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BACKGROUND: Triple negative breast cancer (TNBC), accounting for 15% of all breast cancer cases, was usually considered as the most aggressive subtype. The present study evaluated the prognosis of T1a TNBC and the impact of tumor size on T1 TNBC survival in large-scale population. METHODS: This retrospective study enrolled T1a/T1b/T1c TNBC and HER2(+)/hormone receptor (HoR)(−) patients diagnosed between 2010 to 2012 from the Surveillance, Epidemiology, and End Results database. The following information was extracted for further analyses: demographic variables including age at diagnosis, race, marital status, laterality, histological grade, T/N stage, American Joint Committee on Cancer (AJCC) stage, radiation therapy, survival and cause of death. Kaplan-Meier method and Cox regression were engaged for breast cancer specific survival (BCSS) and overall survival (OS) analyses. RESULTS: In all, the present study enrolled 6,953 TNBC and 2,648 HER2(+)/HoR(−) patients. T1a TNBC which generally omitted adjuvant chemotherapy had worse prognosis than T1a HER2(+)/HoR(−) [BCSS: hazard ratio (HR) 3.23, 95% confidence interval (CI): 1.05–9.09, P=0.03; OS: HR 2.63, 95% CI: 1.25–5.56, P=0.01] and T1b HER2(+)/HoR(−) (BCSS: HR 5.26, 95% CI: 1.61–16.7, P=0.006; OS: HR 3.03, 95% CI: 1.27–7.14, P=0.013) tumors which both were recommended by the National Comprehensive Cancer Network (NCCN) guideline to have chemotherapy. T1a TNBC also showed a trend with poorer prognosis than T1b TNBC, but did not reach statistical significance. CONCLUSIONS: T1a TNBC had the worst prognosis among all small tumors (

Ovarian serous carcinoma (OSC), as a common malignant tumor, poses a serious threat to women's health in that epithelial-mesenchymal transformation (EMT)-related modulation becomes heavily implicated in the invasion and progression of OSC. In this study, two core genes (BUB1B and NDC80) among the 16 hub genes have been identified to be involved in the molecular regulation of EMT and associated with the poor early survival of OSC at stages I+II. Through the Gene Regulatory Networks (GRN) analysis of 15 EMT regulators and core genes, it was revealed that TFAP2A and hsa-miR-655 could elaborately modulate EMT development of OSC. Next genetic variation analysis indicated that EMT regulator ELF3 would also serve as a crucial part in the occurrence and progression of OSC. Eventually, survival investigation suggested that TFAP2A, ELF3 and hsa-miR-655 were significantly associated with the overall survival of progressive OSC patients. Thus, combined with diversified bioinformatic analyses, BUB1B, NDC80, TFAP2A, ELF3 and hsa-miR-655 may act as the key biomarkers for early clinical diagnosis and prognosis evaluation of OSC patients as well as potential therapeutic target-points.

Lymph node metastasis (LNM) is a critical cause for disease progression and treatment failure in cervical cancer. However, the mechanism underlying cervical cancer LNM remains unclear. In this study, HN1 was found to be dramatically upregulated in cervical cancer and patients with higher HN1 expression are more likely to exhibit a higher rate of LNM and lower survival rate. Univariate and multivariate Cox-regression analyses showed that HN1 is an independent prognostic factor in cervical cancer. Meanwhile, HN1 promotes lymphangiogenesis of cervical cancer in vitro. The in vivo experiment also indicates that HN1 enhances LNM in cervical cancer. Furthermore, we also found that HN1 activated the NF-κB signaling pathway to enhance the expression of downstream genes. Taken together, our study suggests that HN1 plays a crucial role in promoting LNM and acts as a prognostic biomarker in cervical cancer.

Background The 21‐gene recurrence score (RS) assay has been recommended by major guidelines for treatment decision in hormone receptor (HR)‐positive early breast cancer (EBC). However, the genomic assay is not accessible and affordable worldwide. Alternatively, an increasing number of studies have shown that traditional immunohistochemistry (IHC) can partially or even completely replace the role of the 21‐gene genomic assay. Here, we developed and validated a predictive model (IHC3 model) combining the Ki‐67 index, progesterone receptor (PR) expression, histologic grade, and tumor size to predict the recurrence risk of HR‐positive EBC. Methods The data from 389 patients (development set) with HR‐positive, human epidermal growth factor receptor 2‐negative, lymph node non‐metastasized invasive breast cancer were used to construct the IHC3 model based on the Surexam® 21‐gene RS and the TAILORx clinical trial criteria. An additional 146 patients with the same characteristics constituted the validation set. The predictive accuracy of the IHC3 model was compared with that of Orucevic et al.’s nomogram. Invasive disease‐free survival (IDFS) was analyzed in the IHC3 predictive low‐recurrence risk (pLR) group and the predictive high‐recurrence risk (pHR) group. The Pearson chi‐square test, Fisher exact test, and log‐rank test were used for analysis. Results The pLR and pHR group could be easily stratified using the decision tree model without network dependence. The accuracies of the IHC3 model were 86.1% in the development set and 87.7% in the validation set. The predictive accuracy of the IHC3 model and Orucevic et al.’s nomogram for the whole cohort was 86.5% and 86.9%, respectively. After a 52‐month of median follow‐up, a significant difference was found in IDFS between of the IHC3 pLR and the pHR groups (P = 0.001) but not in the IDFS between the low‐ and high‐recurrence risk groups according to the Surexam® 21‐gene RS and the TAILORx clinical trial criteria (P = 0.556) or 21‐gene binary RS group (P = 0.511). Conclusions The proposed IHC3 model could reliably predict low and high recurrence risks in most HR‐positive EBC patients. This easy‐to‐use predictive model may be a reliable replacement for the 21‐gene genomic assay in patients with EBC who have no access to or cannot afford the 21‐gene genomic assay.

Objectives: Anlotinib is a novel multi-target tyrosine kinase inhibitor for tumor angiogenesis and proliferative signaling. A previous retrospective study achieved the overall response rate (ORR) of 14.3% and the disease control rate (DCR) of 85.7% in platinum-resistant ovarian cancer (PROC) patients (pts) treated with anlotinib monotherapy, and the ORR of 33.3% and the DCR of 100% with anlotinib plus chemotherapy. The current prospective clinical trial (ChiCTR1800018192) aimed to further assess the efficacy and safety of anlotinib combined with pemetrexed and continued as maintenance therapy for PROC. Methods: Pts who had received at least two different chemotherapy regimens (including the first line platinum-based regimen), with histologically proven recurrent platinum-refractory or platinum-resistant epithelial ovarian cancer (including fallopian tube carcinoma and primary peritoneal carcinoma), ECOG 0-2, were considered eligible for enrollment to receive six 21-days cycles of anlotinib (12 mg QD from day 1 to 14) orally plus pemetrexed intravenously (0.5 g/m2 on day 1). Anlotinib monotherapy was subsequently performed up to 1 year in patients without disease progression or intolerable toxicity. The primary endpoint was ORR, and the secondary endpoints included DCR, progression-free survival (PFS) and safety. Results: As of October 2020, 22 pts were enrolled. The median prior lines of chemotherapy was 4 (range, 2-10) and 55% of pts had ever received antiangiogenic therapy. A total of 17 pts had the confirmed best overall response assessments which inferred the ORR of 41.2% (PR in 7 pts; 95% CI, 18.4-67.1) and the DCR of 100% (PR in 7 pts and SD in 10 pts; 95% CI, 80.5-100). The median PFS was 9.3 months (95% CI, 6.0-12.6). Any grades of adverse events (AEs) were observed in 91% (20/22) of pts, containing frequent hand-foot syndrome (36%), hypertension (32%), allergic eruption (27%), fatigue (23%) and oral ulcer (14%). High grade AEs occurred in 3 pts, including 1 with grade III proteinuria, 1 with grade III ascites increase, and 1 with grade IV hemoglobin reduction. Conclusions: The treatment of anlotinib plus pemetrexed showed encouraging efficacy and satisfactory safety for platinum-resistant and -refractory, recurrent ovarian cancer pts who were previously treated with chemotherapy.

Cancer-initiating/sustaining stem cell subsets (CSCs) have the potential to regenerate cancer cell populations and are resistant to routine therapeutic strategies, thus attracting much attention in anticancer research. In this study, an innovative framework of endogenous microenvironment-renewal for addressing such a dilemma has been just developed. CSCs in three-dimensional multipotent spheroid-engineered biologics were prepared with 150 Gy radiation and inoculated into 15-mo-old BALB/c and C57BL/6 mice bearing diverse advanced tumors covering Mammary 4T1, liver Hepa, lung LL/2, and colon C26 tumors and distant metastases. Subsequently, the systematic microenvironment of tumor-bearing hosts was rapidly remodeled to resettle thymic cortex and medulla rudiment as an endogenous foxn1-thymosin reprogramming TCR-repertoire for resetting MHC-unrestricted multifunction renewal. Postrenewal Vγ4γδT-subsets would bind and lead migrating CSCs into apoptosis. Moreover, TCR repertoire multifunction renewal could reverse tumor metastases from tumoricidal resistance into eventual regression as a blockade of cancer-sustaining Bmi-1/Nanog-Oct4-Sox2 renewal loop with sequent multivalent depletion of both migrating/in situ CSCs and non–stem terminal cancer cell subsets. This study represents a promising start to set up a generalizable strategy of three-dimensional biologics evoking an endogenous integral microenvironment into pluripotent renewal versus advanced cancer.

