Following the publication of the above article, the authors drew to the Editor's attention that they had inadvertently used the same immunohistochemical image to show the experiments depicting the zoledronic acid‑treated MCF‑7/HIF‑1α xenograft (the 'ZOL/MCF‑7/hif' panel) and the fulvestrant‑treated MCF‑7/vector xenograft (the 'FUL/MCF‑7/cdh' panel) in Fig. 3A on p. 5474. Subsequently, upon performing an independent review of the data in this paper, the Editorial Office pointed out to the authors that the same colony‑formation assay image had been included in Fig. 1C to show the 'MCF‑7/cdh‑ZOL' and 'MCF‑7/cdh‑FUL' experiments. The authors re‑examined their original data, and realized that inadvertent errors were made during the compilation of this pair of figures. The corrected versions of Figs. 1 and 3 are shown on the next two pages, now featuring the correct data for the 'MCF‑7/cdh‑ZOL' experiment in Fig. 1C and the 'ZOL/MCF‑7/hif' experiment in Fig. 3A. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of Molecular Medicine Reports for granting them the opportunity to publish this. Furthermore, they regret that these errors were introduced into the paper, even though they did not substantially alter any of the major conclusions reported in the paper, and apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 17: 5470‑5476, 2018; DOI: 10.3892/mmr.2018.8514].

PDF file - 78K, Table S1. List of primer and siRNA sequences; Table S2. Intersection between Predict target of miR-200a and genes that regulate the apoptotic processes; Table S3. The number of zebrafish embryos with migrating tumor (Dil) cells transfected with miR-200a, YAP1 siRNA, miR-Ctrl , Scramble RNA, antagomiR-200a and antagomiR-Ctrl respectively; Table S4. The number of migrated cells per tail vein of zebrafish embryos that had migrating tumor (Dil) cells transfected with miR-200a, YAP1 siRNA, miR-Ctrl and Scramble RNA, antagomiR-200a and antagomiR-Ctrl respectively

PDF file - 250K, The expression of EMT marker in MDA-MB-231 and MCF-7 cells

Translation on this Article from Involvement of a Novel Chemokine Decoy Receptor CCX-CKR in Breast Cancer Growth, Metastasis and Patient Survival

Supplementary Figure S1 from Enhanced Expression of Rab27A Gene by Breast Cancer Cells Promoting Invasiveness and the Metastasis Potential by Secretion of Insulin-Like Growth Factor-II

PDF file - 277K, In vivo lung metastases induced by breast cancer cells

PDF file - 947K, Anoikis induced by suspension culture

PDF file - 208K, Colony formation assay for miR-200a candidate targets

Background and purpose: Currently, several studies have demonstrated that body mass index (BMI) is a prognostic factor in breast cancer. The study aimed to assess the association pattern of BMI with mortality risk among patients of different age groups. Methods: This retrospective cohort study included the clinical characteristics and survival status of 25 629 patients diagnosed with breast cancer and subsequently hospitalized in Fudan University Shanghai Cancer Center between January 1, 2008 and December 31, 2016. The association between BMI and prognosis of breast cancer patients in different age subgroups was analyzed using Cox proportional hazards regression model with restricted cubic splines adjusting the main prognostic factors. Results: BMI and age were both influencing factors of breast cancer prognosis, and there was a significant interaction (P = 0.011). The pattern of association between risk of death and BMI differed among different age groups. A "J-shaped" association between risk of death and BMI was observed in the patients younger than 35 years, with a BMI of 20.16 kg/m2 corresponding to the lowest risk of death. In the age group of 35-60 years, no significant change in the risk of death was observed in patients with BMI below 23 kg/m2, and the risk of death in patients with BMI above 23 kg/m2 increased with increasing BMI; A "U-shaped" association between risk of death and BMI was observed in the patients older than 60 years, with a BMI of 23.86 kg/m2 being the lowest. The risk of death was more sensitive to changes in BMI in patients aged less than 35 years than in those aged 35-60 years and those aged more than 60 years. Conclusion: BMI and age have a significant interaction in the prognosis of breast cancer when adjusted for potential confounding factors. The association pattern between the risk of death and BMI of patients in different age groups is different. For patients under 35 years old, the lowest risk of death corresponds to BMI at diagnosis of about 20 kg/m2, while for patients over 60 years old, the lowest risk of death corresponds to a BMI at diagnosis of about 24 kg/m2.

