siji Zhu, Hui Wang, Ou Huang, Xiaosong Chen, Jianrong He, Li Zhu, Weiguo Chen, Yafen Li, Kunwei Shen, Jiayi Wu. Efficacy of adjuvant chemotherapy stratified by age and the 21 gene recurrence score in estrogen receptor positive breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-28.

Background: It is unknown whether molecular subtype is associated with axillary lymph node (ALN) status (ypN) after neoadjuvant therapy (NAT) in breast cancer patients who achieved breast pathological complete remission (pCR), especially for patients with different clinical stage. Our study aimed to investigate the association of clinical stage and molecular subtype with ALN status (ypN) after NAT in breast cancer patients. Patients and methods: Breast cancer patients receiving ≥ 4 cycles of NAT with complete clinicopathological data were retrospectively included between January 2009 to January 2020. Status of ypN according to breast pCR status was compared in cT1-2N0, cT1-2N1, and local advanced breast cancer (LABC) patients with different molecular subtype. Univariate and multivariate analyses were conducted to identify potential predictive factors for ypN status. Results: A total of 1999 patients were included. cT1-2N0, cT1-2N1, and LABC disease were found in 457 (22.86%), 884 (44.22%) and 658 (32.92%) patients, whose ypN+ rate was 24.5%, 60.3%, and 66.4%, respectively (P < 0.001). Compared with cT1-2N0 patients, ypN+ rate was significantly higher in cT1-2N1 (OR = 5.48, 95%CI = 3.77-7.97, P < 0.001) and LABC (OR = 10.90, 95%CI = 7.12-16.70, P < 0.001). Moreover, ypN+ rate varied across different molecular subtypes, which was 60.0% in Luminal A subtype, 61.4% in Luminal B (HER2-) subtype, 47.6% in Luminal B (HER2+) subtype, 42.2% in HER2-amplified subtype and 52.5% in TNBC (P < 0.001). Patients achieving breast pCR also had a significantly lower ypN+ rate than those without breast pCR (23.9% vs 62.5%, univariate P < 0.001; OR =0.14, 95%CI = 0.09-0.21, P < 0.001). Furthermore, in breast pCR patients, multivariate analyses showed that clinical stage and molecular subtype were substantially related to ypN+ rate: the ypN+ rate was significantly higher in cT1-2N1 (OR = 5.64, 95%CI = 2.31-13.76, P < 0.001) and LABC (OR = 9.80, 95%CI = 3.88-24.77, P < 0.001), compared with cT1-2N0 patients; while it was significantly lower in Luminal B HER2+ (OR =0.20, 95%CI = 0.05-0.82, P = 0.025) and HER2-amplified (OR = 0.19, 95%CI = 0.05-0.83, P = 0.026) subtype, compared with Luminal A subtype. In the cT1-2N0 subgroup, all patients with breast pCR with Luminal B HER2+ or HER2-amplified subtype achieved ALN pCR. Conclusion: Clinical stage and molecular subtype were significantly associated with ypN status in breast pCR patients after NAT. Patients with cT1-2N0 and HER2-positive patients who achieved breast pCR had low ypN+ rate, which possibly guides further clinical ALN management after NAT. Key words: Breast pathological complete remission; Neoadjuvant therapy; Molecular subtype; Clinical stage; Nodal residual burden. Table. Pathological node status stratified by clinical stage between patients with breast pCR and non-pCR.Response in breastpCRnon-pCRypN0 (N, %)ypN+ (N, %)ypN0 (N, %)ypN+ (N, %)Whole population331(76.1)104(23.9)586(37.5)978(62.5)cT1-2N088(93.6)6(6.4)257(70.8)106(29.2)cT1-2N1159(74.3)55(25.7)192(28.7)478(71.3)LABC84(66.1)43(33.9)137(25.8)394(74.2)Luminal A like9(69.2)4(30.8)37(36.3)65(63.7)cT1-2N06(85.7)1(14.3)19(73.1)7(26.9)cT1-2N13(50.0)3(50.0)12(27.9)31(72.1)LABC0(0.0)0(0.0)6(18.2)27(81.8)Luminal B like (HER2-)112(70.4)47(29.6)220(31.4)480(68.6)cT1-2N033(89.2)4(10.8)85(59.0)59(41.0)cT1-2N159(71.1)24(28.9)75(23.8)240(76.2)LABC20(51.3)19(48.7)60(24.9)181(75.1)Luminal B like (HER2+)89(83.2)18(16.8)140(42.4)190(57.6)cT1-2N019(100.0)0(0.0)70(83.3)14(16.7)cT1-2N146(83.6)9(16.4)43(30.5)98(69.5)LABC24(72.7)9(27.3)27(25.7)78(74.3)HER2 amplified66(82.5)14(17.5)97(48.0)105(52.0)cT1-2N014(100.0)0(0.0)42(82.4)9(17.6)cT1-2N125(78.1)7(21.9)32(42.1)44(57.9)LABC27(79.4)7(20.6)23(30.7)52(69.3)TNBC55(72.4)21(27.6)92(40.0)138(60.0)cT1-2N016(94.1)1(5.9)41(70.7)17(29.3)cT1-2N126(68.4)12(31.6)30(31.6)65(68.4)LABC13(61.9)8(38.1)21(27.3)56(72.7)Abbreviations: LABC, locally advanced breast cancer; HER2, human epidermal growth factor receptor 2; TNBC, triple negative breast cancer; pCR, breast pathological complete response. Citation Format: Jin Hong, Yiwei Tong, Ou Huang, Jiayi Wu, Li Zhu, Jianrong He, Weiguo Chen, Yafen Li, Xiaochun Fei, Xiaosong Chen, Kunwei Shen. Molecular subtype and clinical stage influenced axillary lymph node response in breast cancer patients with breast pathological complete remission after neoadjuvant therapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-33.

Background The 21-gene recurrence score (RS) testing can predict the prognosis for luminal breast cancer patients. Meanwhile, patients > 50 years with RS > 25 have improved survival with adjuvant chemotherapy. The current study aimed to develop a nomogram with routine parameters to predict RS. Methods We included patients diagnosed with hormone receptor (HR)-positive, human epidermal growth factor receptor-2 (HER2)-negative who underwent the 21-gene RS testing and aged > 50 years. The primary outcome was high-risk RS (> 25). Univariate and multivariate analyses were performed to identify significant predictors. A predictive nomogram based on logistic model was developed and evaluated with receiver operating characteristic (ROC) curves. The nomogram was internally validated for discrimination and calibration with bootstrapping method, and externally validated in another cohort. We then assessed the nomogram in different subgroups of patients and compared it with several published models. Results A total of 1100 patients were included. Five clinicopathological parameters were used as predictors of a high-risk RS, including tumor grade, histologic subtype, ER expression, PR expression, and Ki-67 index. The area under the curve (AUC) was 0.798 (95% CI 0.772–0.825) and optimism adjusted AUC was 0.794 (95% CI 0.781–0.822). External validation demonstrated an AUC value of 0.746 (95% CI 0.685–0.807), which had no significant difference with the training cohort (P = 0.124). Calibration plots indicated that the nomogram-predicted results were well fitted to the actual outcomes in both internal and external validation. The nomogram had better discriminate ability in patients who had tumors > 2 cm (AUC = 0.847, 95% CI 0.804–0.890). When compared with four other existing models, similar AUC was observed between our nomogram and the model constructed by discriminate Lee et al. Conclusions We developed a user-friendly nomogram to predict the high-risk RS in luminal breast cancer patients who were older than 50 years of age, which could guide treatment decision making for those who have no access to the 21-gene RS testing.