Background: This study aimed to describe the clinical characteristics of periductal mastitis (PDM), propose the practical clinical classification system and evaluate the results of different surgical treatments in different type of PDM patients. Methods: A retrospective study was carried out at department of breast surgery, Peking Union Medical College Hospital, Beijing, China. A total of 152 patients with the diagnosis of PDM were reviewed from March 2012 to December 2016. All of the patients underwent surgery. Data were collected regarding clinical manifestation, treatment, and outcomes. Results: The median age was 36 years. A subareolar breast mass was the most frequent symptom. The most common clinical manifestations were mass (98.0%), rubefaction (41.1%), nipple retraction (36.8%), abscess (36.8%), skin ulceration (25.7%), and mammary duct fistula (19.1%). Fourteen (9.2%) patients were recurrent PDM at first hospitalization. Eight (5.3%) patients had prolactinoma. Five (3.3%) patients were taking antipsychotic medications. Only four (2.6%) patients were smokers. Eight patients were highly suspected to be breast cancer before surgery. A four-type classification system was first proposed according to clinical manifestations. The different surgeries in each category were evaluated. After 3 years median follow-up, 11 (7.2%) patients got recurrence including two initial recurrent PDM. Conclusions: Periductal mastitis is a distinct benign breast condition of unknown etiology. Mass, abscess and fistula are most common manifestations of the disease. Wide surgical excision, fistulectomy and extended excision with transfer of a random breast dermo-glandular flap (BDGF) are effective surgical modalities for different type of PDM.

Background: Apocrine carcinoma was a rare subtype of breast cancer. Due to its rarity and lack of standardized diagnostic criteria, there was no consensus on its biological behaviors. The present study retrospectively analyzed the Surveillance, Epidemiology, and End Results (SEER) database to clarify the impact of apocrine feature on breast cancer prognosis. Materials and Methods: Patient data for invasive apocrine (aBC), mucinous (mBC) or ductal (IDC) breast cancer between 2010 and 2012 were obtained from SEER program. Kaplan-Meier method and Cox proportion hazard regression were adopted for breast cancer-specific survival (BCSS) and overall survival (OS) analyses. Results: There were totally 306 aBC, 2733 mBC and 120127 IDC enrolled. Compared with IDC, aBC tended to occur in elderly patients with higher histological grade, more triple-negative breast cancer (TNBC) and less radiation therapy. Except univariate analysis revealed aBC had shortened BCSS than mBC (HR 5.020, p< 0.001), neither mBC nor IDC revealed BCSS or OS advantage over aBC. As for TNBC, aBC was associated with prolonged BCSS (univariate: HR 0.329, p = 0.020; multivariate: HR 0.183, p = 0.017) and OS (univariate: HR 0.445, p = 0.028; multivariate: HR 0.338, p = 0.016) over IDC. This finding was consistent with the results for hormone receptor negative breast cancers. Conclusion: aBC had the trend with worse BCSS than mBC and comparable prognosis as IDC. Morphological apocrine features indicated favorable prognosis for TNBC and hormone receptor negative subtype. Future studies were warranted to further evaluate the prognostic value of different histological types. Table 1. Clinicopathological characteristics of patients with aBC and IDCCharacteristicsaBC (N=306)IDC (N=120127)p value cMedian Follow-up (months)(IQR)22.0 (10.0-35.8)21.0 (10.0-33.0)Age (Mean ± SD)60.7 ± 11.357.8 ± 11.8< 0.001RaceWhite225 (73.8%)93483 (78.3%)0.108Black39 (12.8%)13690 (11.5%)Others a41(13.4%)12145 (10.2%)Marital StatusMarried166 (57.2%)70109 (61.4%)0.164Not Married b124 (42.8%)44086 (38.6%)LateralityLeft136 (44.4%)60705 (50.5%)0.038Right170 (55.6%)59410 (49.5%)GradeI19 (6.4%)24345 (20.8%)< 0.001II159 (53.9%)48323 (41.3%)III / IV117 (39.7%)44294 (37.9%)AJCC StageI154 (50.3%)64223 (53.5%)0.334II109 (35.6%)41978 (34.9%)III43 (14.1%)13926 (11.6%)T StageT1187 (61.1%)75070 (62.5%)0.358T289 (29.1%)36385 (30.3%)T319 (6.2%)5755 (4.8%)T411 (3.6%)2917 (2.4%)N StageN0202 (66.0%)81605 (68.0%)0.589N173 (23.9%)28830 (24.0%)N220 (6.5%)6413 (5.3%)N311 (3.6%)3228 (2.7%)Molecular SubtypeHER2-/ER+62 (20.3%)83840 (69.8%)0.001HER2+/ER+27 (8.8%)14194 (11.8%)HER2+/ER-54 (17.6%)6331 (5.3%)Triple Negative163 (53.3%)15762 (13.1%)SurgeryBCS156 (53.1%)67965 (58.5%)0.067Mastectomy138 (46.9%)48214 (41.5%)RadiationYes139 (48.4%)64981 (56.4%)0.008No148 (51.6%)50270 (43.6%) Table 2. Clinicopathological characteristics of patients with aBC and mBCCharacteristicsaBC (N=306)mBC (N=2733)p value cMedian Follow-up (months)(IQR)22.0 (10.0-35.8)21.0 (9.0-34.0)Age (Mean ± SD)60.7 ± 11.362.5 ± 12.30.018RaceWhite225 (73.8%)2050 (75.5%)0.709Black39 (12.8%)342 (12.6%)Others a41(13.4%)322 (11.9%)Marital StatusMarried166 (57.2%)1454 (56.1%)0.756Not Married b124 (42.8%)1138 (43.9%)LateralityLeft136 (44.4%)1397 (51.1%)0.031Right170 (55.6%)1335 (48.9%)GradeI19 (6.4%)1538 (60.7%)< 0.001II159 (53.9%)887 (35.0%)III / IV117 (39.7%)110 (4.3%)AJCC StageI154 (50.3%)1773 (64.9%)< 0.001II109 (35.6%)851 (31.1%)III43 (14.1%)109 (4.0%)T StageT1187 (61.1%)1825 (66.8%)0.002T289 (29.1%)741 (27.1%)T319 (6.2%)136 (5.0%)T411 (3.6%)31 (1.1%)N StageN0202 (66.0%)2465 (90.2%)< 0.001N173 (23.9%)221 (8.1%)N220 (6.5%)33 (1.2%)N311 (3.6%)14 (0.5%)Molecular SubtypeHER2-/ER+62 (20.3%)2544 (93.1%)< 0.001HER2+/ER+27 (8.8%)22 (0.8%)HER2+/ER-54 (17.6%)151 (5.5%)Triple Negative163 (53.3%)16 (0.6%)SurgeryBCS156 (53.1%)1769 (66.3%)< 0.001Mastectomy138 (46.9%)898 (33.7%)RadiationYes139 (48.4%)1473 (55.1%)0.037No148 (51.6%)1201 (44.9%) Table 3. Comparison of BCSS and OS between aBC and IDC by multivariate Cox proportional hazard model according to different molecular subtypesUnivariateMultivariateHazard ratio (95% CI)ap valuebHazard ratio (95% CI)ap valuebAll BCSS1.224 (0.611 - 2.450)0.5680.726 (0.180 - 2.933)0.652OS1.100 (0.624 - 1.939)0.7420.394 (0.098 - 1.585)0.190ER+BCSS2.773 (0.893 - 8.609)0.0661.764 (0.440 - 7.092)0.423OS1.358 (0.438 - 4.214)0.5951.012 (0.253 - 4.049)0.987ER-BCSS0.378 (0.157 - 0.910)0.0240.241 (0.077 - 0.751)0.014OS0.517 (0.268 - 0.995)0.0440.409 (0.194 - 0.864)0.019ER+/HER2-BCSS3.961 (1.275 - 12.30)0.0102.370 (0.590 - 9.524)0.224OS1.912 (0.616 - 5.932)0.2541.370 (0.342 - 5.495)0.656ER+/HER2+ cBCSSNANANANAOSNANANANAER-/HER2+BCSS0.601 (0.084 - 4.287)0.6080.840 (0.117 - 6.061)0.862OS0.854 (0.213 - 3.431)0.8241.120 (0.277 - 4.525)0.874TNBCBCSS0.329 (0.123 - 0.880)0.0200.183 (0.046 - 0.736)0.017OS0.445 (0.212 - 0.935)0.0280.338 (0.140 - 0.816)0.016 Table 4. Comparison of BCSS and OS between aBC and mBC by multivariate Cox proportional hazard model according to different molecular subtypesUnivariateMultivariateHazard ratio (95% CI)ap valuebHazard ratio (95% CI)ap valuebAll BCSS5.020 (2.106 - 11.97) Citation Format: Changjun Wang, Yu Song, Hanjiang Zhu, Yidong Zhou, Feng Mao, Yan Lin, Yanna Zhang, Xiaohui Zhang, Songjie Shen, Ying Zhong, Xin Huang, Qiang Sun. Morphological apocrine and mucinous features of breast carcinoma: Does histology matter for survival? [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-06-31.

