Search

Purpose: The residual cancer burden index (RCB) was proposed as a response evaluation criterion in breast cancer patients treated with Neoadjuvant Chemotherapy (NAC). This study evaluated the relevance of RCB with replase-free survival (RFS)., Methods: The clinical data of 254 breast cancer patients who received NAC between 2016 and 2020 were retrospectively collected. The relationship between clinicopathologic factors and RFS was evaluated using Cox proportional hazards regression models. RFS estimates were determined by Kaplan-Meier(K-M) analysis and compared using the log-rank test. Multivariate logistic regression analysis was used to evaluate the risk factors associated with RCB. Receiver operating characteristic (ROC) curves showed the potential of the RCB and MP grading systems as biomarkers for RFS., Results: At a median follow-up of 52 months, 59 patients(23.23%) developed relapse. Multivariate Cox regression showed that older age (P = 0.022), high Pathologic T stage after NAC (P = 0.023) and a high RCB score(P = 0.003) were risk factors for relapse. The outcomes of the multivariate logistic analysis indicated that RCB 0 (pathologic complete response [pCR]) was associated with HER2-positive patients (P = 0.002) and triple-negative breast cancer (TNBC) patients (P = 0.013). In addition, the RCB and MP scoring systems served as prognostic markers for patients who received NAC, and their area under curves (AUCs) were 0.691 and 0.342, respectively., Conclusion: These data suggest that RCB can be equally applied to predict RFS in Chinese patients with NAC. The application of RCB may help guide the selection of treatment strategies., (© 2023. The Author(s).)

Background: The pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) of breast cancer is closely related to a better prognosis. However, there are no reliable indicators to accurately identify which patients will achieve pCR before surgery, and a model for predicting pCR to NAC is required., Methods: A total of 269 breast cancer patients in Shandong Cancer Hospital and Liaocheng People's Hospital receiving anthracycline and taxane-based NAC were prospectively enrolled. Expression profiling using a 457 cancer-related gene sequencing panel (DNA sequencing) covering genes recurrently mutated in breast cancer was carried out on 243 formalin-fixed paraffin-embedded tumor biopsies samples before NAC from 243 patients. The unique personalized panel of nine individual somatic mutation genes from the constructed model was used to detect and analyze ctDNA on 216 blood samples. Blood samples were collected at indicated time points including before chemotherapy initiation, after the 1 st NAC and before the 2 nd NAC cycle, during intermediate evaluation, and prior to surgery. In this study, we characterized the value of gene profile mutation and circulating tumor DNA (ctDNA) in combination with clinical characteristics in the prediction of pCR before surgery and investigated the prognostic prediction. The median follow-up time for survival analysis was 898 days., Results: Firstly, we constructed a predictive NAC response model including five single nucleotide variant (SNV) mutations (TP53, SETBP1, PIK3CA, NOTCH4 and MSH2) and four copy number variation (CNV) mutations (FOXP1-gain, EGFR-gain, IL7R-gain, and NFKB1A-gain) in the breast tumor, combined with three clinical factors (luminal A, Her2 and Ki67 status). The tumor prediction model showed good discrimination of chemotherapy sensitivity for pCR and non-pCR with an AUC of 0.871 (95% CI, 0.797-0.927) in the training set, 0.771 (95% CI, 0.649-0.883) in the test set, and 0.726 (95% CI, 0.556-0.865) in an extra test set. This tumor prediction model can also effectively predict the prognosis of disease-free survival (DFS) with an AUC of 0.749 at 1 year and 0.830 at 3 years. We further screened the genes from the tumor prediction model to establish a unique personalized panel consisting of 9 individual somatic mutation genes to detect and analyze ctDNA. It was found that ctDNA positivity decreased with the passage of time during NAC, and ctDNA status can predict NAC response and metastasis recurrence. Finally, we constructed the chemotherapy prediction model combined with the tumor prediction model and pretreatment ctDNA levels, which has a better prediction effect of pCR with the AUC value of 0.961., Conclusions: In this study, we established a chemotherapy predictive model with a non-invasive tool that is built based on genomic features, ctDNA status, as well as clinical characteristics for predicting pCR to recognize the responders and non-responders to NAC, and also predicting prognosis for DFS in breast cancer. Adding pretreatment ctDNA levels to a model containing gene profile mutation and clinical characteristics significantly improves stratification over the clinical variables alone., (© 2023. The Author(s).)

