Background: The metastatic breast cancer (MBC) is yet incurable with high mortality, thereby requiring improved biomarkers for predicting the outcome of palliative therapy in patients. The present study evaluated the correlation of serum platelet and endothelial cell adhesion molecule-1 (PECAM-1) with the prognosis of MBC patients.Methods: Thirty women initially diagnosed as MBC before any palliative treatment, were divided according to the median value of serum PECAM-1 level, Group A (<4,058.89 pg/mL) and Group B (>4,058.89 pg/mL). After median 78 months follow-up from the preliminary surgery, 15 patients died of breast cancer. The Kaplan-Meier method and Cox regression analysis were used to determine progression-free survival (PFS) and overall survival (OS) rates. Other data were analyzed by the Chi-square test and t-test.Results: The 3-year survival of MBC patients in Group A was higher than Group B. More patients in Group B accepted the adjuvant endocrine therapy than Group A. The serum CA125 level was higher in Group A than Group B. The serum total cholesterol (TC), low-density lipoprotein (LDL), and fasting glucose were significantly higher in Group A than Group B patients (P=0.02, P<0.001, and P<0.001, respectively). Cox regression analysis of OS showed that the fasting glucose was an independent prognosis factor in MBC patients. No significant differences were seen between Group A and B either in PFS or OS (P>0.05).Conclusions: High serum level of PECAM-1 is related to a decline in 3-year survival of MBC. Whether serum PECAM-1 could predict the long-term survival of MBC necessitates additional clinical trials.
Supplementary Data from First-in-human HER2-targeted Bispecific Antibody KN026 for the Treatment of Patients with HER2-positive Metastatic Breast Cancer: Results from a Phase I Study
Supplementary Figure from First-in-human HER2-targeted Bispecific Antibody KN026 for the Treatment of Patients with HER2-positive Metastatic Breast Cancer: Results from a Phase I Study
Breast cancer is one of the highest rates of malignancy of women, approximate 70% metastatic breast cancer are hormone receptor positive (HR+) and human epidermal growth factor receptor 2 negative (HER2-). Hormone therapy is the primary strategy of HR+/HER2- metastatic breast cancer. With the permission of cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i), progress free survival and overall survival were significantly licensed. However, inevitable outcome of CDK4/6i resistance has become the main reason that restricts the clinical benefit of patients. In recent years, the research on dealing with drug resistance has become a hot topic, a large number of molecular mechanisms have been focused, and a lot of experiments have been carried out at the preclinical level. This review summarizes the current knowledge of CDK4/6i resistance mechanism, systematically expounds the signaling pathways and targets leading to CDK4/6i resistance, analyzes different ways and mechanisms, and provides theoretical guidance for the clinical reversal of endocrine therapy resistance.
Developing guidelines for the diagnosis and treatment of common cancers in China based on the evidence-based practice, the availability of diagnosis and treatment products, and the up-to-date advances in precision medicine is one of the basic tasks of the Chinese Society of Clinical Oncology (CSCO).In recent years, the availability of medical resources has become a major concern in clinical guidelines, which is particularly important for developing countries or socioeconomically diverse countries and territories.China is the world's largest developing country, with a large territory and uneven economic and academic developments.The CSCO guidelines must take into account the differences in regional development, the availability of medicines and diagnostic methods, and the social value of cancer treatment.Therefore, for each clinical problem and intervention in the CSCO guidelines, the levels of evidence should be graded according to the currently available evidences and expert consensuses, and the grades of recommendations should be based on the availability and cost-effectiveness of the products.Protocols with high evidence level and good availability are used as the Level I recommendations; protocols with relatively high evidence level but slightly lower expert consensus or with poor availability are used as the Level II recommendations; and protocols that are clinically applicable but with low evidence level are regarded as the Level III recommendations.Based on the findings of clinical research at home and abroad and the opinions of CSCO experts, the CSCO guidelines determine the levels of recommendations for clinical application.The CSCO Guidance Working Group firmly believes that evidence-based, availability-concerned, and consensus-based guidelines will be more feasible for clinical practice.Again, any comments from our readers are greatly appreciated and will be considered in updates of these guidelines, so as to maintain the accuracy, fairness, and timeliness of the CSCO guidelines.