PurposeTo evaluate the influence of obesity on clinicopathological characteristics of breast cancer; to explore the effect of obesity on the prognosis and performance of endocrine therapy in breast cancer patients.MethodsPatients with luminal/HER2-negative early breast cancer were included and categorized into the non-obese (BMI2) and obese (BMI≥28kg/m2) groups according to body mass index (BMI). Clinicopathological characteristics and treatment modalities were compared between groups. Interaction of adjuvant endocrine therapy with obesity was analyzed.ResultsA total of 2,875 patients were included: 2,598 non-obese and 277 obese. A higher rate of patients with comorbidities (OR: 2.83, 95%CI 2.13-3.74, PP=0.037) were identified in the obese group. Obesity was not associated with disease recurrence (P=0.839) or overall survival (P=0.140) in the whole population. Subgroup analysis did show an association with worse relapse-free survival (RFS, HR 3.48, 95%CI 1.31-9.22, P=0.012) and overall survival (OS, HR 4.67, 95%CI 1.28-16.95, P=0.019) in luminal A breast cancer. These results could not be reproduced in the luminal B subtype with a RFS (HR 0.78, 95%CI 0.41-1.49, P=0.454) or OS (HR 1.17, 95%CI 0.50-2.74, P=0.727). Furthermore, obesity did not impact endocrine therapy effectiveness in Tamoxifen or the aromatase inhibitor group (RFS: interact P=0.381; OS: interact P=0.888).ConclusionsThe impact of obesity on prognosis interacted with luminal subtype status in Chinese breast cancer patients which was not related with endocrine treatment modality.

Stretchable electrodes are one of the essential building blocks for stretchable electronics. However, most of the reported stretchable electrodes show a considerable conductivity decrease under large stretchability. Until now, it has still been a big challenge to develop appropriate geometric structures to realize stretchable metal electrodes with a negligible conductivity change under large stretchability. Here, inspired by the armadillo, we develop a novel micro-foldable structure on polydimethylsiloxane (PDMS) using a suspended plasma etching method. This novel structure could endow the obtained stretchable electrodes with excellent properties including high metallic conductivity (>40 000 S cm−1) at released and stretched states, slight resistance change (13%) over a large tensile range (190%), a fully-covered conductive area, excellent cyclic operational stability (over 10 000 times), and a robust interface adhesion strength (>0.28 MPa). These figures of merit are very prominent compared to the reported stretchable gold electrodes, indicating the superiority of this novel micro-foldable structure. Furthermore, these stretchable electrodes show excellent performance in electromyography (EMG) signal detection, stretchable conducting wires and capacitive stretchable sensors. This work provides a novel and efficient avenue for the preparation of stretchable electronics.

BACKGROUND Immunosuppression is an important factor in the incidence of infections in transplant recipient. Few studies are available on the management of immunosuppression (IS) treatment in the liver transplant (LT) recipients complicated with infection. The aim of this study is to describe our experience in the management of IS treatment during bacterial bloodstream infection (BSI) in LT recipients and assess the effect of temporary IS withdrawal on 30 d mortality of recipients presenting with severe infection. AIM To assess the effect of temporary IS withdrawal on 30 d mortality of LT recipients presenting with severe infection. METHODS A retrospective study was conducted with patients diagnosed with BSI after LT in the Department of Liver Surgery, Renji Hospital from January 1, 2016 through December 31, 2017. All recipients diagnosed with BSI after LT were included. Univariate and multivariate Cox regression analysis of risk factors for 30 d mortality was conducted in the LT recipients with Gram-negative bacterial (GNB) infection. RESULTS Seventy-four episodes of BSI were identified in 70 LT recipients, including 45 episodes of Gram-positive bacterial (GPB) infections in 42 patients and 29 episodes of GNB infections in 28 patients. Overall, IS reduction (at least 50% dose reduction or cessation of one or more immunosuppressive agent) was made in 28 (41.2%) cases, specifically, in 5 (11.9%) cases with GPB infections and 23 (82.1%) cases with GNB infections. The 180 d all-cause mortality rate was 18.5% (13/70). The mortality rate in GNB group (39.3%, 11/28) was significantly higher than that in GPB group (4.8%, 2/42) (P = 0.001). All the deaths in GNB group were attributed to worsening infection secondary to IS withdrawal, but the deaths in GPB group were all due to graft-versus-host disease. GNB group was associated with significantly higher incidence of intra-abdominal infection, IS reduction, and complete IS withdrawal than GPB group (P < 0.05). Cox regression showed that rejection (adjusted hazard ratio 7.021, P = 0.001) and complete IS withdrawal (adjusted hazard ratio 12.65, P = 0.019) were independent risk factors for 30 d mortality in patients with GNB infections after LT. CONCLUSION IS reduction is more frequently associated with GNB infection than GPB infection in LT recipients. Complete IS withdrawal should be cautious due to increased risk of mortality in LT recipients complicated with BSI. IS

Multi-gene assays have emerged as crucial tools for risk stratification in early-stage breast cancer. This study aimed to evaluate the prognostic significance of the 21-gene recurrence score (RS) in Chinese patients with pN0-1, estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer. Among 800 patients recruited between 2009 and 2016, the median RS was 24 (0-69), with 27.4%, 46.8%, and 25.9% patients classified into low-, intermediate-, and high-risk groups. Cox regression analysis demonstrated that the high-risk category was associated with significantly higher odds of invasive disease-free survival (IDFS) and distant disease-free survival (DDFS) events compared with the low-risk category (IDFS: HR = 2.450, 95% CI 1.017-5.902, P = 0.046; DDFS: HR = 2.829, 95% CI 1.013-7.901, P = 0.047). No significant association between RS category and overall survival (OS) was found (intermediate vs. low: HR= 1.244, 95% CI 0.292-5.297, P = 0.768; high vs. low: HR = 2.933, 95% CI 0.759-11.327, P = 0.119). RS, as a continuous variable, was a highly significant predictor for IDFS (HR= 1.028, 95% CI 1.010-1.047, P = 0.002), DDFS (HR= 1.030, 95% CI 1.010-1.051, P = 0.003), and OS (HR= 1.034, 95% CI 1.007-1.063, P = 0.014). Our findings suggested that RS may predict IDFS in Chinese patients with ER+/HER2- breast cancer with N0 or N1 disease.