Lysine-specific demethylase 1 (LSD1), a critical chromatin modulator, functions as an oncogene by demethylation of H3K4me1/2. The stability of LSD1 is governed by a complex and intricate process involving ubiquitination and deubiquitination. Several deubiquitinases preserve LSD1 protein levels. However, the precise mechanism underlying the degradation of LSD1, which could mitigate its oncogenic function, remains unknown. To gain a better understanding of LSD1 degradation, we conducted an unbiased siRNA screening targeting all the human SCF family E3 ligases. Our screening identified FBXO24 as a genuine E3 ligase that ubiquitinates and degrades LSD1. As a result, FBXO24 inhibits LSD1-induced tumorigenesis and functions as a tumor suppressor in breast cancer cells. Moreover, FBXO24 exhibits an inverse correlation with LSD1 and is associated with a favorable prognosis in breast cancer patient samples. Taken together, our study uncovers the significant role of FBXO24 in impeding breast tumor progression by targeting LSD1 for degradation., Implications: Our study provides comprehensive characterization of the significant role of FBXO24 in impeding breast tumor progression by targeting LSD1 for degradation., (©2023 American Association for Cancer Research.)

Pyrotinib, an irreversible pan-ErbB inhibitor, has been approved for treating HER2-positive advanced breast cancer in China. We conducted a nationwide, prospective observational study to examine the real-world data of pyrotinib-based therapy in this population. Patients from 61 sites across China were included. Pyrotinib-based regimens were prescribed at local physician's discretion. Demographics, treatment patterns, prognosis and safety were evaluated. The primary outcome was real-world progression-free survival (rwPFS). Of 1129 patients, pyrotinib-based therapy was prescribed as first-, second- and third- or later-line treatment in 437 (38.7%), 476 (42.2%) and 216 (19.1%) patients, respectively. Median rwPFS (mrwPFS) was 14.3 (95% CI, 13.3-15.2) months in the total population, with the longest mrwPFS of 17.8 (95% CI, 15.2-24.9) months in the first-line setting, followed by 14.4 (95% CI, 12.9-15.3) months in the second-line setting. Patients with third- or later-line treatment also achieved a mrwPFS of 9.3 (95% CI, 8.4-11.8) months. Patients with trastuzumab- or trastuzumab-pertuzumab-treated disease achieved a mrwPFS of 14.3 and 13.6 months, respectively. Dual HER2 blockade with pyrotinib plus trastuzumab showed a mrwPFS of 16.2 months in the total population, with data not mature in the first-line setting. For patients with baseline brain metastases, the mrwPFS was 11.7 months. The most common adverse event was diarrhea (any grade, 73.5%; grade ≥ 3, 15.3%). In real world, pyrotinib-based therapy shows promising effectiveness in the first-, as well as second- and later-line treatment, with acceptable tolerability. Further investigations regarding front-line use or novel combinations of pyrotinib might facilitate to maximize its anti-tumor potential., (© 2023 UICC.)

