Thyroid Metastases from Breast Cancer Case Report and Literature Review.

BACKGROUND: Thyroid metastasis arising from primary breast cancer is a rare phenomenon, with only a handful of cases documented in both national and international literature. The management approach and prognosis of this occurrence have sparked debates and uncertainties. CASE PRESENTATION: Herein, we report the case of a 55-year-old woman with breast cancer. She previously underwent extensive excision of the breast lesion with adjuvant chemotherapy and endocrine therapy. After 9 years, she presented with neck discomfort and examination suggested right thyroid metastasis and lymph node metastasis in the neck. Imaging showed pulmonary and bone metastases. Furthermore, the patient received endocrine therapy. After 7 months of follow- up, the patient survived without any new distant metastases. Thyroid metastases originating from breast cancer often unfold with a subtle, intricate nature, making early detection challenging. They tend to emerge inconspicuously, intertwining with widespread systemic metastases, hinting at a less favorable prognosis. CONCLUSION: Given the unusual clinical indicators, identifying heterochronic thyroid metastases in patients with tumors poses a distinct challenge, requiring clinicians to navigate the follow-up process with heightened sensitivity. The key lies in timely detection and early intervention, factors that can significantly enhance the overall quality of life for patients.

Development of Tumor Markers for Breast Cancer Immunotherapy.

Although breast cancer treatment has been developed remarkably in recent years, it remains the primary cause of death among women. Immune checkpoint blockade therapy has significantly altered the way breast cancer is treated, although not all patients benefit from the changes. At present, the most effective mechanism of immune checkpoint blockade application in malignant tumors is not clear and efficacy may be influenced by many factors, including host, tumor, and tumor microenvironment dynamics. Therefore, there is a pressing need for tumor immunomarkers that can be used to screen patients and help determine which of them would benefit from breast cancer immunotherapy. At present, no single tumor marker can predict treatment efficacy with sufficient accuracy. Multiple markers may be combined to more accurately pinpoint patients who will respond favorably to immune checkpoint blockade medication. In this review, we have examined the breast cancer treatments, developments in research on the role of tumor markers in maximizing the clinical efficacy of immune checkpoint inhibitors, prospects for the identification of novel therapeutic targets, and the creation of individualized treatment plans. We also discuss how tumor markers can provide guidance for clinical practice.

Efficacy of anti-HER2 drugs in the treatment of patients with HER2-mutated cancers: a systematic review and meta-analysis.

Anti-human epidermal growth factor receptor-2 (anti-HER2) therapy has shown excellent efficacy in patients with HER2 overexpression and amplification. Although HER2 mutations are rarely expressed in several cancers, when they occur, they can activate the HER2 signaling pathway. In recent years, studies have shown that anti-HER2 drugs have promising efficacy in patients with HER2 mutations. Based on keywords, we searched databases, such as PubMed, Embase, and Cochrane Library, and the main conference abstracts. We extracted data on objective response rate (ORR), clinical benefit rate (CBR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) from studies on the efficacy of anti-HER2 therapies in patients with HER2-mutated cancers, and analyzed grade 3 or higher adverse events (AEs). We included 19 single-arm clinical studies and 3 randomized controlled trials (RCTs), containing a total of 1017 patients with HER2 mutations, involving seven drugs and nine cancers, and 18 studies enrolled a high proportion of heavily pretreated patients who had received multiple lines of therapy. Our results showed pooled ORR and CBR of 25.0% (range, 3.8-72.7%; 95% CI, 18-32%) and 36.0% (range, 8.3-63.0%; 95% CI, 31-42%) for anti-HER2 therapy in HER2-mutated cancers. The pooled median PFS, OS, DOR were 4.89 (95% CI, 4.16-5.62), 12.78 (95% CI, 10.24-15.32), and 8.12 (95% CI, 6.48-9.75) months, respectively. In a subgroup analysis, we analyzed the ORR for different cancers, showing 27.0, 25.0, 23.0, and 16.0% for breast, lung, cervical, and biliary tract cancers, respectively. ORR analyses were performed for different drugs as monotherapy or in combination, showing 60.0% for trastuzumab deruxtecan (T-DXd), 31.0% for pyrotinib, 26.0% for neratinib combined with trastuzumab, 25.0% for neratinib combined with fulvestrant, 19.0% for trastuzumab combined with pertuzumab, and 16.0% for neratinib. In addition, we found that diarrhoea, neutropenia, and thrombocytopenia were the most common grade ≥ 3 AEs associated with anti-HER2 therapeutic agents. In this meta-analysis of heavily pretreated patients with HER2 mutations, anti-HER2 therapies, DS-8201 and trastuzumab emtansine, showed promising efficacy and activity. Anti-HER2 therapies showed different efficacies in different or the same cancer settings and all had a tolerable safety profile.

