Effectiveness and Safety of Pyrotinib-Based Therapy in the Treatment of HER2-Positive Breast Cancer Patients with Brain Metastases: A Multicenter Real-World Study.

BACKGROUND: Approximately 30% to 50% of patients with human epidermal growth factor receptor 2-positive metastatic breast cancer develop brain metastasis (BMs). Pyrotinib has shown promising efficacy in these patients. However, real-world evidence supporting its use is scarce. Therefore, we evaluate the efficacy and safety of pyrotinib-based regimens in the real world. MATERIALS AND METHODS: We enrolled patients with BMs from various healthcare facilities in China's Shandong region and used an updated breast-graded prognostic assessment (breast-GPA) to predict survival outcomes. RESULTS: Efficacy and toxicity were assessed in 101 patients. Overall, the median progression-free survival (PFS) was 11.0 months (95% CI, 7.6-14.4 months). PFS was shorter in patients with a breast-GPA of 0 to 2.0 (P< .001). Previous treatment with pertuzumab plus trastuzumab (P = .039) and varying numbers of BMs (P = .028) had a significant positive correlation with PFS. Additionally, radiotherapy (P = .033) for BMs, especially pyrotinib concurrent with radiotherapy (P = .013), significantly prolonged the PFS. In patients with a breast-GPA of 0 to 2.0, a significant difference in PFS was observed depending on whether the brain was the first metastatic site (P< .001). Furthermore, a breast-GPA (0-2.0 vs. 2.5-4.0), and radiotherapy for BMs were found to be independent predictors of PFS. Overall, the objective response rate was 42.6%, while the disease control rate was 88.1%. Diarrhea emerged as the most common adverse event. CONCLUSION: Pyrotinib-based therapy is effective and tolerable in human epidermal growth factor receptor 2-positive metastatic breast cancer with BMs. Patients who underwent radiotherapy for BMs, particularly those who received pyrotinib concurrently with radiotherapy, exhibited a more favorable prognosis.

Efficacy and safety of pyrotinib combined with albumin-bound paclitaxel as first-line treatment for HER2-positive metastatic breast cancer in patients previously treated with adjuvant and/or neoadjuvant trastuzumab therapy: The stage 1 results of a single-arm, phase 2 prospective clinical trial.

OBJECTIVE: It has been observed that the prognosis of patients with HER2-positive metastatic breast cancer has improved significantly with HER2-targeted agents. However, there is still a lack of evidence regarding first-line anti-HER2 treatment options for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer. Besides, there are no reliable markers that can predict the efficacy of anti-HER2 treatment in these patients. METHODS: Patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer were enrolled. Pyrotinib plus albumin-bound paclitaxel were used as first-line treatment. The primary endpoint was the objective response rate (ORR). The safety profile was also assessed. In order to explore predictive biomarkers using Olink technology, blood samples were collected dynamically. RESULTS: From December 2019 to August 2023, the first stage of the study involved 27 eligible patients. It has not yet reached the median PFS despite the median follow-up being 17.8 months. Efficacy evaluation showed that the ORR was 92.6%, and the DCR was 100%. Adverse events of grade 3 or higher included diarrhoea (29.6%), leukopenia (11.1%), neutropenia (25.9%), oral mucositis (3.7%), and hand-foot syndrome (3.7%). Toll-like receptor 3 (TLR3) and Proto-oncogene tyrosine-protein kinase receptor (RET) were proteins with significant relevance to PFS in these patients. CONCLUSIONS: This study demonstrates that pyrotinib plus albumin-bound paclitaxel as a first-line treatment regimen shows good efficacy and manageable safety for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer. Besides, a significant association was identified between the expression levels of TLR3 and RET and the PFS in patients.

Relationship between fear of progression and symptom burden, disease factors and social/family factors in patients with stage-IV breast cancer in Shandong, China.