We managed to explore the function of HFY-4A, a novel histone deacetylases (HDACs) inhibitor, on breast cancer as well as its potential mechanisms. MCF7 and T47D cells were treated with 0.8, 1.6 or 3.2 μM HFY-4A for 0-72 h, following of which CCK-8, colony formation, EdU staining, flow cytometry, Transwell, and wound healing assays were carried out. Western blot, immunohistochemistry, and ELISA were conducted for assaying the expression of immunogenic cell death (ICD)-related proteins. The interaction between HFY-4A, HDAC1, and tumor suppressor candidate 2 (TUSC2) was evaluated by chromatin immunoprecipitation assay. Further, the function of HFY-4A in breast cancer progression in vivo was evaluated using xenograft mouse models. HFY-4A inhibited the proliferation, migration, and invasion, and induced apoptosis of breast cancer cells in a dose-dependent manner. HFY-4A dose-dependently caused the ICD of breast cancer cells, as evidenced by the significant high levels of high-mobility group box 1 (HMGB1), calreticulin (CRT), heat shock protein 70 (HSP70), and HSP90. Interestingly, HFY-4A could facilitate TUSC2 transcription by promoting acetylation of histones on the TUSC2 promoter. The results of rescue assays revealed that HFY-4A repressed proliferation and mobility, but enhanced apoptosis and ICD through facilitating TUSC2 transcription in breast cancer. In breast cancer xenograft mouse models, HFY-4A was verified to inhibit tumor growth via upregulating TUSC2. HFY-4A could inhibit breast cancer cell proliferation and mobility, and enhanced apoptosis and ICD through facilitating TUSC2 transcription., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Although neoadjuvant trastuzumab and pertuzumab (HP)-based regimens are recommended for human epidermal receptor-positive (HER2 +)/lymph node-positive (N +) breast cancer (BC) patients according to NCCN guidelines, it is undeniable that many patients achieved pathological complete response (pCR) after trastuzumab (H)-based regimens without adding pertuzumab to treatment. Patients who specifically benefit from pertuzumab must be identified. The aim of this retrospective study was to evaluate progesterone receptor (PR) status as a predictor of response to the addition of pertuzumab in HER2 + /N + breast cancer., Methods: One hundred forty-two patients who were diagnosed as HER2 + /N + BC without distant metastasis and followed by neoadjuvant HP-based or H-based therapy were retrospectively included. The endpoints were pCR and disease-free survival (DFS) times., Results: In total, the pCR occurred in 25 of 87 patients (28.74%) in group H compared with 32 of 55 (58.18%) in group HP. The results revealed that hormone receptor (HR) status was significantly different on pCR in group HP. The odds of pCR for patients who have HR-positive tumors were 0.160 times (P = 0.011) that for patients with HR-negative tumors by multivariable analysis. Moreover, a similar probability of PR-positive (PR +) patients, whatever estrogen receptor (ER) status was, achieving pCR in group HP was observed. The ROC curves showed different anti-HER2 regimens provide worst predictive value in the PR + cohort (N = AUC = 0.521, 95% CI: 0.348-0.694, P = 0.813) compared with the overall cohort (AUC = 0.644, 95% CI: 0.550-0.738, P = 0.004) and ER + cohort (AUC: 0.559, 95% CI: 0.405-0.713, P = 0.451). And PR status (AUC = 0.760, 95% CI: 0.626-0.894, P = 0.001) had a greater predictive value than ER status (AUC = 0.658, 95% CI: 0.508-0.807, P = 0.048) in group HP. DFS analyses were done on 141 patients. Although ER and PR status did not show significant difference in group HP (P = 0.789 and 0.088, respectively), HP-based therapy contributed to better DFS in the ER - and PR - cohorts (P = 0.035 and 0.015, respectively)., Conclusions: Compared with ER status, PR status might be a more valuable factor predicting the efficacy of adding pertuzumab into neoadjuvant therapy for HER2 + /N + BC. PR + patients benefit little from the addition of pertuzumab., (© 2023. BioMed Central Ltd., part of Springer Nature.)

This study is aimed to develop and validate a novel nomogram model that can preoperatively predict axillary lymph node pathological complete response (pCR) after NAT and avoid unnecessary axillary lymph node dissection (ALND) for breast cancer patients. A total of 410 patients who underwent NAT and were pathologically confirmed to be axillary lymph node positive after breast cancer surgery were included. They were divided into two groups: patients with axillary lymph node pCR and patients with residual node lesions after NAT. Then the nomogram prediction model was constructed by univariate and multivariate logistic regression. The result of multivariate logistic regression analysis showed that molecular subtypes, molybdenum target (MG) breast, computerized tomography (CT) breast, ultrasound (US) axilla, magnetic resonance imaging (MRI) axilla, and CT axilla (all p < 0.001) had a significant impact on the evaluation of axillary lymph node status after NAT. The nomogram score appeared that AUC was 0.832 (95% CI 0.786-0.878) in the training cohort and 0.947 (95% CI 0.906-0.988) in the validation cohort, respectively. The decision curve represented that the nomogram has a positive predictive ability, indicating its potential as a practical clinical tool., (© 2023. The Author(s).)