So far, thymus involution in adults is believed to be irreversible, and endogenous innovation for thymus‐related immunodeficiency remains to be an intractable puzzle. With the expectation of addressing this dilemma, human ovarian surface epithelium (OSE) has been reengineered as epithelial‐mesenchymal transition (EMT)‐tridimensional‐spheroid biologics (ETSB) using a dynamic EMT‐3D‐floating system along with 160 Gy X‐ray‐amelioration, which inoculates subcutaneously into aging rhesus and athymic Balb/cnu/nu mice. Herein, it is bioinformatically validated that ETSB can reset Clock/Arntl‐Per3/Tim molecule rhythm dynamics to re‐prime thymus residual (parathyroid or fatty‐like invalid vesicles yet no thymic architecture) to evolutionary transcription with overall cortex‐medulla endogenized by TECs undergoing MET/EMT reversion. Rhythm dynamics immediately resettles the bHLH‐LTβR‐NFκB‐RelA/B loop as a cascade to provoke the core immune microenvironment for multifunctional innovation of dynamic TCR orchestration, with harmonious naïve T‐subsets and TRECs renewals (P < 0.005). Subsequently, peripheral biological burden and tumor metastasis dynamics are addressed by innovative TCR‐defense/attack dynamics quickly (P < 0.005 vs Control), yet without autoimmune indication to hosts. Moreover, a functional blockade of core‐rhythm dynamics deeply impedes the endogenous innovation of invalid thymus residual. Thus this study may help pioneer a prospective strategy to innovate panoramic central‐peripheral immune microenvironments and defense dynamics for immune‐deficient/aging victims., Epithelial‐mesenchymal transition (EMT)‐tridimensional‐spheroid biologics (ETSB) could reset Clock/Arntl‐Per3/Tim molecule rhythm dynamics to reprime thymus residual (parathyroid or fatty‐like invalid vesicles yet no thymic architecture) to evolutionary transcription with overall cortex‐medulla endogenized by thymic epithelial cells (TECs) undergoing MET/EMT reversion. Rhythm dynamics immediately resettles bHLH‐LTβR‐NFκB‐RelA/B loop as cascade to provoke core immune microenvironment for multifunctional innovation of dynamic TCR orchestration, with harmonious naïve T‐subsets and T cell receptor excision circles (TRECs) renewals.

We aimed to determine whether the detection-to-treatment interval of non-symptomatic breast cancer is associated with factors that can predict survival outcomes. A retrospective review of the Breast Surgery Department Database at Peking Union Medical College Hospital (PUMCH) was performed, and a total of 1084 non-symptomatic invasive breast cancer patients were included. The findings revealed that detection-to-treatment interval was significantly longer for women who were older (p = 0.001), lived in rural areas (p = 0.024), had lower education (p = 0.024), and had detection in other institutions (p = 0.006). Other sociodemographic and clinicopathological characteristics were not associated to longer interval. A median follow-up of 35 months (range: 6–60 months) was carried out and a long delay at more than 90 days did not significantly decrease the DFS (univariate, P = 0.232; multivariate, P = 0.088). For triple negative breast cancer, there was a worse DFS if the interval was longer than 90 days both in multivariate analysis (hazard ratio [HR] = 3.40; 95% CI, 1.12–10.35; P = 0.031) and univariate analysis (HR = 2.86; 95% CI, 1.03–7.91; P = 0.042). Further studies on care before initial treatment of non-symptomatic breast cancers are warranted.

The primary challenge facing treatment of epithelial ovarian cancer (EOC) is the high frequency of chemoresistance, which severely impairs the quality of life and survival of patients with EOC. Our study aims to investigate the mechanisms by which upregulation of NR2F6 induces chemoresistance in EOC. The biological roles of NR2F6 in EOC chemoresistance were explored in vitro by Sphere, MTT and AnnexinV/PI assay, and in vivo using an ovarian cancer orthotopic transplantation model. Bioinformatics analysis, luciferase assay, CHIP and IP assays were performed to identify the mechanisms by which NR2F6 promotes chemoresistance in EOC. The expression of NR2F6 was significantly upregulated in chemoresistant EOC tissue, and NR2F6 expression was correlated with poorer overall survival. Moreover, overexpression of NR2F6 promotes the EOC cancer stem cell phenotype; conversely, knockdown of NR2F6 represses the EOC cancer stem cell phenotype and sensitizes EOC to cisplatin in vitro and in vivo. Our results further demonstrate that NR2F6 sustains activated Notch3 signaling, resulting in chemoresistance in EOC cells. Notably, NR2F6 acts as an informative biomarker to identify the population of EOC patients who are likely to experience a favorable objective response to gamma‐secretase inhibitors (GSI), which inhibit Notch signaling. Therefore, concurrent inhibition of NR2F6 and treatment with GSI and cisplatin‐based chemotherapy may be a novel therapeutic approach for NR2F6‐overexpressing EOC. In summary, we have, for the first time, identified an important role for NR2F6 in EOC cisplatin resistance. Our study suggests that GSI may serve as a potential targeted treatment for patients with NR2F6‐overexpressing EOC., What's new? Chemoresistance is a major challenge in women afflicted with epithelial ovarian cancer (EOC), but molecular mechanisms of EOC chemoresistance remain unclear. Here the authors connect nuclear receptor subfamily 2 group F member 6 (NR2F6) with this process. They find NR2F6 upregulated in tissues from chemoresistant EOC patients. High NR2F6 expression promoted a cancer stem cell phenotype and suppressed cisplatin‐induced apoptosis by transcriptionally upregulating Notch3 signaling, thereby promoting EOC chemoresistance.

Background The primary obstacle to treat cervical cancer is its high prevalence of metastasis, which severely affects patients’ quality of life and survival time. Nucleolar and spindle associated protein 1 (NUSAP1) has been implicated in the development, progression, and metastasis in several types of cancer. However, its oncogenic role in cervical cancer remains unclear. Methods Western blot assay and immunohistochemistry were used to determine the expression of NUSAP1 in 21 clinical fresh Cervical cancer tissues and 233 clinicopathologically characterized cervical cancer specimens. The biological roles of NUSAP1 in the metastasis of cervical cancer were investigated both in vitro by EMT, Side population analysis and Transwell assays and so on, and in vivo using a mouse 4w model of hematogenous metastasis and lymph node metastasis. Bioinformatics analysis, luciferase reporter analysis, immunoprecipitation and immunoblotting of nuclear and cytoplasmic cellular fractions were applied to discern and examine the relationshipbetween NUSAP1 and its potential targets. Results The results demonstrated that NUSAP1 was upregulated in cervical cancer cells and tissues, correlated positively with metastasis and poor clinical outcome of patients. High expression of NUSAP1 promoted metastasis by enhancing cancer stem cell (CSC) traits and epithelial-mesenchyme transition (EMT) progression, while silencing of NUSAP1 reduced CSC traits and EMT progression. Mechanistically, upregulation of NUSAP1 induced SUMOylation of TCF4 via interacting with SUMO E3 ligase Ran-binding protein 2 (RanBP2) and hyperactivated Wnt/β-catenin signaling in cervical cancer cells. Additionally, NUSAP1-induced cervical cancer cells metastasis and the cancer stem cell phenotype were abrogated with the Wnt/β-catenin signaling inhibitor XAV-939 treatment. Importantly, co-therapy of conventional treatment and XAV-939 will provide a novel and effective treatment for NUSAP1-ovexpressed cervical cancer patients. Conclusions Our results demonstrate thatNUSAP1 upregulation contributes to metastasis of cervical cancer by promoting CSC properties and EMT via Wnt/β-catenin signaling and XAV-939 might serve as a potential tailored therapeutic option for patients with NUSAP1-ovexpressed cervical cancer. Electronic supplementary material The online version of this article (10.1186/s13046-019-1037-y) contains supplementary material, which is available to authorized users.

5533 Background: Non-platinum chemotherapy is widely used in platinum-resistant recurrent ovarian cancer treatment but with limited efficacy. Combing chemotherapy with angiogenic inhibitors is a new therapeutic choice. Anlotinib is a novel tyrosine kinase inhibitor targeting multiple receptors involved in tumor proliferation, vasculature, and tumor microenvironment. The study aimed to further assess the efficacy and safety of anlotinib combined with pemetrexed in platinum-resistant ovarian cancer. Methods: Patients who had received at least two different chemotherapy regimens (including the first line platinum-based regimen), with histologically proven recurrent platinum-resistant or platinum-refractory epithelial ovarian cancer (including salpingocarcinoma and peritoneal carcinoma), ECOG 0-2, were considered eligible for enrollment to receive six 21-days cycles of anlotinib (12 mg QD from day 1 to 14; 21 days per cycle) orally plus pemetrexed intravenously (0.5 g/m2 on day 1; 21 days per cycle). Subsequent maintenance treatment was anlotinib monotherapy (12 mg QD from day 1 to 14; 21 days per cycle) till disease progression or intolerant toxicity. The primary endpoint was objective response rate (ORR), and the secondary endpoints included disease control rate (DCR), progression-free survival (PFS) and safety. Results: As of Jan 2021, 27 patients were enrolled. The median number of chemotherapy was 4 (range, 2-10) and 51.9% (14/27) of patients had ever received antiangiogenic therapy. The ORR was 36.4% (partial response (PR) in 8 patients; 95% CI, 17.2-59.3). The DCR was 100.0% (PR in 8 patients and stable disease (SD) in 14 patients; 95% CI, 73.5-100). The median time of the first response was 1.6 months (range, 1.3-4.4). The median PFS was 9.3 months (95% CI, NE-NE). Furthermore, the ORR of patients with and without prior antiangiogenic therapy was 16.7% (95%CI, 2.1-48.4) and 60.0% (95%CI, 26.2-87.8) respectively (P = 0.074). Any grades of adverse events (AEs) were observed in 92.6% (25/27) of patients, containing allergic eruption (33.3%), hand-foot syndrome (29.6%), hypertension (25.9%), and fatigue (25.9%). The grade 3-4 adverse events were only observed in 5 patients, including 1 with grade 3 proteinuria, 1 with grade 3 ascites, 1 with grade 3 fatigue, 1 with grade 3 edema limbs and 1 with grade 4 anemia. Conclusions: The treatment of anlotinib plus pemetrexed showed a promising antitumor activity with tolerable toxicity for patients in platinum-resistant and refractory ovarian cancer. Clinical trial information: ChiCTR2000029654.

