Breast cancer (BC) is the most common type of malignancy and the leading cause of cancer-associated mortality in women worldwide. As such, assessing the metabolic changes during human breast carcinogenesis is key for developing disease prevention methods and treatment. In the present study, non-targeted metabolomics with chemometrics based on ultra-high performance liquid chromatography-high-resolution mass spectrometry were performed to assess differences in serum metabolite patterns between patients with BC and healthy individuals. A total of 3,246 metabolites in the sera of healthy controls and patients with BC were found. Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that arginine, proline, nicotinate, nicotinamide, caffeine and arachidonic acid metabolism, as well as fatty acid biosynthesis were significantly altered in patients with BC in comparison with controls. These results suggested that serum metabolic profiling has potential for discovering molecular biomarkers for the detection of BC. It may also further the understanding of the underlying mechanisms associated with this disease.

Background Lung metastasis is a significant adverse predictor of prognosis in patients with breast cancer. Accurate estimation for the prognosis of patients with lung metastasis and population-based validation for the models are lacking. In the present study, we aimed to establish the nomogram to identify prognostic factors correlated with lung metastases and evaluate individualized survival in patients with lung metastasis based on SEER (Surveillance, Epidemiology, and End Results) database. Methods We selected 1197 patients diagnosed with breast cancer with lung metastasis (BCLM) from the SEER database and randomly assigned them to the training group ( n = 837) and the testing group ( n = 360). Based on univariate and multivariate Cox regression analysis, we evaluated the effects of multiple variables on survival in the training group and constructed a nomogram to predict the 1-, 2-, and 3-year survival probability of patients. The nomogram were verified internally and externally by Concordance index (C-index), Net Reclassification (NRI), Integrated Discrimination Improvement (IDI), Decision Curve Analysis (DCA), and calibration plots. Results According to the results of multi-factor Cox regression analysis, age, histopathology, grade, marital status, bone metastasis, brain metastasis, liver metastasis, human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), progesterone receptor (PR), surgery, neoadjuvant therapy and chemotherapy were considered as independent prognostic factors for patients with BCLM. The C-index in the training group was 0.719 and the testing group was 0.695, respectively. The AUC values of the 1-, 2-, and 3-year prognostic nomogram in the training group were 0.798, 0.790 and 0.793, and the corresponding AUC values in the testing group were 0.765, 0.761 and 0.722. The calculation results of IDI and NRI were shown. The nomograms significantly improved the risk reclassification for 1-, 2-, and 3-year overall mortality prediction compared with the AJCC 7th staging system. According to the calibration plot, nomograms showed good consistency between predicted and actual overall survival (OS) values for the patients with BCLM. DCA showed that nomograms had better net benefits at different threshold probabilities at different time points compared with the AJCC 7th staging system. Conclusions Nomograms that predicted 1-, 2-, and 3-year OS for patients with BCLM were successfully constructed and validated to help physicians in evaluating the high risk of mortality in breast cancer patients.

癌细胞通过调节代谢方式以提供大量的ATP和生物分子,来满足细胞生长、分裂和生存的需要.近年来,癌细胞中脂质代谢的变化受到越来越多的关注,因为脂肪酸不仅是膜基质的主要成分,也是ATP和次级信使的主要来源.乳腺癌细胞的脂质代谢受Warburg效应的调控,癌细胞合成大量脂肪酸并促进其生成膜磷脂来进行信号传导和癌细胞的日常代谢.脂肪酸合成酶FASN是脂肪酸从头合成的关键酶,越来越多的研究认为FASN过表达可促进乳腺癌细胞对治疗的抵抗.本综述中,我们重点介绍FASN诱导乳腺癌全身系统治疗抵抗方面的最新进展,并展望靶向抑制FASN为乳腺癌治疗增敏的潜在临床应用价值.