Breast cancer has become the most prevalent cancer, globally. Adriamycin is a first-line chemotherapeutic agent, however, cancer cells acquire resistance to it, which is one of the most common causes of treatment failure. ROS and NRF2 are essential oxidative stress factors that play a key role in the oxidative stress process and are associated with cancer. Our goal is to create novel therapeutic drugs or chemical sensitizers that will improve chemotherapy sensitivity. The optimal concentration and duration for MCF-7 and MCF-7/ADR cells in ADR and CYT were determined using the CCK-8 assay. We found that ADR + CYT inhibited the activity of MCF-7 and MCF-7/ADR cells in breast cancer, as well as causing apoptosis in MCF-7 and MCF-7/ADR cells and blocking the cell cycle in the G0/G1 phase. ADR + CYT induces apoptosis in MCF-7 and MCF-7/ADR cells through ROS generation and the P62/NRF2/HO-1 signaling pathway. In breast cancer-bearing nude mice, ADR + CYT effectively suppressed tumor development in vivo. Overall, our findings showed that CYT in combination with ADR has potent anti-breast cancer cell activity both in vivo and in vitro, suggesting CYT as the main drug used to improve chemosensitivity., (© 2023. The Author(s).)

Ras-related protein in brain (Rab) proteins are dysregulated in cancer cells and affect the proliferation and metastasis of cancer cells, thereby reducing the survival rate of cancer patients. Brain-derived neurotrophic factor (BDNF) and its receptor Tropomyosin-related kinase B (TrkB) play an important role in the occurrence and development of tumors. In this research, we investigate the interaction of Rab8A and TrkB in regulating the progression of breast cancer. Rab8A is upregulated in breast cancer tissues. The knockdown of Rab8A inhibits the proliferation, migration, and invasion of breast cancer cells through inhibiting TrkB. Moreover, the phosphorylation of AKT and ERK1/2 is suppressed by Rab8A knockdown. Rab8A interacts with TrkB, as revealed by co-immunoprecipitation assay to promote the surface expression of TrkB. However, Rab8A induced no significant changes in TrkB internalization. Functionally, BDNF promotes the expression of Rab8A through inhibiting Rab8A degradation. The TrkB inhibitor K252a blocks cell proliferation, migration and invasion as well as the activation of the AKT and ERK1/2 signaling pathway, which is induced by Rab8A in breast cancer cells. Our results reveal that Rab8A is upregulated by BDNF, and that Rab8A increases the surface expression of TrkB to promote the growth of breast cancer through the activation of the AKT and ERK1/2 signaling pathway. These results suggest that inhibiting Rab8A level could inhibit the progression of breast cancer., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The previous studies had demonstrated the promising effectiveness and acceptable safety of pyrotinib in patients with HER2-positive metastatic breast cancer. We aimed to investigate the real-world data of pyrotinib in complex clinical practice and complement the findings of clinical trials. Two hundred and eighteen patients were included for effectiveness analysis. A total of 62.0% had received two or more lines of systematic therapy, and 95.4% had been exposed to prior anti-HER2 therapy, with 95.4% receiving trastuzumab, 5.0% receiving pertuzumab, and 40.8% receiving lapatinib. The median progression-free survival (PFS) was 9.3 months and the objective response rate (ORR) was 44.0%. Patients treated with pyrotinib-based therapy as first, second, or later line had a median PFS of 15.0, 10.3, and 6.8 months, respectively. Patients treated with pyrotinib and trastuzumab received significant benefit in terms of median PFS compared with pyrotinib alone (10.7 (9.1-12.3) vs. 8.8 (8.1-9.5), p = 0.016). Patients pretreated with lapatinib had a median PFS of 6.9 months. The median PFS time was 7.0 months in patients with brain metastasis. Multivariate Cox regression analyses showed that lines of pyrotinib-based therapy (1 vs. 2 vs. ≥3), prior treatment with lapatinib, and combination treatments with