Feasibility and tolerability of eribulin-based chemotherapy versus other chemotherapy regimens for patients with metastatic triple-negative breast cancer: a single-centre retrospective study.

Background: Patients with Triple-negative breast cancer (TNBC) face a poor prognosis and limited therapeutic options. Current data on eribulin usage to treat TNBC is scarce. Therefore, we sought to compare the feasibility and tolerability of eribulin-based regimens with other chemotherapy regimens in patients with TNBC. Method: This retrospective study was conducted at Fujian Medical University Cancer Hospital and included 159 patients with TNBC enrolled between October 2011 and January 2023. Patients underwent treatment with eribulin-based and other chemotherapy regimens. The study's primary endpoints were progression-free survival (PFS) and overall survival (OS), while its secondary endpoint was objective response rate (ORR), disease control rate (DCR), and safety. Tumour response was assessed using RECIST V.1.1 criteria. Results: Of the 159 participants in the study, 42 individuals (26.4%) received treatment with eribulin, whereas 117 participants (73.6%) were administered alternative chemotherapy regimens, which included nab-paclitaxel-based therapy (n = 45) and platinum-based therapy (n = 51). The follow-up period for all patients ended on 31 December 2022, and the median follow-up time was 18.3 months (range:0.7-27.5). Following propensity score matching (PSM), eribulin-based treatment resulted in longer median progression-free survival compared to platinum-based (hazard ratio (HR) = 0.41, p = 0.006), nab-paclitaxel-based (hazard ratio = 0.36, p = 0.001) and other chemotherapy (HR = 0.39, p < 0.001). Also, eribulin induced a remarkable prolongation of the median overall survival duration in all three comparative groups. The group receiving eribulin treatment showed significantly reduced incidences of any grade of anaemia, peripheral neuropathy, nausea and vomiting, and hair loss compared to other chemotherapy groups. Conclusion: For the salvage treatment of advanced TNBC, treatment with eribulin produced longer median PFS and OS than other chemotherapy regimens, with a well-tolerated safety profile. Therefore, further investigation of eribulin-based treatment in larger randomized trials for patients with advanced TNBC is warranted.

A real-world study of the effectiveness and safety of apatinib-based regimens in metastatic triple-negative breast cancer.

PURPOSE: This investigation sought to examine the efficacy and safety of low-dose apatinib used alongside chemotherapy in the clinical management of patients with metastatic triple-negative breast cancer (TNBC) within a real-world setting, whilst comparing the outcomes with those treated solely with chemotherapy. METHODS: This case series study analyzed clinical data and treatment outcomes of 163 patients with metastatic TNBC who underwent rescue treatment at the Medical Oncology Department of Clinical Oncology, Fujian Cancer Hospital, School of Fujian Medical University, China, between October 2011 and January 2023. All the patients underwent rescue treatment with either chemotherapy alone or apatinib (250 mg/day) combined with chemotherapy. The study's primary outcome was progression-free survival (PFS), whereas the secondary outcomes included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety profiles. RESULTS: The study was designed to compare two groups [1]. Out of the 163 TNBC patients who participated in the study, 107 individuals (65.6%) received treatment based on chemotherapy, whereas 56 patients (34.4%) were given treatment based on a combination of low-dose apatinib (250 mg/day) and other treatments, including chemotherapy. After propensity score matching (PSM), the objective response rate (ORR) and disease control rate (DCR) of patients with advanced triple-negative breast cancer (TNBC) who received apatinib-based treatment were 50.0 and 90.0%, respectively, while they were 6.7 and 20.0%, respectively, for the chemotherapy-based group (P < 0.001). The group that received apatinib-based treatment showed superior results in both PFS and OS compared to the group that received chemotherapy. The median PFS and OS for the apatinib-based group were 7.8 and 20.3 months, respectively, while they were only 2.2 months and 9.0 months, respectively, for the chemotherapy-based group (P < 0.001) [2]. Patients who were administered combo therapies, including PD-1 inhibitors, were excluded. In total, 97 patients received chemotherapy alone, while 34 patients were treated with apatinib in combination with chemotherapy. After propensity score matching (PSM), the ORR and DCR for the total group who received combo therapies were 44.4 and 81.5%, respectively, while they were 11.1 and 22.2%, respectively, for the chemotherapy alone group (P < 0.001). The group receiving both apatinib and chemotherapy displayed notable advantages over the group solely receiving chemotherapy in regards to PFS and OS for the entirety of the population. The PFS was found to be 7.8 months in comparison to 2.1 months (P < 0.001) and the OS was 21.1 months in contrast to 9.0 months (P < 0.001). Apatinib combined with chemotherapy induced grade 3/4 hematological toxicities, including neutropenia (8.8%) and thrombocytopenia (2.9%). Additionally, non-hematological toxicities were commonly observed, such as Hand-foot syndrome (35.3%), proteinuria (26.5%), hypertension (61.8%), higher alanine aminotransferase levels (26.5%), and fatigue (35.3%). The most frequent non-hematological grade 3/4 toxicities were Hand-foot syndrome (2.9%) and hypertension (5.9%). The study did not report any fatal adverse effects. CONCLUSIONS: The combination of low-dose apatinib with chemotherapy has proven to be more effective than chemotherapy alone in treating metastatic triple-negative breast cancer (TNBC). Additionally, the occurrence of grade 3/4 non-hematologic toxicities was significantly lower compared to the recommended dose of apatinib.

