Fanfan Li

Background: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations are among the most common genetic alterations in breast cancer and have important implications for tumor biology, subtype-specific behavior, and targeted therapy. This study provides a comprehensive bibliometric analysis of global research on PIK3CA mutations in breast cancer, highlighting critical research hotspots and evolving trends. We aim to address the current lack of an integrated understanding in this vital area. Methods: Publications related to PIK3CA and breast cancer from 2000 to 2024 were retrieved from the Web of Science Core Collection. Bibliometric cluster analyses were performed using VOSviewer, CiteSpace, and R-bibliometrix to delineate collaboration networks, journal distributions, and thematic clusters. Results: A total of 2,135 publications were analyzed, predominantly from the US, China, and the UK. Harvard University and Unicancer emerged as leading institutions, with significant contributions from authors such as Gordon B. Mills and Jorge S. Reis-Filho. Keyword analysis identified six major research hotspots, categorized into basic research (molecular mechanisms, signaling pathways, genomics, biomarkers, tumor biology) and clinical research (clinical trials, therapeutic strategies, cancer subtypes, drug resistance, tumor microenvironment). Citation burst analysis indicated an early focus on molecular mechanisms and gene mutations, while recent studies have shifted toward precision medicine, including liquid biopsy, advanced breast cancer subtypes, and targeted therapies such as alpelisib and fulvestrant, reflecting evolving priorities toward personalized treatment. Conclusions: This bibliometric study identifies six key research hotspots in PIK3CA and breast cancer, demonstrating the transition from basic mechanisms to clinical applications. Recent research trends, including liquid biopsy, advanced subtypes, and combination therapies, are closely tied to precision medicine and individualized treatment approaches.

Breast invasive carcinoma (BRCA) is the most common type of cancer affecting women worldwide. Biomarkers such as estrogen receptor, progesterone receptor and HER2 are currently utilized in clinical practice for breast cancer diagnosis; yet their sensitivity and specificity remain limited. However, Ras‑GTPase‑activating protein SH3 domain‑binding protein 1 (G3BP1), an RNA‑binding protein, has been implicated in tumor progression in various cancers, yet its clinical relevance and mechanistic role in BRCA still remain unclear. The present study integrated multi‑omics data analysis and experimental validation to address this. G3BP1 mRNA and protein expression levels in BRCA were analyzed using The Cancer Genome Atlas, Tumor Immune Estimation Resource (TIMER) and Clinical Proteomic Tumor Analysis Consortium databases. Kaplan‑Meier survival analysis and Cox regression were employed to evaluate the prognostic value of G3BP1. Gene set enrichment analysis (GSEA) was performed to identify associated signaling pathways and immune cell infiltration correlations were assessed using CIBERSORT and TIMER. Additionally, 38 samples of BRCA and adjacent normal tissue were collected for immunohistochemical (IHC) validation and diagnostic efficacy was evaluated using receiver operating characteristic (ROC) curves. G3BP1 was significantly upregulated in BRCA tissues at both mRNA and protein levels (P<0.05). High G3BP1 expression was associated with the advanced cancer lymph node stage (P=0.005) and a poor prognosis [overall survival, disease‑free survival (DFS), distant metastasis‑free survival and post‑progression survival; all P<0.05]. Differential gene analysis identified 67 upregulated and 9 downregulated genes. GSEA revealed G3BP1 enrichment in key pathways such as PI3K/AKT/mTOR signaling and ubiquitin‑mediated proteolysis. Immune analysis showed a significant positive association between G3BP1 and M2 macrophage infiltration (P<0.05) and a significant negative association between G3BP1 and CD8+ T cells (P<0.05). IHC confirmed higher G3BP1 expression in BRCA compared with normal tissues (P<0.001), with an area under the ROC curve (AUC) of 0.777 and a 5‑year DFS prediction AUC of 0.730. The present findings indicate that G3BP1 is a potential independent prognostic biomarker for BRCA. Its upregulation promotes tumor progression by activating the PI3K/AKT/mTOR signaling pathway and modulating the tumor immune microenvironment. These findings provide a theoretical foundation for targeting G3BP1 in BRCA diagnosis and immunotherapy.