trastuzumab proved to be independent predictors of PFS. Two hundred and forty-eight patients were included in the safety analysis, and the results showed that the toxicity of pyrotinib was tolerable, with the most common grade 3/4 adverse event being diarrhea (19.8%). Pyrotinib-based therapy demonstrated promising efficacy and tolerable toxicity in first-, second-, and later-line treatments and in lapatinib-treated patients. The combination of pyrotinib and trastuzumab showed advantages in PFS, even for patients resisting trastuzumab. Pyrotinib-based therapy could be the preferred choice for brain metastasis patients, especially when combined with brain radiotherapy., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

SNAI1 is widely regarded as a master driver of epithelial-mesenchymal transition (EMT) and associated with breast cancer progression and metastasis. This pro-malignant role is strongly linked to posttranslational modification, especially phosphorylation, which controls its protein levels and subcellular localization. While multiple kinases are implicated in regulation of SNAI1 stability, the precise mechanism by which SNAI1 is stabilized in tumors remains to be fully elucidated. Methods : A series of in vitro and in vivo experiments were conducted to reveal the regulation of SNAI1 by Serine/Threonine Kinase 39 (STK39) and the role of STK39 in breast cancer metastasis. Results: We identified STK39, a member of Stem 20-like serine/threonine kinase family, as a novel posttranslational regulator that enhances the stability of SNAI1. Inhibition of STK39 via knockdown or use of a specific inhibitor resulted in SNAI1 destabilization. Mechanistically, STK39 interacted with and phosphorylated SNAI1 at T203, which is critical for its nuclear retention. Functionally, STK39 inhibition markedly impaired the EMT phenotype and decreased tumor cell migration, invasion, and metastasis both in vitro and in vivo . These effects were rescued by ectopic SNAI1 expression. In addition, depletion of STK39 dramatically enhanced sensitivity to chemotherapeutic agents. Conclusions: Our study demonstrated that STK39 is a key mediator of SNAI1 stability and is associated with the pro-metastatic cellular process, highlighting the STK39-SNAI1 signaling axis as promising therapeutic targets for treatments of metastatic breast cancer., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Lymphangiogenesis is thought to contribute to promote tumor cells to enter lymphatic vessels and plant at a secondary site. Endothelial cells are the cornerstone of the generation of new lymphatic vessels. NADPH oxidase 4 (Nox4) is the most abundant one of NADPH oxidases in endothelial cells and the most studied one in relevance with cancer. Our purpose is to analyze the relationship between Nox4 and lymphangiogenesis and find out whether the newborn lymphatic vessels lead to cancer metastasis. We first explored the expression of Nox4 in lymphatic endothelial cells of primary invasive breast tumors and human normal mammary glands using GEO databases and found that Nox4 was upregulated in primary invasive breast tumors samples. In addition, its high expression correlated with lymph node metastasis in breast cancer patients. Nox4 could increase the tube formation and lymphatic vessel sprouting in a three-dimensional setting. In vivo, inhibition of Nox4 in 4T1 tumor-bearing mice could significantly decrease the tumor lymphangiogenesis and metastasis. Nox4 may increase tumor lymphangiogenesis via ROS/ERK/CCL21 pathway and attract CCR7-positive breast cancer cells to entry lymphatic vessels and distant organs. In conclusion, our results show that Nox4 is a factor that promotes lymphangiogenesis and is a potential target of antitumor metastasis., (© 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Background: Despite therapeutic advances in HER2-positive metastatic breast cancer, resistance to trastuzumab inevitably develops. In the PHOEBE study, we aimed to assess the efficacy and safety of pyrotinib (an irreversible pan-HER inhibitor) plus capecitabine after previous