Background Invasive ductal carcinoma (IDC) is often accompanied by ductal carcinoma in situ (DCIS). Whether the DCIS component affects the 21-gene recurrence score (RS) is unclear. Methods Consecutive ER-positive, HER2-negative, N0–1 patients with RS results were included. Patients were divided into pure IDC and IDC with DCIS (IDC/DCIS) groups. The RS, the expression of its 16 cancer genes and prognosis were compared between IDC and IDC/DCIS patients. Results A total of 1458 patients were enrolled, 320 of whom had concomitant DCIS. DCIS component was independently associated with lower RS (P = 0.038). IDC/DCIS patients more often had a low-risk RS (P = 0.018) or intermediate-risk RS (P = 0.024). Regarding individual genes in the RS panel, Ki67, CCNB1 and MYBL2 in the proliferation group and MMP11 and CTSL2 in the invasion group were significantly lower among IDC/DCIS patients than pure IDC patients. Among IDC/DCIS patients, lower RS was independently correlated with a higher DCIS proportion and lower DCIS grade. Within a median follow-up of 31 months, the DCIS component in IDC did not significantly influence prognosis. Conclusions IDC with DCIS component is associated with a lower 21-gene RS, possibly due to lower expression of proliferation and invasion genes. DCIS proportion and grade independently influenced the 21-gene RS in IDC/DCIS patients. Due to the relatively short follow-up period and low recurrence rate, the impact of the DCIS component in IDC on prognosis needs further evaluation.

Co-expression of human epidermal growth factor receptor-2 (HER2) and hormone receptor (HR) predicted worse prognosis in early breast cancer before trastuzumab was developed. We aimed to investigate whether HER2 positivity was still associated with worse outcome in high-risk estrogen receptor (ER) positive patients treated with trastuzumab and chemotherapy. In the present study, 227 ER+/HER2+ patients treated with trastuzumab and chemotherapy (HER2-pos-T group) and 1097 ER+/HER2-patients treated with chemotherapy alone (HER2-neg group) during 2009 and 2015 were retrospectively enrolled for the comparison of disease-free survival (DFS) and overall survival (OS). At a median follow-up of 59 months, 174 DFS events and 69 deaths were observed. The estimated 5-year DFS rate was 94.2% in the HER2-pos-T group and 87.4% in the HER2-neg group (Log-rank P = 0.014). HER2-pos-T group was associated with significantly better DFS in multivariate analysis (HR 0.38, 95% CI: 0.22–0.67, Log-rank P = 0.001). The estimated 5-year OS rates for the two groups were 97.2% and 95.7%, respectively (Log-rank P = 0.183). In multivariable analysis, patients in the HER2-pos-T group had significantly better OS compared with those in the HER2-neg group (HR 0.40, 95% CI: 0.17–0.95, Log-rank P = 0.037). We concluded that high-risk ER+/HER2+ breast cancer patients treated with chemotherapy and trastuzumab had superior prognosis compared with ER+/HER2-patients. Therefore, HER2 positivity itself may not be considered as an unfavorable factor for ER + patients in the era of trastuzumab., Highlights • ER+/HER2+ early breast cancer patients treated with trastuzumab-based chemotherapy had superior prognosis. • ER+/HER2+ early breast cancer patients had distinct patterns of relapse or death from those of ER+/HER2-patients. • HER2 positivity itself may not be considered as an unfavorable factor for ER + patients in the era of trastuzumab.

The tradeoff between sensitivity and detection range (maximum and minimum stretchability) is a key limitation in strain sensors; to resolve this, we develop an efficient and novel strategy herein to fabricate a highly sensitive and stretchable strain sensor inspired by the membrane–shell structure of poultry eggs. The developed sensor comprises a soft and stretchable surface-grafting polypyrrole (s-PPy) film (acting as the membrane) and a brittle Au film (acting as the shell), wherein both films complement each other at the electrical and mechanical levels. Au forms cracks under strain contributing to its high sensitivity and low detection limit, and s-PPy can bridge Au cracks and increase stretchability which has not been used in strain sensors before. The surface-grafting strategy not only enhances interface adhesion but also tunes the brittle property of native PPy to render it stretchable. Utilizing the synergetic effect of the membrane–shell complementary structure, the strain sensors achieve ultrahigh sensitivity (>107), large stretchability (100%), and an ultralow detection limit (0.1%), demonstrating significant progress in the field of strain sensors. The membrane–shell (Au/s-PPy)-structured strain sensor can successfully detect finger motion, wrist rotation, airflow fluctuation, and voice vibration; these movements produce strain in the range of subtle to marked deformations. Results evidence the ultrahigh performance and bright application prospects of the developed strain sensors.

Carbapenem-resistant Klebsiella pneumoniae infection is a major cause of morbidity and mortality after solid-organ transplant and hematopoietic stem cell transplant. Here, we report a 57-year-old man with hepatitis B virus-related decompensated liver cirrhosis, huge splenic artery aneurysm, and hypersplenism who underwent liver transplant from a deceased brain-dead donor. Recipient sputum surveillance showed carbapenem-resistant Klebsiella pneumoniae when he entered the intensive care unit, and combined tigecycline, meropenem, and fosfomycin were administered. At 1 week posttransplant, the recipient's hepatic artery was eroded by disseminated carbapenem-resistant Klebsiella pneumoniae infection, and the patient developed acute kidney injury. Our experience suggests that colonization of carbapenem-producing organisms may be included during surveillance posttransplant and that the infected graft artery must be removed instead of noninfected vessels.

Background Multidisciplinary team (MDT) discussions are widely held to facilitate the diagnosis and treatment of breast cancer, but patient compliance with the MDT recommendations and the impact of compliance on disease outcome are uncertain. Methods We conducted a retrospective review of data from a prospective database of breast cancer patients treated at Shanghai Ruijin Hospital between April 2013 and August 2018. MDT discussions were held for all patients before they started adjuvant therapy. The patients were classified into compliant and non-compliant groups according to whether they received the MDT-recommended regimens. We also analyzed which clinicopathological factors were associated with compliance and prognosis. Results Of 4501 breast cancer patients, 3681 (81.8%) and 820 (18.2%) were included in the compliant and non-compliant groups, respectively. Age >70 years (P, Highlights • A large consecutive breast cancer cohort with MDT-based treatment recommendation. • Factors identified associated with non-compliance with MDT recommendations. • A significantly better survival in patients compliant with MDT recommendation.

Background The interplay between biomarkers of insulin and the insulin-like growth factor (IGF) axis in the context of breast cancer risk is unclear. Methods We measured the concentrations of insulin, C-peptide, IGF1, and IGF binding protein 3 (IGFBP3) and calculated the homeostasis model assessment of insulin resistance (HOMA-IR) index and the IGF1/IGFBP3 ratio among 2536 patients with breast cancer and 2528 patients with benign breast disease recruited from Ruijin Hospital, Shanghai, China, between 2012 and 2017. Results Multivariable-adjusted odds ratios (ORs) for breast cancer associated with the highest quartiles versus the lowest quartiles of insulin and IGF factors were 1.45 (95% CI, 1.20-1.75) for insulin, 1.32 (1.08-1.60) for C-peptide, 1.53 (1.26-1.85) for HOMA-IR, and 1.27 (1.05-1.53) for IGF1; these associations did not differ substantially across stratifications of age, body mass index, age at menarche, or menopausal status (all P for interaction >0.05). In the joint analysis, the highest quartile of IGF1 was associated with the greatest risk of breast cancer in the highest quartiles of insulin (OR, 1.77; 95% CI, 1.29-2.44), C-peptide (1.60; 1.17-2.20), and HOMA-IR (1.90; 1.38-2.62), compared with the risks associated with the combination of the lowest quartiles of IGF1 and each insulin factor. In stratification analysis, the positive association between IGF1 and breast cancer was stronger in the highest quartiles of insulin (P[interaction] = 0.29), C-peptide (P[interaction] = 0.020), and HOMA-IR (P[interaction] = 0.075). Conclusion Our findings indicate effect modifications of insulin, C-peptide, and insulin resistance on the relationship between IGF1 and breast cancer risk in Chinese women.