Abstract Background Gynecomastia is a common condition in clinical practice. The present study aimed to review the clinical data of ER-positive gynecomastia patients treated by tamoxifen (TAM) versus surgery and discussed the clinical effects of the two treatment strategies. Method We retrospectively collected the clinical indicators of patients with unilateral or bilateral gynecomastia who received treatment at our hospital between April 2018 and December 2021. Depending on the treatment received, the patients were divided into TAM and surgery groups. Result A total of 170 patients were recruited, including 91 patients in TAM group and 79 patients in surgery group. The age of the patients differed significantly between the TAM and surgery groups (P < 0.01). The estrogen level was closer in patients with stable and progressive disease, but significantly different in patients of glandular shrinkage in TAM group (P < 0.01). The proportion of patients achieving stable disease was higher among those with clinical grade 1–2. Among patients classified as clinical grade 3, the proportion of patients achieving glandular shrinkage of the breast was higher after TAM treatment (P < 0.05). The age and length of hospital stay were significantly different in patients undergoing open surgery than minimally invasive rotary cutting surgery and mammoscopic-assisted glandular resection (P < 0.01). Patients had significantly different complications including mild postoperative pain, hematoma, nipple necrosis, nipple paresthesias and effusions among the surgery subgroups (all P < 0.05). The estrogen level and the type of surgery were significantly different between the surgical recurrence and non-recurrence subgroups (P < 0.05). The difference in the thickness of glandular tissues upon the color Doppler ultrasound also reached a statistical significance between the two groups (P = 0.050). An elevated estrogen level was a factor leading to TAM failure. Among surgical patients, the thickness of glandular tissues, estrogen level, and type of surgery performed were risk factors for postoperative recurrence (all P < 0.05). Conclusion Both treatment strategies can effectively treat gynecomastia, but different treatment methods can benefit different patients. TAM treatment is more beneficial than surgery for patients who cannot tolerate surgery, have a low estrogen level, and are clinical grade 1–2. Surgery treatment is better than TAM for patients of clinical grade 3. Different surgery options may lead to different complications. Patients with a greater glandular tissue thickness and a higher estrogen level were shown to have a higher risk of recurrence.

In recent years, breast cancer attracts more and more attention because of its high incidence. To explore the molecular functions and mechanisms, we performed RNA sequencing on the tumor tissues and their paired normal tissues from three breast cancer patients. By differential expression analysis, we found 3764 differentially expressed (DE) mRNAs, 5416 DE lncRNAs, and 148 DE circRNAs. Enrichment analysis suggested that the DE lncRNAs and DE circRNAs were enriched in mitochondria and nucleus, which indicated that they may participate in the vital metabolism directly or indirectly, such as fatty acid metabolism. Subsequently, the protein-protein interaction (PPI) network was constructed and we got 8 key proteins, of which the matrix metalloproteinase-9 (MMP9; degree 5) draws our attention. Based on the 38 up-regulated circRNAs and 14 down-regulated circRNAs, we constructed competing endogenous RNA (ceRNA) networks, from which the has-miR-6794-5p has been identified to enriched in the up-regulated network and correlated with the circNFIX directly. At this point, we presented that the circNFIX and MMP9 may play a significant role by regulating fatty acid metabolism in breast cancer.

Abstract Background: Ubiquitin-conjugating enzyme E2T (UBE2T), an E2 ubiquitin-conjugating enzyme, is verified to play an important role in the tumorigenesis of various cancers. By downregulation of BRCA1, UBE2T affects the growth of BC cells. However, the clinical significance of UBE2T is uncertain. To explore the role of UBE2T in breast cancer (BC). Methods: Firstly, we analyzed the correlations between UBE2T and clinicopathological characteristics of BC by the TCGA database. Next, Cox regression and Kaplan-Meier analysis were utilized for association between clinicopathological features and the overall survival (OS). Kaplan-Meier analysis and ROC plotter were used for survival analysis and drug sensitivity. Results：UBE2T was significantly upregulated in BC in comparison with para cancer tissue(p<0.001). The high expression of UBE2T is related to lager tumor sizes (p=0.006) and later clinical stages (p=0.001). UBE2T is verified to be correlated with ER, PR, HER2 status of BC. The expression level of UBE2T varies in different molecular subtypes of BC. Further research revealed that UBE2T mainly affected the recurrence-free time of BC in subgroups. Conclusions: Univariate analysis and multivariate analysis certified that UBE2T was an independent indicator for BC prognosis. UBE2T is proven to be a good biomarker for predicting the responds of BC patients to aromatase inhibitor (AI).

