Background Recent evidence shows that inducing ferroptosis may improve efficacy of tumor therapy. However, ferroptosis-related genes have been little studied in patients with breast cancer especially in the neoadjuvant setting. ACSL4 and GPX4 have been well established as the positive and negative regulator of ferroptosis, respectively. This study aimed to explore the predictive value of ACSL4 and GPX4 for patients with breast cancer administered neoadjuvant chemotherapy. Methods This study included patients treated with paclitaxel-cisplatin-based neoadjuvant chemotherapy. Immunohistochemistry staining of ACSL4 and GPX4 was carried out on the core needle biopsy specimens. Logistic regression was performed to explore the predictive biomarkers of pathological complete response (pCR). Survival analyses were examined by log-rank test and Cox proportional hazard regression. Findings A total of 199 patients were included for the analyses. Both ACSL4 expression and ACSL4/GPX4 combination status could serve as independent predictive factors for pCR. The interaction for pCR was observed between ACSL4 and clinical tumor stage. Besides, ACSL4 expression, GPX4 expression, and their combination status were independent prognostic factors for disease-free survival. Analyses of the Kaplan-Meier Plotter database suggested that higher ACSL4 expression is related to better overall survival, and higher GPX4 expression is related to better distant metastasis-free survival. Pathway analyses revealed that ACSL4 and GPX4 might function in crucial pathways including apoptosis, autophagy, cell adhesion, lipid metabolism, etc . Interpretation This study revealed the critical value of ACSL4 and GPX4 serving as novel predictive and prognostic biomarkers for patients with breast cancer receiving neoadjuvant chemotherapy. It might be a novel strategy to induce ferroptosis to promote chemosensitivity. Future studies are required to elucidate the potential mechanisms. Funding This work was supported by Shanghai Natural Science Foundation [grant number 19ZR1431100], Clinical Research Plan of Shanghai Hospital Development Center [grant numbers SHDC2020CR3003A, 16CR3065B, and 12016231], Shanghai “Rising Stars of Medical Talent” Youth Development Program for Youth Medical Talents - Specialist Program [grant number 2018-15], Shanghai “Rising Stars of Medical Talent” Youth Development Program for Outstanding Youth Medical Talents [grant number 2018-16], Shanghai Collaborative Innovation Center for Translational Medicine [grant number TM201908], Multidisciplinary Cross Research Foundation of Shanghai Jiao Tong University [grant numbers YG2017QN49, ZH2018QNA42, and YG2019QNA28], Nurturing Fund of Renji Hospital [grant numbers PYMDT-002, PY2018-IIC-01, PY2018-III-15, and PYIII20-09], Science and Technology Commission of Shanghai Municipality [grant numbers 20DZ2201600 and 15JC1402700], and Shangha...
Purpose: Despite accumulating evidence on dual blockade of HER2 for locally advanced HER2-positive breast cancer, no robust evidence supports the addition of pyrotinib to trastuzumab in the neoadjuvant setting. The NeoATP trial aimed to evaluate the efficacy and safety of pyrotinib with neoadjuvant trastuzumab and chemotherapy. Patients and Methods: The phase II NeoATP trial included female patients with histologically confirmed stage IIA to IIIC and HER2-positive primary invasive breast cancer. Eligible patients received pyrotinib and trastuzumab with weekly paclitaxel–cisplatin neoadjuvant chemotherapy for four cycles. The primary endpoint was pathologic complete response (pCR; ypT0 ypN0) rate. Key secondary endpoints included locoregional pCR (ypT0/is ypN0) rate, biomarker analysis, and safety. Results: Among 53 enrolled patients (median age, 47 years; 73.58% stage III), 52 completed the study treatment and surgery. Overall, 37 patients (69.81%) achieved pCR. For women with hormone receptor–negative and –positive tumors, the pCR rates were 85.71% and 59.38% (P = 0.041), while the corresponding rates were 69.23% and 70.00%, respectively, for those with and without PIK3CA mutation (P = 0.958). The most frequently reported Grade 3 to 4 adverse events were diarrhea (45.28%), leukopenia (39.62%), and neutropenia (32.08%). No deaths occurred, and no left ventricular ejection fraction <50% or >10 points drop from baseline to before surgery was reported. Conclusions: The addition of pyrotinib to trastuzumab plus chemotherapy is an efficacious and safe regimen for patients with HER2-positive locally advanced breast cancer in the neoadjuvant setting. The randomized controlled clinical trial is warranted to validate our results.
Success in curing breast cancer largely depends on the stage at diagnosis. Circulating microRNAs are becoming a promising noninvasive biomarker. We postulate that a postoperative decline in circulating microRNAs might have diagnostic and prognostic value. Applying high-throughput microarrays, we screened the dysregulated microRNAs in paired serum samples before and after surgery. The relative concentrations of putative markers between the early breast cancer and cancer-free groups were evaluated in the training set and verified in the validation set. Sensitivity, specificity, and receiver operating characteristic (ROC) curves were used to assess diagnostic value. Survival analysis was performed using Kaplan–Meier estimates and a Cox proportional hazards model. Five microRNAs significantly reduced after surgery were selected for the training set. We found that miR-130b-5p, miR-151a-5p, miR-206, and miR-222-3p were significantly higher in the breast cancer group. Each of the four microRNAs had potential diagnostic value. The combined four microRNAs (training set: area under the curve (AUC) 0.8457; validation set: AUC 0.9309) had better diagnostic value than each single microRNA. MiR-222-3p was an independent prognostic factor for disease-free survival (HR = 13.19; 95% CI, 1.06–163.59; P = 0.045). Patients with no fewer than three highly expressed miRNAs had shorter DFS than patients with 0–2 highly expressed miRNAs (HR = 2.293; 95% CI, 1.128–0.662; P = 0.022). Our findings indicate that postoperatively downregulated circulating miR-130b-5p, miR-151a-5p, miR-206, and miR-222-3p may be potential biomarkers for breast cancer diagnosis and prognosis.