Background Features in preoperative ultrasound could predict the prognosis of triple‐negative breast cancer (TNBC), while its prognostic value in other molecular subtypes of breast cancer (BC) was unknown. The study aimed to assess the prognostic value of preoperative sonographic features, including orientations, on long‐term outcomes in BC and its association with different molecular subtypes. Methods Women diagnosed with invasive BC > 5 mm who underwent surgery were retrospectively reviewed. Clinical, pathological, and sonographic profiles were collected and recurrence‐free survival (RFS) and breast cancer‐specific survival (BCSS) were reported. Interactions between clinicopathological features and tumor orientations in predicting RFS and BCSS were analyzed. Competing risk model was performed to estimate prognostic values of sonographic features for RFS and BCSS. Results A total of 2812 patients were included. With a median follow‐up of 60.0 months, 268 (9.5%) patients suffered from recurrences and 104 (3.7%) died of BC. The prognostic values of vertical orientation in predicting RFS (P = .001) and BCSS (P = .001) were strongly associated with molecular subtypes. Non‐TNBC tumors with vertical orientation had less recurrence events compared with parallel orientation (6.3% vs 8.7%, P = .035), whereas failed to predict disease outcomes in multivariate analysis (P > .05). Oppositely, in TNBC, vertical orientation was associated with worse RFS (HR = 3.50; 95% confidence interval [CI] 1.69‐7.24; P, Vertical orientation in preoperative ultrasound strongly interacted with molecular subtypes in predicting recurrence‐free survival (RFS) (P = .001) and breast cancer‐specific survival (BCSS) (P = .001). Vertical orientation independently related with worse RFS (HR = 3.50; 95% confidence interval [CI] 1.69‐7.24; P

Liver cancer is the second most frequent cause of cancer-related death globally. The main histological subtype is hepatocellular carcinoma (HCC), which is derived from hepatocytes. According to the epidemiologic studies, the most important risk factors of HCC are chronic viral infections (HBV, HCV, and HIV) and metabolic disease (metabolic syndrome). Interestingly, these carcinogenic factors that contributed to HCC are associated with MDM2–p53 axis dysfunction, which presented with inactivation of p53 and overactivation of MDM2 (a transcriptional target and negative regulator of p53). Mechanically, the homeostasis of MDM2–p53 feedback loop plays an important role in controlling the initiation and progression of HCC, which has been found to be dysregulated in HCC tissues. To maintain long-term survival in hepatocytes, hepatitis viruses have lots of ways to destroy the defense strategies of hepatocytes by inducing TP53 mutation and silencing, promoting MDM2 overexpression, accelerating p53 degradation, and stabilizing MDM2. As a result, genetic instability, chronic ER stress, oxidative stress, energy metabolism switch, and abnormalities in antitumor genes can be induced, all of which might promote hepatocytes’ transformation into hepatoma cells. In addition, abnormal proliferative hepatocytes and precancerous cells cannot be killed, because of hepatitis viruses-mediated exhaustion of Kupffer cells and hepatic stellate cells (HSCs) and CD4+T cells by disrupting their MDM2–p53 axis. Moreover, inefficiency of hepatic immune response can be further aggravated when hepatitis viruses co-infected with HIV. Unlike with chronic viral infections, MDM2–p53 axis might play a dual role in glucolipid metabolism of hepatocytes, which presented with enhancing glucolipid catabolism, but promoting hepatocyte injury at the early and late stages of glucolipid metabolism disorder. Oxidative stress, fatty degeneration, and abnormal cell growth can be detected in hepatocytes that were suffering from glucolipid metabolism disorder, and all of which could contribute to HCC initiation. In this review, we focus on the current studies of the MDM2–p53 axis in HCC, and specifically discuss the impact of MDM2–p53 axis dysfunction by viral infection and metabolic disease in the transformation of normal hepatocytes into hepatoma cells. We also discuss the therapeutic avenues and potential targets that are being developed to normalize the MDM2–p53 axis in HCC.

To evaluate the role of 21-gene recurrence score (RS) assay in adjuvant chemotherapy decision-making among older patients with early breast cancer.Consecutive hormonal receptor-positive, aged ≥60 patients with breast cancer were enrolled from Shanghai Ruijin Hospital between January 2014 and December 2017. Treatment decisions were made by multi-disciplinary team (MDT) before and after 21-gene RS testing, and the actual treatment for each patient was also analyzed.A total of 511 patients were enrolled, with 331 (64.8%) aged between 60 and 69, 140 (27.4%) between 70 and 79, and 40 (7.8%) over 80 years. There were 138 (27.0%), 287 (56.2%), and 86 (16.8%) patients classified as low, intermediate, and high risk RS, respectively. Multivariable analysis demonstrated that age, tumor stage, nodal status, PR expression, Ki-67, and 21-gene RS were independent impact factors for chemotherapy recommendations (P .05). Patients with high risk RS and intermediate risk RS (both P .001) were more often recommended to receive chemotherapy than patients with low risk RS. Treatment recommendations changed in 74 (14.5%) patients after 21-gene RS testing: 17 (3.3%) from chemotherapy to no chemotherapy and 57 (11.2%) from no chemotherapy to chemotherapy. Overall compliance rate to MDT recommendation after 21-gene RS testing was 95.7%.An intermediate and/or high risk 21-gene RS assay was independently associated with receiving adjuvant chemotherapy among older patients with breast cancer. However, it showed a limited impact on adjuvant chemotherapy decision-making. After 21-gene RS testing, compliance with MDT recommendation was relatively high in older patients with breast cancer.

The optimal time to adjuvant chemotherapy (TTC) for breast cancer (BC) patients remains uncertain. Herein, we aim to evaluate the association between TTC and prognosis among different subtypes in modern era of adjuvant chemotherapy. BC patients receiving operation and adjuvant chemotherapy between January 2009 and December 2015 were included. Enrolled patients were categorized into TTC ≤4 weeks and >4 weeks groups. Relapse-free survival (RFS) and overall survival (OS) were compared according to TTC and analyzed among different BC molecular subtypes. A total of 2611 patients were included. Elder age (P = 0.005), more comorbidities (P P = 0.001), non-invasive ductal carcinoma (P = 0.012), and HER2-positivity (P <0.001) were associated with prolonged TTC. Among whole BC population, no significant difference was observed between two TTC groups in terms of RFS (P = 0.225) or OS (P = 0.355). However, for triple negative (TNBC) patients, TTC >4 weeks was independently related with worse RFS (5-year RFS 81.9% vs 89.3%; HR, 1.89; 95% CI, 1.09 to 3.27; P = 0.024) and OS (5-year OS 84.0% vs 94.0%; HR, 2.49; 95% CI, 1.30 to 4.76; P = 0.006) compared with those TTC ≤4 weeks. Prolonged TTC >4 weeks after BC surgery was not associated with worse survival outcomes in the whole BC patients. However, TTC >4 weeks may increase risk of relapse or death in TNBC patients, which deserves further clinical evaluation.