The Efficacy and Safety of Inetetamab and Pyrotinib in Combination with Vinorelbine for Second-line Therapy and Beyond in HER2-positive Metastatic Breast Cancer: A Single-institution Clinical Experience.

BACKGROUND AND OBJECTIVE: This study aimed to observe the efficacy and safety of inetetamab and pyrotinib in combination with vinorelbine in second-line therapy and beyond in HER2-positive metastatic breast cancer (MBC). METHODS: Patients with HER2-positive MBC admitted to our hospital from January 2016 to December 2021 were selected. For patients who could not receive antibody‒drug conjugates (ADCs) during second-line (2nd-line) or third-line and beyond (≥3rd-line) anti-HER2 therapy, inetetamab + pyrotinib + vinorelbine was used for treatment until unacceptable adverse events occurred or the disease progressed, as evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 every 2 cycles. The progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR), and adverse reactions were recorded. Multivariate Cox regression analysis was performed to explore the prognostic factors influencing the curative effect. RESULTS: Overall, 52 patients were included; 13 patients received 2nd-line treatment, and 39 patients received ≥3rd-line treatment. The median PFS (mPFS) for all patients treated with inetetamab + pyrotinib + vinorelbine was 7 months. The mPFS of the 2nd-line subgroup was significantly better than that of the ≥3rd-line subgroup (17 vs. 5 months, P = 0.001). The mPFS of the subgroups that received trastuzumab (H) or trastuzumab and pertuzumab (HP) only was significantly better than that of the H or HP and tyrosine kinase inhibitor (TKI) subgroups (8 vs. 5 months, P = 0.030). The mPFS of the HER2 resistance subgroup was better than that of the HER2 refractoriness subgroup (14 vs. 7 months, P = 0.025). Cox regression analysis showed that the treatment line (2nd-line more so than ≥3rd-line) was an independent prognostic factor for PFS. In addition, the ORR and CBR of 2nd-line patients were significantly higher than those of ≥3rd-line patients (69.2% vs. 30.8% and 92.3% vs. 64.1%, respectively). The most common hematological toxicities were leukopenia and neutropenia, and the most common nonhematological toxicity was diarrhea. CONCLUSION: Inetetamab and pyrotinib in combination with vinorelbine have good efficacy in ≥2ndline treatment of HER2-positive MBC with controllable toxicity, and the combination is a new treatment option, especially for patients who cannot use ADCs in 2nd-line treatment.

Tumor mutational burden in non-immunotherapy patients with heavily pretreated metastatic breast cancer: long-term outcomes from a single institution.

