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简介：AbstractBackground:Although breast-conserving surgery is one of the standard treatments for breast cancer, few studies have assessed its recent implementation in China. We aimed to clarify the current real-world status of breast-conserving surgery in China.Methods:This cross-sectional survey relied on data collected by the Chinese Society of Breast Surgery (CSBrS) to examine patients who underwent this surgery between January 2018 and December 2018. The survey was conducted using a uniform electronic questionnaire to collect information, including clinical and pathological data on these patients.Results:Overall, 4459 breast-conserving surgeries were performed in 34 member units of CSBrS, accounting for 14.6% of all breast cancer surgeries performed in these units during the study period. In patients who underwent breast-conserving surgery with information on tumor size available, more than half (61.2%) of the tumors were smaller than 2 cm in diameter, and only 87 (3.2%) tumors were larger than 4 cm in diameter. Among patients who underwent breast-conserving surgeries, 457 (10.2%) patients received neoadjuvant therapy before the surgery. Among patients with a reported margin width, 34 (2.0%) patients had a margin of ≤2 mm, and 1530 (88.2%) of them had a margin of >5 mm.Conclusions:This study demonstrated the rates of breast-conserving surgery in member units of the CSBrS, and introduced the characteristics and surgical margins of patients who underwent this surgery. This information helps describe the real-world status of breast-conserving surgery in China.Trial registration:chictr.org.cn, ChiCTR1900026841; http://www.chictr.org.cn/showproj.aspx?proj=42783

简介：AbstractBackground:Inflammatory breast cancer (IBC) is an aggressive type of cancer with poor prognosis and outcomes. This study aimed to investigate clinicopathological features, molecular characteristics, and treatments among Chinese patients diagnosed with IBC.Methods:We collected data of 95 patients with IBC who were treated by members of the Chinese Society of Breast Surgery, from January 2017 to December 2018. The data, including demographic characteristics, pathological findings, surgical methods, systemic treatment plans, and follow-up, were obtained using a uniform electronic questionnaire. The clinicopathological features of different molecular types in patients without distant metastases were compared using the Kruskal-Wallis (H) test followed by post hoc analyses.Results:Lymph node metastasis was noted in 75.8% of all patients, while distant metastasis was noted in 21.4%. Pathological findings indicated invasive ductal and lobular carcinomas in 86.8% and 5.3% of cases, respectively. Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) (41.5%) and HR-/HER2+ (20.1%) were the most common biologic subtypes, followed by HR+/HER2+ (19.1%) and HR-/HER2-(19.1%). Stage III IBC was treated via pre-operative neoadjuvant chemotherapy in 87.7% of the cases, predominantly using anthracycline and taxanes. A total of 91.9% of patients underwent surgical treatment. Among them, 77.0% of the patients underwent modified radical mastectomy, 8.1% of whom also underwent immediate breast reconstruction. The Kruskal-Wallis test revealed that the efficacy of chemotherapy significantly differed among those with HR+/HER2 -and HR-/HER2-tumors (adjusted P = 0.008), and Ki-67 expression significantly differed in HR-/HER2+ and HR+/HER2+ molecular subtypes (adjusted P = 0.008).Conclusion:Our study provides novel insight into clinicopathological characteristics and treatment status among patients with IBC in China, and might provide a direction and basis for further studies.Trial registration:chictr.org.cn, No. ChiCTR1900027179; http://www.chictr.org.cn/showprojen.aspx?proj=45030

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简介：AbstractBreast neuroendocrine carcinoma is a rare entity. It constitutes less than 0.5% of breast malignancies, and is usually diagnosed in older women. The occurrence of this type in young patients during pregnancy is extremely rare. Only 2 cases were previously reported. Both were diagnosed at earlier stage with the appearance of a palpable breast mass. Hereby, we present the case of a young patient at 28 weeks’ gestation admitted for severe diffuse back pain and neurologic deficit due to spinal cord compression at the level of C5 vertebra, and nerve root compression at the level of L5 vertebrae. To the best of our knowledge, this is the first case of oncologic emergency during pregnancy due to a metastatic poorly differentiated breast carcinoma with neuroendocrine differentiation in the absence of a detectable primary focus of malignancy in the breast. We also discuss the management and the obstetrical outcome of this patient.