The current study was conducted to compare the therapeutic effects of proximal femoral nail antirotation (PFNA-II) and artificial total hip arthroplasty (THA) on elderly Chinese patients with unstable intertrochanteric femoral fracture combined with severe osteoporosis. There were 60 people in each group. The duration of surgery, blood loss, and weight-bearing period when standing on the floor were compared between the two groups (P > 0.05). Harries function scores of both groups increased over time. Scores of THA group were significantly higher than those of PFNA-II group during six- and twelve-months follow-up visit (P < 0.05). In addition, excellent and good rates of hip joint function in THA group were higher than those of PFNA-II group during twelve-month follow-up visit (P < 0.05). The occurrence rates of follow-up complications in both groups showed no statistical significance (P > 0.05). Thus, both PFNA-II and THA have good effects on Chinese elderly patients with unstable intertrochanteric femoral fracture combined with severe osteoporosis.

Objectives Triple negative breast cancer (TNBC) is a heterogenous disease and associated with unfavorable outcomes. The role of sonographic features and its association with disease outcome in TNBC is uncertain. Our study aimed to determine the prognosis predictive value of sonographic features in TNBC. Methods Women with TNBC patients treated between January 2009 and December 2015 were retrospectively included. Patients’ clinic-pathological, sonographic features, recurrence-free survival (RFS), and breast cancer-specific survival (BCSS) events were reviewed and analyzed. Kaplan–Meier analysis and multivariable Cox regression were used to determine the prognostic factors in TNBC. Results A total of 433 TNBC patients were included. With a median follow-up of 4.8 years, 58 (13.4%) RFS and 35(8.1%) BCSS events were detected. Besides lymphatic vascular invasion (LVI), nuclear grade III, tumor >2.0 cm, and positive axillary lymph node (ALN), multivariable analysis found that vertical orientation in ultrasound imaging was independently associated with worse RFS (Hazard Ratio (HR) = 3.238; 95% Confidential Interval (CI), 1.661–6.312; P = 0.001) and BCSS (HR = 7.028; 95% CI, 3.199–15.436; P, Highlights • In TNBC, vertical orientation in US was associated with inferior RFS. • Vertical orientation in US independently predicted worse BCSS in TNBC. • Vertical orientation in US was related with more ALN metastasis in TNBC patients.

Objectives: This study aims to evaluate influence factors for adjuvant chemotherapy regimen choice on the basis of trastuzumab in older human epidermal growth factor receptor 2 (HER2)-positive breast cancer under multi-disciplinary team (MDT) modality. Materials and Methods: HER2-positive breast cancer patients aged ≥ 60 years who received breast cancer surgery between April 2013 and December 2017 in Shanghai Ruijin Hospital were retrospectively enrolled. Clinical and pathological features, MDT recommendations, administration of adjuvant treatment, cardiotoxicity, and disease outcome information were reviewed and analyzed. Results: A total of 222 older HER2-positive breast cancer patients were included and recommended to receive adjuvant chemotherapy plus trastuzumab therapy. Paclitaxel plus trastuzumab (PH, 41/222, 18.5%), docetaxel plus carboplatin and trastuzumab (TCH, 62/222, 27.9%), and antharcyclines plus cyclophosphamide followed by taxanes and trastuzumab (AC-TH, 119/222, 53.6%) were the three main regimens. Patients with T1a-b (P

PurposeWith the application of “less extensive surgery” in breast cancer treatment, the pattern of locoregional recurrence (LRR) has significantly changed. This study aims to evaluate the risk and prognostic factors of LRR in a recent large breast cancer cohort.MethodsConsecutive early breast cancer patients who received surgery from January 2009 to March 2018 in Shanghai Ruijin Hospital were retrospectively analyzed. LRR was defined as recurrence at the ipsilateral breast (IBTR), chest wall, or regional lymph nodes and without concurrent distant metastasis (DM). Patients’ characteristics and survival were compared among these groups.ResultsAmong 5,202 patients included, 87 (1.7%) and 265 (5.1%) experienced LRR and DM as first event after a median 47.0 (3.0–122.5) months’ follow-up. LRR was significantly associated with large tumor size and positive lymph node status (p < 0.05). Forty (46.0%) patients received further salvage surgery after LRR and had a significantly better 3-year post-recurrence overall survival than those who did not (94.7% vs. 60.7%, p = 0.012). Multivariate analysis showed that salvage surgery for LRR was independently associated with better survival (HR = 0.12, 95% CI 0.02–0.93, p = 0.043) along with estrogen receptor (ER) positivity (HR = 0.33, 95% CI 0.12–0.91, p = 0.033).ConclusionLRR rate was relatively low in recent era of breast cancer treatment. Tumor size and lymph node status were associated with risk of LRR, and salvage surgery for selected LRR patients achieved an excellent outcome.

BackgroundComprehensive investigations of the associations between 21-gene recurrence assay and metabolic profiles in Chinese breast cancer patients are limited.MethodsWe evaluated the relations of the 21-gene recurrence risk score (RS) and the expression of cancer-related genes with metabolic factors and biomarkers of insulin and the insulin-like growth factor (IGF) axis, and examined the interactions between the 21-gene RS and these metabolic profiles on breast cancer recurrence in Chinese women with HR-positive, HER2-negative early-stage breast cancer.ResultsThe 21-gene RS was inversely associated with body mass index ([BMI]β: −0.178 kg/m2; P=0.040), the homeostasis model assessment of insulin resistance index ([HOMA-IR] β: −0.031; P=0.042), insulin (β: −0.036 uIU/ml; P=0.009), and C-peptide (β: −0.021 ug/L; P=0.014) and was positively associated with high-density lipoprotein cholesterol (β: 0.025 mmol/L; P=0.004), which were driven by the relation patterns between specific cancer-related genes and these metabolic profiles. Each 10-unit increase in the 21-gene RS was associated with 28% (95% CI: 5–47%) higher risk of breast cancer recurrence; this association was also observed in patients with favorable metabolic profiles in relevant to an absence of obesity, insulin resistance, hyperglycemia, hypertension, or dyslipidemia (28–44% higher risk) and among women with a low level of insulin, C-peptide, or the IGF1/IGFBP3 ratio (41–155% higher risk).ConclusionsThe 21-gene RS was related to favorable metabolic profiles including lower BMI, HOMA-IR, insulin, and C-peptide, and higher HDL in Chinese breast cancer patients, and its prognostic impact on breast cancer recurrence was more likely to present among patients with relatively favorable metabolic profiles.

