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More than half of the metastatic breast cancer patients with brain metastases (BCBM) are HER-2 negative, and the prognosis of HER2-negative BCBM is dismal. But few clinical trials have investigated systemic therapies for this subgroup of patients. This real-world study included 58 HER2-negative BCBMs who received low-dose apatinib (250 mg daily) in combination with chemotherapy between 18 March 2017 and 31 December 2021. The objective response rate (ORR) of the central nervous system, clinical benefit rate (CBR), progression-free survival of central nervous system (CNS-PFS) and overall survival (OS) were analyzed. Univariate and multivariate Cox regression model was used to estimate the prognostic factors for CNS-PFS and OS. At the cut-off date, the median follow-up time was 28.2 months. Of the 58 patients, 36 patients were HR+/HER2-, and 22 patients were TNBC. The CNS-ORR was 17.2% (95%CI 9.6% to 28.9%) and the CBR was 53.4% (95%CI 40.8% to 65.7%). The median duration of CNS-PFS for the entire cohort was 6.4 months, and the median OS was 10.7 months. The median CNS-PFS and OS were not affected by hormone receptor status, disease-free survival, the number of prior lines of therapy and local treatment. The most common grade 2–3 adverse events associated with low-dose apatinib were hypertension (20.6%), elevated bilirubin (10.4%), hypothyroidism (10.3%), and hand-foot skin reaction (10.3%). Apatinib-based chemotherapy demonstrates potential feasibility with acceptable tolerance for HER2-negative BCBM. Its clinical application in BCBM still needs further verification. HER2-negative breast cancer patients with brain metastases (BCBM) face an extremely poor prognosis, and a lack of effective treatment options. Apatinib, as a small molecule anti-angiogenic TKI, might have special central nervous system activity. Apatinib-based chemotherapy exhibits good tolerance and gains a favorable survival for HER2-negative BCBM. [ABSTRACT FROM AUTHOR]

For patients with hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (mBC), the treatment choices become more complex after progression on first-line CDK4/6 inhibitors combined with endocrine therapy. Currently, there are no guidelines that provide a unified standard protocol for this situation. Almost half of patients with mBC develop brain metastases (BMs), and once BMs occur, the survival of the patient is often significantly reduced. An anti-angiogenic drug and chemotherapy combination of has demonstrated synergistic effects in an mBC cell line. Anti-angiogenic drugs have shown therapeutic efficacy in the treatment of mBC, and utidelone has shown the ability to cross the blood-brain barrier and achieve a high concentration in brain tissue in preclinical studies. The present case report describes a patient with HR+/HER2− mBC and BMs that developed resistance to two CDK4/6 inhibitors and treatments with anthracyclines/taxanes. The patient received a fourth-line treatment regimen combining utidelone with a small-molecule anti-angiogenic drug, namely apatinib or anlotinib. The patient achieved a partial response with this combined regimen, and a progression-free survival (PFS) of 7.6 months, which was the best therapeutic outcome in the entire course of the illness. This result was superior to the second-line treatment with nab-paclitaxel, which resulted in a PFS of 8 months and best overall response of stable disease with slight shrinkage. The present case indicates that a combination of utidelone with apatinib/anlotinib exhibited antitumor activity in a patient with HR+/HER2− mBC with BMs. Therefore, this combination offers a promising therapeutic option for the clinical treatment of patients with breast cancer and BMs. [ABSTRACT FROM AUTHOR]

Although human epidermal growth factor receptor 2 (HER2)-targeted therapy significantly improves the prognosis of patients with HER2-positive breast cancer, most patients with advanced breast cancer eventually progress due to drug resistance. At present, there is no standard treatment after patients become resistant to HER2-targeted therapy. Previous studies have indicated that anti-angiogenesis drugs have potential efficacy in the treatment of advanced breast cancer. The present study reported on a case of a pretreated patient with HER2-positive advanced breast cancer with brain metastases who developed resistance to multiple lines of HER2-targeted treatment. The patient was treated with apatinib combined with trastuzumab and albumin-bound paclitaxel. The patient achieved partial response to the third-line treatment with a progression-free survival of 9 months. After combination treatment, the symptoms of headache and vomiting were relieved and all the brain metastases were significantly reduced. The present case indicated that apatinib may have anti-tumor activity in patients with HER2-positive breast cancer with HER2-targeted drug resistance. The present case provides valuable information and may offer a new possibility for the treatment of patients with breast cancer with brain metastases who progressed after clinical treatment with small-molecule anti-HER2 tyrosine kinase inhibitor drugs. [ABSTRACT FROM AUTHOR]

