Background: MicroRNAs contribute to chemotherapy response in different types of cancer. We hypothesized that plasma miRNAs are potentially associated with chemotherapy response in patients with metastatic breast cancer. Patients and Methods: Fourteen candidate microRNAs were chosen from the literature, and their plasma levels were measured by quantitative polymerase chain reaction (PCR). Forty metastatic breast cancer patients were chosen as the training groups. The potential significant microRNAs were validated in another 103 plasma samples. Results: In the training set, we identified 3 microRNAs (miR-200a, miR-210, and miR-451) as significantly dysregulated miRNAs between sensitive group (partial response (and stable disease) and resistant group (progressive disease). Then, in the validation set, miR-200a (area under the curve = 0.881, sensitivity = 94.1%, specificity = 76.7%) and miR-210 (area under the curve = 0.851, sensitivity = 88.2%, specificity = 72.1%) showed high diagnostic accuracy for distinguishing sensitive group from resistant group. Furthermore, the plasma level of miR-200a was significantly associated with the stage in surgery (P = .035), and the high level of miR-210 expression was associated with internal organ metastasis (liver, lung, and brain; P = .024). Conclusions: Plasma miR-200a and miR-210 could be effective biomarkers for the prediction of chemotherapy resistance in metastatic breast cancer patients.

Purpose: In patients with first-line advanced breast cancer (ABC), the correlation between ctDNA variant allele frequency (VAF) and tumor disease burden, and its prognostic value remains poorly investigated. Methods: This study included patients with ABC diagnosed at Peking University Cancer Hospital who performed ctDNA test before receiving first-line treatment. Baseline plasma samples were collected for assessing ctDNA alterations and VAF with next-generation sequencing. The sum of tumor target lesion diameters (SLD) was measured with imaging methods according to RECIST 1.1 criteria. Results: The final cohort included 184 patients. The median age of the cohort was 49.4 (IQR: 42.3–56.8) years. The median VAF was 15.6% (IQR: 5.4%-33.7%). VAF showed positive correlation with SLD in patients with relatively large tumor lesions (r = 0.314, p = 0.003), but not in patients with small tumor lesions (p = 0.226). VAF was associated with multiple metastasis sites (p = 0.001). Multivariate Cox regression analysis showed that high VAF was associated with shorter overall survival (OS) (HR: 3.519, 95% confidence interval (CI): 2.149–5.761), and first-line progression-free survival (PFS) (HR: 2.352, 95%CI: 1.462–3.782). Combined VAF and SLD improved prediction performance, both median OS and PFS of patients in VAF(H)/SLD(H) group were significantly longer than VAF(L)/SLD(L) group (mOS: 49.3 vs. 174.1 months; mPFS: 9.6 vs. 25.3 months). Conclusion: ctDNA VAF associated with tumor disease burden, and was a prognostic factor for patients with ABC. A combination of ctDNA test and radiographic imaging might enhance tumor burden evaluation, and improve prognosis stratification in patients with ABC.

This study aimed to examine the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) and other clinicopathological features in HER2+ MBC patients who received first-line anti-HER2 therapy. A total of 129 patients were assigned to NLR-low and NLR-high groups based on a cutoff value of 3.0 at baseline. Peripheral blood lymphocyte subsets and gene mutations in circulating tumor DNA were analyzed by flow cytometry and Next-generation sequencing, respectively. Survival was evaluated by the Kaplan–Meier method and Cox regression analysis. Of the 129 patients, 77 and 52 were assigned to the NLR-low (≤3) and NLR-high (>3) groups, respectively. Compared with NLR-high patients, the NLR-low patients had significantly longer median progression-free survival (PFS) (11.7 vs. 7.7 months) (p = 0.001, HR = 2.703 95% CI 1.543–4.736 and overall survival (OS) (37.4 vs. 28.7 months) (p = 0.044, HR = 2.254 95% CI 1.024–4.924). Furthermore, this association was independent of metastatic sites or estrogen receptor status. Peripheral blood CD3+ (p = 0.034) and CD4+ (p = 0.010) T cell numbers were significantly higher in the NLR-low group than the NLR-high group. The mutational profile of MBC was generally similar between the two groups. Baseline NLR was a prognostic factor of PFS and OS for patients with HER2+ MBC in the first-line setting. These results may facilitate the selection of patients who will benefit most from anti-HER2 treatment.

Anti-angiogenesis offers an important treatment strategy for metastatic breast cancer (MBC). Metronomic chemotherapy (MCT) provides antiangiogenic effects without increased toxicities, making it good partner for antiangiogenic therapy. We conducted the present retrospective study to evaluate the efficacy and safety of anlotinib plus MCT for HER2 negative MBC. Patients with HER2 negative MBC who received metronomic chemotherapy (Vinorelbine (NVB), Capecitabine (CAPE), Etoposide (VP-16)) with anlotinib were retrospectively analyzed from Jan 2019 to Dec 2021. The primary end point was progression free survival (PFS). Secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. 48 patients with HER2 negative MBC were enrolled. 19 (39.6%) patients received NVB, 17 (35.4%) patients received CAPE and 12 (25.0%) patients received VP-16. The overall ORR and DCR were 8.3% (4/48) and 87.5% (42/48) respectively. The median PFS was 5.6 months (95% CI 4.3-7.0 months), and the median OS was 25.2 months (95% CI 20.2-30.1 months). The patients with age ≥ 50 (5.3 vs. 7.7 months, P = 0.014, HR = 0.407) and pathologic grade 1 or 2 (6.2 vs. 3.2 months, P = 0.023, HR = 2.471) had significantly longer PFS. The patients with hormone receptor (HR) positive (5.3 vs. 7.7 months, P = 0.004, HR = 0.206) and pathologic grade 1 or 2 (6.2 vs. 3.2 months, P = 0.020, HR = 3.882) had significantly longer OS. The incidence of all grades adverse events (AEs) was 56.3% (27/48) and grade 3–4 AEs was 12.5% (6/48). Within the context of real-world clinical practice, anlotinib in combination with metronomic chemotherapy provides a well-tolerated and effective treatment option for HER2-negative MBC, which warrants further investigation in the future.

Cancer is a malignant disease that threatens human life and health. Among cancer types, breast cancer is one of the most common malignant tumors in women worldwide and ranks among the top cancer types in terms of incidence rate of malignant tumors in Chinese women. Aptamers are a class of DNA or RNA sequences that can bind to specific targets through their three‑dimensional structures, and are screened and obtained via systematic evolution of ligands by exponential enrichment technology. Aptamers have advantages of high affinity and specificity, strong stability, low immunogenicity, a wide range of targets and ease of preparation and purification. As effective molecular targeting tools and drug delivery carriers, aptamers and their conjugates show therapeutic potential in the early diagnosis and treatment of breast cancer. The present article reviewed the properties and screening techniques of aptamers, as well as their applications and research progress in the diagnosis and treatment of breast cancer, with the aim of providing new strategies and directions for the realization of precision medicine for breast cancer via aptamers.