Grain boundary, which is ubiquitous in thin-film devices, plays a negative role in device performance. High-resolution top-contact electrodes provide an effective approach to reduce the channel length for weakening the grain boundary effect in the conducting channel. In this study, polystyrene-based shadow masks are fabricated to produce top-contact electrodes with a channel length of 5 μm. With the aid of these high-resolution electrodes, the mobility of DPA-based thin-film transistors could be improved up to 19.22 cm2 V−1 s−1, which is a new breakthrough for the DPA thin-film transistors. Furthermore, this approach can also be extended to more organic semiconducting systems, e.g., pentacene, copper phthalocyanine (CuPc) and copper-hexadecafluorophthalocyanine (F16CuPc), to optimize their performance to one of the best values compared with previous reports. We believe this technology will provide us a good stage to further process top-contact highly integrated organic circuits.

PurposeThis retrospective study aimed to evaluate the distribution pattern and prognostic value of 21-gene recurrence score (RS) in Chinese patients with mucinous breast cancer (MC) and compared with infiltrating ductal carcinoma (IDC).Materials and MethodsPatients diagnosed with MC or IDC from January 2010 to January 2017 were retrospectively recruited. Reverse transcriptase–polymerase chain reaction assay of 21 genes was conducted to calculate the RS. Univariate and multivariate analyses were performed to assess the association between RS and clinicopathological factors. Survival outcomes including disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier method and compared by log-rank test.ResultsThe MC cohort included 128 patients and the IDC cohort included 707 patients. The proportions of patients with a low (RS < 18), intermediate (18-30), or high risk (RS > 30) were 32.0%, 48.4%, and 19.5% in MC cohort, and 26.9%, 46.8% and 26.3% in IDC cohort. The distribution of RS varied significantly according to different Ki-67 index and molecular subtype in both cohorts. Moreover, the receipt of chemotherapy was associated with RS in both cohorts. Among patients with MC, tumor stage was related to the DFS (p=0.040). No significant differences in DFS and OS were found among MC patients in different RS risk groups (OS, p=0.695; DFS, p=0.926).ConclusionRS was significantly related to Ki-67 index and molecular subtypes in MC patients, which is similar in IDC patients. However, RS was not able to predict DFS and OS in patients with MC.

Inflammatory breast cancer (IBC) is a fatal form of breast cancer. IBC patients present with unfavorable prognosis mainly attributable to high risk of distant metastasis. Thus, in this cohort study, we aimed to explore metastatic profiles of different molecular subtypes of IBC and elucidate the clinical and prognostic characteristics among different metastatic sites. Patients diagnosed as IBC between 2010 and 2016 were identified from the Surveillance, Epidemiology and End Results (SEER) database. Chi-square tests were performed to compare metastatic distribution among different molecular subtypes. We further used odds ratio calculation to analyze the combined metastatic patterns. Kaplan-Meier methods and multivariate Cox regression models were applied to analyze survival data among different metastatic organs. In total, we enrolled 635 IBC patients between 2010 and 2014 as the training cohort and 242 IBC patients between 2015 and 2016 as the validation cohort, All the included patients were recorded with known metastatic status, follow-up data and molecular subtype. In the present study, we elaborated the following three points: (1) Elucidating the distribution of single-organ metastases in IBC. Bone and brain were the most and least common metastatic lesions for all subtypes of IBC, separately. (2) Clarifying the combined metastatic patterns and tendency of co-metastases. Bi-organ metastasis occurred most frequently among all combined metastases. Several combinations, such as liver and bone, lung and brain, were preferential for bi-organ metastasis. (3) Analyzing prognostic values of single-organ and bi-organ metastases. All single-organ distal metastases were independent risk factors indicating an unfavorable prognosis. In conclusion, our results would provide more information for clinical decision and future studies.

Purpose: To evaluate the association of clinical early response and pathological complete remission (pCR) in breast cancer patients with different molecular subtypes. Materials and methods: Breast cancer patients who received neoadjuvant treatment (NAT) with clinical early response assessment from October 2008 to October 2018 were retrospectively analyzed. Clinical early response was defined as tumor size decreasing ≥30% evaluated by ultrasound after two cycles of NAT. Chi-square test was used to compare the pCR rates between the responder and non-responder groups with different molecular subtypes. Multivariate logistic regression was used to identify independent factors associated with the pCR. Results: A total of 328 patients were included: 100 responders and 228 non-responders. The progesterone receptor (PR) expression was an independent factor associated with clinical early response (OR=2.39, 95%CI=1.41-4.05, P=0.001). The pCR rate of breast was 50.0% for responders and 18.0% for non-responders (P

Background: Clinical-pathological factors and 21-gene recurrence score (RS) influence adjuvant chemotherapy (ACT) decision for early breast cancer patients. We investigated the decision-making of ACT in patients with discordant risk classifications of clinical-pathological factors and RS. Methods: Patients with hormonal receptor (HR)+/ human epidermal growth factor receptor 2 (HER2)-, early breast cancer, who underwent 21-gene RS testing were identified from Ruijin Hospital (RJBC) and the Surveillance, Epidemiology, and End Results (SEER) database. According to Adjuvant! Online and RS (≤25 or >25), discordant risk classifications were defined as: clinical low-risk/ RS high-risk (C-low/ RS-high) and clinical high-risk/ RS low-risk (C-high/RS-low). McNemar's test was used to assess the changes between pre- and post-RS recommendations. Breast cancer-specific survival (BCSS) was estimated using the Kaplan-Meier methods. Results: Among 727 RJBC patients, the C-low/RS-high group and the C-high/RS-low group represented 19.7% and 21.3% of the cohort. After receiving 21-gene RS results, treatment recommendations were changed for 22.1% patients with discordant risk classifications: ACT rate increased from 41.9% to 75.5% in the C-low/RS-high group and decreased from 63.9% to 60.0% in the C-high/RS-low group. Among 2958 patients from the SEER cohort, 18.4% of the C-high/RS-low group and 59.2% of the C-low/RS-high group received ACT. There was no significant difference in the estimated 3-year BCSS between ACT or not among the C-low/RS-high group (p=0.708) and the C-high/RS-low groups (p=0.391). Conclusion: For patients with discordant risk classifications, physicians were apt to adopt the 21-gene RS rather than routine clinical-pathological factors to guide ACT selection.