IMPORTANCE: There is no current consensus on the role of chemotherapy in addition to radiation for postoperative adjuvant treatment of patients with early-stage cervical cancer with adverse pathological factors. OBJECTIVE: To evaluate the clinical benefits of sequential chemoradiation (SCRT) and concurrent chemoradiation (CCRT) compared with radiation alone (RT) as a postoperative adjuvant treatment in early-stage cervical cancer. DESIGN, SETTING, AND PARTICIPANTS: After radical hysterectomy at 1 of 8 participating hospitals in China, patients with FIGO (International Federation of Gynecology and Obstetrics) stage IB to IIA cervical cancer with adverse pathological factors were randomized 1:1:1 to receive adjuvant RT, CCRT, or SCRT. Data were collected from February 2008 to December 2018. INTERVENTIONS: Patients received adjuvant RT (total dose, 45-50 Gy), CCRT (weekly cisplatin, 30-40 mg/m(2)), or SCRT (cisplatin, 60-75 mg/m(2), plus paclitaxel, 135-175 mg/m(2)) in a 21-day cycle, given 2 cycles before and 2 cycles after radiotherapy, respectively. MAIN OUTCOMES AND MEASURES: The primary end point was the rate of disease-free survival (DFS) at 3 years. RESULTS: A total of 1048 women (median [range] age, 48 [23-65] years) were included in the analysis (350 in the RT group, 345 in the CCRT group, and 353 in the SCRT group). Baseline demographic and disease characteristics were balanced among the treatment groups except that the rate of lymph node involvement was lowest in the RT group (18.3%). In the intention-to-treat population, SCRT was associated with a higher rate of DFS than RT (3-year rate, 90.0% vs 82.0%; hazard ratio [HR], 0.52; 95% CI, 0.35-0.76) and CCRT (90.0% vs 85.0%; HR, 0.65; 95% CI, 0.44-0.96). Treatment with SCRT also decreased cancer death risk compared with RT (5-year rate, 92.0% vs 88.0%; HR, 0.58; 95% CI, 0.35-0.95) after adjustment for lymph node involvement. However, neither DFS nor cancer death risk was different among patients treated with CCRT or RT. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, conducted in a postoperative adjuvant treatment setting, SCRT, rather than CCRT, resulted in a higher DFS and lower risk of cancer death than RT among women with early-stage cervical cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00806117

// Qian-Qian Xu 1 , Bo Pan 1 , Chang-Jun Wang 1 , Yi-Dong Zhou 1 , Feng Mao 1 , Yan Lin 1 , Jing-Hong Guan 1 , Song-Jie Shen 1 , Xiao-Hui Zhang 1 , Ya-Li Xu 1 , Ying Zhong 1 , Xue-Jing Wang 1 , Yan-Na Zhang 1 , Qiang Sun 1 1 Department of Breast Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P. R. China Correspondence to: Qiang Sun, email: sunqiangpumc@126.com Keywords: HER2-positive breast cancer, HER2 amplification, prognosis, trastuzumab-based treatment, adjuvant setting Received: June 21, 2016 Accepted: August 17, 2016 Published: August 23, 2016 ABSTRACT Background: Trastuzumab-based therapy is a standard, targeted treatment for HER2-positive breast cancer in the adjuvant setting. However, patients do not benefit equally from it and the association between HER2 amplification level and patients’ survival remains controversial. A systematic review and meta-analysis was conducted by incorporating all available evidence to evaluate the association between disease free survival (DFS) and HER2 amplification level. Results: Three cohort studies involving 1360 HER2-positive breast cancer patients stratified by HER2 amplification magnitude were eligible for meta-analysis. The combined HRs for DFS were 1.05 (95% CI: 0.80−1.36, p = 0.74) and 0.97 (95% CI: 0.73−1.29, p = 0.83) for HER2 gene copy number (GCN) and HER2/CEP 17 ratio. No evidence of heterogeneity or public bias was found. Methods: Databases including PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL), were searched for eligible literature. HER2 amplification level was evaluated by fluorescence in situ hybridization (FISH) in terms of gene copy number (GCN) and HER2/CEP17 ratio. Hazard ratios (HRs) for DFS with 95% confidence interval (CI) according to the amplification level of HER2 were extracted. The outcomes were synthesized based on a fixed-effects model. Conclusions: HER2 amplification level is not a prognostic factor for HER2-positive breast cancer with trastuzumab-based targeted therapy in the clinical adjuvant setting.

// Bo Pan 1,* , Ru Yao 1,* , Jie Shi 2,* , Qian-Qian Xu 1 , Yi-Dong Zhou 1 , Feng Mao 1 , Yan Lin 1 , Jing-Hong Guan 1 , Xue-Jing Wang 1 , Yan-Na Zhang 1 , Xiao-Hui Zhang 1 , Song-Jie Shen 1 , Ying Zhong 1 , Ya-Li Xu 1 , Qing-Li Zhu 3 , Zhi-Yong Liang 2 and Qiang Sun 1 1 Department of Breast Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China 2 Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China 3 Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China * These authors have contributed equally to this work Correspondence to: Qiang Sun, email: // Keywords : mucinous breast cancer, subtype, prognosis Received : February 21, 2016 Accepted : April 04, 2016 Published : April 18, 2016 Abstract Purpose: The heterogeneous nature of the mucinous breast cancer (MBC), with its pure (PMBC) and mixed subtypes (MMBC), calls for precise prognosis assessment. Methods: We analyzed 197 consecutive MBC patients, including 117 PMBC and 80 MMBC, who were treated from 1983 to 2014. The clinicopathological features, treatment choice, disease-free survival (DFS) and overall survival (OS) were compared among PMBC, MMBC and MMBC subgroups. Prognostic factors of PMBC and MMBC were identified. Results: Compared to PMBC, MMBC had more lymph node metastasis (p = 0.043), Her2 positivity ( p = 0.036), high Ki-67 index (defined as>20%, p = 0.026) and anti-Her2 targeted therapy ( p = 0.016). The 5-year DFS of PMBC and MMBC were 90.4% and 86.2%, whereas the 5-year OS were 99.0% and 98.7%. No significant difference was found in DFS or OS among all MBC subtypes. High Ki-67 ( p = 0.020) appeared as DFS factor in PMBC, while anti-Her2 targeted therapy ( p = 0.047) as the DFS predictors in MMBC. Conclusion: MMBC manifested similar 5-year survival to PMBC in Chinese woman, suggesting that intra-tumoral heterogeneity might not interfere with MBC short-term prognosis.

Yan-na Zhang, Xiao-gang Duan, Wen-hui Zhang, Ai-ling Wu, Huan-Huan Yang, Dong-ming Wu, Yu-Quan Wei, Xian-cheng Chen State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China Abstract: Cancer stem cells (CSCs) are critical for tumor initiation/maintenance and recurrence or metastasis, so they may serve as a potential therapeutic target. However, CSC-established multitherapy resistance and immune tolerance render tumors resistant to current tumor-targeted strategies. To address this, renewable multiepitope-integrated spheroids based on placenta-derived mesenchymal stem cells (pMSCs) were X-ray-modified, at four different irradiation levels, including 80, 160, 240, and 320Gy, as pluripotent biologics, to inoculate hosts bearing Lewis lung carcinoma (LL2) and compared with X-ray-modified common LL2 cells as control. We show that the vaccines at the 160/240Gy irradiation levels could rapidly trigger tumor cells into the apoptosis loop and evidently prolong the tumor-bearing host’s survival cycle, in contrast to vaccines irradiated at other levels (P