目的 探讨分子分型、肿瘤直径、淋巴结情况、增殖细胞核抗原(Ki)-67表达等对乳腺癌患者新辅助化疗效果的影响.方法 收集接受新辅助化疗的44例中晚期乳腺癌患者的临床资料,分析分子分型、肿瘤直径、淋巴结情况、Ki-67表达与新辅助化疗临床疗效间的关系.结果 44例乳腺癌患者病灶影像学评价完全缓解率为6.0％,部分缓解率为54.8％,总缓解率为61.3％,疾病进展率为9.0％,疾病稳定率为29.5％,无效率为38.6％.多因素分析结果显示分子分型、肿瘤直径及Ki-67表达情况均与疗效相关,而淋巴结情况与疗效无显著相关性.结论 分子分型、肿瘤直径、Ki-67表达可作为乳腺癌患者新辅助化疗疗效参考指标,新辅助化疗的疗效可作为其预后指标.

乳腺癌是全球女性发病率最高的恶性肿瘤, 2020年全球乳腺癌新发病例高达226万例,超过了肺癌成为全球第一大肿瘤,严重威胁着女性健康[1].乳腺癌是高度异质性的疾病,第2代测序技术证实,在93个编码蛋白质的乳腺癌基因中携带可能的驱动突变[2].因此,现行的基于乳腺癌临床病理特征以及雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)及人表皮生长因子受体 2 (human epidermal growth factor receptor 2, HER2)的表达制定综合方案,并非适用于所有的乳腺癌患者.传统的二维细胞培养和人源性肿瘤异种移植模型为乳腺癌的研究探索提供了大量的材料,但由于实验技术缺陷、培养周期长等因素难以满足深入的研究要求.因此,建立一种能够准确模拟人体肿瘤特征的实验模型成为迫切需要.近年来,通过优化各种培养条件建立的乳腺癌类器官模型,由于其取材方便、培养周期短和遗传稳定等特点,能够最大程度的还原乳腺癌细胞在体内的组织和分子特性,重现部分乳腺功能[3],有望在乳腺癌发病机制研究、个体化治疗、新药开发等领域发挥重要作用.

Neuroendocrine carcinoma of the breast (NECB) is a rare type of breast cancer. The clinical features and morphology between NECB and other subtypes of breast cancer are indistinguishable. Currently, the diagnosis of NECB mainly relies on immunohistochemical markers including chromogranin and synaptophysin. It is urgent to find new diagnostic markers for NECB. Some evidence suggests a link between high prolactin level and breast cancer development, however, it is unclear whether NECB may be associated with hyperprolactinemia. Here we report two cases of primary NECB with hyperprolactinemia. One patient had a history of mental disorder, while the other experienced pregnancy. Metastatic and associated tumors were not found in both cases, and postoperative studies showed one case was hormone-receptor-dependent, but the other was hormone-receptor-independent. The cases presented here suggest hyperprolactinemia may contribute to NECB development.

Gynecomastia is the most common benign disease in males with an increasing prevalence in recent years. It may cause local pain and psychological disorders. The vacuum-assisted breast biopsy system has been reported to be a novel surgical approach for the treatment of gynecomastia. However, there are little detailed reports comparing the curative effect between traditional surgery and vacuum-assisted breast biopsy for gynecomastia. Besides, there was little study which compared the application of two different systems for the treatment of gynecomastia. Our study aimed to investigate the effectiveness of vacuum-assisted breast biopsy systems for patients with gynecomastia. We retrospectively reviewed 83 patients with gynecomastia between January 2015 and December 2019. Open surgery was performed in 56 patients, and vacuum-assisted breast biopsy was performed in 27 patients. The characteristics of patients as well as the curative effects between the two groups were analyzed. The two vacuum-assisted breast biopsy systems (Mammotome and Encor) were performed for the patients with gynecomastia. The efficacy, safety, complications, and patient satisfactions were recorded during postoperative follow-up periods. Compared with the open surgery group, the vacuum-assisted breast biopsy group had significantly smaller scar sizes left after the operation (5.5 ± 1.3 cm vs 0.8 ± 0.2 cm, p < 0.001), and shorter hospital stay time (5.5 ± 2.4 ds vs 3.1 ± 1.6 ds, p < 0.001). Patients in vacuum-assisted breast biopsy group had a better cosmetic outcome than those in open surgery group. There were no statistically significant differences between the two vacuum-assisted breast biopsy systems according to the mean age, the mean operation time, sites, or grade. In addition, no serious complications were observed in vacuum-assisted breast biopsy group. All the patients recovered well and were satisfied with the cosmetic outcomes. The vacuum-assisted breast biopsy system can be used as a feasible and minimally invasive approach for the treatment of gynecomastia. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Objective: The aim of this study to examine the expression of FOXA1, ER, and PR in breast cancer and investigate the association between FOXA1 expression and clinical parameters. Materials and Methods: One hundred one cases with primary breast cancer were collected and immunohistochemistry was employed to examine the expression of FOXA1, ER, and PR. The correlation of FOXA1 and ER, PR expression with menopausal status, tumor size, clinical stage, histological grade, recurrence, and clinical index relationship was further analyzed. Results: The positive expression of FOXA1 was 67.3%. The positive expression rate of ER in positive FOXA1 group was 66.2% (45/68). The positive expression rate of PR in positive FOXA group was 57.4% (39/68). There was no correlation between FOXA1 expression and menopausal status. Analysis of the relationship between FOXA1 and tumor diameter showed that the percentage of tumor diameter <= 2 cm, 2-5 cm, and > 5cm was 52.9%, 32.4%, and 14.7% in positive FOXA1 group. The correlation with clinical staging showed that the percentage of Stages I, II, and III was 33.8%, 41.2% and 25%, respectively, in positive FOXA1 group. Analysis of histological grade showed that the percentage of grades 1, 2, and 3 was 48.5%, 20.6%, and 23.5%, respectively, in positive FOXA1 group. The positive expression rate of P53 was 30.9%, the recurrence rate was 14.7%, and the positive expression of FOXA1 had better DFS.