背景 与目的:目前已有研究表明体重指数(body mass index,BMI)是乳腺癌患者预后的影响因素.本研究旨在分析不同年龄段的乳腺癌患者的BMI与其死亡风险的关联.方法:回顾性收集2008年1月1日—2016年12月31日在复旦大学附属肿瘤医院住院治疗的25629例初诊乳腺癌患者的临床特征和生存状况,经调整主要预后影响因素,以限制性立方样条Cox比例风险回归模型分析在不同年龄亚组中BMI与乳腺癌患者预后的关联.结果:BMI与年龄均为乳腺癌预后的影响因素,且存在显著的交互作用.不同年龄组患者的死亡风险与BMI的关联模式有所不同.在年龄小于35岁组观察到死亡风险与BMI呈现"J"型的关联,BMI为20.16 kg/m2的患者死亡风险最低;在年龄35～60岁组观察到BMI在23 kg/m2以下的患者死亡风险随着BMI的增加没有明显变化,BMI在23 kg/m2以上的患者死亡风险随着BMI的增加而增加;而在年龄大于60岁组观察到死亡风险与BMI呈现"U"型的关联,BMI为23.86 kg/m2的女性死亡风险最低.年龄小于35岁组患者的死亡风险对BMI变化的敏感程度相较于年龄35～60岁组和大于60岁组更高.结论:在校正了相关预后因素后,BMI与年龄对乳腺癌患者预后的影响有显著的交互作用,不同年龄组患者的死亡风险与BMI的关联模式有所不同,对于年轻患者,死亡风险最低对应的诊断时BMI约为20 kg/m2,而对于60岁以上患者,死亡风险最低对应的诊断时BMI约为24 kg/m2.

Importance The value of platinum-based adjuvant chemotherapy in patients with triple-negative breast cancer (TNBC) remains controversial, as does whether BRCA1 and BRCA2 (BRCA1/2) germline variants are associated with platinum treatment sensitivity. Objective To compare 6 cycles of paclitaxel plus carboplatin (PCb) with a standard-dose regimen of 3 cycles of cyclophosphamide, epirubicin, and fluorouracil followed by 3 cycles of docetaxel (CEF-T). Design, Setting, and Participants This phase 3 randomized clinical trial was conducted at 9 cancer centers and hospitals in China. Between July 1, 2011, and April 30, 2016, women aged 18 to 70 years with operable TNBC after definitive surgery (having pathologically confirmed regional node-positive disease or node-negative disease with tumor diameter >10 mm) were screened and enrolled. Exclusion criteria included having metastatic or locally advanced disease, having non-TNBC, or receiving preoperative anticancer therapy. Data were analyzed from December 1, 2019, to January 31, 2020, from the intent-to-treat population as prespecified in the protocol. Interventions Participants were randomized to receive PCb (paclitaxel 80 mg/m(2)and carboplatin [area under the curve = 2] on days 1, 8, and 15 every 28 days for 6 cycles) or CEF-T (cyclophosphamide 500 mg/m(2), epirubicin 100 mg/m(2), and fluorouracil 500 mg/m(2)every 3 weeks for 3 cycles followed by docetaxel 100 mg/m(2)every 3 weeks for 3 cycles). Main Outcomes and Measures The primary end point was disease-free survival (DFS). Secondary end points included overall survival, distant DFS, relapse-free survival, DFS in patients with germline variants in BRCA1/2 or homologous recombination repair (HRR)-related genes, and toxicity. Results A total of 647 patients (mean [SD] age, 51 [44-57] years) with operable TNBC were randomized to receive CEF-T (n = 322) or PCb (n = 325). At a median follow-up of 62 months, DFS time was longer in those assigned to PCb compared with CEF-T (5-year DFS, 86.5% vs 80.3%, hazard ratio [HR] = 0.65; 95% CI, 0.44-0.96; P = .03). Similar outcomes were observed for distant DFS and relapse-free survival. There was no statistically significant difference in overall survival between the groups (HR = 0.71; 95% CI, 0.42-1.22, P = .22). In the exploratory and hypothesis-generating subgroup analyses of PCb vs CEF-T, the HR for DFS was 0.44 (95% CI, 0.15-1.31; P = .14) in patients with the BRCA1/2 variant and 0.39 (95% CI, 0.15-0.99; P = .04) in those with the HRR variant. Safety data were consistent with the known safety profiles of relevant drugs. Conclusions and Relevance These findings suggest that a paclitaxel-plus-carboplatin regimen is an effective alternative adjuvant chemotherapy choice for patients with operable TNBC. In the era of molecular classification, subsets of TNBC sensitive to PCb should be further investigated.