Patients with heavily pretreated (≥3rd-line treatment) metastatic breast cancer (MBC) had poor outcomes and lack prognostic biomarkers. Tumor mutational burden (TMB) was a prognostic biomarker for immunotherapy, but is not well defined in non-immunotherapy. Forty-nine heavily pretreated MBC not received immunotherapy were enrolled between March 2016 and September 2018. TMB of metastatic tumor tissue was evaluated by targeted next-generation sequencing of a 247-genes panel. CBRs (clinical benefit rates) were 47.7% (9 months), 36.2% (12 months) in high TMB patients, higher than 16.1% (9 months), 8.1% (12 months) in low TMB patients, respectively. After a median follow-up of 38 months, patients with high TMB had a longer mPFS (median progress-free survival) compared to low TMB patients in 3rd-line treatment group (13.5 versus 7 months, HR 0.32, p = 0.019) but not in >3rd-line treatment group. Cox regression showed TMB and line of treatment were the two independent prognostic factors for prolonged mPFS in heavily pretreated MBC, with a HR of 0.34 (p = 0.009) for high TMB and 0.37 (p = 0.013) for 3rd-line treatment. In luminal subtype, mPFS was longer with endocrine therapy (ET) alone than with endocrine therapy + chemotherapy (ET + CT) in high TMB cohort (p = 0.037) but shorter mPFS with ET alone than with ET + CT in low TMB cohort (p = 0.047). High TMB and line of treatment are two independent prognostic factors for prolonged mPFS in heavily pretreated MBC patients. TMB may be a predictive biomarker of efficacy with ET alone or ET + CT in luminal subtype.

Corrigendum: The Depression Anxiety Stress Scale-21 in Chinese Hospital Workers: Reliability, Latent Structure, and Measurement Invariance Across Genders.

[This corrects the article DOI: 10.3389/fpsyg.2020.00247.].

Differences in the clinicopathological characteristics of pure and mixed invasive micropapillary breast carcinomas from eastern China.

BACKGROUND: Invasive micropapillary carcinoma of the breast (IMPC) is a rare pathologic subtype of breast cancer. Since the differences in the pathological features of pure and mixed IMPCs are not fully understood, we aimed to investigate the difference in clinicopathological characteristics between localized pure and mixed IMPCs. METHODS: A total of 121 localized IMPC cases were included. The clinicopathological features and survival estimates of the pure IMPC and mixed IMPC groups were compared. Targeted sequencing was performed to investigate the genomic profile of paired primary breast cancer and metastatic tissue samples from two pure IMPCs and four mixed IMPCs. RESULTS: Overall, 48 cases were pure IMPC and 73 were mixed IMPC. The pure group had a significantly higher proportion of Luminal B compared to the mixed group (37.5% vs. 15.1%). The pure group had a similar HER2 overexpression rate (31.2% vs. 32.9%) and mean age at diagnosis (51.0 vs. 50.2 years), compared with the mixed group. The pure group had a significantly higher proportion of stage IIIC cases compared with the mixed group (38.3% vs. 17.8%). We found no significant difference in the 3-year disease-free survival (DFS) between the two groups (83.7% vs. 80.0%), but the mixed group had a better overall survival (OS) compared with the pure group [HR =0.28 (0.091-0.868), P=0.047]. CONCLUSIONS: We found that pure IMPC had a more aggressive behavior with locally advanced disease and a higher proportion of Luminal B than mixed IMPC. Mixed IMPC had a longer OS compared to pure IMPC, but there was no significant difference in the 3-year DFS between the two groups.

Pseudoprogression After Palbociclib with Aromatase Inhibitors Treatment in Metastatic Breast Cancer.

A 62-year-old postmenopausal woman was diagnosed with breast cancer in her left breast and received modified radical mastectomy (molecular type: hormone-receptor-positive human epidermal growth factor receptor-2 negative). After that, she received postoperative chemotherapy and radiotherapy. After 2 years of tamoxifen adjuvant endocrine treatment, the patient inccurred recurrence with metastasis. PET-CT scanning showed metastasis in the left thoracic wall, the sixth left rib, and the right lower lobe of the lung. Multiple lymph node metastases were observed throughout the body. Palbociclib in combination with an aromatase inhibitor (AI) was used, but the metastatic lesion at the sixth left rib increased than before. Subsequently, the lesion shrunk and the clinical symptoms were relieved, which was considered as a pseudoprogression. Herein, we reported a pseudoprogression in the breast cancer patient after treatment with palbociclib plus AI.