Background With the extensive application of autologous fat grafting (AFG) to the breasts, postoperative complications such as breast lumps attract high attention. Breast lumps greatly reduce patient satisfaction and bring mental stress. However, there are few detailed reports about minimally invasive treatment strategies for breast lumps after AFG. Our study aimed to investigate the effectiveness of the vacuum-assisted breast biopsy (VABB) system for patients with lumps after AFG. Materials and Methods We retrospectively reviewed 37 patients with breast lumps between April 2015 and January 2019. The characteristics of patients and breast lumps were analyzed. Breast lumps were classified into four types, including cystic, solid, complex and calcification. The vacuum-assisted breast biopsy (Mammotome and Encor) was performed for the patients with lumps after AFG. The efficacy, safety, complications and patient satisfactions were recorded during postoperative follow-up periods. Results Under the guidance of ultrasound, the breast lumps could be thoroughly and accurately excised by the vacuum-assisted biopsy system. No patient experienced breast infections or major complications requiring treatment. Hematoma was observed in only 2 patients and gradually resolved without any special management. With a median follow-up of 29 months, no recurrence was observed. Furthermore, there were no statistical differences in duration of the procedures and complications between the two VABB systems. All the patients recovered well and were satisfied with the cosmetic outcome. Conclusion The vacuum-assisted breast biopsy system can be used as an effective and minimally invasive approach for the surgical management of lumps after AFG. Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Long non-coding RNA is a kind of endogenous RNA with more than 200 nucleotides in length that cannot be coded to proteins.The dysregulation of lncRNAs have been observed in various malignancies.Aberrant ex-pression of lncRNAs levels are closely associated with various malignant biological processes,including carcinogenesis, progression,drug resistance,metastasis and metabolism,through transcriptional,posttranscriptional and epigenetic regu-lation of different genes.Nowadays,breast cancer has become the most common malignant tumor and the leading course of cancer-related death among women in China.lncRNAs are significant in a series of biological processes and may be served as a potential biomarker in breast cancer.Based on the latest research evidence,the present review will summa-rize the role of lncRNA in breast cancer,which will provide a better understanding of lncRNAs in preventing,diagnos-ing,and treating breast cancer.

BACKGROUND Long noncoding RNA HOTAIR has been detected in the serum of patients with various malignances and may be served as novel biomarker for diagnosis and prognosis prediction of breast cancer. However, the value of circulating HOTAIR to predict the response to neoadjuvant chemotherapy (NAC) remains unclear. OBJECTIVE In the present study, we analyzed whether pretreatment circulating HOTAIR levels predict the response to NAC and investigated prognostic impact of circulating HOTAIR on disease-free survival (DFS) in breast cancer patients treated with NAC. METHODS Circulating HOTAIR levels in the serum of 112 breast cancer patients before NAC were measured using quantitative real-time PCR. The correlation of circulating HOTAIR with the clinicopathologic status and the response to NAC were analyzed. Kaplan-Meier survival analysis and log-rank test were used to estimate the DFS. RESULTS In 112 serum samples obtained before NAC, high circulating HOTAIR was associated with larger tumor size, more positive lymph nodes as well as more distant metastasis. However, there was no significant correlation between the circulating HOTAIR levels and age, Ki67 status or hormone receptor. Furthermore, patients with high circulating HOTAIR achieved less clinical response as well as pathologic complete response than those with low circulating HOTAIR (p< 0.05). The Kaplan-Meier survival curve with a median follow-up of 48 months demonstrated that patients with high circulating HOTAIR expression had a worse disease-free survival than those with low circulating HOTAIR (log-rank p= 0.012). CONCLUSIONS High circulating HOTAIR level correlates with less response to neoadjuvant chemotherapy as well as a worse prognosis in breast cancer patients. Therefore, the present study provides a favorable basis to use circulating HOTAIR as a predictor of neoadjuvant chemotherapy response.