Background and purpose: The study described 5- and 10-year observed survival and disease-free survival (DFS) of over 35 thousand breast cancer patients from a hospital-based cancer registry database, aiming to provide real world evidence of long-term survival among Chinese breast cancer patients. Methods: A total of 35 872 hospitalized breast cancer patients in Fudan University Shanghai Cancer Center (FUSCC) from Jan. 1, 2003 to Dec. 31, 2017 were included in the analysis. Medical records review, telephone visits and death registry data linkage were carried out for collecting endpoint data. The last follow-up date was Nov. 30, 2019. Kaplan-Meier method was uesd to evaluate the 1-year, 3-year, 5-year and 10-year overall survival (OS) and DFS rate for all, and data were stratified by age group, gender and calendar periods. Results: With a median follow-up time of 4.7 years, the 5-year and 10-year OS of all patients was 92.5% and 83.0%, while DFS was 86.6% and 77.0% respectively. OS and DFS among different age groups were significantly different, while no significant difference existed between females and males. The 5-year OS and DFS for patients diagnosed during the five periods of 2003-2005, 2006-2008, 2009-2011, 2012-2014, 2015-2017 were 85.8%, 92.0%, 92.1%, 92.9%, 93.8% and 70.2%, 84.7%, 86.0%, 87.8%, 90.1%, respectively. The 10-year OS for patients during 2003-2005 and 2006-2008 was 71.0% and 82.6%, while DFS was 56.0% and 75.2%, showing an improvement of 11.6% on OS and 19.2% on DFS in 2006-2008 compared with in 2003-2005, respectively. Conclusion: It is the first report on survival up to 10 years among Chinese breast cancer patients, showing that the patients have experienced significant improvement on OS and DFS during consecutive calendar periods between 2003 and 2017, which might be contributed to early diagnosis from cancer screening and novel treatments. Besides, patients younger than 35 experience poor survival and need more concern in the future.

Background The current randomized, controlled, multicenter clinical trial was conducted to investigate the efficacy of concurrent neoadjuvant chemotherapy (NCT) and estrogen deprivation in patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Methods Eligible patients with AJCC stage IIB to stage IIIC, ER-positive, HER2-negative breast cancer were enrolled and randomly assigned to receive NCT with or without estrogen deprivation. The primary endpoint was the objective response rate (ORR). Results A total of 249 patients were assigned to either neoadjuvant chemoendocrine therapy (NCET) (125 patients) or the NCT group (124 patients). In the intention-to-treat analysis, the ORR was found to be significantly higher in the NCET group compared with the NCT group (84.8% vs 72.6%; odds ratio, 2.11 [95% CI, 1.13-3.95; P = .02). The efficacy of NCET was more prominent in tumors with a higher Ki-67 index (>20%), with an ORR of 91.2% reported in the NCET group versus 68.7% in the NCT group (P = .001). The pathologic complete response and pathological response rates did not differ significantly between the 2 groups. Although there was no significant difference with regard to progression-free survival (PFS) between the 2 groups (P = .188), patients with a higher baseline Ki-67 index appeared to derive a greater PFS benefit from NCET (2-year PFS rate of 91.5% in the NCET group vs 76.5% in the NCT group; P = .058). Adding endocrine agents to NCT did not result in significant differences in adverse events (grade 3 or 4; graded according to National Cancer Institute Common Terminology Criteria for Adverse Events [version 3.0]) between the 2 groups. Conclusions The addition of estrogen deprivation to NCT appears to improve the clinical response in patients with ER-positive, HER2-negative breast cancer, especially for those individuals with a higher Ki-67 index. Patients with a higher Ki-67 index might derive more PFS benefit from concurrent neoadjuvant treatment.