Psychometric Properties of a Simplified Chinese Version of the Secondary Trauma Questionnaire in a Potentially Traumatized Study Sample.

BACKGROUND: Screening for secondary traumatic stress (STS) is lacking in China. It is unclear whether Western models of STS can be adapted satisfactorily for use in non-Western regions. The 20-item Secondary Trauma Questionnaire (STQ) is a self-report measure of traumatic stress symptoms in individuals who have been influenced indirectly by suicide or violent injury of people important to the respondents. METHODS: Here, we assessed the psychometric properties of a newly developed Chinese version of the STQ in a potentially traumatized sample (N = 875) composed of doctors, nurses, teachers, civic administration staff, and social workers in China. We performed reliability and validity analyses. Subsequently, we split the total sample into two subsamples for exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) for measurement invariance analyses. RESULTS: The full scale demonstrated good internal consistency (Cronbach's α = 0.95-0.97), convergent validity, discriminant validity, and factorial validity. CFA affirmed a one-factor structure; the configural, metric, scalar, and strict invariances of the STQ were acceptable across genders. CONCLUSION: The present results indicate that the STQ is a reliable and valid self-report assessment for use with potentially traumatized people in China, and further supports the notion that the STQ is amenable to additional future cross-cultural adaptation.

Corrigendum: The Depression Anxiety Stress Scale-21 in Chinese Hospital Workers: Reliability, Latent Structure, and Measurement Invariance Across Genders.

[This corrects the article DOI: 10.3389/fpsyg.2020.00247.].

Protective effect of hsa-miR-570-3p targeting CD274 on triple negative breast cancer by blocking PI3K/AKT/mTOR signaling pathway.

To find out the role of hsa-miR-570-3p targeting CD274 in triple negative breast cancer (TNBC) via PI3K/AKT/mTOR signaling pathway. Hsa-miR-570-3p and CD274 expressions in 175 TNBC patients were detected by qRT-PCR and immunohistochemistry respectively. The human TNBC cell lines (MDA-MB-468 and MDA-MB-231) were used to verify the targeting relationship between hsa-miR-570-3p and CD274 via dual-luciferase reporter gene assay. Then, MDA-MB-468 and MDA-MB-231 cells were divided into Blank, miR-NC, miR-570-3p mimics, NC siRNA, CD274 siRNA, and miR-570-3p inhibitors + CD274 siRNA groups. Next, the biological activities of cells were detected by MTT, Cell-Light EdU, Annexin-V-FITC/PI, wound healing and Transwell invasion assays. Western blotting was conducted to detect protein expressions.MiR-570-3p expression was lower in tumor tissues than that in adjacent normal tissues, which was more obvious in CD274-positive TNBC patients, which targeted CD274 in TNBC cell lines. MiR-570-3p inhibited cell proliferation, invasion and migration, but induced cell apoptosis accompanying the upregulation of apoptotic proteins and downregulation of anti-apoptotic protein. CD274 siRNA had the similar results of miR-570-3p mimics, which could be reversed by miR-570-3p inhibitors. Besides, both miR-570-3p mimics and CD274 siRNA blocked PI3K/AKT/mTOR signaling pathway in TNBC cell lines. Hsa-miR-570-3p was downregulated and CD274 was upregulated in TNBC patients. Besides, hsa-miR-570-3p targeted CD274 to inhibit cell proliferation, invasion, migration, and induce cell apoptosis, which may be related to the suppression of PI3K/AKT/mTOR pathway.

The Depression Anxiety Stress Scale-21 in Chinese Hospital Workers: Reliability, Latent Structure, and Measurement Invariance Across Genders.