OBJECTIVE: To assess fear of progression (FoP)'s relationship with symptom burden and disease and social/family factors, as well as, determine the status of FoP in women with stage-IV breast cancer in Shandong, China. METHODS: Two hundred and sixteen women were recruited from the department of breast cancer internal medicine, Shandong Cancer Hospital and Institute. Data for this observational study were collected between October 2020 and January 2021 using the MD Anderson Symptom Inventory, the Fear of Progression Questionnaire-Short Form (FoP-Q-SF) and a participant information scale. SPSS 23.0 was used for statistical analysis. RESULTS: After excluding invalid responses, the data of 200 participants were analysed. The average total FoP-Q-SF score was 29.39 ± 9.39 (95% confidence interval, 21.81-27.64). The FoP level among the participants was relatively low. For disease and social/family factors, FoP statistically significantly differed by satisfaction with family emotional support and the Eastern Cooperative Oncology Group (ECOG) score. The ECOG score was positively correlated with FoP. Furthermore, symptom burden was positively correlated with FoP. CONCLUSIONS: Among patients with stage-IV breast cancer, satisfaction with family emotional support, ECOG score and symptom burden play key roles in FoP. Interventions, including providing appropriate emotional support from family, improving physical fitness and relieving symptom burden, must be considered in future studies, which may improve patients' overall physical and mental status and provide a supportive therapeutic environment.

Dynamic analysis of circulating tumor DNA to predict the prognosis and monitor the treatment response of patients with metastatic triple-negative breast cancer: A prospective study.

Background: Limited data are available on applying circulating tumor DNA (ctDNA) in metastatic triple-negative breast cancer (mTNBC) patients. Here, we investigated the value of ctDNA for predicting the prognosis and monitoring the treatment response in mTNBC patients. Methods: We prospectively enrolled 70 Chinese patients with mTNBC who had progressed after ≤2 lines of chemotherapy and collected blood samples to extract ctDNA for 457-gene targeted panel sequencing. Results: Patients with ctDNA+, defined by 12 prognosis-relevant mutated genes, had a shorter progression-free survival (PFS) than ctDNA- patients (5.16 months vs. 9.05 months, p=0.001), and ctDNA +was independently associated with a shorter PFS (HR, 95% CI: 2.67, 1.2-5.96; p=0.016) by multivariable analyses. Patients with a higher mutant-allele tumor heterogeneity (MATH) score (≥6.316) or a higher ctDNA fraction (ctDNA%≥0.05) had a significantly shorter PFS than patients with a lower MATH score (5.67 months vs.11.27 months, p=0.007) and patients with a lower ctDNA% (5.45 months vs. 12.17 months, p<0.001), respectively. Positive correlations with treatment response were observed for MATH score (R=0.24, p=0.014) and ctDNA% (R=0.3, p=0.002), but not the CEA, CA125, or CA153. Moreover, patients who remained ctDNA +during dynamic monitoring tended to have a shorter PFS than those who did not (3.90 months vs. 6.10 months, p=0.135). Conclusions: ctDNA profiling provides insight into the mutational landscape of mTNBC and may reliably predict the prognosis and treatment response of mTNBC patients. Funding: This work was supported by the National Natural Science Foundation of China (Grant No. 81902713), Natural Science Foundation of Shandong Province (Grant No. ZR2019LZL018), Breast Disease Research Fund of Shandong Provincial Medical Association (Grant No. YXH2020ZX066), the Start-up Fund of Shandong Cancer Hospital (Grant No. 2020-PYB10), Beijing Science and Technology Innovation Fund (Grant No. KC2021-ZZ-0010-1).

Durable Effect of Pyrotinib and Metronomic Vinorelbine in HER2-Positive Breast Cancer With Leptomeningeal Disease: A Case Report and Literature Review.