PIK3CA gene mutations have been identified in various malignancies, but the prevalence of specific mutations and their role in breast cancer development remain uncertain. This study aimed to investigate the clinicopathological significance and prognostic impact of PIK3CA mutations in breast cancer. Five common PIK3CA mutations (H1047R and H1047L in exon 20, and E542K, E545K, and E545D in exon 9) were identified in breast cancer patients using amplification refractory mutation system (ARMS) allele-specific PCR. The study examined the relationships between these mutations and clinicopathologic factors, such as age, HR status, Her2 status, lymph node involvement, distant metastasis, clinicopathologic stage, and progression-free survival (PFS). A total of 40 female breast cancer patients were included in this study. Twenty mutations were detected, with 12 located in exon 20 and 8 in exon 9. The most frequent mutation was H1047R in exon 20, present in 11 patients (14.8%). PIK3CA mutations were more commonly observed in patients with HR + breast cancer (P < 0.05). No significant correlation was found between PIK3CA mutations and age, Her2 status, lymph node involvement, distant metastasis, clinicopathologic stage, or Ki-67 expression. Database analysis from the cBioPortal online database showed that the median PFS (95%CI) of the PIK3CA unaltered group [22.93 (17.25–48.30) months] was higher than that of the altered group [12.98 (8.18–18.14) months]. In this study, PIK3CA mutant-type group [13.00 (10.56–15.45) months] had lower median PFS than that of the wild-type group [25.00 (13.46–36.55) months] in all breast cancer patients, the difference was significant (P = 0.004). Further, compared with PIK3CA wild-type, mutant-type was associated with poor PFS in HR + and Her2 + breast cancer patients (P < 0.05). In addition, positive H1047R mutation in PIK3CA was associated with poor PFS of breast cancer (P < 0.05). Our data and public database research show that the PIK3CA mutation is a significant gene change in breast cancer, and the PIK3CA mutation was associated with a shorter PFS in all, HR + and Her2 + breast cancer patients. This research confirmed the important role of PIK3CA in breast cancer.

Background: Single photon emission computed tomography (SPECT) is becoming increasingly popular in oncology. This study endeavors to scrutinize the radiation protection knowledge, attitude, and practice (KAP) exhibited by healthcare professionals involved in this imaging modality.Methods: This cross-sectional study was conducted between September 23, 2023, and October 23, 2023, at the Second Affiliated Hospital of Anhui Medical University, the First Affiliated Hospital of Anhui Medical University, and the People’s Hospital of Liuan. Demographic data and KAP scores were acquired through the administration of questionnaires.Results: A total of 450 healthcare professionals participated in the study. Correlation analyses revealed significant positive correlations between knowledge and attitude, knowledge and practice, as well as attitude and practice. Multivariate analysis indicated that being over 40 years old was independently associated with good knowledge, as well as positive attitudes. Occupations as nurses and having no contact with SPECT patients were independently associated with a lower level of knowledge, as well as negative attitudes. Furthermore, being female, having an occupation as a nurse, and not having received relevant training were independently associated with negative practice.Conclusion: Oncology healthcare professionals had suboptimal knowledge, negative attitude and inactive practice towards radiation protection in SPECT.

Using updated National Health and Nutrition Examination Survey (NHANES) follow-up data, and a large nationwide representative sample of adult U.S. citizens, the aim of this study was to explore the relationship between dietary flavonol intake, all-cause and cause-specific mortality risks. In this prospective cohort study based on NHANES (2007–2008, 2009–2010, and 2017–2018), a total of 11,679 participants aged 20 years and above were evaluated. The amount and type of food taken during a 24-h dietary recall were used to estimate dietary flavonol intake, which includes total flavonol, isorhamnetin, kaempferol, myricetin, and quercetin. Each analysis of the weighted data was dealt with in accordance with the NHANES reporting requirements' intricate stratification design. The Cox proportional risk regression model or Fine and Gray competing risks regression model were applied to evaluate all-cause and cause-specific mortality risks, respectively. The follow-up period was calculated using the time interval between the baseline and the death date or December 31, 2019 (whichever occurs first). Each data analysis was performed between October 1, 2023, and October 22, 2023. Dietary flavonol intake included total flavonol, isorhamnetin, kaempferol, myricetin, and quercetin. Up to December 31, 2019, National Death Index (NDI) mortality data were used to calculate mortality from all causes as well as cause-specific causes. A total of 11,679 individuals, which represents 44,189,487 U.S. non-hospitalized citizens, were included in the study; of these participants, 49.78% were male (n = 5816), 50.22% were female (n = 5, 863); 47.56% were Non-Hispanic White (n = 5554), 18.91% were Non-Hispanic Black (n = 2209), 16.23% were Mexican American (n = 1895), and 17.30% were other ethnicity (n = 2021); The mean [SE] age of the sample was 46.93 [0.36] years, with a median follow-up of 7.80 years (interquartile range, 7.55–8.07 years). After adjusting covariates, Cox proportional hazards models and fine and gray competing risks regression models for specific-cause mortality demonstrated that total flavonol intake was associated with all-cause (HR 0.64, 95% CI 0.54–0.75), cancer-specific (HR 0.45, 95% CI 0.28–0.70) and CVD-specific (HR 0.67, 95% CI 0.47–0.96) mortality risks; isorhamnetin intake was associated with all-cause (HR 0.72, 95% CI 0.60–0.86), and cancer-specific (HR 0.62, 95% CI 0.46–0.83) mortality risks; kaempferol intake was associated with all-cause (HR 0.74, 95% CI 0.63–0.86), and cancer-specific (HR 0.62, 95% CI 0.40–0.97) mortality risks; myricetin intake was associated with all-cause (HR 0.77, 95% CI 0.67–0.88), AD-specific (HR 0.34, 95% CI 0.14–0.85), and CVD-specific (HR 0.61, 95% CI 0.47–0.80) mortality risks; quercetin intake was associated with all-cause (HR 0.66, 95% CI 0.54–0.81), cancer-specific (HR 0.54, 95% CI 0.35–0.84), and CVD-specific (HR 0.61, 95% CI 0.40–0.93) mortality risks; there was no correlation observed between dietary flavonol intake and DM-specific mortality. According to the current study, all-cause, AD, cancer, and CVD mortality risks declined with increased dietary flavonoid intake in the U.S. adults. This finding may be related to the anti-tumor, anti-inflammatory, and anti-oxidative stress properties of flavonol.