e18078 Background: Anlotinib (AL3818) is a novel multi-target tyrosine kinase inhibitor that has previously shown clinical antitumor activity in various cancers, including the phase I study on tumors of female reproductive system. This phase II study (ChiCTR1800018192) aims to further evaluate the safety and efficacy of anlotinib combined with pemetrexed in patients with recurrent platinum-resistant advanced epithelial ovarian cancer. Methods: Patients who underwent cytoreductive operation, with histopathologically advanced epithelial ovarian cancer ( FIGO staging III or IV), and failed to previously platinum-based chemotherapies were considered eligible for enrollment to receive combined treatment of anlotinib (12 mg per day, days 1-14; 21 days per cycle) plus pemetrexed (0.5 g/m2, day 1; 21 days per cycle). Total duration of combined treatment contained 6 cycles, and subsequent maintenance treatment was anlotinib monotherapy (12 mg per day, days 1-14; 21 days per cycle) till disease progression or intolerant toxicity. The primary endpoint of this study was objective response rate (ORR) and the secondary endpoints were disease control rate (DCR), progression-free survival (PFS) and safety. Results: Between 2018 July and 2019 October, 13 patients (female) with a median age of 55 years (range: 41 - 65), FIGO histopathological stage IIIA (7.7%) or IIIC (76.9%) or IV (15.4%) were enrolled. Over a mean follow-up period of 5.9 (95% CI: 3.4-8.3) months, therapeutic evaluation showed the incidence of partial response, stable disease, and progression disease was 38.5%, 53.8% and 7.7% respectively, yielding the ORR of 38.5% (5/13; 95% CI: 13.9%-68.4%) and the DCR of 92.3% (12/13; 95% CI: 64.0%-99.8%). The median PFS was not reached. Frequently occurring adverse events (AEs) were grade 1 or 2, including hand-foot syndrome (53.8%), allergic eruption (38.5%), mild hypertention (30.8%), fatigue (23.1%), diarrhea (23.1%), gum-pain (15.4%), and dry cough (15.4%). High grade AE was only observed in 1 patients with hemoglobin reduction of grade 4. Neither unexpected safety signals nor treatment related death occurred. Conclusions: Anlotinib (AL3818) plus pemetrexed showed a promising activity with an acceptable safety profile for previously platinum-treated patients with recurrent advanced epithelial ovarian cancer. Clinical trial information: ChiCTR1800018192.

6007 Background: There are limited data from previous studies regarding whether the addition of chemotherapy to adjuvant radiation after radical surgery improves outcomes among patients with early-stage cervical cancer and adverse pathological factors. Methods: This was a prospective randomized trial including patients with FIGO 2009 stage IB1-IIA2 cervical cancer and squamous-cell, adenocarcinoma, or adenosquamous carcinoma with at least one adverse factor after radical hysterectomy. Patients were randomized 1:1:1 to receive adjuvant radiation alone, concurrent chemoradiation with weekly cisplatin (30-40 mg/m2), or sequential chemoradiation with cisplatin (60-75 mg/m2) plus paclitaxel (135-175 mg/m2) in 21 day cycles, given 2 cycles before and 2 cycles after radiotherapy respectively. The primary outcome was the rate of disease-free survival at 3 years. Results: A total of 1,048 patients were included in the study (350, radiation alone; 345, concurrent chemoradiation; and 353, sequential chemoradiation). Overall, the median follow-up was 56 months and the median age of patients was 48 years. Most patients (75%) had stage IB1 or IIA1 disease. The three groups were similar with respect to histologic subtypes, the rate of lymphovascular invasion, parametrial, surgical margin and deep stromal involvement, tumor grade, rate of use of minimally invasive surgery, and neoadjuvant chemotherapy, except for lymph-node involvement that was lowest in radiation alone arm. In the intention-to-treat population, sequential chemoradiation was associated with a higher rate of disease-free survival than radiation alone (3-year rate, 90·0% vs. 82·0%; HR 0·52; 95% CI, 0·35 to 0·76) and concurrent chemoradiation (90·0% vs. 85·0%; HR 0·65; 95% CI, 0·44 to 0·96), differences remained after adjustment for lymph-node involvement. Sequential chemoradiation was also associated with a higher rate of overall survival than radiation alone (5-year rate, 92·0% vs. 88·0%; HR for death from cancer, 0·58; 95% CI, 0·35 to 0·95). However, neither disease-free survival nor cancer death risk was different between patients treated with concurrent chemoradiation or radiation alone. Conclusions: In this trial, sequential chemoradiation, rather than concurrent chemoradiation, resulted in a higher disease-free survival and lower risk of cancer death than radiation alone among women with early-stage cervical cancer after radical surgery. Clinical trial information: NCT00806117.

Han Li,1,* Weijing Zhang,1,* Xiaoying Sun,1,* Jueming Chen,1 Yue Li,1 Chunhao Niu,2 Benke Xu,3 Yanna Zhang1 1Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China; 2Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, Guangdong, China; 3Department of Anatomy, Medical School of Yangtze University, Jingzhou, China *These authors contributed equally to this work Background: KIF20A plays an indispensable role in cytokinesis regulation, which is important for tumor proliferation and growth. Recently, the oncogenic role of KIF20A has been well documented in several cancers. However, its clinical role in epithelial ovarian cancer (EOC) remains not reported yet. We investigated its expression and its role in promoting invasion and chemoresistance in EOC cells.Patients and methods: KIF20A transcription and translation levels were investigated in normal ovarian epithelial cell, ovarian cancer cells, and 10 pairs of fresh EOC tissues and adjacent normal ovarian tissues by real-time quantitative polymerase chain reaction and Western blots. Moreover, KIF20A protein level was also examined by immunohistochemistry in 150 EOC tissues. The correlation between KIF20A expression and clinical variables was analyzed by statistical methods. We also used wound healing assay, transwell assay MTT, and Annexin V/PI to explore KIF20A functions.Results: KIF20A expression was obviously elevated at both mRNA and protein levels in EOC cell lines and clinical cancer tissues compared with normal ovarian epithelial cell and adjacent normal ovarian tissues. KIF20A protein expression was highly correlated with International Federation of Gynecology and Obstetrics stage (P=0.008), lymph node metastasis (P=0.002), intraperitoneal metastasis (P

A novel monomeric amine sodium montmorillonite swelling inhibitor: N1, N2-ditetradecy- N1, N1, N2, N2-tetrakis (2-hydroxyethyl) ethane-1,2-diaminium bromide was obtained from diethanolamine, 1-bromotetradecane, and 1, 2-dibromoethane. N1, N2-ditetradecy- N1, N1, N2, N2-tetrakis (2-hydroxyethyl) ethane-1,2-diaminium bromide was characterized by means of Fourier transform infrared, 1H NMR spectroscopy, elemental analysis, linear swelling tests, particle size distribution tests, X-ray diffraction, and thermogravimetric. Linear swelling tests showed that the swelling height of sodium montmorillonite in 1.0 wt% N1, N2-ditetradecy- N1, N1, N2, N2-tetrakis (2-hydroxyethyl) ethane-1,2-diaminium bromide solution was only 2.0 mm after 16 h (fresh water was 5.0 mm). Particle size distribution tests exhibited that the median diameter and mean particle size of sodium montmorillonite in 1.0 wt% N1, N2-ditetradecy- N1, N1, N2, N2-tetrakis (2-hydroxyethyl) ethane-1,2-diaminium bromide solution obviously increased to 16.1 and 85.4 µm, respectively (fresh water was 8.1 and 21.8 µm). In thermogravimetric tests, in comparison with pure sodium montmorillonite, the decrease of water content in sodium montmorillonite/ N1, N2-ditetradecy- N1, N1, N2, N2-tetrakis (2-hydroxyethyl) ethane-1,2-diaminium bromide indicated N1, N2-ditetradecy- N1, N1, N2, N2-tetrakis (2-hydroxyethyl) ethane-1,2-diaminium bromide expelled the water molecules out of the interlayer, which was beneficial to wellbore stability. Fourier transform infrared spectra of certain concentration N1, N2-ditetradecy- N1, N1, N2, N2-tetrakis (2-hydroxyethyl) ethane-1,2-diaminium bromide/sodium montmorillonite indicated the successful physical adsorption and interaction between N1, N2-ditetradecy- N1, N1, N2, N2-tetrakis (2-hydroxyethyl) ethane-1,2-diaminium bromide with sodium montmorillonite. In addition, the results of X-ray diffraction tests showed the obtained 1.0 wt% N1, N2-ditetradecy- N1, N1, N2, N2-tetrakis (2-hydroxyethyl) ethane-1,2-diaminium bromide solution could remarkably reduce the interlayer distance of wet sodium montmorillonite (from 1.94 to 1.37 nm).

CSCs are able to survive routine anticancer procedures and peripheral-immune attack. Here we develop and detail a framework of CSC elimination governed by 3D-biologics. Pluripotent cells-engineered 3D-biologics (PMSB) and control non-3D-biologics were prepared from placenta-based somatic stem cells (PSCs) and inoculated respectively into senile hosts bearing progressive mammary, lung, colon carcinomas and melanoma. We demonstrate that PMSB evokes in vivo central-immune microenvironment with subsequent re-expression of thymosin-α1 ~ β4 in thymic cortex-medulla borderline for rapid MHC-unrestricted renewal of γδT-dominated immunocompetence. The post-renewal γδT-subsets could accurately bind and drive CSCs into apoptosis. Finally, with central/peripheral integral microenvironment renewal and TERT/Wnt/β-catenin pathway blockade, the CSC-subsets are fully depleted, leading to substantial cure of diverse tumors by PMSB inoculation (P < 0.01), yet not by non-3D-biologics. Thus, our study may contribute to open up a new avenue for tumor remission via pluripotent cells-engineered 3D-biologics addressing quick renewal of central-thymus and peripheral immune-microenvironment.