trastuzumab., Methods: This is an open-label, randomised, controlled, phase 3 trial done at 29 hospitals in China. Patients with pathologically confirmed HER2-positive metastatic breast cancer, aged 18-70 years, who had an Eastern Cooperative Oncology Group performance status of 0 or 1, and had been previously treated with trastuzumab and taxanes were randomly assigned (1:1) to receive oral pyrotinib 400 mg or lapatinib 1250 mg once daily plus oral capecitabine 1000 mg/m 2 twice daily on days 1-14 of each 21-day cycle. Randomisation was done via a centralised interactive web-response system with a block size of four or six and stratified by hormone receptor status and previous lines of chemotherapy for metastatic disease. The primary endpoint was progression-free survival according to masked independent central review. Efficacy and safety were assessed in all patients who received at least one dose of the study drugs. Results presented here are from a prespecified interim analysis. This study is registered with ClinicalTrials.gov, NCT03080805., Findings: Between July 31, 2017, and Oct 30, 2018, 267 patients were enrolled and randomly assigned. 134 patients received pyrotinib plus capecitabine and 132 received lapatinib plus capecitabine. At data cutoff of the interim analysis on March 31, 2019, median progression-free survival was significantly longer with pyrotinib plus capecitabine (12·5 months [95% CI 9·7-not reached]) than with lapatinib plus capecitabine (6·8 months [5·4-8·1]; hazard ratio 0·39 [95% CI 0·27-0·56]; one-sided p<0·0001). The most common grade 3 or worse adverse events were diarrhoea (41 [31%] in the pyrotinib group vs 11 [8%] in the lapatinib group) and hand-foot syndrome (22 [16%] vs 20 [15%]). Serious adverse events were reported for 14 (10%) patients in the pyrotinib group and 11 (8%) patients in the lapatinib group. No treatment-related deaths were reported in the pyrotinib group and one sudden death in the lapatinib group was considered treatment related., Interpretation: Pyrotinib plus capecitabine significantly improved progression-free survival compared with that for lapatinib plus capecitabine, with manageable toxicity, and can be considered an alternative treatment option for patients with HER2-positive metastatic breast cancer after trastuzumab and chemotherapy., Funding: Jiangsu Hengrui Medicine and National Key R&D Program of China., Translations: For the Chinese translation of the abstract see Supplementary Materials section., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The aim of this study was to evaluate the effectiveness of lapatinib in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer., Methods: We retrospectively reviewed the medical records of patients who received lapatinib for salvage treatment at any line setting from January 1, 2007 to August 31, 2019 at Shandong Cancer Hospital and Institute., Results: A total of 115 (89.1%) patients were included in the study. In the overall cohort, the median disease-free survival (DFS) was 19.0 months; the median progression-free survival (PFS), 6.3 months; and median overall survival (OS), 88.0 months, with 32.2% of patients alive at 5 years. In the second line setting, the median PFS among trastuzumab, lapatinib, and trastuzumab plus lapatinib were 4.2 months, 5.2 months, and 7.3 months, respectively ( P = 0.004). No significant differences between the median PFSs and OSs of the different line salvage treatments with lapatinib was observed (all P > 0.05). For brain metastasis patients, the median PFSs in first line, second line, and more than 3 lines were 7.2 months, 4.5 months, and 6.3 months, respectively., Conclusions: Our findings suggest that patients would benefit more from trastuzumab plus lapatinib than from lapatinib or trastuzumab alone for second line treatment in the advanced stages of the disease. Lapatinib could be used as an alternative selection for HER2-positive metastasic breast cancer patients when there is disease progression after trastuzumab or pyrotinib treatment, which is used as part of China's national health insurance.