Background and purpose: BRCA1 and BRCA2 are two most common genes associated with hereditary breast cancers. Our research intended to discover the pathologic features of Chinese breast cancers with BRCA1/2 mutations. Methods: We included 287 breast cancers between 2011 and 2017, and BRCA1/2 germline mutation tests were carried out. The pathologic features of each patient were collected at Department of Pathology in Fudan University Shanghai Cancer Center for comparative study. Results: Of the 287 breast cancers, 66 cases were BRCA1 mutation positive, 47 cases were BRCA2 mutation positive and 174 cases were BRCA1/2 mutation negative. BRCA1 mutation breast cancer had higher nuclear grade tumors than the other two groups (P<0.001), 72.7% of BRCA1 mutation breast cancers were, whereas 25.5% of BRCA2 and 19.0% of non-BRCA1/2 mutation breast cancers were triple negative (P<0.001). BRCA1 and BRCA2 mutated breast cancers had lower human epidermal growth factor receptor 2(HER2) expression than non-BRCA1/2 mutated breast cancers (P<0.001). The positive expressions of cytokeratin 5/6 (CK5/6) and epidermal growth factor receptor (EGFR) in BRCA1 mutation breast cancer were about 50%, significantly higher than those of the other two groups (P<0.001), and androgen receptor (AR) positive was less frequently seen in BRCA1 mutation breast cancers. Conclusion: These results suggest that BRCA1 mutation-associated breast cancers had clinical pathologic characteristics, such as triple negative, more positive CK5/6 or EGFR status. BRCA1/2 mutated breast cancers had lower HER2 expression.

腋窝淋巴结状态是判断乳腺癌患者分期的重要指标,也是影响患者预后的一项独立危险因素.腋窝淋巴结处理是乳腺癌外科治疗的重要组成部分,前哨淋巴结活检已是临床淋巴结阴性患者的腋窝标准处理.随着前哨淋巴结研究的进展,前哨淋巴结阳性的腋窝处理方式及新辅助治疗患者的前哨淋巴结活检问题已成为近期研究的热点.本文就腋窝淋巴结管理的理念变迁及前哨淋巴结活检技术的新进研究进展作一探讨.

To investigate ovarian function and therapeutic efficacy among estrogen receptor (ER)-positive, premenopausal breast cancer patients treated with gonadotropin-releasing hormone agonist (GnRHa) and chemotherapy simultaneously or sequentially.