The present study was performed to investigate the biological functions of microRNA‑320a in human breast cancer and the underlying mechanisms. MicroRNA‑320a expression was downregulated in human breast cancer, compared with the normal control. Overexpression of microRNA‑320a induced apoptosis, and inhibited cell viability and invasion in MDA‑MB‑231cells while downregulation of microRNA‑320a reduced apoptosis, and increased cell viability and invasion in MDA‑MB‑231 cells. Then, overexpression of microRNA‑320a suppressed insulin‑like growth factor 1 receptor (IGF‑1R), p‑AKt and cyclin D1 protein expression in MDA‑MB‑231cells. In addition, the downregulation of microRNA‑320a induced IGF‑1R, p‑Akt and cyclin D1 protein expression in MDA‑MB‑231cells. Furthermore, the IGF‑1R inhibitor increased the effects of microRNA‑320a on the apoptosis of MDA‑MB‑231 cells. The p‑Akt inhibitor (MK 2206 dihydrochloride, 2.5 nM) increased the effects of microRNA‑320a on the apoptosis of MDA‑MB‑231 cells. These results revealed that microRNA‑320a suppresses tumor cell growth and invasion of human breast cancer by targeting IGF‑1R.

Stonin 2 (STON2), which functions in adjusting endocytotic complexes, is probably involved in the monitoring of the internalization of dopamine D2 receptors which have an inhibitory action of dopamine on tumor progression. However, its clinical significance in tumor progression and prognosis remains unclear. We explored the association between STON2 and the clinicopathological characteristics of epithelial ovarian cancer (EOC). The STON2 levels in ovarian cancer and normal cell lines and tissues were detected by real-time PCR and Western blot analyses. STON2 protein expression was also detected by an immunohistochemical analysis. The clinical significance of STON2 expression in ovarian cancer was statistically analyzed. STON2 significantly increased in the ovarian cancer cell lines and tissues compared to the normal ones. In the 89 EOC samples tested, STON2 expression was significantly correlated with intraperitoneal metastasis, intestinal metastasis, intraperitoneal recurrence, ascites containing tumor cells, and CA153 level. Moreover, patients with STON2 protein overexpression were more likely to exhibit platinum resistance and to have undergone neoadjuvant chemotherapy. Patients with high STON2 protein expression had a tendency to have a shorter overall survival and a poor prognosis. A multivariate analysis showed that STON2 was an independent prognostic predictor for EOC patients. In conclusion, STON2 plays an important role in the progression and prognosis of ovarian carcinoma, especially in platinum resistance, intraperitoneal metastasis, and recurrence. STON2 can be a novel antitumor drug target and biomarker which predicts an unfavorable prognosis for EOC patients.

TIMELESS is a highly conserved protein required for the maintenance of normal mammalian circadian oscillations and for controlling cellular metabolism and proliferation. Recently, TIMELESS was implicated in the tumorigenesis of certain cancers. However, little is known on TIMELESS protein expression and its potential as a prognostic factor in cervical cancer. Here, we investigate TIMELESS expression pattern and its clinicopathological significance in early-stage cervical carcinoma. TIMELESS mRNA and protein expression was evaluated by real-time PCR and western blot analysis in cervical cancer cell lines, a normal cervical cell line, as well as in six pairs of surgically removed cervical cancer and adjacent normal cervical tissues. A total of 189 paraffin-embedded cervical carcinoma specimens were detected and diagnosed by immunohistochemistry (IHC), and the clinical significance of TIMELESS expression was further analyzed. Aberrant TIMELESS mRNA and protein expression were demonstrated in cervical cancer cell lines compared with the normal cervical cell line. TIMELESS mRNA and protein expression were significantly increased in cervical cancer specimens compared with adjacent non-cancerous cervical specimens. TIMELESS protein expression was significantly associated with the age (P=0.011), clinical stage (P

Background The kinesin family member 20a (KIF20A) protein has been implicated in the development and progression of many human cancers; however, its precise function and role in cervical cancer remain largely unclear. This study aimed to investigate the expression profile and prognostic value of KIF20A in patients with early-stage cervical squamous cell carcinoma. Methods We examined the mRNA and protein levels of KIF20A in eight cervical cancer cell lines and eight paired cervical cancer samples, compared with normal cervical epithelial cells and adjacent normal cervical tissues, respectively. Immunohistochemistry was performed to detect the expression of KIF20A in paraffin-embedded specimens from 169 early-stage cervical squamous cell carcinoma patients. Statistical analyses were applied to analyze the association between KIF20A expression and clinical variables, as well with patient survival. Results The mRNA and protein expression levels of KIF20A were significantly elevated in cervical cancer cell lines and lesions compared with normal cells and corresponding normal tissues (P < 0.05). Immunohistochemistry analysis in 169 cervical cancer cases revealed that increased KIF20A expression was strongly associated with human papillomavirus (HPV) infection (P = 0.008), clinical stage (P = 0.001), tumor recurrence (P = 0.016), vital status (P < 0.001), the property of the surgical margin (P = 0.032), the lymphovascular space involvement (P = 0.014), and pelvic lymph node metastasis (P = 0.001). The overall survival and disease-free survival of patients with high levels of KIF20A expression were significantly poorer than those with low KIF20A expression. KIF20A was an independent survival prognostic factor, as evidenced by univariate and multivariate analysis. Conclusions Our results illustrate that elevated KIF20A expression correlates with HPV infection, clinical stage, tumor recurrence, lymphovascular space involvement, pelvic lymph node metastasis, and poor outcome in early-stage cervical squamous cell carcinoma patients. KIF20A aberrant expression is a novel independent unfavorable prognostic factor and may present a potential therapeutic target for cervical cancer.

Introduction It is well established that patients with von Recklinghausen disease, also called neurofibromatosis type 1 (NF1), have an increased Clinical Pra What is already known about this subject? ● Neurofibromatosis type 1 (NF1) increases the chance of breast cancer developing and belongs to a high-risk population for early screening. ● The diagnosis of breast cancer in patients with NF1 is usually delayed because the patient mistakenly identifies the breast lump as neurofibroma. ● Appendices on the nipple of patients with NF1 are neurofibromas in contrast to simple hyperplasia. ● The diagnosis of breast cancer in patients with NF1 is difficult, and most cases are diagnosed at an advanced stage. ● Chinese women are younger and have denser and smaller breasts when breast cancer develops than is true of their Western counterparts, and ultrasonography might be a better screening imaging test in China. What are the new findings? ● The nipples of patients with NF1 can be remarkably enlarged because of multiple neurofibroma appendi

Objective The aim of this study was to explore the difference of long-term prognosis of different treatment regimens in patients with stage IB2, IIA2 cervical cancer.

Background LncRNA-FENDRR is a kind of endothelial genes critical for vascular development. Moreover, miR-126 and vascular endothelial growth factor A (VEGFA) are also involved in the physiological process of vascular endothelial cells. This study aimed to the underlying mechanism of FENDRR involving miR-126 and VEGFA in hypertensive intracerebral hemorrhage (HICH). Methods C57BL/6 mice were chosen to establish HICH model. The expression of FENDRR, miR-126, and VEGFA at mRNA level was determined by qRT-PCR. The protein expression of VEGFA was assessed using Western blot. RIP assay and RNA pull-down assay were used to the relationship between FENDRR and miR-126. Flow cytometry was used to analyze cell apoptosis. Results The levels of FENDRR and VEGFA were increased, and miR-126 expression was decreased in vascular endothelial cells (VECs) from the right brain of model mice and human brain microvascular endothelial cells (HBMECs) treated by thrombin. Overexpression of FENDRR promoted the apoptosis of HBMECs. FENDRR regulating VEGFA participated in HBMECs apoptosis through targeting miR-126. Downregulation of FENDRR was indicated to relieve the HICH in mice. Conclusions FENDRR could promote the apoptosis of HBMECs via miR-126 regulating VEGFA in HICH.

5529Background: To determine whether the addition of concurrent chemotherapy (CCT) or sequential chemotherapy (SCT) to adjuvant pelvic radiotherapy (RT) will improve prognosis of patients with earl...

5515Background: Anti-angiogenic therapy combined with chemotherapy could improve the outcome of platinum-resistant ovarian cancer. Apatinib is an oral tyrosine kinase inhibitor which selectively in...

BACKGROUND:The β1,3-N-acetylglucosaminyltransferase-3 gene (B3GNT3) encodes a member of the B3GNT family that functions as the backbone structure of dimeric sialyl-Lewis A and is involved in L-selectin ligand biosynthesis, lymphocyte homing and lymphocyte trafficking. B3GNT3 has been implicated as an important element in the development of certain cancers. However, the characteristics of B3GNT3 in the development and progression of cancer remain largely unknown. Thus, our study aimed to investigate the expression pattern and the prognostic value of B3GNT3 in patients with early-stage cervical cancer. METHODS:The mRNA and protein levels of B3GNT3 expression were examined in eight cervical cancer cell lines and ten paired cervical cancer tumors, using real-time PCR and western blotting, respectively. Immunohistochemistry (IHC) was used to analyze B3GNT3 protein expression in paraffin-embedded tissues from 196 early-stage cervical cancer patients. Statistical analyses were applied to evaluate the association between B3GNT3 expression scores and clinical parameters, as well as patient survival. RESULTS:B3GNT3 expression was significantly upregulated in cervical cancer cell lines and lesions compared with normal cells and adjacent noncancerous cervical tissues. In the 196 cases of tested early-stage cervical cancer samples, the B3GNT3 protein level was positively correlated with high risk TYPES of human papillomavirus (HPV) infection (P = 0.026), FIGO stage (P < 0.001), tumor size (P = 0.025), tumor recurrence (P = 0.004), vital status (P < 0.001), concurrent chemotherapy and radiotherapy (P = 0.016), lymphovascular space involvement (P = 0.003) and most importantly, lymph node metastasis (P = 0.003). Patients with high B3GNT3 expression had a shorter overall survival (OS) and disease-free survival (DFS) compared with those with low expression of this protein. Multivariate analysis suggested that B3GNT3 expression is an independent prognostic indicator for cervical cancer patients. CONCLUSIONS:Our study demonstrated that elevated B3GNT3 expression is associated with pelvic lymph node metastasis and poor outcome in early-stage cervical cancer patients. B3GNT3 may be a novel prognostic marker and therapeutic target for the treatment of cervical cancer.

