BRCA mutation status and pathological characterization of breast cancer in Zhoushan Islands, China.

OBJECTIVE: To investigate BRCA1/2 gene mutations and their relationship with clinicopathological features in patients with breast cancer in Zhoushan Islands. METHODS: High-throughput whole-exome gene sequencing was used to detect BRCA1/2 mutations in 776 breast cancer patients in Zhoushan Islands. RESULTS: The BRCA1/2 mutation rate of breast cancer patients in Zhoushan Islands was 4.38% (34/776). BRCA1 mutations were significantly correlated with age, molecular type, and family history of breast and ovarian cancers. BRCA2 mutations were most commonly found in invasive lobular carcinoma. Moreover, the BRCA2 mutation rate of cancers with molecular type luminal B (receptor protein-tyrosine kinase [HER2]-negative) was also relatively high. CONCLUSION: The rate of BRCA1/2 mutations in breast cancer patients from Zhoushan Islands is approximately 4.38%, and BRCA1 mutation is related to age, molecular type, and family history of breast and ovarian cancers.

PD-1 inhibitor monotherapy versus combination therapy: A real-world study of patients with recurrent or metastatic advanced esophageal squamous cell carcinoma after first-line chemotherapy.

Context: Although programmed death 1 (PD-1) inhibitors are a standard second-line treatment for esophageal squamous cell carcinoma (ESCC), their efficacy when used in combination with chemotherapy or anti-angiogenesis targeted therapy is unclear. Aim: To compare the efficacy and safety of PD-1 inhibitor monotherapy with that of combination therapy. Setting and Design: A retrospective study was conducted at the Shandong Cancer Hospital. Materials and Methods: Based on records, patients with advanced ESCC, treated with second-line or above PD-1 inhibitor-containing regimens from August 15, 2019 to April 12, 2021 were divided into combination (PD-1 inhibitors plus chemotherapy or anti-angiogenesis targeted therapy) and monotherapy groups. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical Analysis Used: The baseline differences between subgroups were assessed using the χ2-test, Fisher's exact test, or Student's t-test. Follow-up period, PFS, OS, median survival, and 95% confidence intervals (CIs) were estimated using Kaplan‒Meier analysis. The log-rank test was used to compare subgroups. Results: In the 169 patients included, clinical features were well balanced between both groups. The median PFS of the combination group was better than that of the monotherapy group (8.5 months [95%CI 6.3-10.7] vs. 3.2 months [95%CI 0.0-6.5]; hazard ratio (HR) = 0.34 [95%CI 0.13-0.92]; P < 0.001). The median OS showed the same trend (18.9 months [95%CI 14.4-23.3] vs. 9.8 months [95%CI 6.3-13.2]; HR = 0.47 [95%CI 0.21-1.04]; P = 0.010). Conclusion: Using PD-1 inhibitors in a combination treatment may improve PFS and OS, with acceptable toxicities.

Efficacy and safety comparison of PD-1 inhibitors vs. PD-L1 inhibitors in extensive-stage small-cell lung cancer: a retrospective comparative cohort study.

Background: Evidence from clinical research and meta-analyses have suggested that programmed cell death 1 (PD-1) inhibitors and programmed cell death ligand 1 (PD-L1) inhibitors plus chemotherapy could achieve a significant survival benefit for extensive-stage small-cell lung cancer (ES-SCLC) patients. However clinical researches concerned about the comparation between the PD-1 and PD-L1 inhibitors were relatively lacking. Methods: We collected the data of ES-SCLC patients treated with PD-1 inhibitors or PD-L1 inhibitors. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoint included adverse events (AEs). Results: The data of 221 ES-SCLC patients treated with PD-1 (n=146) or PD-L1 inhibitors (n=75) between February 2017 and June 2020 were retrospectively collected. The median OS (mOS) and median PFS (mPFS) were 19.07 and 8.27 months, respectively, in patients treated with PD-1 inhibitors. In the PD-L1 group, mOS has not been reached, and mPFS was 7.95 months. No significant differences were observed between the 2 groups in OS [hazard ratio (HR), 1.472; 95% confidence interval (CI), 0.847-2.220; P=0.198] and PFS (HR, 0.816; 95% CI, 0.577-1.155; P=0.251). The rates of patients showed AEs of any grade treated with PD-1 or PD-L1 were 67.12% and 64.00%, with no significant difference (P=0.642, χ2=0.216), ≥3 grade AEs occurred in 42 (28.76%) and 16 (21.33%) patients treated with PD-1 and PD-L1 inhibitors separately, also no significant difference (P=0.234, χ2=1.415) was observed. According to subgroup analysis, camrelizumab revealed a longer mPFS (15.17 months) compared with other immune-checkpoint inhibitors (ICIs). PD-1 and PD-L1 inhibitors revealed comparable efficacy in ES-SCLC patients with brain metastases, with no significant differences in OS (HR, 1.505; 95% CI, 0.684-3.311; P=0.309) and PFS (HR, 0.649; 95% CI, 0.356-1.182; P=0.157). Conclusions: PD-1 and PD-L1 inhibitors might achieved comparable survival benefit and safety in ES-SCLC patients. A longer PFS was observed in patients treated with PD-1 inhibitors in the first-line treatment, and the PD-1 inhibitor camrelizumab might have achieved a better PFS compared with other ICIs.

Hyperlipoproteinemia (a) is associated with breast cancer in a Han Chinese population.

To investigate the relationship between serum lipoprotein (a) (LP(a)) levels and breast cancer as well as the clinicopathologic characteristics of breast cancer in a Han Chinese population.This study included 314 breast cancer patients, 51 patients with benign breast tumors, and 185 healthy control subjects. All study subjects were Han Chinese with similar socio-economic backgrounds, who were local residents of Zhoushan, Zhejiang, China or who had lived in Zhoushan for a long period of time. Serum concentrations of LP(a) were determined using a latex-enhanced immunoturbidimetric assay. Clinicopathological characteristics of patients were retrieved from medical records, which included the histopathological type, grade, stage, and molecular subtype of the disease, the expression of estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki67, and the level of reproductive hormones. Correlations between 2 groups were evaluated using the Spearman correlation analysis. Associations among ≥3 groups were interpreted using the Kruskal-Wallis H test or the logistic regression test.Elevated serum LP(a) levels were detected in breast cancer patients compared with healthy control subjects, but no significant differences in LP(a) were detected between breast cancer and benign tumor or between benign tumor and healthy control. In breast cancer patients, serum LP(a) levels were inversely associated with HER2 expression, but they were not significantly correlated with any other clinicopathologic characteristics of breast cancer evaluated in this study.Elevated serum LP(a) levels were associated with breast cancer in a Han Chinese population.