Leptomeningeal metastases (LM) are rare and catastrophic for metastatic breast cancer (MBC). The prognosis of HER2-positive breast cancer (BC) with LM is extremely poor. There is no high-quality evidence of treatment regimens in HER2-positive BC with LM yet. Here, we present a case of LM in a 50-year-old woman with HER2-positive BC. Immunohistochemistry revealed invasive ductal carcinoma, estrogen receptor negative, progesterone receptor negative, HER2 3+, P53 positive 80%, and Ki-67 positive 35%. Reported for the first time, the patient was given pyrotinib-targeted therapy (400 mg, oral, every day), metronomic vinorelbine (40 mg, oral, three times a week), and intrathecal methotrexate (10 mg, infrequent and irregular use due to poor compliance) synchronously. The patient received and benefited from the treatment regimen for 16 months. And the quality of life, as self-reported, improved significantly. We also comprehensively summarized all the case reports, observational studies, and clinical trials related to HER2-positive BC with LM in the PubMed database and ClinicalTrials.gov. Intrathecal chemotherapy (methotrexate, cytarabine, thiotepa), intrathecal trastuzumab, whole-brain radiotherapy, and systemic therapy are commonly used treatment options according to a review of the literature and research. Pembrolizumab and trastuzumab deruxtecan (DS-8201) as novel drugs are promising in LM. Furthermore, trastuzumab emtansine (T-DM1) and tyrosine kinase inhibitors (TKIs) such as tucatinib and neratinib have exhibited good efficacy in HER2-positive BC with central nervous system (CNS) metastases and deserve further exploration. In our report, combining pyrotinib-targeted therapy with metronomic chemotherapy is a potential regimen, which has presented satisfactory therapeutic efficacy and also warrants additional investigation in HER2-positive BC with LM.

Survival analysis and nomogram for early-stage occult breast cancer with positive lymph nodes based on the SEER database.

Background: Occult breast cancer (OBC) is a rare type of breast cancer, which accounts for 0.3-1.0% of all breast cancers. However, the treatment of OBC remains controversial, especially the local treatment. We aimed to analyze the impact of different treatment and N stage on survival in early-stage OBC patients, and construct a nomogram to predict the prognosis. Methods: The data of patients with early-stage breast cancer were obtained from 17 registries in the Surveillance, Epidemiology, and End Results (SEER) database. Patient characteristics and breast cancer-specific survival (BCSS) were compared among the groups. Cox proportional risk models were used for both the univariate and multivariate analyses. Variables with a P value <0.07 in the univariate analysis were included in the multivariate analysis. The independent prognostic factors were included in the nomogram and validated internally. Results: A total of 492 early-stage OBC patients were randomized at a 7:3 ratio into the training cohort (n=348) and the testing cohort (n=144). N2+ stage patients had a worse prognosis than N1 stage patients (P=0.0051). Triple-negative breast cancer (TNBC) patients had the worst prognosis. Early-stage OBC patients benefited from surgery (P=0.0093) and radiotherapy (P=0.0102), but not chemotherapy (P=0.4030). An analysis of OBC patients with different N stages showed that in terms of treatment, N1 stage patients benefited from surgery (P=0.023), but did not benefit significantly from radiotherapy (P=0.0793), whereas N2+ stage patients benefited from radiotherapy (P=0.0098), but the benefit from surgery was not significant (P=0.1005). In the multivariate analysis, N stage, surgery, and radiotherapy remained statistically significant. Based on the results of the multivariate analysis, we constructed a nomogram for estimating the 3- and 5-year BCSS of OBC patients. The concordance index and the calibration plots show that our nomogram had sufficient accuracy and good coordination. Conclusions: N stage, surgery, and radiotherapy were identified as independent prognostic factors for OBC. We successfully constructed a nomogram using these independent risk factors and demonstrated that it could help predict the 3- and 5-year BCSS of OBC patients. Further data analyses need to be conducted to revise the treatment of early-stage OBC.

A missense variant in EZH2 is associated with colorectal cancer risk in a Chinese population.