Abstract Background: HER2 overexpression/amplification occurs in ˜15–20% of primary breast cancers (BC) in western populations, although the incidence of HER2+ BC in Asia may be higher (20–44% depending on the country). Neratinib is an irreversible tyrosine kinase inhibitor of HER1, 2 and 4, with demonstrated efficacy in trastuzumab-pretreated and trastuzumab-naïve HER2+ metastatic BC. To better understand the effects of neratinib in Asian patients (pts), we performed a pooled analysis of 6 phase I/II clinical trials in pts with metastatic HER2+ BC or other solid tumors. Methods: Six prospective phase I/II or II clinical studies of neratinib, alone or in combination with other targeted or chemotherapeutic agents, in pts with metastatic HER2+ BC or other solid tumors were included. A pooled analysis of data from these trials was performed to compare efficacy and safety outcomes with neratinib-based therapy in pts from centers in Asian countries (China, Hong Kong, Japan, Korea, Malaysia, Singapore, and Taiwan) vs pts from other regions (Europe, North/South America, Australasia). Analyses were descriptive in nature. All trials were registered (Clinicaltrials.gov identifiers: NCT00445458; NCT00706030; NCT00398567; NCT00915018; NCT00741260; NCT00300781). Results: A total of 966 pts were included (Asia, n=329; other regions, n=637). Most pts had HER2+ BC (96.8%); the remaining pts had other solid tumors (3.2%). Baseline characteristics were similar in pts from Asia vs other regions: median age, 52 vs 53 years; ECOG performance status 0/1, 98% vs 97%; hormone receptor-positive, 50% vs 48%. Neratinib was given as monotherapy (n=136) or in combination with paclitaxel (n=352), capecitabine (n=105), vinorelbine (n=91) or trastuzumab (n=45). Median duration of neratinib treatment in pts from Asia vs other regions was 338 vs 213 days; 47.3% vs 26.5% of pts received treatment for >1 year. Efficacy outcomes in pts with HER2+ BC are summarized in the table. AsiaOther regionsEndpoint(n=239)a(n=435)aORR, n (%)171 (71.5)243 (55.9)CBR, n (%)183 (76.6)275 (63.2)Median PFS (95% CI), weeks56.1 (48.0-67.7)39.3 (32.7-44.1)CBR, clinical benefit rate; ORR, objective response rate; PFS, progression-free survival; a. Excluded phase I, non-BC and non-neratinib–treated pts Incidence rates of grade 3/4 adverse events (Asia, 62.4% vs other regions, 66.0%) and grade 3/4 diarrhea were similar in both cohorts (25.6% vs 27.2%), but pts from Asia appeared to experience more grade 3/4 hematological events (neutropenia: 21.4% vs 9.8%; leukopenia: 13.0% vs 4.9%). Dose modifications were similar between cohorts, but Asian pts were less likely to withdraw from therapy (2.1% vs other regions, 4.7%). Conclusions: Asian pts in the pooled metastatic trials appeared to have better ORR, CBR and PFS with neratinib-based therapy than pts from other regions. The safety and tolerability profile of neratinib was broadly similar between regions, except for a higher rate of grade 3/4 hematological events among Asian pts; however, Asian pts were less likely to withdraw from neratinib and stayed on treatment longer, a possible contributing factor to the better clinical outcomes observed in this cohort. Citation Format: Xu B, Kim S-B, Inoue K, Shen Z-Z, Lee JR, Zhang B, Chow L. Efficacy, safety and tolerability of neratinib-based therapy in patients from Asia with metastatic HER2+ breast cancer and other solid tumors: A pooled analysis of 6 clinical trials [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-21-17.

Background and purpose: Many factors have impacts on the surgery approach of breast cancer. The purpose of this study was to analyze the influence factors of breast reconstruction for patients with breast cancer, focusing on the relationship between travel distance and breast reconstruction. Methods: Retrospective review of all female breast cancer patients staging 0-Ⅱ who underwent unilateral or bilateral mastectomy with or without breast reconstruction at Fudan University Shanghai Cancer Center from 1999 to 2015 was conducted in the study. Analysis of travel distance and breast reconstruction rate was performed. Results: Non-Shanghai patients have higher breast reconstruction rate after mastectomy compared with Shanghai patients (6.1％ vs 4.5％, P＜0.001). Travel distance may have an influence on the breast reconstruction rate (P=0.035). Univariate regression analysis showed that the increase of travel distance was the predictor of breast reconstruction, and that the increase of age or body mass index (BMI), or the later TNM stage had a negative correlation with breast reconstruction (P＜0.001). Multiple regression analysis demonstrated that the increase of age or BMI, or the later TNM stage was the independent predictor of the refusal of breast reconstruction (P＜0.001), but travel distance was not (P＞0.05). No significant correlation between the travel distance and breast reconstruction types was indicated. Negative correlation was observed between age and travel distance (P＜0.001). Conclusion: Age, BMI and tumor stage are the main influence factors of breast reconstruction, while travel distance shows a linear correlation with it.

认识改变:从“单一”到“多样” 近几十年来,随着分子生物学的发展、对肿瘤特性的了解,我们对肿瘤的认识不再单一化,开始认识到不同肿瘤的生物机制完全不同,认识变得多样化. 过去,人们对肿瘤发展模式的认识是肿瘤先在局部生长,然后转移到淋巴结,最后转移到血道,因而扩大局部手术切除范围能提高生存率.可是随着时间的推移,我们发现应针对肿瘤不同的生物学特性,采取不同的治疗方法,来提高治愈率.