Background: Upper arm lymphedema (LE) is a common complication after axillary lymph node dissection (ALND) in breast cancer patients. This retrospective cohort study aimed to validate a published nomogram to predict the risk of LE in the Chinese breast cancer patients.Methods: A total of 409 breast cancer patients who underwent breast cancer surgery and ALND (level I and II) were identified. Cox regression analysis was used to identify the risk factors for LE. The nomogram predictive of LE of breast cancer was evaluated by receiver-operating curve analysis, calibration plots, and Kaplan-Meier analysis in our study population.Results: With a median follow-up of 68 months, the 5-year cumulative incidence of LE was 22.3%. Higher body mass index (hazard ratio [HR] = 1.06, 95% CI: 1.00-1.13), neoadjuvant chemotherapy (HR = 3.76, 95% CI: 2.29-6.20), larger extend of axillary surgery (level I/II/III versus level I/II: HR = 2.39, 95% CI: 1.30-4.37), and radiotherapy (HR = 4.90, 95% CI: 1.90-12.5) were independently associated with LE. The AUC value of the nomogram was 0.706 (95% CI: 0.648-0.752). A high-risk subgroup of patients defined by nomogram had significantly higher cumulative risk of LE than those in the low-risk subgroups (P < 0.01). The calibration plots revealed that the nomogram was well calibrated (Hosmer-Lemeshow test, P = 0.0634).Conclusions: The nomogram to predict the risk of LE in breast cancer patients with ALND has been validated to be discriminative and accurate. More studies are needed to evaluate the impact of other factors (lifestyle, behaviors, and so forth) on the performance of the nomogram. (C) 2016 Elsevier Inc. All rights reserved.

AIM: To investigate the expression of forkhead box protein A1(FOXA1) BRCA1 protein,P53 and vascular endothelial growth factor(VEGF) in triple negative breast cancer(TNBC) and non-TNBC,and the relevance with the clinicopathological parameters for evaluating the prognosis.METHODS: The tumor samples were collected from 113 cases of breast cancer patients in the First Affiliated Hospital of Jinan University,and divided into TNBC group,luminal subtype group and HER-2 overexpression subtype group by the immunohistochemical results of estrogen receptor,progesterone receptor and HER-2.EnVision two-step method was used to detect the expression of FOXA1,BRCA1,P53 and VEGF in the tumor samples.RESULTS: Total FOXA1 positive expression rate was 63.7%(72/113),with 45.2%(19/42) in TNBC,88.0%(44/50) in luminal subtype and 42.9%(9/21) in HER-2 overexpression subtype.The statistically sigfnificant difference among the 3 groups was observed(P0.01).Total BRCA-1 positive expression rate was 47.8%(54/113),with 66.7%(28/42) in TNBC,44.0%(22/50) in luminal subtype and 19.0%(4/21) in HER-2 overexpression subtype.The statisticallysignificant difference among the 3 groups was also observed(P0.01).In the cases of clinical stages Ⅰ～Ⅱand histological grades 1～2,FOXA1 positive rate was higher than the FOXA1 negative rate(P0.01).Negative correlations between FOXA1 positive rate and expression of P53/VEGF,and between FOXA1 positive rate and the recurrence rate were found(P0.05).In the cases of clinical stages Ⅱ～Ⅲ and histological grades 2～3,the BRCA1 positive rate was higher than the BRCA1 negative rate(P0.05).Positive correlations between BRCA-1 positive rate and the expression of P53/VEGF,and between BRCA1 positive rate and the recurrence rate were also observed(P0.05).CONCLUSION: Expression of FOXA1 and BRCA1 in breast cancer is different.BRCA1 may be an adverse prognostic indicator for triple negative breast cancer.