The Depression Anxiety Stress Scale-21 (DASS-21) is an instrument in the assessment of mental health status. The current study recruited 1,532 Chinese hospital workers [74.4% female; mean age = 31.97 (SD = 9.70) years] to examine the reliability, latent structure, and measurement invariance of the DASS-21 between genders. The Cronbach's α values were greater than 0.90 for total score. This study examined four possible models of the DASS-21 using the confirmatory factor analysis (CFA) in Chinese hospital workers. The results from CFA revealed that the latent structure of the DASS-21 in medical staffs is best represented by a one-factor model. Then we used the one-factor model to examine measurement invariance across genders by using a multiple-group categorical CFA. All values of root mean square error approximation (RMSEA) were less than 0.08, all Comparative Fix Index (CFI) and Tucker-Lewis Index values were greater than 0.90, all ΔCFI (changes in CFI) values were less than 0.010, and ΔRMSEA (the changes in RMSEA) were less than 0.015. These findings supported the gender invariance of the DASS-21 among Chinese hospital workers.

The Prognostic Impact of Hormonal Receptor and HER-2 Expression Discordance in Metastatic Breast Cancer Patients.

BACKGROUND: Hormone receptor (HR) and human epidermal growth factor receptor (HER2) discordance between primary and metastatic breast cancer lesions is common. However, its impact on long-term survival remains unclear. We aimed to determine the prognostic value of this discordance in patients with metastaticf breast cancer (MBC). METHODS: A total of 270 patients with MBC who were underwent re-biopsy of progressive metastases at Zhejiang Cancer Hospital from January 1, 2012 to December 31, 2015 with patients consent and then review their primary tumors pathological findings. The HR and HER2 status in both primary and progressive metastatic lesions was determined by immunohistochemistry and/or fluorescence in situ hybridization. The discordance rates were correlated with the clinicopathologic characteristics, metastatic lesions, salvage treatment, and survival analysis in this population. RESULTS: A total of 142 (52.6%) MBC patients were diagnosed with discordant HR and HER2 status. Alterations in estrogen receptor (ER), progesterone receptor (PR), and HER2 status were observed in 20.70%, 37.78%, and 11.48% cases, respectively. Chemotherapy (P=0.0192) and endocrine therapy (P=0.048) significantly affected the conversion of HR status. Endocrine therapy was positively correlated with PR discordance (P=0.002), while ER discordance was associated with adjuvant chemotherapy (P=0.031). Survival analysis showed that ER status alterations between primary and metastatic lesions were associated with overall survival (P=0.002). The clinical prognosis was significantly worse with HR losses than with persistent HR positivity (P=0.023). In Cox multivariate analysis, the loss of HR expression and conversion to triple negative were independent prognostic indicators. CONCLUSION: Discordance in HR status between primary and metastatic lesions may impact the prognosis of MBC, and HR conversion has independent prognostic value.

A Novel Framework to Predict Breast Cancer Prognosis Using Immune-Associated LncRNAs.

Background: Breast cancer (BC) is one of the most frequently diagnosed malignancies among females. As a huge heterogeneity of malignant tumor, it is important to seek reliable molecular biomarkers to carry out the stratification for patients with BC. We surveyed immune- associated lncRNAs that may be used as potential therapeutic targets in BC. Methods: LncRNA expression data and clinical information of BC patients were downloaded from the TCGA database for a comprehensive analysis of candidate genes. A model consisting of immune-related lncRNAs enriched in BC cancerous tissues was established using the univariate Cox regression analysis and the iterative Lasso Cox regression analysis. The prognostic performance of this model was validated in two independent cohorts (GSE21653 and BC-KR), and compared with known prognostic biomarkers. A nomogram that integrated the immune-related lncRNA signature and clinicopathological factors was constructed to accurately assess the prognostic value of this signature. The correlation between the signature and immune cell infiltration in BC was also analyzed. Results: The Kaplan-Meier analysis showed that the OS of Patients in the low-risk group had significantly better survival than those in the high-risk group, Clinical subgroup analysis showed that the predictive ability was independent of clinicopathological factors. Univariate/multivariate Cox regression analysis showed immune lncRNA signature is an important prognostic factor and an independent prognostic marker. In addition, GSEA and GSVA analysis as well as comprehensive analysis of immune cells showed that the signature was significantly correlated with the infiltration of immune cells. Conclusion: We successfully constructed an immune-associated lncRNA signature that can accurately predict BC prognosis.