Centrosomal protein 55 (CEP55) is a cell cycle regulator implicated in development of certain cancers. However, characteristics of CEP55 expression and its clinical/prognostic significance are unclear in human epithelial ovarian carcinoma (EOC). Therefore, we investigated the expression and clinicopathological significance of CEP55 in patients with EOC and its role in regulating invasion and metastasis of ovarian cell lines. CEP55 mRNA and protein expression levels were detected by quantitative real-time PCR (qRT-PCR), Western blotting, and immunohistochemistry (IHC). Potential associations of CEP55 expression scores with clinical parameters and patient survival were evaluated. CEP55 function was investigated further using RNA interference, wound healing assay, transwell assay, immunofluorescence analysis, qRT-PCR, and Western blotting. CEP55 was significantly upregulated in ovarian cancer cell lines and lesions compared with normal cells and adjacent noncancerous ovarian tissues. In the 213 EOC samples, CEP55 protein levels were positively correlated with clinical stage (P

Background: Milestone studies showed that ultrasound (US) was an effective primary screening test for breast cancer both in the western world and in China [PMID: 26712110, 26715161, and 25668012]. Ultrasound has been officially designated to be the initial imaging test for breast cancer screening in Beijing and several other cities in China, due to its improved sensitivity in Chinese women who usually have denser breasts and develop breast cancer earlier than Caucasian counterparts. Study showed that it would take 40 years to screen each woman in the target age group once [PMID: 26808342].The mainstay modality of breast cancer screening in China is the hospital-based opportunistic screening among asymptomatic self-referred women. However, there is little data about the tumor biology and long-term survival of the US-detected non-palpable breast cancer (NPBC) in hospital-based Chinese population. Methods: From January 2001 to December 2014, 3,786 asymptomatic women with positive (BI-RADS 4 and 5) initial screening US underwent biopsies in Peking Union Medical College Hospital, and 572 NPBC in 556 women were diagnosed. Women without dense breasts (defined as BI-RADS category C and D) also received screening mammography (MG) after physical examination and ultrasound. 788 patients with positive (BI-RADS 4 and 5) mammogram (MG) and normal US (BI-RADS 1, 2 and 3) underwent MG-guided biopsies and another 127 NPBC were diagnosed in 126 women. The clinicopathological features, treatment choice, 10-year disease-free survival (DFS) and overall survival (OS) were reviewed and compared between the US-detected and MG-detected NPBC. Prognostic factors of NPBC were identified. Results: Overall, US could detect more invasive NPBC (83.4% vs 54.3%, p Table 1. Kaplan-Meier estimates of DFS and OS between US-NPBC and MG-NPBC§.Patients (No.)10-year DFS (%)P value10-year OS (%)P valueAllUS-NPBC (572)90.60.73896.10.142 MG-NPBC (127)92.7 100.0 DCISUS-NPBC (94)100.00.060100.0- MG-NPBC (58)93.8 100.0 InvasiveUS-NPBC (478)88.60.68095.20.239 MG-NPBC (69)92.0 100.0 § Kaplan-Meier survival curves between each two subgroups would be displayed in the poster. Conclusion: Compared to MG, US detected more invasive NPBC with positive lymph node in hospital-based asymptomatic self-referred Chinese women, who could achieve comparable 10-year DFS and OS as MG-detected NPBC. US could serve as the feasible initial imaging modality in hospital-based opportunistic screening Chinese women. Citation Format: Yao R, Pan B, Zhu Q, Xu Q, Zhou Y, Zhang J, Mao F, You S, Lin Y, Shi J, Guan J, Wang X, Zhang Y, Zhang X, Shen S, Zhong Y, Xu Y, Liang Z, Jiang Y, Sun Q. Biology and long-term prognosis of screening detected non-palpable breast cancer by ultrasound in hospital-based Chinese population (2001-2014) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-02-05.

The CDGSH iron sulfur domain2 (CISD2) is an evolutionarily conserved gene. It functions to control mammalian life span and regulate human breast cancer cells proliferation. However, the characteristics of CISD2 expression and its clinical/prognostic significance are unclear in human tumor. Our study aimed to investigate the expression pattern and clinicopathological significance of CISD2 in patients with early-stage cervical cancer. The mRNA and protein expression levels of CISD2 were analyzed in eight cervical cancer cell lines and eight paired cervical cancer tumors by real-time PCR and Western blotting, respectively. Immunohistochemistry was performed to examine CISD2 protein expression in paraffin-embedded tissues from 149 early-stage cervical cancer patients. Statistical analyses were used to evaluate the clinicopathological significance of CISD2 expression. CISD2 expression was significantly upregulated in cervical cancer cells at both the mRNA and protein levels. Statistical analysis showed a significant correlation of CISD2 expression with the squamous cell carcinoma antigen (P = 0.000), myometrium invasion (P = 0.003), recurrence (P = 0.012), lymphovascular space involvement (P = 0.019) and especially pelvic lymph node metastasis (PLNM; P = 0.000). Patients with higher CISD2 expression had shorter overall survival duration than patients with lower CISD2 expression. Multivariate analysis suggested that CISD2 expression might be an independent prognostic indicator for the survival of patients with early-stage cervical cancer. Our results for the first time suggested that high CISD2 expression was closely correlated with PLNM and poor prognosis in early-stage cervical cancer patients. CISD2 protein might be a novel biomarker for early-stage cervical cancer progression.

The use of ultrasound in the diagnosis of axillary lymph node metastases from breast cancer in a Chinese population was investigated. Data for 1,049 with breast cancer were retrospectively collected. All patients had undergone pre-operative axillary ultrasound and then axillary lymph node dissection. The sensitivity, specificity and accuracy of axillary ultrasound in this cohort were 69.4%, 81.8% and 77.0%, respectively. The overall false-negative rate of ultrasound images was 30.6% (123/402). False-negative ultrasound rates for pathologic N1, N2 and N3 patients were 46.2%, 21.8% and 9.3%, respectively. In patients with stage T1 disease and fewer than three metastatic lymph nodes, the false-negative ultrasound rate was 52.2% (47/90). Moreover, breast cancer patients with a false-negative axillary ultrasound were more likely to have a large tumor (p < 0.001) and high tumor grade (p = 0.009). However, there were no statistically significant differences between accuracy of axillary ultrasound and age of patients or experiences of ultrasound practitioners. In conclusion, the sensitivity, specificity and accuracy of ultrasound in the diagnosis of breast cancer metastasis to the axillary lymph nodes in Chinese patients were assessed. These data could help us to carefully use axillary ultrasound to diagnose and predict breast cancer axillary lymph node metastasis.

Background We carried out this meta-analysis to demonstrate efficacies of neoadjuvant chemotherapy (NACT) and adjuvant chemotherapy (AC) for nasopharyngeal carcinoma (NPC) patients based on randomized, controlled trials (RCTs). Patients and methods We comprehensively searched electronic databases and manuscripts for RCTs and extracted data from eligible studies for meta-analysis. Overall survival (OS) with hazard ratios (HRs), locoregional recurrence rate (LRR) and distant metastasis rate (DMR) with relative risks (RRs) were concerned using random and/or fixed-effects models. Subgroup and sensitivity analyses were also carried out. Results Six trials in NACT group (n = 1418) and five in AC group (n = 1187) were eligible. HR of death for NACT was 0.82 [95% confidence interval (CI) 0.69–0.98, P = 0.03], corresponding to an absolute survival gain of 5.13% after 3 years. Significant reduction of DMR (P = 0.0002; RR 0.69, 95% CI 0.56–0.84) was also found from NACT. But no decrease in LRR (P = 0.49; RR 0.90, 95% CI 0.66–1.22) was observed. Patients receiving additional AC had lower LRR (P = 0.03; RR 0.71, 95% CI 0.53–0.96). But no benefit of OS and DMR were seen in AC. Conclusions NACT can effectively enhance OS and reduce DMR, not LRR in NPC. And AC only helps to better control locoregional recurrence of NPC.