Purpose The purpose of this study was to investigate the changes of tumor infiltrating lymphocytes (TILs) between core needle biopsy (CNB) and surgery removed sample (SRS) in early stage breast cancer patients and to identify the correlating factors and prognostic significance of TILs changes. Materials and Methods A retrospective study was carried out on 255 patients who received CNB and underwent surgical resection for invasive breast cancer. Stromal TILs levels of CNB and SRS were evaluated respectively. Tumors with ≥50% stromal TILs were defined as lymphocyte-predominant breast cancer (LPBC). Clinicopathological variables were analyzed to determine whether there were factors associated with TILs changes. Log-rank tests and Cox proportional hazards models were used to analyze the influences of TILs and TILs changes on survival. Results SRS-TILs (median, 10.0%) were significant higher than CNB-TILs (median, 5.0%; p

The 21-gene recurrence score (RS) assay is prognostic and predictive for hormone receptor (HR)+/HER2-/node- breast cancer (BC) patients. However, its clinical value in node + patients hasn’t been elucidated. HR+/HER2-/pN1 patients operated in Comprehensive Breast Health Center, Shanghai Ruijin Hospital from January 2014 to December 2018, with available RS results were retrospectively included. Clinico-pathological characteristics were compared. Adjuvant chemotherapy recommendations pre-/post- RS assay and actual usage were analyzed. A total of 303 patients were included, with 59, 178, 66 RS P P = 0.013), and RS category (P P P = 0.003) RS were more likely to be recommended with chemotherapy. RS independently influence chemotherapy decision in postmenopausal population as well. Chemotherapy recommendation changed for 9.57% patients after RS assay. Patient adherence rate to chemotherapy recommendation was 94.72% (287/303). The 21-gene RS independently influenced chemotherapy recommendation in pN1 BC patients, which could provide additional information to guide chemotherapy decision with relatively good treatment adherence rate.

Ductal carcinoma in situ (DCIS) is widely recognized as the precursor of invasive ductal carcinoma (IDC). We aimed to analyze the clinicopathological characteristics and clinical outcomes of coexisting DCIS component in IDC and its clinical significance according to molecular subtypes. Data from 3001 patients with IDC (79.4%) and IDC/DCIS (20.6%) who underwent surgery from January 2009 to June 2016 were retrospectively assessed. The clinical outcomes of IDC with coexistent DCIS in different molecular subtypes were evaluated. IDC/DCIS patients were more likely to be younger (P

Yi-Wei Tong, Gen Wang, Jia-Yi Wu, Ou Huang, Jian-Rong He, Li Zhu, Wei-Guo Chen, Ya-Fen Li, Xiao-Song Chen, Kun-Wei ShenComprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of ChinaPurpose: HER2-positive breast cancer (BC) achieving pathological complete remission (pCR) after neoadjuvant therapy (NAT) had a superior disease outcome. Dysmetabolism and stimulation of insulin-like growth factor 1 (IGF-1)-axis would increase BC risk, but we are lacking data for their association with pCR in HER2-positive+ BC. We aim to evaluate the pCR predictive value of above factors in HER2-positive BC patients receiving NAT.Patients and methods: HER2-positive BC patients receiving NAT ± trastuzumab were retrospectively included between January 2013 and December 2016. Data were compared between baseline at biopsy and surgery. Median value of IGF-1 expression was used as cutoff value to classify patients into low or high group. pCR was defined as no residual invasive carcinoma in breast and axilla.Results: Overall, 101 patients were included. Metabolic syndrome was diagnosed in 29 (28.71%) with an average of 1.71±1.51 metabolic disorders at baseline, significantly increased after NAT (2.12±1.54, P

Background: Immune responses play an important role in the development of breast cancer. Trastuzumab can activate antibody-dependent cellular cytotoxicity (ADCC) in human epidermal growth factor receptor-2 (HER-2)-positive breast cancer. Many studies have demonstrated that inflammatory markers, such as the neutrophil-to-lymphocyte ratio (NLR) and absolute lymphocyte count (ALC), are associated with prognosis in breast cancer. The aim of this study was to explore whether preoperative NLR, ALC or the absolute neutrophil count (ANC) is associated with prognosis in HER-2-positive breast cancer patients who received adjuvant trastuzumab. Patients and methods: Three hundred sixty-seven female patients with HER-2-positive invasive breast cancer who were treated with one-year adjuvant trastuzumab were analysed in this retrospective study. Preoperative haematological parameters, clinicopathological data and survival data were obtained. The cut-off points for ALC, ANC and NLR were based on the median values. Disease-free survival (DFS) and Overall survival (OS) were analysed by the Kaplan-Meier method. Multivariable Cox regression was used to determine the independent prognostic significance of ALC, ANC and NLR. Results: Survival analysis revealed that the 3-year DFS in patients with high ALC was 89.0%, which was significantly worse than 95.0% in patients with low ALC (p=0.014). Kaplan-Meier analysis also showed that patients with low NLR had a poorer 3-year DFS than patients with high NLR (89.7% vs 94.0%, respectively; p=0.047). Multivariate analysis showed that ALC was an independent prognostic factor for DFS (HR=2.723; 95% CI=1.211-6.122; p=0.015). Neither ANC, ALC nor NLR could predict OS independently. Conclusion: In HER-2-positive breast cancer patients who were treated with adjuvant trastuzumab, a high ALC is significantly associated with a poor DFS.

Background Breast cancer patients with suspicious axillary lymph node (ALN) at ultrasound and positive fine-needle aspiration (FNA) results were required to receive ALN dissection (ALND), which was not certain in the post-ACOSOG Z0011 era. We aim to evaluate the ALN metastasis burden in these patients, thus to illustrate whether they can follow the ACOSOG Z0011 trial procedure. Methods Clinically, T1–2 N0 breast cancer patients with positive preoperative ALN biopsy (FNA group) or 1–2 positive sentinel nodes (SLNB group) were retrospectively analyzed. ALN metastasis burden was compared between the two groups, which were further analyzed in certain subtypes. An association between clinicopathological factors and ≥ 3 ALN metastasis was also analyzed. Results A total of 388 patients were included: 202 in the FNA group and 186 in the SLNB group. The FNA group had a significantly higher number of positive ALN (5.18 vs. 1.77, P

Purpose To evaluate the predictive and prognostic value of tumor‐infiltrating lymphocytes (TILs) before and after neoadjuvant chemotherapy (NAC) in patients with breast cancer. Patients and methods Consecutive breast cancer patients treated with NAC between August 2008 and November 2019 were retrospectively analyzed. TIL levels were evaluated of invasive tumor samples, and high expression was defined as TILs >10%. Total pathological complete response (pCR) was defined as no invasive tumor in the breast or lymph nodes. Univariate and multivariate analyses were used to assess factors associated with pCR rate, disease‐free survival (DFS), and overall survival. Results A total of 461 patients were included. The mean pre‐NAC TIL level was higher among patients with pCR than among patients without pCR (24.28% ± 2.34% vs. 11.34% ± 0.60%, respectively, p

BackgroundBiomarker discrepancy between primary and recurrent/metastatic breast cancer is well known, however its impact on prognosis and treatment after relapse is still unclear. Current study aims to evaluate biomarkers discrepancy between primary and recurrent/metastatic lesions as well as to investigate its association with following treatment pattern and disease outcome.Patients and methodsWe retrospectively included consecutive breast cancer patients undergoing surgery in our center from Jan. 2009 to Dec. 2016 and reported disease recurrence. Patients with re-biopsy and paired biomarkers statuses on primary and recurrent/metastatic lesions were further analyzed. Kappa test was used to analyze the concordance rate of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) status. Post-recurrence survival (PRS) was compared between subgroups by Kaplan-Meier curve. Cox regression model was applied to identify impact factors for PRS.ResultsA total of 156 patients were finally included, of whom 70 and 86 had loco-regional and distant recurrence, respectively. Concordance rates of ER, PR and HER2 were 83.3%, 66.7%, and 97.1%, respectively, which was similarly distributed among different recurrent sites (all P > 0.05). Primary ER-positivity (vs ER-negativity, P = 0.014) and loco-regional recurrence (vs distant metastasis, P = 0.001) were independently associated with superior PRS, while patients with visceral metastasis (P < 0.001) had the worst disease outcome. Hormone receptor/HER2 status discrepancy was observed in 28 patients. Fifteen of them changed systemic treatment based on biomarker statuses of recurrent lesion, however, their PRS was not improved compared to those 13 patients who continued the same treatment according to primary biomarkers statuses (P = 0.298).ConclusionBiomarker discrepancy was observed between primary and recurrent/metastatic breast cancer lesions and had certain influence on treatment strategies after relapse. However, its impact on disease outcome wasn’t established in the current study, which deserves further evaluation.