Randomized controlled clinical trial of polyethylene glycol recombinant human granulocyte colony-stimulating factor in the treatment of neutropenia after chemotherapy for breast cancer.

PURPOSE: To explore the efficacy and safety of daily administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF), and a single subcutaneous injection of polyethylene glycol recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF, a sustained-duration rhG-CSF) in neutropenia induced after chemotherapy. METHODS: Each patient received two cycles of chemotherapy. In the trial cycle, the patients received a single subcutaneous injection of PEG-rhG-CSF 100 µg/kg 72 h after completion of chemotherapy; and in the control cycle, rhG-CSF 5 µg/kg/day was subcutaneous injected once a day which began 72 h after completion of chemotherapy for continued 14 days or until the absolute neutrophil count (ANC) was ≥ 10.0 × 109/l twice. Therapeutic effect on primary endpoint was the incidence and duration of grade IV ANC neutropenia: comparing the incidence and the mean time of duration of PEG-rhG-CSF with those of rhG-CSF under the circumstance of ANC < 0.5 × 109/l. The immune populations evaluated included, CD3+ T cells, CD4+ T cells, CD8+ T cells, and NK cells. RESULTS: After chemotherapy, comparing to PEG-rhG-CSF, the CD4/CD8 ratio (0.84 ± 0.19 vs.1.06 ± 0.25) and the number of NK cells of rhG-CSF group (12.18 ± 2.13 vs. 15.78 ± 2.57) decreased significantly. The number of NK cells (12.18 ± 2.13 vs. 13.78 ± 2.57) of rhG-CSF group after chemotherapy is significantly less than that before chemotherapy, and the number of CD3+ (54.31 ± 7.51 vs. 57.96 ± 5.55), CD4+ (26.28 ± 6.25 vs. 29.48 ± 6.44), CD8+ (29.97 ± 6.47 vs. 31.68 ± 5.96) is lower than that before chemotherapy in rhG-CSF group, but the difference is not significant. CONCLUSION: The efficacy and side effects of a single subcutaneous injection of PEG-rhG-CSF were similar to that of rhG-CSF multiple administrations. PEG-rhG-CSF may have the effect of promoting immune function repairing.

The efficacy and safety of endostar combined with taxane-based regimens for HER-2-negative metastatic breast cancer patients.

The purpose of the present study was to prospectively evaluate the efficacy and safety of endostar, a recombinant product of endostatin, combined with taxane-based regimens for HER-2 negative metastatic breast cancer (MBC) patients. Women with ages between 18-70 years with histologically confirmed MBC documented as HER-2-negative were included. Endostar was administered at 7.5 mg/m2, d1-14, q21d and was continued until progressive disease, unacceptable toxicity, consent withdrawal, or completion of 24 months of endostar, whichever came first. Taxane-based chemotherapy was continued until progressive disease, unacceptable toxicity, consent withdrawal, or up to 8 cycles. The primary endpoint was overall response rate (ORR). Fifty-seven patients were recruited. The ORRs for the whole population, first-, second-, and third-line therapy or beyond were 68.4%, 79.3%, 54.5%, and 16.7%, respectively. The median PFS was 10.8 (8.0-12.1) months, yet the median OS was still not attained. For the patients receiving first-, second-, and third-line therapy or beyond, median PFS was 11.9, 7.5, and 7.4 months, respectively (P=0.048). No significant difference in median PFS between hormonal receptor-positive and -negative patients was observed. The most common drug-related grade 3-4 hematologic toxicities were neutropenia (80.7%) and leukopenia (77.2%). Six (10.5%) patients experienced febrile neutropenia. The most frequent drug-related grade 3-4 non-hematologic toxicities were liver dysfunction (10.5%) and peripheral neurotoxicity (8.8%). No treatment-related deaths were reported. We conclude that Endostar combined with taxane-based regimens may be effective and safe for the treatment of HER-2-negative MBC. However, further investigations on its long-term efficacy and toxicity are warranted.