简介：AbstractBackground:Angiogenesis and hypoxia-inducible factor 1α (HIF-1α) play major roles in solid tumors. This study aimed to establish a longitudinal and multimodal imaging model for in vivo evaluation of HIF1α and angiogenesis in breast cancer.Methods:By transfection of a 5 hypoxia-responsive element (HRE)/green fluorescent protein (GFP) plasmid, the cell line Ca761-hregfp was established, which emitted green fluorescence triggered by HIF-1α under hypoxia. The cells were subjected to CoCl2-simulated hypoxia to confirm the imaging strategy. We grew Ca761-hre-gfp cells in the left rear flanks of twelve 615 mice. Experiments were conducted on days 4, 9, 15, and 19. For in vivo analysis, Ca761-hre-gfp subcutaneous allografted tumors were imaged in vivo using contrast-enhanced ultrasound (CEUS) and fluorescence imaging (FLI) during tumor development. The tumor size, CEUS peak intensity, and FLI photons were measured to evaluate tumor growth, angiogenesis, and HIF-1α activity, respectively. After each experiment, three mice were randomly sacrificed and tumor specimens were collected to examine HIF-1α activity and the microvessel density (MVD).Results:In vitro, both green fluorescence and HIF-1α expression were detected in Ca761-hre-gfp cells treated with CoCl2, indicating the suitability of the cells to detect HIF-1α activity. In vivo, HIF-1α activity first increased and then decreased, which was significantly correlated with angiogenic changes (r = 0.803, P = 0.005). These changes were confirmed by immunohistochemical staining of HIF-1α and MVD.Conclusions:The findings validated the Ca761-hre-gfp murine allograft model for reliable evaluation of HIF-1α activity and angiogenesis longitudinally using both molecular and pre-clinical non-invasive imaging modalities. The cell line may be useful for studies of anti-HIF pathway therapies.

简介：AbstractIncreasing numbers of targeted drugs are used in hormone receptor (HR)-positive metastatic breast cancer (MBC) to overcome or delay resistance to endocrine therapy. This study will systemically review the progress made in endocrine therapy combined with targeted therapy in the treatment of HR-positive MBC. From the "AI (aromatase inhibitor) era" represented by aromatase inhibitors, we have gradually entered the "post-AI era" represented by fulvestrant. Under the guidance of research on the molecular mechanism of endocrine therapy resistance, the "combination of endocrine therapy and targeted therapy" era is approaching. The development of drugs that target endocrine therapy resistance has concentrated on cyclin-dependent kinase 4/6 inhibitors, histone deacetylase inhibitors, and inhibitors of drug targets in the phosphatidylinositol 3 kinase-protein kinase B-mammalian target of rapamycin (PI3K-AKT-mTOR) pathway, providing new strategies for HR-positive MBC. Exploring biomarkers to guide the more precise use of targeted drugs in endocrine therapy for MBC is the focus of current and future research.

简介：AbstractBackground:Nipple discharge cytology is a simple non-invasive method that may provide valuable information for detecting underlying malignancy. Several studies have investigated the diagnostic value of cytology in breast cancer patients with pathological nipple discharge, but the results have been highly variable. Herein we presented a systematic review and meta-analysis of published studies pertaining to the diagnostic capacity of nipple discharge cytology in patients with breast cancer.Methods:A systematic literature search was performed (Medline/PubMed, Embase, Cochrane Library databases, and Google Scholar) to identify studies that investigated the diagnostic capacity of cytology with regard to breast cancer in patients with pathologic nipple discharge. Two independent researchers identified articles that assessed the sensitivity and specificity of cytological evaluation for breast cancer detection in patients with pathologic nipple discharge published between January 2000 and October 2018. Articles were only included in the meta-analysis if they met predetermined criteria. The characteristics of each study and the data they yielded were summarized. Quality assessment of all articles included was performed using the Methodological Index for Non-randomized Studies Criteria (MINORS) and the Quality Assessment of Diagnostic Accuracy Study 2 (QUADAS-2). Heterogeneity was tested via Cochran Q test and the I2 statistic using Stata 12.0 and Meta-DiSc 1.4 software, and meta-analysis was performed.Results:A total of 286 articles were identified, of which 12 articles including a total of 1476 patients were deemed eligible for inclusion in the meta-analysis. A random-effects model assessing the capacity of nipple discharge cytology to predict breast cancer yielded pooled sensitivity 63% (95% confidence interval [CI]: 53%-72%), specificity 95% (95% CI: 87%-98%), positive likelihood ratio 12.35 (95% CI: 4.87-31.34), and negative likelihood ratio 0.39 (95% CI: 0.30-0.50). The diagnostic odds ratio was 31.88 (95% CI: 11.30-89.98). The area under the summary receiver operating characteristic curve was 0.79 (95% CI: 0.75-0.82). Conclusion: The current meta-analysis suggests that nipple discharge cytology is a useful diagnostic modality for detection of breast cancer in patients with pathological nipple discharge, with moderate sensitivity and high specificity.

