Nanoparticle-assisted axillary staging: an alternative approach after neoadjuvant chemotherapy in patients with pretreatment node-positive breast cancers.

PURPOSE: In order to achieve an optimized method of axillary staging after neoadjuvant chemotherapy (NAC) in breast cancer patients with pretreatment positive axillary lymph nodes, we evaluated the feasibility and accuracy of nanoparticle-assisted axillary staging (NAAS) which combines carbon nanoparticles with standard sentinel lymph node biopsy (SLNB) with radioisotope and blue dye. METHODS: Invasive breast cancer patients with pre-NAC positive axillary lymph nodes who converted to ycN0 and received surgeries from November 2020 to March 2021 were included. All patients underwent ipsilateral NAAS followed by axillary lymph node dissection. Detection rate (DR), false-negative rate (FNR), negative predictive value (NPV) and accuracy of axillary staging were calculated. RESULTS: Eighty of 136 (58.8%) breast cancer patients converted to ycN0 after NAC and received NAAS. The DR, NPV and accuracy was 95.0%, 93.3% and 97.4% for NAAS, respectively. And the FNR was 4.2% (2/48) for NAAS, which was lower than that of standard dual-tracer SLNB (SD-SLNB) (9.5%, 4/42). Pretreatment clinical T4 classification was a risk factor for detection failure in NAAS (p = 0.016). When patients with pretreatment inflammatory breast cancers were excluded from analysis, FNR dropped to 2.2% (1/45) for NAAS. CONCLUSION: NAAS revealed great performance in invasive breast cancer patients with pre-NAC positive axillary lymph nodes who converted to ycN0. The application of NAAS reached a better balance between more accurate axillary evaluation and less intervention. Trial registration Chictr.org.cn (ChiCTR2000039814). Registered Nov 11, 2020.

Excipient of paclitaxel induces metabolic dysregulation and unfolded protein response.

Taxane-based reagents, such as Taxol, Taxotere, and Abraxane, are popular anti-cancer drugs that can differ in their clinical efficacy. This difference is generally attributed to their active pharmaceutical ingredients. Here, we report a serendipitous discovery that Taxol induces metabolic dysregulation and unfolded protein response. Surprisingly, these effects of Taxol are entirely dependent on its excipient, Cremophor EL (CrEL). We show that CrEL promotes aerobic glycolysis and in turn results in drastic upregulation of angiopoietin like 4 (ANGPTL4), a major regulator of human blood lipid profile. Notably, premedication with dexamethasone further enhances the expression of ANGPTL4. Consistently, we find that the amplitude and frequency of increase in triglycerides is more prominent in Taxol-treated patients with breast cancer. In addition, we find that CrEL activates the unfolded protein response pathway to trigger proinflammatory gene expression and caspase/gasdermin E-dependent pyroptosis. Finally, we discuss the implications of these results in anti-cancer therapies.

Ultrasensitive Nanopore Sensing of Mucin 1 and Circulating Tumor Cells in Whole Blood of Breast Cancer Patients by Analyte-Triggered Triplex-DNA Release.

The characterization of circulating tumor cells (CTCs) by liquid biopsy has a great potential for precision medicine in oncology. Here, a universal and tandem logic-based strategy is developed by combining multiple nanomaterials and nanopore sensing for the determination of mucin 1 protein (MUC1) and breast cancer CTCs in real samples. The strategy consists of analyte-triggered signal conversion, cascaded amplification via nanomaterials including copper sulfide nanoparticles (CuS NPs), silver nanoparticles (Ag NPs), and biomaterials including DNA hydrogel and DNAzyme, and single-molecule-level detection by nanopore sensing. The amplification of the non-DNA nanomaterial gives this method considerable stability, significantly lowers the limit of detection (LOD), and enhances the anti-interference performance for complicated samples. As a result, the ultrasensitive detection of MUC1 could be achieved in the range of 0.0005-0.5 pg/mL, with an LOD of 0.1 fg/mL. Moreover, we further tested MUC1 as a biomarker for the clinical diagnosis of breast cancer CTCs under double-blind conditions on the basis of this strategy, and MCF-7 cells could be accurately detected in the range from 5 to 2000 cells/mL, with an LOD of 2 cells/mL within 6 h. The detection results of the 19 clinical samples were highly consistent with those of the clinical pathological sections, nuclear magnetic resonance imaging, and color ultrasound. These results demonstrate the validity and reliability of our method and further proved the feasibility of MUC1 as a clinical diagnostic biomarker for CTCs.