Background: Sentinel lymph node biopsy (SLNB) plays a vital role in breast cancer surgery, and the identified number of sentinel nodes determines its accuracy for representing the status of the axillae. There are two types of tumor biopsies in breast cancer: preoperative and intraoperative biopsies. We compared the effects of the two different biopsies on the results of SLNB., Methods: Patients with clinical stages T1-3, N0 (cT1-3 N0) tumors were enrolled in this study. A total of 53% of patients received preoperative tumor biopsy, and 47% received intraoperative excisional biopsy. To identify the sentinel lymph nodes, patients received dual tracer injection. The number of SLNs detected and the false-negative rate were compared between groups., Results: A total of 204 patients were enrolled, 108 received preoperative tumor biopsy, and 96 received intraoperative excisional biopsy. Among all the patients, 160 received axillary lymph node dissection (ALND) following SLNB. Preoperative tumor biopsy detected more SLNs than intraoperative biopsy (mean rank 113.87 vs. 90.9, p = 0.004). The false-negative rates in the preoperative and intraoperative tumor biopsy groups were 3% and 18%, respectively., Conclusions: Patients in the preoperative tumor biopsy group had more SLNs identified than intraoperative biopsy patients. The false-negative rate was also lower in the preoperative biopsy group.

The aim of this study was to compare the expression of PD-1/PD-L1 in primary breast tumours to that in metastatic axillary lymph nodes and to determine the correlation between the PD-1/PD-L1 status and clinicopathologic characteristics. In total, 47 paired breast tumour and metastatic axillary lymph node samples were collected in this study. Immunohistochemical technology was used to determine the positivity or negativity of PD-1/PD-L1. Other patient information was retrieved from medical records. Significant differences in PD-L1 expression were observed between primary breast tumours and paired axillary lymph nodes. We also observed that the presence of PD-1/PD-L1 positivity in metastatic lymph nodes was significantly associated with poor prognostic features, such as a high Ki-67 index (p = 0.048), a high TNM stage (p = 0.012), a large number of metastatic lymph nodes (p = 0.002), and a high histology grade (p = 0.029). Since heterogeneity exists, it is necessary to determine the PD-L1 status in both the primary tumour and metastatic lymph nodes.

Aim: To evaluate the efficacy and toxicity of vinorelbine and gemcitabine (NG) versus vinorelbine and cisplatin (NP) in anthracycline- and taxane-pretreated patients with HER2-negative advanced breast cancer., Patients and Methods: Patients were randomly assigned on a 1:1 schedule to receive no more than six cycles of NG or NP. Dosing for the NG group was 25 mg/m 2 vinorelbine and 1,000 mg/m 2 gemcitabine, given on days 1 and 8 every 3 weeks; for the NP group,25 mg/m 2 vinorelbine was given on days 1 and 8, and 75 mg/m 2 cisplatin was given on day 1 every 3 weeks. The primary endpoint was disease control rate (DCR). The secondary endpoints were the progression-free survival (PFS), overall survival (OS) and safety., Results: The full analysis set comprised of 37 patients receiving NG and 37 receiving NP. The DCR was 70.3% with NG and 64.9% with NP (p=0.619). Median PFS were 7 months (95% CI=5.88-8.12) and 6 months (95% CI=5.29-6.71) respectively in NG and NP group [hazard ratio (HR)=1.696; 95% confidence interval (CI)=0.73-3.93; p=0.217)]. Corresponding median OS was 18 (95% CI=10.35-13.65) months and 12 (95% CI=15.83-20.17) months (HR=1.219; 95% CI=0.67-2.23; p=0.521). For adverse events, neutropenia and nausea/vomiting were milder in the NG group than in the NP group (all p<0.05)., Conclusion: Although no significant differences were observed in terms of DCR, PFS and OS, with milder toxicity, NG appeared to be a more valuable first-line treatment regimen than NP in anthracycline- and taxane-pretreated patients with HER2-negative advanced breast cancer., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Tumor-to-tumor metastasis (TTM) is a rare phenomenon. We present a case of an invasive ductal carcinoma (IDC) of the breast metastasizing to a clear cell renal cell carcinoma (RCC). Breast cancer (BC) metastasis to the RCC is rarely reported, especially in resected kidney tumor. In several cases reported, IDC was the exclusively histologic type of BC metastasized to RCC. It seems that the different molecular type of IDC doesn't affect the metastatic tendencies to RCC. TTM was an indicator of diffuse disease. For any patient with a history of breast cancer, especially with multi-organs metastasis, resection of kidney tumor should be carefully considered.