简介：AbstractNearly 70% of breast cancer (BC) is hormone-receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, and endocrine therapy is the mainstay of treatment for this subtype. However, intrinsic or acquired endocrine resistance can occur during the endocrine treatment. Based on insights of endocrine resistance mechanisms, a number of targeted therapies have been and continue to be developed. With regard to HR-positive, HER2-negative advanced BC, aromatase inhibitor (AI) is superior to tamoxifen, and fulvestrant is a better option for patients previously exposed to endocrine therapy. Targeted drugs, such as cyclindependent kinases (CDK) 4/6 inhibitors, mammalian target of rapamycin (mTOR) inhibitors, phosphoinositide-3-kinase (PI3K) inhibitors, and histone deacetylase (HDAC) inhibitors, play a significant role in the present and show a promising future. With the application of CDK4/6 inhibitors becoming common, mechanisms of acquired resistance to them should also be taken into consideration.

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简介：AbstractBackground:After neoadjuvant chemotherapy (NAC), non-pathological complete response of breast cancer patients can benefit from tailored adjuvant chemotherapy. However, it is difficult to select patients with poorer prognosis for additional adjuvant chemotherapy to maximize the benefits. Our study aimed to explore whether the subtypes of tumor-infiltrating lymphocytes (TILs) in residual tumors (RT) is related to the prognosis of triple-negative breast cancer (TNBC) after NAC.Methods:Data from patients with primary TNBC consecutively diagnosed at the Breast Disease Center of Peking University First Hospital from 2008 to 2014 were retrieved, and the cases with RT in the breast after NAC were enrolled. TILs subtypes in RT were observed by double-staining immunohistochemistry, and counted with the median TILs value per square millimeter as the cut-off to define high versus low TILs density in each subtype. The relationships between the TIL density of each subgroup and the clinicopathological characteristics of the RT after NAC patients were analyzed by Fisher exact test. Disease-free survival (DFS) and overall survival (OS) were analyzed by the Kaplan-Meier method and log-rank statistics.Results:A total of 37 eligible patients were included in this study, and the median follow-up period was 50 months (range 17–106 months). There was no significant correlation between the infiltrate density of CD4+, CD8+, CD20+, and CD68+ lymphocytes and clinic-pathological characteristics. Significantly better prognosis was observed in patients with high CD4+-TILs (DFS: P = 0.005, OS: P = 0.021) and high CD8+-TILs (DFS: P = 0.018) and low CD20+-TILs (OS: P = 0.042). Further analysis showed that patients with CD4+/CD20+ ratio greater than 1 (DFS: P = 0.001, OS: P = 0.002) or CD8+/CD20+ ratio greater than 1 (DFS: P = 0.009, OS: P = 0.022) had a better prognosis.Conclusions:Subtypes of TILs in RT is a potential predictive biomarker of survival in TNBC patients after NAC.

简介：AbstractHistorically, breast cancer has been regarded as an immunogenic "cold" tumor. However, the discovery of immune checkpoint inhibitors has made immunotherapy becoming an emerging new treatment modality for breast cancer. This review discusses the immune system, immune features of breast cancer, and the programmed cell death protein-1/programmed cell death protein ligand-1 (PD-1/PD-L1) inhibitors used in the treatment of breast cancer. High T lymphocyte infiltration and mutation burden were observed in triple-negative breast cancer and human epidermal growth factor receptor 2 positive breast cancer. Increasing breast cancer immunogenicity and modulating the tumor microenvironment has been reported to improve the therapeutic efficacy of immunotherapy. Recent clinical trials involving PD-1/PD-L1 inhibitors monotherapy in breast cancer has revealed little efficacy, which highlights the need to develop combinations of PD-1/PD-L1 inhibitors with chemotherapy, molecularly targeted therapies, and other immunotherapies to maximize the clinical efficacy. Collectively, the immunotherapy might be a promising therapeutic strategy for breast cancer and several clinical trials are still on-going.

简介：摘要目的对比乳腺癌不同重建方式术后放疗的并发症、满意度及生活质量，寻求重建与放疗的最佳结合方式。方法收集2014-2019年肿瘤医院收治的105例乳腺癌重建术后放疗病例。根据重建类型不同分为A组(自体重建组，54例)及B组(假体重建组，51例)，B组根据重建时机不同分为B1组(一步法重建组，30例)及B2组(二步法重建组，21例)。比较A与B组、B1与B2组的并发症发生率及BREAST-Q评分，采用多元线性回归分析BREAST-Q评分的影响因素。结果A组远期并发症和总并发症发生率低于B组(1.9%∶37.3%，P<0.001和9.3%∶43.1%，P<0.001)，A组社会心理健康和乳房满意度评分高于B组[71(15)∶66(22)，P＝0.027和53(8)∶53(8)，P＝0.032]，B1与B2组并发症发生率和BREAST-Q评分均相近(均P>0.05)。乳房体积、并发症是BREAST-Q评分的预测因素(P<0.001、<0.001)。结论乳腺癌自体重建术后放疗较假体重建而言并发症少，BREAST-Q评分部分较优；假体一步法与二步法重建术后放疗的并发症及BREAST-Q结果相当；乳房较大或有并发症的患者BREAST-Q评分较低。

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