For patients with end-stage renal disease (ESRD), peritoneal dialysis (PD) and hemodialysis (HD) are important renal replacement treatments. Patients on dialysis usually have a high incidence rate of malignant tumors. In 2020, breast cancer has become the malignant tumor with the highest incidence rate in the world. Human epidermal growth factor receptor-2-positive (HER-2+) breast cancer accounts for 20%-30% of the total breast cancer patients. It is highly invasive and has a poor prognosis. Anti-HER-2 treatment is an important therapy for this type of cancer. There are few case reports of anti-HER2-targeted therapy in dialysis patients. We report a 56-year-old Chinese woman with breast cancer (cT3N1MX, Her-2+/HR-). She underwent peritoneal dialysis for 11 years since she had suffered end-stage renal disease. The clinician prescribed the regimen (pyrotinib 320mg qd + capecitabine 1g bid D1-D14 Q3W). The tumor was significantly reduced after 1 month of single administration of pyrotinib, and partially relieved after 2 months of pyrotinib + capecitabine. The main side effects were grade II hand foot syndrome and grade II diarrhea. This case shows that the combination of pyrotinib and capecitabine has potential therapeutic benefits in HER-2+ breast cancer patients with end-stage renal disease.

Boron neutron capture therapy (BNCT) is a binary modality that is used to treat a variety of malignancies, using neutrons to irradiate boron-10 (¹⁰B) nuclei that have entered tumor cells to produce highly linear energy transfer (LET) alpha particles and recoil ⁷Li nuclei (¹⁰B [n, α] ⁷Li). Therefore, the most important part in BNCT is to selectively deliver a large number of ¹⁰B to tumor cells and only a small amount to normal tissue. So far, BNCT has been used in more than 2000 cases worldwide, and the efficacy of BNCT in the treatment of head and neck cancer, malignant meningioma, melanoma and hepatocellular carcinoma has been confirmed. We collected and collated clinical studies of second-generation boron delivery agents. The combination of different drugs, the mode of administration, and the combination of multiple treatments have an important impact on patient survival. We summarized the critical issues that must be addressed, with the hope that the next generation of boron delivery agents will overcome these challenges.