The accurate positioning of sentinel lymph node (SLN) by tracers during surgery is an important prerequisite for SLN biopsy. A major problem of traditional tracers in SLN biopsy is the short surgery window due to the fast diffusion of tracers through the lymphatics, resulting in a misjudgment between SLN and second echelon lymph node (2nd LN). Here, a nontoxic Raman nanoparticle tracer, termed gap‐enhanced Raman tags (GERTs), for the accurate intraoperative positioning of SLNs with a sufficient surgical time window is designed. In white New Zealand rabbit models, GERTs enable precise identification of SLNs within 10 min, as well as provide the surgeon with a more than 4 h time window to differentiate SLN and 2nd LN. In addition, the ultrahigh sensitivity of GERTs (detection limit is 0.5 × 10−12 m) allows detection of labeled SLNs before surgery, thereby providing preoperative positioning information for minimally invasive surgery. Comprehensive biosafety evaluations carried out in the context of the Food and Drug Administration and International Standard Organization demonstrate no significant toxicity of GERTs, which supports a promising clinical translation opportunity of GERTs for precise SLN identification in breast cancer.
Hypoxia-induced chemotherapy resistance is the main hindrance for solid tumor treatment. Hypoxia inducible factor-1α (HIF1α), an adaptive gene of hypoxia condition, played an important role in affecting chemotherapy sensitivity for many cancer types and various therapeutic regimens. This study focused on the impact of HIF1α on predicting response and survival of taxane-based neoadjuvant therapy (NAT) for breast cancer (BC) patients and the concrete mechanism that HIF1α mediated paclitaxel chemo-insensitivity. We evaluated HIF1α expression immunohistochemically from biopsies of 108 BC patients receiving paclitaxel–cisplatin NAT. Univariate and multivariate logistic regression analysis revealed that high HIF1α expression led to lower rate of pathological complete response (pCR) and worse prognosis. Analysis of GEO datasets also indicated negative association between HIF1α expression and response of taxane-based NAT in BC patients. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of differential expression genes (DEGs) in different HIF1α expression groups from TCGA database showed that HIF1α participated in interleukin 17 (IL-17) signaling pathway. Correlation analysis suggested that HIF1α was positively related to the IL-17 pathway. CXC motif chemokine ligand 10 (CXCL10) was the only DEG in the IL-17 pathway inversely relating to NAT response. Experiments in vitro verified that HIF1α/IL-17 pathway influences paclitaxel sensitivity to BC cells. Correlation analysis between HIF1α/IL-17A/CXCL10 and infiltration of immune cells in BC uncovered that high expression of all the above three genes were positively correlated to neutrophil infiltration in BC. Collectively, our findings shed novel insight into the mechanism of chemotherapy resistance and implied that HIF1α inhibitor may be a promising drug combined with traditional chemotherapeutic drug to increase the chemotherapy efficacy.
Background: Homologous recombination deficiency is associated with platinum-based chemosensitivity, whereas few studies reported the predictive value of family history of cancer for breast cancer in the neoadjuvant setting. This study aimed to construct a novel family history scoring system and to explore its association with clinical outcomes for patients with breast cancer receiving neoadjuvant platinum-based chemotherapy. Methods: This study included 262 patients with locally advanced breast cancer enrolled in the SHPD001 and SHPD002 trials from October 2013 to June 2018. The Neo-Family History Score (NeoFHS) was calculated according to cancer type, age at diagnosis, kinship, and number of affected relatives. Findings: Clinical tumor stage (p=0¢048), estrogen receptor status (p=0¢001), progesterone receptor status (p=0¢036), human epidermal growth factor receptor 2 status (p=0¢013), and molecular subtype (p=0¢016) were significantly related to NeoFHS. NeoFHS could serve as an independent predictive factor of pathological complete response (pCR) (OR=2¢262, 95% CI 1¢159-4¢414, p=0¢017) and an independent prognostic factor of relapse-free survival (adjusted HR=0¢305, 95% CI 0¢102-0¢910, p=0¢033). Alopecia (p=0¢001), nausea (p=0¢001), peripheral neuropathy (p=0¢018), diarrhea (p=0¢026), constipation (p=0¢037) of any grade and leukopenia of grade 3 or greater (p=0¢005) were more common in patients with higher NeoFHS. Interpretation: NeoFHS is a practical and effective biomarker for predicting not only pCR and survival outcomes but also chemotherapy-induced adverse events for neoadjuvant platinum-based chemotherapy in breast cancer. It may help screen candidate responders and guide safety managements.
Aim: Benefit of longer course of taxane-anthracycline-based adjuvant chemotherapy is yet to be identified. Patients & methods: We conducted a retrospectively matched-pair analysis to compare four cycles of fluorouracil, epirubicin and cyclophosphamide followed by four cycles of docetaxel (4FEC-4T) with three cycles of FEC followed by three cycles of docetaxel (3FEC-3T) as adjuvant chemotherapy for early-stage breast cancer. One hundred and thirty-seven patients treated with 4FEC-4T were matched to 411 in 3FEC-3T. The primary end point was event-free survival (EFS). The secondary end point was distant disease-free survival (DDFS). Results: The 4FEC-4T resulted in significantly longer EFS than matched 3FEC-3T (p = 0.020). Furthermore, DDFS was superior in the 4FEC-4T to that in the 3FEC-3T (p = 0.046). Conclusion: Extending taxane-anthracycline-based regimens with identical schedules significantly improves EFS and DDFS for early-stage breast cancer.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.