Background: There is an abnormal expression of nuclear receptor subfamily 2 group F member 6 (NR2F6) in human cancers such as breast cancer, colon cancer, and acute myelogenous leukemia. However, its clinical significance in cervical cancer has not been established. We explored NR2F6 expression and its clinicopathological significance in early-stage cervical cancer. Methods: NR2F6 expression in cervical cancer cell lines and cervical cancer tissues was determined by Western blotting, real-time PCR, and immunochemistry (IHC). NR2F6 expression in 189 human early-stage cervical cancer tissue samples was evaluated using IHC. The relevance between NR2F6 expression and early-stage cervical cancer prognosis and clinicopathological features was determined. Results: There was marked NR2F6 mRNA and protein overexpression in the cervical cancer cells and clinical tissues compared with an immortalized squamous cell line and adjacent noncancerous cervical tissues, respectively. In the 189 cervical cancer samples, NR2F6 expression was positively related to International Federation of Gynecology and Obstetrics (FIGO) stage (p = 0.006), squamous cell carcinoma antigen (p = 0.006), vital status (p < 0.001), tumor recurrence (p = 0.001), chemotherapy (p = 0.039), and lymph node metastasis (p < 0.001). Overall and disease-free survival was shorter in patients with early-stage cervical cancer and higher NR2F6 levels than in patients with lower levels of NR2F6. Univariate and multivariate analysis determined that NR2F6 was an independent prognostic factor of survival in early-stage cervical cancer. Conclusions: Taken together, our findings suggest that high NR2F6 expression predicts pelvic lymph node metastasis, tumor recurrence and poor prognosis in early-stage cervical cancer. NR2F6 might be a novel prognostic biomarker and potential therapeutic target of cervical cancer.

Background: The heterogeneous nature of the mucinous breast cancer (MBC), with its subtypes of pure (PMBC) and mixed carcinoma (MMBC), calls for more precise individualized prognosis assessment. PMBC showed favorable prognosis in both Chinese and Caucasian women, with nodal status and TNM stage as the prognostic predictors [PMID: 18026874, 22451233]. However, few studies had investigated tumor biology and prognosis of MMBC in Chinese population, especially with respect to the different co-existing cancer components. Methods: From January 1983 to December 2014, 197 consecutive MBC patients, including 117 PMBC and 80 MMBC, received breast cancer surgery in Peking Union Medical College Hospital. The clinicopathological characteristics, treatment choice, disease-free survival (DFS) and overall survival (OS) were compared both between PMBC vs MMBC, and among subgroups of MMBC according to the mixed entities, including 24 women with ductal caricinoma in situ (DCIS) and 45 with IDC. Univariate and Cox multivariate analyses were performed to identify the prognostic factors. Results: The 197 MBC comprised 1.9% of contemporary 10,192 breast cancer (BC). Compared to PMBC, MMBC had significantly more lymph node metastasis (p=0.038), Her2 positivity (p=0.036), high Ki-67 index (defined as >20%, p=0.026) and anti-Her2 targeted therapy (p=0.006). All these differences remained significant when the comparison were performed among PMBC, MBC+DCIS and MBC+IDC, and additional significant difference were identified in tumor size (p=0.036), pTNM stage (p=0.003) and chemotherapy (p=0.003). However, no significant difference was found in DFS or OS between any two subtypes/subgroups of MBC, including PMBC, MMBC, MBC+DCIS and MBC+IDC. Table 1. Comparison of survival outcomes among PMBC, MBC+DCIS and MBC+IDC§SurvivalPMBC (N=117, Median, range, and Mean±SD)MBC+DCIS (N=24, Median, range, and Mean±SD)MBC+IDC (N=45, Median, range, and Mean±SD)P-ValueDFS (months)43 (1-233), 52.7±45.227 (1-84), 34.3±25.326 (1-113), 33.1±26.60.187OS (months)46 (1-312), 56.9±51.827 (1-84), 34.4±25.326 (1-113), 34.8±28.70.628§ Kaplan-Meier survival curves would be displayed in the poster High Ki-67 index (p=0.046) appeared to be the significant DFS related prognostic factor for PMBC, whereas estrogen receptor (ER) status (univariate p=0.000, multivariate p=0.062) and immunophenotype (luminal, her2, or triple-negative, univariate p=0.000, multivariate p=0.079) might be the potential DFS predictors for MMBC. None of the above-mentioned clinicopathological factors could serve as OS predictors for MBC. Conclusion: This population-based study showed that there were significant difference in nodal status, Ki-67, Her2 positivity and targeted therapy between PMBC and MMBC, and furthermore in tumor size, stage and chemotherapy among PMBC and subgroups of MMBC such as MBC+DCIS and MBC+IDC. However, survival outcomes were similar between these clinical entities and subgroups, suggesting the intra-tumoral heterogeneity might not interfere with survival outcomes of MBC in Chinese woman. High Ki-67 index was identified as the significant DFS related prognostic factor for PMBC, whereas ER status and immunophenotype as the potential DFS predictors for MMBC. Citation Format: Yao R, Pan B, Sun Q, Zhou Y, Mao F, Lin Y, Guan J, Wang X, Zhang Y, Zhang X, Shen S, Zhong Y, Xu Y, Shi J, Zhu Q, Cai F, Liang Z. Prognosis of subtypes of the mucinous breast carcinoma in Chinese women: A population-based study of 32-year experience (1983-2014). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-05-12.

This study was aimed at investigating the role and molecular mechanism of Sam68 in cervical cancer lymph node metastasis.Sam68 expression profile was detected by quantitative polymerase chain reaction, western blotting and immunohistochemical staining. Short hairpin RNA interfering approach was employed to suppress endogenous Sam68 expression in cervical cancer cells to determine its role in metastasis and the possible mechanism.Sam68 expression in cervical cancer was significantly up-regulated at both messenger RNA and protein levels compared with that in normal cervical tissues. The high expression level of Sam68 and its cytoplasmic localization were significantly associated with risk factors including pelvic lymph node metastasis (P0.001), and served as independent prognostic factors for predicting shortening of the overall survival time and disease-free survival time in patients with early-stage cervical cancer. Moreover, down-regulation of Sam68 in cervical cancer cells remarkably inhibited cellular motility and invasion. In addition, down-regulation of Sam68 reversed epithelial-mesenchymal transition through inhibiting the Akt/ GSK-3β/Snail pathway.This study demonstrated that Sam68 could induce cervical cancer lymph node metastasis through regulating epithelial-mesenchymal transition, and Sam68 expression profile possessed the potential to serve as predictors of pelvic lymph node metastasis in cervical cancer patients.

We aimed to determine the efficacy and toxicity of treating locally advanced cervical cancer (LACC) with a neoadjuvant chemotherapy (NAC) regimen combining docetaxel and cisplatin followed by radical surgery.We retrospectively reviewed the clinical records of patients with stage IB2 - IIB (tumor diameter ≥ 4 cm) disease admitted between January 2007 and July 2009 who, before radical hysterectomy and pelvic lymph node dissection, received two to three courses of an NAC regimen comprising docetaxel (75 mg/m²) and cisplatin (70 - 75 mg/m²).Fifty-two patients with LACC received 109 cycles of NAC. The objective response rate was 86.5% (26.9% CR and 17.3% pathological CR). Stage IB2 disease had a more favorable response to NAC (95.7%, p = 0.019). Deep stromal invasion and lymph-vascular space metastasis rates were significantly lower in NAC responders (p = 0.033) than in nonresponders (p = 0.012). Most side effects of NAC were mild or moderate. Log-rank test showed the 2-year overall survival and progression-free survival rates were 100 and 90.3% for NAC responders, compared with only 57.1% (p = 0.000) and 68.6% for nonresponders (p = 0.012), respectively.Neoadjuvant docetaxel combined with cisplatin yielded a high response rate with well tolerable toxicity for LACC and could decrease pathological risk factors in NAC responders.

Aim: Nomograms are powerful methods for individually predicting prognosis of cancer patients through combining extensive significant prognostic factors. The aim of this study was to develop a nomogram to predict overall survival (OS) of non-metastatic nasopharyngeal carcinoma (NPC) patients who had undergone curative therapy (radiochemotherapy). Methods: We retrospectively collected a consecutive cohort of 1520 NPC patients who received treatment at Cancer Center of Sun Yat-sen University during November 2000 to September 2003. Multivariate stepwise Cox regression analysis was used to identify prognostic factors which were then integrated to establish the nomogram. The predictive accuracy and discriminative ability was measured by concordance index (C-index) and risk group stratification. The nomogram was subjected to bootstrap internal validation as well as external validation with a separate cohort of 464 patients who received intensity modulated radiation therapy (IMRT) in our center. Results: From 16 variables being examined, we identified 7 independent prognostic factors (age, T stage, N stage, body mass index, neutrophil-lymphocyte ratio, serum level of lactate dehydrogenase and alkaline phosphatase). A nomogram was built by incorporating these factors. The calibration curves showed that prediction of 1, 3, and 5-year OS were in good concordance with the actual observation in the bootstrap validation, but were slightly underestimated in the IMRT cohort. The C-index of the nomogram was statistically higher than that of the 7th edition TNM stage for predicting survival (0.68 vs. 0.62, P = 0.01). The stratification into different risk groups allowed significant segregation of survival curves in each TNM stage respectively, which could be also applied to IMRT cohort. Conclusions: We developed and validated a novel nomogram that provided more accurate prediction for OS of non-metastatic NPC patients who had undergone curative therapy, compared with the TNM staging system. In addition, this prognostic model could project to patients who received IMRT. External validation is ongoing. Disclosure: All authors have declared no conflicts of interest.

e13516 Background: Depression is commonly seen in women with breast cancer, which is associated with worse survival. In China, we have treated breast cancer patients with Chinese medicinal herbs fo...