Purpose: Splenic metastases (SM) from breast cancer (SMBC) are exceedingly rare. To date, the relevant literature is primarily based on pan-tumour species, with only a few studies exploring SM specifically in relation to breast cancer. As such, the present retrospective study explored the clinicopathological characteristics and prognoses of patients with SMBC at the breast care centre of the authors' hospital., Methods: Data from patients newly diagnosed with metastatic breast cancer (MBC) between June 2017 and June 2022 were extracted from medical records at the authors' hospital. Clinicopathological characteristics and their associations with progression-free survival (PFS [time from diagnosis of initial recurrence and/or metastasis to diagnosis of SM]), first overall survival ( 1st OS [time from diagnosis of breast cancer to death or last follow-up visit]), and second overall survival ( 2nd OS [time from diagnosis of SM to death or last follow-up visit]) were analysed in patients with SMBC., Results: In total, 1009 patients with MBC were identified, of whom 18 (1.7%) had SM. T1 and T2 stages were documented in 15 (83.3%) patients, whereas N2 and N3 were documented in 13 (62.2%). 14 (77.8%) patients were oestrogen receptor and/or progesterone receptor positive. A Ki-67 index ≥ 30% accounted for 72.2% (13/18) of cases, and all patients were histological grade II or III. Liver and/or lung metastases were documented in all 18 (100%) patients. Median PFS was 6.3 months. The median 1st OS and 2nd OS were 41.8 and 10.6 months, respectively. The number of previous treatment lines before diagnosis of SM was a significant adverse prognostic factor for PFS, and disease-free survival was a significant adverse prognostic factor for 1st OS., Conclusion: SMBC commonly presents with diffuse multiple organ metastases in the terminal stage of malignancy and has a poor prognosis, which may provide deeper insight into SMBC for clinicians., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Rationale: Hormone receptor-positive, HER2-negative advanced breast cancer complicated by pulmonary lymphangitic carcinomatosis (PLC) poses significant therapeutic challenges due to the lack of standardized treatment protocols. Despite various therapeutic interventions and supportive care, prognosis remains dismal., Patient Concerns: Herein, a 48-year-old Chinese woman presented with a persistent cough, unresponsive to anti-infective treatment for 1 month. A computed tomography (CT) scan revealed lymphatic vessel infiltration and a diffuse nodular pattern, suggestive of PLC., Diagnoses: Hormone receptor-positive, HER2-negative advanced breast cancer complicated by PLC., Interventions: The patient was treated with a regimen comprising low-dose apatinib, capecitabine, and albumin-bound paclitaxel., Outcomes: The patient achieved a partial response, with a progression-free survival exceeding beyond ten months. Symptoms of dyspnea and dry cough significantly improved, alongside a notable reduction in lymphangitic carcinomatosis., Lessons: This case highlights the potential antitumor activity of apatinib in breast cancer patients with presenting with PLC. While further studies are necessary, this therapeutic approach could represent a viable option for managing breast cancer in the context of a visceral crisis. The case also emphasizes the importance of individualized treatment strategies and further research to substantiate these promising findings., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer for which there is no effective treatment. Previously, we and others demonstrated that CXCR4 surface expression is an independent prognostic factor for disease relapse and survival in breast cancer. In this study, we investigated the effects of CXCR4 gene silencing on cisplatin chemosensitivity in human triple-negative breast cancer cell lines. We found that CXCR4 silencing significantly inhibited cell growth, decreased colony formation, and enhanced cisplatin sensitivity while overexpression of CXCR4 rendered cells more resistant to cisplatin. Moreover, the percentage of apoptosis and cell cycle arrest at the G2/M phase of cisplatin-treated CXCR4 knockdown cells was significantly higher than control cells. Furthermore, we demonstrated CXCR4 knockdown cells showed lower levels of mutant p53 and Bcl-2 protein than the control group, while also having higher levels of caspase-3 and Bax. However overexpression of CXCR4 had the reverse effect. In vivo experiments confirmed that downregulation of CXCR4 enhanced cisplatin anticancer activity in tumor-bearing mice, and that this enhanced anticancer activity is attributable to tumor cell apoptosis. Thus, this study indicates that CXCR4 can modulate cisplatin sensitivity in TNBC cells and suggests that CXCR4 may be a therapeutic target for TNBC.

Objective: To establish a CDDP-resistant cell line from human nasopharyngeal carcinoma and evaluate its biological characteristics., Method: By continuously exposing and gradually increasing dose of cisplatin (CDDP), a resistant nasopharyngeal carcinoma cell line (HNE1/CDDP) was established. Drug sensitivity of this cell line was detected by MTT assay; the alterations of its biological characteristics were determined using light microscopy, cell counting and flow cytometry (FCM); its ability of adhesion, migration and invasion were also evaluated., Result: HNE1/CDDP cell line was developed after 10 months with stable resistance to cisplatin with the resistance index was 5.83. HNE1/CDDP cell exhibited cross-resistance to many other chemotherapeutic agents (carboplatin, oxaliplatin and etoposide, etc). The morphology of HNE1/CDDP changed; doubling time prolonged; and the cell number of S-phase and G2/M-phase decreased while of G0/G1 phase increased compared with parental cells. The ability of adhesion, migration and invasion had no difference between the parental and the resistant cells., Conclusion: HNE1/CDDP cell line shows the typical and stable resistant phenotype and can be used as a research model.

Background: Arsenic trioxide (As2O3) induced apoptosis and differentiation of acute promyelocytic leukaemia. A few in vivo experimental investigations of its efficacy in solid tumours have been done. This study was designed to explore the differentiation-inducing effect, and the possible mechanisms involved, of As2O3 on human nasopharyngeal carcinoma CSNE-1 xenografts., Methods: Nasopharyngeal carcinoma cell CSNE-1 was established as a xenograft in nude mice. The tumour-bearing mice were treated with As2O3 at a dose of 5 mg/kg/day. To assess tumour differentiation, tumour growth was observed and histological changes were analysed under light and electron microscopy. Expression of latent membrane protein 1 (LMP1) and cytokeratin 4 (CK4) was determined by immunohistochemistry. A PCR-based telomeric repeat amplification protocol assay (TRAP-ELISA) was used to measure telomerase activity., Results: The xenografts underwent differentiation. LMP 1 of the cells decreased significantly and there was a pronounced decline in telomerase activity., Conclusion: As2O3 can inhibit xenograft growth and induce morphological and functional differentiation of CSNE-1 cells. The As2O3-induced differentiation was associated with downregulation of telomerase activity.