BackgroundThe 21-gene recurrence score (RS) can predict chemotherapy benefit in estrogen receptor-positive, human epidermal growth factor receptor-2-negative (ER+/HER2-) early breast cancer patients. Age would influence the interaction between RS and chemotherapy effect. The current study aimed to determine RS thresholds which were predictive of chemotherapy benefit in young and old women, respectively.MethodsPatients diagnosed with pN0–1, ER+/HER2- breast cancer between 2009 and 2016 were retrospectively reviewed. Propensity score matching was performed according to chemotherapy usage. After stratifying patients with different cutoffs of age, the RS threshold indicating chemotherapy benefit in each age strata were determined by cox proportional hazard models.ResultsA total of 1227 patients were included. The median age was 58 years and the median RS was 24. After matching, the RS thresholds suggesting chemotherapy benefit varied with age. For patients ≤55 years, chemotherapy benefit was observed in those having RS > 25 (P = 0.03), with 4-year invasive disease-free survival (IDFS) of 97.0 and 89.3% in patients receiving chemotherapy or not. While patients derived no benefit from chemotherapy if they had RS ≤25 (P = 0.66, 4-year IDFS: 95.3% vs. 94.6%). For patients > 55 years, adjuvant chemotherapy was associated with better prognosis in those with RS > 36 (P = 0.014, 4-year IDFS: 94.7% vs. 76.2%), but not in those having RS ≤36 (P = 0.13, 4-year IDFS: 92.3% vs. 95.8%).ConclusionsOld patients need higher RS thresholds to demonstrate the chemotherapy benefit. Further efforts are warranted to investigate the association between age and predictive RS thresholds.

Purpose To evaluate the rates of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 heterogeneity in multifocal or multicentric breast cancer (MMBC) and its association with treatment pattern and disease outcomes. Methods MMBC patients with ER, PR, HER2, and Ki67 results for each tumor focus were retrospectively analyzed and categorized into the Homo group and the Hetero group. Chi-square test were performed to compare the treatment options between the groups. Disease-free survival (DFS) and overall survival (OS) rates were estimated from Kaplan-Meier curves and compared between two groups. Results A total of 330 patients were included and 53 (16.1%) were classified into the Hetero group. Adjuvant endocrine therapy was more frequently assigned for patients in the Hetero group than in the Homo group (84.9% vs. 71.7%, P = 0.046). There was no difference in terms of adjuvant anti-HER2 therapy (28.3% vs. 19.6%, P = 0.196) and chemotherapy (69.9% vs. 69.8%, P = 0.987) usage between two groups. At a median follow-up of 36 months, DFS rates were 81.2% for the Hetero group and 96.5% for the Homo group (HR = 2.81, 95% CI: 1.00-7.88, P = 0.041). The estimated 3-year OS rates for the groups were 95.8% and 99.5%, respectively (HR = 4.31, 95% CI: 0.83–22.46, P = 0.059). Conclusion Heterogeneity of ER, PR, HER2, or Ki67 was present in 16.1% patients with MMBC. Biomarkers heterogeneity influenced adjuvant endocrine therapy usage and was associated with worse disease outcomes, indicating further clinical evaluation.

Interface stress revealed by sum frequency generation spectroscopy is the origin of instability in organic optoelectronic devices., Interface stresses are pervasive and critical in conventional optoelectronic devices and generally lead to many failures and reliability problems. However, detection of the interface stress embedded in organic optoelectronic devices is a long-standing problem, which causes the unknown relationship between interface stress and organic device stability (one key and unsettled issue for practical applications). In this study, a kind of previously unknown molecular conformation–induced stress is revealed at the organic embedded interface through sum frequency generation (SFG) spectroscopy technique. This stress can be greater than 10 kcal/mol per nm2 and is sufficient to induce molecular disorder in the organic semiconductor layer (with energy below 8 kcal/mol per nm2), finally causing instability of the organic transistor. This study not only reveals interface stress in organic devices but also correlates instability of organic devices with the interface stress for the first time, offering an effective solution for improving device stability.

Due to the high absorption rate of traditional autologous fat grafting, cell-assisted lipotransfer (CAL) and platelet-rich plasma (PRP)-assisted lipotransfer were developed. The purpose of this article was to evaluate the efficacy and safety of CAL and PRP in promoting the survival of autologous fat grafting through systematic review and meta-analysis. We searched Pubmed, Cochrane Library, Web of Science, and EMBASE for clinical studies on CAL and PRP-assisted lipotransfer published from January 2010 to January 2020. Then a meta-analysis was performed to assess the efficacy of CAL and PRP-assisted lipotransfer through data analysis of fat survival rate. We also assessed the incidence of complications and multiple operations to analyze their safety. A total of 36 studies (1697 patients) were included in this review. Regardless of the recipient area, CAL and PRP-assisted lipotransfer significantly improved the fat survival rate (CAL vs non-CAL: 71% vs 48%, P < 0.0001; PRP vs non-PRP: 70% vs 40%, P < 0.0001; CAL vs PRP: 71% vs 70%, P = 0.7175). However, in large-volume fat grafting, such as breast reconstruction, both increased the incidence of complications and did not decrease the frequency of multiple operations after lipotransfer. Further prospective studies are needed to evaluate the clinical benefits of CAL and PRP-assisted lipotransfer.

Metabolic syndrome is a type of multifactorial metabolic disease with the presence of at least three factors: obesity, diabetes mellitus, low high-density lipoprotein, hypertriglyceridemia, and hypertension. Recent studies have shown that metabolic syndrome and its related components exert a significant impact on the initiation, progression, treatment response, and prognosis of breast cancer. Metabolic abnormalities not only increase the disease risk and aggravate tumor progression but also lead to unfavorable treatment responses and more treatment side effects. Moreover, biochemical reactions caused by the imbalance of these metabolic components affect both the host general state and organ-specific tumor microenvironment, resulting in increased rates of recurrence and mortality. Therefore, this review discusses the recent advances in the association of metabolic syndrome and breast cancer, providing potential novel therapeutic targets and intervention strategies to improve breast cancer outcome.