Background Pertuzumab is a humanized monoclonal antibody for the treatment of breast cancer. HLX11 is a biosimilar of pertuzumab developed by Shanghai Henlius Biotech, Inc. We conducted a bioequivalence study for HLX11 and pertuzumab (United States [US]-, European Union [EU]-, and China [CN]-approved products). Objectives This study compared the biosimilarity in pharmacokinetics (PK), safety, and immunogenicity between HLX11 and reference pertuzumab (approved in the US, the EU, and CN) in healthy Chinese male participants after a single infusion and further characterized the PK profile of HLX11. Methods Eligible individuals were randomized 1:1:1:1 to receive a single dose of 420 mg HLX11, US-, EU-, or CN-pertuzumab via intravenous infusion over 60 min. The primary endpoints were maximum serum drug concentration (C_max), area under the serum concentration–time curve (AUC) from time 0 to time of the last quantifiable concentration (AUC_0–t), and AUC from time 0 to infinity (AUC_0–∞). PK bioequivalence was established if the 90% confidence intervals (CIs) of the geometric mean ratios of the primary endpoints were between 80.0 and 125.0%. Secondary endpoints included other PK parameters, safety, and immunogenicity. Results A total of 160 participants were enrolled and randomly assigned to each group (n = 40 per group). The 90% CIs of the geometric mean ratios of the primary endpoints were all within the prespecified equivalence margins (HLX11 vs. pertuzumab [US-, EU-, CN-approved products]: C_max 97.03–115.06%, 91.39–109.80%, 94.53–110.65%; AUC_0–t 87.65–99.68%, 87.07–100.79%, 86.29–101.09%; AUC_0–∞ 87.66–99.90%, 87.54–101.05%, 89.23–103.20%). The incidence of adverse drug reactions was comparable across the four groups. The presence of anti-drug antibodies or neutralizing antibodies had no obvious effect on PK. Conclusion The PK, safety, and immunogenicity of HLX11 were highly similar to those of reference pertuzumab (US-, EU-, CN-approved products). The established bioequivalence supports further clinical trials of HLX11 in cancer treatment. Trial Registration This study was registered with ClinicalTrials.gov (NCT04411550) and Chinadrugtrials.org.cn (CTR20200618).

Objective: To explore the correlation between HER-2 status and pathological complete response (pCR) in HER-2-positive breast cancer after dual anti-HER-2 neoadjuvant therapy with trastuzumab and pertuzumab.Methods: A total of 57 HER-2-positive breast cancer patients admitted to the Second Affiliated Hospital of Anhui Medical University and Xijing Hospital Affiliated to Air Force Military Medical University, between January 1, 2019 and September 30, 2020, were enrolled in this multicenter retrospective study. HER-2 status, including HER-2/CEP17 ratio and HER-2/cell number ratio, was detected by FISH. The correlation between HER-2 status/clinicopathological data and pCR was analyzed. The ROC curve was drawn to determine the cutoff value.Results: IHC assessment revealed 40 (70.18%) patients with IHC 3+ and 17 (29.82%) with IHC 2+. 41/57 (71.93%) patients achieved pCR. FISH revealed that the ratio of HER-2/chromosome 17 centromere (HER-2/CEP17) (p<0.001) and the ratio of HER-2/cell number (p<0.001) was significantly correlated with the pCR rate. ROC analysis showed that patients with an HER-2/CEP17 ratio ≥4.495 or HER-2/cell number ≥11.650 have a high pCR rate after dual anti-HER-2 neoadjuvant therapy, suggesting its predictive significance.Conclusion: The response to dual-targeted neoadjuvant therapy with trastuzumab and pertuzumab was adequate in hormone receptor-negative, HER-2-positive breast cancer patients. HER-2/CEP17 ratio and HER-2/cell number ratio were crucial for predicting efficacy.

Background: Adipocytokines were known to play a relevant role in metabolism, inflammation responses and carcinogenesis of several malignancies. Our aims were to detect the expression of serum adipocytokines, explore their potential diagnostic ability and relationship with clinicopathological characteristics of lung cancer. Methods: Adipocytokines, insulin-like growth factor binding protein 1 (IGFBP-1), resistin, tumor necrosis factors (TNF alpha), TNF RI and TNF RH, vascular endothelial growth factor (VEGF), leptin, interleukin (IL)-6 and IL-10, chemerin, brain-derived neurotrophic factor (BDNF), plasminogen activator inhibitor-1 (PAI-1) were assessed in 49 untreated lung cancer patients and 20 healthy controls. The protein chip was used to detect the serum levels of adipocytokines. Results: Lung cancer patients exhibited significantly elevated serum IGFBP-1, TNF RI, VEGF, TNF RII, PAI-1 and IL-6 levels compared to controls (P<0.05) and most of these adipocytokines revealed a modest discriminative ability for the diagnosis of lung cancer, while BDNF were lower in patients (P<0.05). TNF RI was associated with distant metastasis of lung cancer, while there was no relation between other adipocytokines and the patient clinicopathological features. Conclusions: These results suggest that cytokines IGFBP-1, TNF RI, VEGF, TNF RH, PAI-1 and IL-6 may be involved in the development and progression of lung cancer, and TNF RI may be involved in distant metastasis of lung cancer. Additionally, IGFBP-1, TNF RI, VEGF and TNF RII probably represent potentially useful biomarkers for the diagnosis of lung cancer.