Colorectal cancer (CRC) ranks the fifth leading cause of cancer death in China. EZH2 is a member of Polycomb-group (PcG) family and associated with transcriptional repression and cancer development. In this study, we report the association between a missense variant in EZH2 and risk of CRC. Through a systematic selection of variants in EZH2, we identified rs2302427 in the exon region of EZH2 and genotyped this variant in 852 CRC patients and 1,303 healthy controls using Taqman genotyping assay. The association between this variant and CRC risk was calculated using logistic regression with adjustment of sex, age, smoking status and drinking status. The result showed that rs2302427 was significantly associated with CRC susceptibility under an additive model (P=0.0068). Compared with CC genotype carriers, CG genotype and GG genotype carriers were associated with risk of CRC with odds ratio being 0.78 (95% CI: 0.63-0.96, P=0.0198) and 0.54 (95% CI: 0.24-1.18, P=0.1224), respectively. When stratified by sex, age, smoking status or drinking status, significant associations were observed only in younger individuals (OR=0.67, 95% CI: 0.50-0.89, P=0.0067) or smokers (OR=0.65, 95% CI: 0.48-0.88, P=0.0051). This study provides new insights into the personalized prevention of colorectal cancer.

Oxalate-assisted formation of uniform carbon-confined SnO2 nanotubes with enhanced lithium storage.

SnO2 nanotubes are synthesized via an oxalate-assisted "redox etching and precipitating" route between MnOOH nanowires and Sn2+ ions. The addition of oxalate is found to be crucial to guide the formation of uniform SnO2 nanotubes. To further improve the conductivity and stability, the as-obtained SnO2 nanotubes are coated with a thin carbon layer. The resulting carbon-confined SnO2 nanotubes possess superior rate performance as an anode material for lithium-ion batteries.

Solvent-Free Synthesis of Uniform MOF Shell-Derived Carbon Confined SnO2 /Co Nanocubes for Highly Reversible Lithium Storage.

Tin dioxide (SnO2 ) has attracted much attention in lithium-ion batteries (LIBs) due to its abundant source, low cost, and high theoretical capacity. However, the large volume variation, irreversible conversion reaction limit its further practical application in next-generation LIBs. Here, a novel solvent-free approach to construct uniform metal-organic framework (MOF) shell-derived carbon confined SnO2 /Co (SnO2 /Co@C) nanocubes via a two-step heat treatment is developed. In particular, MOF-coated CoSnO3 hollow nanocubes are for the first time synthesized as the intermediate product by an extremely simple thermal solid-phase reaction, which is further developed as a general strategy to successfully obtain other uniform MOF-coated metal oxides. The as-synthesized SnO2 /Co@C nanocubes, when tested as LIB anodes, exhibit a highly reversible discharge capacity of 800 mAh g-1 after 100 cycles at 200 mA g-1 and excellent cycling stability with a retained capacity of 400 mAh g-1 after 1800 cycles at 5 A g-1 . The experimental analyses demonstrate that these excellent performances are mainly ascribed to the delicate structure and a synergistic effect between Co and SnO2 . This facile synthetic approach will greatly contribute to the development of functional metal oxide-based and MOF-assisted nanostructures in many frontier applications.

[Topotecan in combination with cisplatin in the treatment of recurrent small cell lung cancer].

BACKGROUND: There is no effective regimen for recurrent small cell lung cancer patients now. The aim of this study is to assess the activity and toxicity of topotecan combined with cisplatin in the treatment of recurrent small cell lung cancer patients. METHODS: Twenty-eight patients with progressive disease after one first-line regimen enrolled in the study from May 2002 to October 2004. Topotecan was given at the dose of 1.2mg/m² from 1st to 4th days and cisplatin was administered at the dose of 25mg/m² from 5th to 7th days in a cycle of 3 weeks. The patients could be evaluated at least after 2 cycles. RESULTS: One patient got complete response and ten patients got partial response in this group. The overall response rate was 39.3% , and the response rate of refractory group and sensitive group was 37.5% (3/8) and 40.0% (8/20) respectively. The median time to progression was 4.2 months. The main toxicity was hematological toxicity. Grade III+IV neutropenia occurred in 42.9% (12/28) of the patients. CONCLUSIONS: The regimen of topotecan and cisplatin shows better activity in retreated small cell lung cancer patients. The main toxicity is hematological toxicity and can be tolerated.