Abstract Purpose To evaluate the efficacy and safety of pamiparib in patients with locally advanced or metastatic human epidermal growth factor receptor 2-negative (HER2−) breast cancer, with deleterious or suspected deleterious germline BRCA1/2 mutations (g BRCA1/2 m). Methods In this open-label, phase II, multicenter study in China (NCT03575065), patients with triple-negative breast cancer (TNBC cohort) or hormone receptor-positive (HR+)/HER2− breast cancer (HR+/HER2− cohort) and ≤ 2 prior lines of chemotherapy received pamiparib 60 mg orally twice daily in 28-day, continuous cycles. The primary endpoint was objective response rate (ORR; RECIST v1.1) by independent review committee. Results In total, 88 patients were enrolled (TNBC cohort: 62; HR+/HER2− cohort: 26). Median age was 45.5 (range: 27–67) years, and 60 patients (68.2%) had received 1 or 2 prior lines of chemotherapy; 42 patients (47.7%) had previously received platinum chemotherapy. In the TNBC cohort, ORR was 38.2% (95% confidence interval [CI] 25.4–52.3) and median duration of response (DoR) was 7.0 months (95% CI 3.9–not estimable). In the HR+/HER2− cohort, ORR was 61.9% (95% CI 38.4–81.9) and median DoR was 7.5 months (95% CI 5.6–14.8). The most common treatment-emergent adverse events (TEAEs), treatment-related TEAEs, and ≥ Grade 3 TEAEs were hematologic (including anemia, decreased neutrophil count, and decreased white blood cell count). Overall, 64.8% of patients had TEAEs leading to dose reduction and 2.3% had TEAEs leading to treatment discontinuation. Conclusion Pamiparib showed encouraging efficacy and an acceptable safety profile in patients with locally advanced and metastatic HER2− breast cancer with g BRCA1/2 m. Trial registration ClinicalTrials.gov, NCT03575065; July 2, 2018.
e13024 Background: The immune system reveals to play a pivotal role in HER2 positive breast cancer responsiveness to trastuzumab therapy. The platelet-lymphocyte ratio (PLR) is representative blood markers of systemic inflammatory responses. It is suggested as an immunity biomarker in gastric, lung cancer and other cancers, but is less well known in breast cancer. The aim of this study is to investigate the predictive role of PLR in HER2 positive metastatic breast cancer patients treated with first-line trastuzumab therapy. Methods: This study retrospectively includes 287 HER2 positive metastatic breast cancer patients with first-line trastuzumab therapy in Cancer Hospital of the University of Chinese Academy of Science from January 2010 to November 2021. The Peripheral blood cell count of these patients before trastuzumab treatment is evaluated to calculate PLR. All patients are separated into PLR high or PLR low cohort according to cut-off value defined as median value. Median value of PLR is 154.5, more than 154.5 is defined by PLR high , otherwise defined as PLR low . Kaplan–Meier curves is performed to assess progression-free survival (PFS). Univariate and multivariate analyses were performed using a logistic regression model. Results: Of 287 patients, 228 patients’ peripheral blood cell count were available. 114 patients are PLR high and 114 patients are PLR low . Patients with PLR high achieved a significantly worse PFS compared to those with PLR low (median PFS: 8.47 months vs.9.92 months, HR:1.475, 95% CI:1.068-2.038, P = 0.014). Besides, mean corpuscular volume (< 89.2fL), lymphocyte (< 1.3), mean hemoglobin (< 30PG) are also related to worse PFS ( P= 0.003,0.033,0.055,respectively). Importantly, PLR high , mean corpuscular volume, remain independent predictors in the multivariate COX analysis (HR 0.689,95%CI 0.493-0.962, P = 0.028;HR1.646,95%CI 1.177-2.302, P = 0.004). Conclusions: Patients with pre-treatment PLR high showed less sensitivity to trastuzumab therapy for metastatic breast cancer patients independent of other molecular characteristics. The pre-treatment PLR levels might serve as a predictive biomarker for HER2 positive breast cancer with trastuzumab therapy.