Cyclin-dependent kinase 4 and 6 inhibitors in combination with neoadjuvant endocrine therapy in estrogen receptor-positive early breast cancer: a systematic review and meta-analysis.

The combination of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors and endocrine treatment has benefited patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER + /HER2-) metastatic breast cancer; however, its effects in the neoadjuvant setting for ER + /HER2- early breast cancer (EBC) are unclear. Systematic searches were performed in PubMed, Embase, Cochrane Library, and major oncological meetings for trials of CDK4/6 inhibitors plus neoadjuvant endocrine treatment (NET) vs. NET/neoadjuvant chemotherapy (NACT) alone up to January 30, 2021. We assessed the efficacy of CDK4/6 inhibitors plus NET vs. NET/NACT alone in ER + /HER2- EBC. Six studies that included 803 patients treated with CDK4/6 inhibitors plus NET vs. NET/NACT alone were used. Compared with NET/NACT alone, CDK4/6 inhibitors plus NET increased the complete cell cycle arrest (CCCA) rate (OR, 9.00; 95% CI, 5.42-14.96; P < 0.001). Nonsignificant differences between CDK4/6 inhibitors and NET/NACT alone occurred in the preoperative endocrine prognostic index (PEPI)-0 rate (OR, 1.13; 95% CI, 0.59-2.18; P = 0.71), pathological complete response (pCR) rate (OR, 0.75; 95% CI, 0.13-4.29; P = 0.74), objective response rate (ORR) (OR, 0.70; 95% CI, 0.21-2.29; P = 0.55), and disease control rate (DCR) (OR, 1.16; 95% CI, 0.47-2.89; P = 0.74). CDK4/6 inhibitors plus NET indicated a high risk of neutropenia (OR, 56.43; 95% CI, 15.76-202.11; P < 0.001) as an adverse effect (AE) and elevated alanine aminotransferase (ALT) level (OR, 15.30; 95% CI, 2.02-115.98; P = 0.008) as grade 3/4 AEs. Compared with NET/NACT alone, CDK4/6 inhibitors plus NET increased CCCA rate in ER + /HER2- EBC patients. CDK4/6 inhibitors plus NET did not substantially improve the PEPI-0 rate, pCR rate, ORR, or DCR. The combination increased the risk of neutropenia and elevated ALT levels. In the neoadjuvant setting, addition of CDK4/6 inhibitors to NET may be an option for treating ER + /HER2- EBC.

Association between high body mass index and prognosis of patients with early-stage breast cancer: A systematic review and meta-analysis.