Pattern of Time-to-Surgery in Patients With Breast Cancer at Different Stages of the COVID-19 Pandemic.

BACKGROUND: The management of cancer surgeries is under unprecedented challenges during the COVID-19 pandemic, and the breast cancer patients may face a time-delay in the treatment. This retrospective study aimed to present the pattern of time-to-surgery (TTS) and analyze the features of breast cancer patients under the different stages of the COVID-19 pandemic. METHODS: Patients who received surgeries for breast cancers at West China Hospital between February 15, 2020 and April 30, 2020 (the outbreak and post-peak stages), and between March 10, 2021 and May 25, 2021 (the normalization stage) were included. TTS was calculated as the time interval between the pathological diagnosis and surgical treatment of breast cancer patients. And the pandemic was divided into three stages based on the time when the patients were pathologically diagnosed and the severity of pandemic at that time point. TTS, demographic and clinicopathological features were collected from medical records. RESULTS: A total of 367 patients were included. As for demographic features, it demonstrated statistically significant differences in insurance type (p<0.001) and regular screening (p<0.001), as well as age (p=0.013) and menstrual status (p=0.004). As for clinicopathological features, axillary involvement (p=0.019) was a factor that differed among three stages. The overall TTS was 23.56 ± 21.39 days. TTS for patients who were diagnosed during the outbreak of COVID-19 were longer than those diagnosed during pandemic post-peak and normalization stage (p<0.001). Pandemic stage (p<0.001) and excision biopsy before surgery (OR, 6.459; 95% CI, 2.225-18.755; p=0.001) were markedly correlated with the TTS of patients. CONCLUSIONS: TTS of breast cancer patients significantly varied in different stages of the COVID-19 pandemic. And breast cancer patients' daily lives and disease treatments were affected by the pandemic in many aspects, such as health insurance access, physical screening and change of therapeutic schedules. As the time-delay may cause negative influences on patients' disease, we should minimize the occurrence of such time-delay. It is vital to come up with comprehensive measures to deal with unexpected situations in case the pandemic occurs.

Lipid Changes During Endocrine Therapy in Breast Cancer Patients: The Results of a 5-Year Real-World Retrospective Analysis.

BACKGROUND: The aim of this study was to investigate the status of serum lipids during endocrine therapy. METHODS: We retrospectively analysed lipid profiles during the 5-year treatment of 1487 consecutive postoperative BC patients. Lipid parameters included triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL-C) and high-density lipoprotein (HDL-C). Those biomarkers were measured at baseline and 1, 2, 3, 4 and 5 years following the initiation of endocrine therapy. RESULTS: For premenopausal BC patients, LDL levels rapidly decreased at 1 year in the tamoxifen (TAM) group compared with baseline levels (p<0.05), and this decline remained for the following 4 years. Additionally, LDL levels were significantly lower in the TAM group than in the nonendocrine group at all assessment time points (p<0.05). Similarly, TC levels also decreased in the TAM group compared with baseline levels at all assessment time points (p<0.05), and compared with the levels in the nonendocrine group, TC levels were also lower for the first 4 years. For postmenopausal BC patients, there was no significant difference in the lipid profiles (TG, TC, LDL and HDL) in the letrozole (LET), anastrozole (ANA) or exemestane (EXE) groups compared with the nonendocrine group. For patients who received TAM, compared with the nonendocrine group, TC levels decreased at 1 year, and LDL levels decreased at 1 and 2 years. CONCLUSIONS: TAM may improve LDL and TC levels in premenopausal BC patients. In postmenopausal BC patients, aromatase inhibitors (AIs) may have no adverse effects on lipid profiles, and TAM may have limited beneficial effects on serum lipids.