Carriers with BRCA1/2 germline pathogenic variants are associated with a high risk of breast and ovarian cancers (also pancreatic and prostate cancers). While the spectrum on germline BRCA mutations among the Chinese population shows ethnic specificity, the identification of carriers with germline BRCA mutation before cancer onset is the most effective approach to protect them. This review focused on the current status of BRCA1/2 screening, the surveillance and prevention measures, and discussed the issues and potential impact of BRCA1/2 population screening in China. We conducted literature research on databases PubMed and Google Scholar, as well as Chinese databases CNKI and Wangfang Med Online database (up to 31 March 2022). Latest publications on germline BRCA1/2 prevalence, spectrum, genetic screening as well as carrier counseling, surveillance and prevention were captured where available. While overall 15,256 records were retrieved, 72 publications using germline BRCA1/2 testing were finally retained for further analyses. Germline BRCA1/2 mutations are common in Chinese patients with hereditary breast, ovarian, prostate and pancreatic cancers. Within previous studies, a unique BRCA mutation spectrum in China was revealed. Next-generation sequencing panel was considered as the most common method for BRCA1/2 screening. Regular surveillance and preventive surgeries were tailored to carriers with mutated-BRCA1/2. We recommend that all Chinese diagnosed with breast, ovarian, pancreatic or prostate cancers and also healthy family members, shall undergo BRCA1/2 gene test to provide risk assessment. Subsequently, timely preventive measures for mutation carriers are recommended after authentic genetic counseling.
The WHO analgesic guidelines for treatment of cancer pain have been proven safe and effective for most patients. However, there is still inadequate analgesia following that guideline based on pain degree.An 82-year-old man with history of right ceruminous gland carcinoma was treated by tumor resection following numerous courses of chemotherapy. He developed progressive pain ranging from 4 to 8 or 9 on the 0-10 numeric rating scale (NRS) involving the right side of face and neck area. Based on the WHO analgesic ladder, the primary prescription for the man contained tramal (100 mg/d) and celebrex (400 mg/d). However, pain relief was unsatisfied with this prescription even when dose of tramal increased to 200 mg/d. Then, tramal was replaced with morphine sulfate tablets at 15 mg at every 8 hours, but the pain was only modest relieved. After revaluation by pain physicianbased on etiology and mechanism of pain using ID pain questionnaire, the patient was identified to experiencing neuropathic pain. Finally, the pain was successfully relieved by gabapentin as an adjuvant to tramal.The successful pain relief of the patient in this case indicates that treatment of pain that based on mechanism might be worth promoting. According to the etiology of pain, specific drugs or measures should be selected for the individual patient. This approach have certain advantages, such as timely pain relief, reduction of medical cost, and effective improvement of life quality of cancer patients.
To research the repair effect of transplantation of glial cell line-derived neurotrophic factor (GDNF) modified olfactory ensheathing cells (OECs) combination with injecting axonal growth inhibiting protein antibody (IN-1) in vivo.To construct lentivirus vector with GDNF gene and infect OECs in vitro, use the immunoblotting (Western Blot) to observe the expression of GDNF was detected through Western Blot. Fifty adult female SD rats which to establish thoracic spinal cord transection injury model were randomly divided into A (control group), B (IN-1 antibody group), C (OECs group), D (GDNF-OECs group), and E (GDNF-OECs+IN-1 group) 5 groups of each 10 rats. To observe regeneration of the impaired nerve axon by NF200 immunohistochemistry, Biotinylated dextran amine (BDA) anterograde tracing corticospinal tract. Basso, Beattie and Bresnahan (BBB) score was used to evaluating hindlimb motor function recovery.Add up to 13 rats died post operation. OECs labeled by hoechst still survived and migrated in spinal cord 8 weeks post operation. Lots of confused and disorderly regenerated axons which crossing the injured region of spinal cord were displayed between spinal cord stumps in GDNF-OECs+IN-1 group and GDNF-OECs group; some of axons existed in OECs group, but there is no obviously continue nerve fibers crossing the injured region of spinal cord;in contrast to IN-1 and control groups, few of regenerated axons and atrophy of spinal cord stumps were observed. The results of BBB hindlimb motor rating scale were 7.70+/-0.24, 7.89+/-0.15, 10.50+/-0.25, 11.43+/-0.23 and 12.81+/-0.40 for the control group, IN-1 group, OECs group, GDNF-OECs group and the allied treatment group respectively.The transplantation of GDNF-OECs combination with IN-1 antibody may benefit the survival and regeneration of the injured axons, and accelerate the repair of the injured spinal cord and functional recover of hindlimb locomotor in rats in a more efficient way than that with OECs or IN-1 alone.
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