Background: A high body mass index (BMI) can indicate overweight or obesity and is a crucial risk factor for breast cancer survivors. However, the association between high BMI and prognosis in early-stage breast cancer (EBC) remains unclear. We aimed to assess the effects of high BMI on the prognosis of patients with EBC. Methods: The PubMed, Embase, and Cochrane Library databases and proceedings of major oncological conferences related to the effects of BMI on the prognosis of breast cancer were searched up to November 2021. Fixed- and random-effects models were used for meta-analyses. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for disease-free survival (DFS) and overall survival (OS) were extracted from the included literature. Results: Twenty retrospective cohort studies with 33,836 patients with EBC were included. Overweight patients had worse DFS (HR: 1.16, 95% CI: 1.05-1.27, P = 0.002) and OS (HR: 1.20; 95% CI: 1.09-1.33, P < 0.001). Obesity also had adverse effects on DFS (HR: 1.17, 95% CI: 1.07-1.29, P = 0.001) and OS (HR: 1.30, 95% CI: 1.17-1.45, P < 0.001). Likewise, patients with high BMI had worse DFS (HR: 1.16, 95% CI: 1.08-1.26, P < 0.001) and OS (HR: 1.25, 95% CI: 1.14-1.39, P < 0.001). In subgroup analyses, overweight had adverse effects on DFS (HR: 1.11, 95% CI: 1.04-1.18, P = 0.001) and OS (HR: 1.18, 95% CI: 1.11-1.26, P < 0.001) in multivariate analyses, whereas the relationship that overweight had negative effects on DFS (HR: 1.21, 95% CI: 0.99-1.48, P = 0.058) and OS (HR: 1.39, 95% CI: 0.92-2.10, P = 0.123) was not statistically significant in univariate analysis. By contrast, obesity had adverse effects on DFS (HR: 1.21, 95% CI: 1.06-1.38, P = 0.004 and HR: 1.14, 95% CI: 1.08-1.22, P < 0.001) and OS (HR: 1.33, 95% CI: 1.15-1.54, P < 0.001 and HR: 1.23, 95% CI: 1.15-1.31, P < 0.001) in univariate and multivariate analyses, respectively. Conclusions: Compared with normal weight, increased body weight (overweight, obesity, and high BMI) led to worse DFS and OS in patients with EBC. Once validated, these results should be considered in the development of prevention programs.

Immune checkpoint inhibitors plus neoadjuvant chemotherapy in early triple-negative breast cancer: a systematic review and meta-analysis.

PURPOSE: Some studies have shown that Immune checkpoint inhibitors (ICIs) have a favorable efficacy in advanced triple negative breast cancer (TNBC) patients, but the results are controversial in neoadjuvant chemotherapy (NACT) stage. The purpose of this study is to evaluate the efficacy and safety after NACT plus ICIs in early TNBC patients. METHODS: After searching PubMed, EMBASE, the Cochrane library and several mainly oncology conferences up to 30 January 2021 systematically, and define randomized controlled trials (RCTs) exploring the efficacy and safety of programmed death protein-1/programmed cell death-Ligand 1(PD-1/PD-L1) inhibitors plus neoadjuvant chemotherapy in TNBC patients. The primary endpoint was the pathological complete response (pCR) in intention-to-treat populations (ITT), and the secondary endpoints were event-free survival (EFS) and safety analysis in the ITT populations. RESULTS: Six RCTs (N = 2142) were included in our meta-analysis; NACT plus ICIs increased pCR rates compared with NACT in intention-to-treat (ITT) populations (OR: 1.91; 95% CI: 1.32-2.78, P < 0.001). The pCR rate also increased in both PD-L1 positive (OR: 1.65; 95% CI: 1.26-2.16, P < 0.001) and PD-L1 negative patients (OR: 1.56; 95% CI: 1.04-2.33, P = 0.03), especially in PD-L1 positive patients. The benefit was also observed in nodal-positive populations (OR: 2.52; 95% CI: 1.69-3.77, P < 0.001) and Eastern Cooperative Oncology Group performance-status score (ECOG PS) 0 subgroup (OR: 1.90; 95% CI: 1.42-2.53, P < 0.001). Three RCTs (N = 1615) reported EFS and the results showed that adding PD-1/PD-L1 inhibitors increased EFS (HR 0.65, 95% CI 0.50-0.83, P = 0.0007) in ITT populations with a short follow-up time. In the safety analysis of 2205 patients with early TNBC from five eligible studies, NACT plus ICIs had a higher risk of grade 3-4 diarrhea (OR: 2.54; 95% CI: 1.21-5.32; P = 0.01), any grade of adverse effects(AEs)including vomiting (OR: 1.37; 95% CI: 1.00-1.86; P = 0.05), hyperthyroidism (OR: 6.04; 95% CI: 2.39-15.29; P < 0.001), and hypothyroidism (OR: 5.04; 95% CI: 3.02-8.39; P < 0.001). CONCLUSIONS: PD-1/PD-L1 inhibitors combined with chemotherapy can improve pCR rates and EFS, and with an increased incidence of some immune-related AEs compared with chemotherapy alone. NACT plus ICIs might be an option in patients with in PD-L1 positive and high-risk populations with positive nodal disease early TNBC.

The effectiveness of early prophylactic hypothermia in adult patients with traumatic brain injury: A systematic review and meta-analysis.

OBJECTIVES: Previously published systematic reviews have explored the effects of therapeutic hypothermia on adult patients with traumatic brain injury (TBI). However, none explored the effect of early prophylactic hypothermia (within 6 h from injury to hypothermia induction). Animal studies indicated that early prophylactic hypothermia may reduce secondary injury and improve neurological outcomes. This systematic review aimed to investigate the effects of early prophylactic hypothermia on adult TBI regarding mortality, favourable outcomes, and complications. DATA SOURCE: We searched electronic databases including Cochrane CENTRAL, PubMed, MEDLINE, CINAHL, EMBASE, Web of Science, OpenGrey, and ClinicalTrials.gov from inception to June 12, 2019. Manual search was conducted for additional information. REVIEW METHODS: Only randomised controlled trials were included. The Cochrane Collaboration Risk of Bias Tool was used to assess the quality of included studies. We extracted general demographic characteristics, the initiation timing, methods of cooling, duration, target temperature, rewarming rate, mortality, neurological outcomes, and complications. RESULTS: Six studies with a total of 1207 participants were included. Meta-analyses showed no significant difference in mortality and favourable outcomes (risk ratio = 1.11, 95% confidence interval = 0.90-1.37, P = 0.32; risk ratio = 1.03, 95% confidence interval = 0.91-1.16, P = 0.65, respectively). Similar results were found regarding different durations of hypothermia and different rewarming rates. Various complications were reported in the included studies. No statistical difference was found in three studies, while complications were reported to be significantly higher in the hypothermia group in the other three studies. CONCLUSIONS: This review does not support the use of early prophylactic hypothermia (within 6 h after injury) as a neurological protection strategy in adult patients with TBI, irrespective of the short term or long term. No significant benefits were found regarding hypothermia with different rewarming rates. Owing to the limited number of studies, more randomised controlled trials with higher quality are required to establish true effects of early hypothermia in adult TBI.

A new hybrid gyroscope with electrostatic negative stiffness tuning.

A variety of gyroscopes have been extensively studied due to their capability of precision detection of rotation rates and extensive applications in navigation, guidance and motion control. In this work, a new Hybrid Gyroscope (HG) which combines the traditional Dynamically Tuned Gyroscope (DTG) with silicon micromachined technology is investigated. The HG not only has the potentiality of achieving the same high precision as the traditional DTG, but also features a small size and low cost. The theoretical mechanism of the HG with a capacitance transducer and an electrostatic torquer is derived and the influence of the installation errors from the capacitance plate and the disc rotor module is investigated. A new tuning mechanism based on negative stiffness rather than the traditional dynamic tuning is proposed. The experimental results prove that the negative stiffness tuning is practicable and a tuning voltage of as high as 63 V is demonstrated. Due to the decreased installation error, the non-linearity of the scale factor is reduced significantly from 11.78% to 0.64%, as well as the asymmetry from 93.3% to 1.56% in the open loop condition. The rebalancing close-loop control is simulated and achieved experimentally, which proves that the fundamental principle of the HG is feasible.