Mechanisms of traditional Chinese medicine overcoming of radiotherapy resistance in breast cancer

Breast cancer stands as the most prevalent malignancy among women, with radiotherapy serving as a primary treatment modality. Despite radiotherapy, a subset of breast cancer patients experiences local recurrence, attributed to the intrinsic resistance of tumors to radiation. Therefore, there is a compelling need to explore novel approaches that can enhance cytotoxic effects through alternative mechanisms. Traditional Chinese Medicine (TCM) and its active constituents exhibit diverse pharmacological actions, including anti-tumor effects, offering extensive possibilities to identify effective components capable of overcoming radiotherapy resistance. This review delineates the mechanisms underlying radiotherapy resistance in breast cancer, along with potential candidate Chinese herbal medicines that may sensitize breast cancer cells to radiotherapy. The exploration of such herbal interventions holds promise for improving therapeutic outcomes in the context of breast cancer radiotherapy resistance

De-escalated radiotherapy for HER2-overexpressing breast cancer patients with 1-3 positive lymph nodes undergoing anti-HER2 targeted therapy

BackgroundIn the era of anti-HER2 targeted therapy, the potential clinical feasibility of considering HER2-overexpressing breast cancer cases presenting with 1-3 positive axillary lymph nodes as low-risk, and thereby contemplating postoperative radiotherapy reduction, remains an important subject for in-depth examination. The aim of this retrospective study was to evaluate the effectiveness of de-escalated radiotherapy in T1-2N1M0 HER2-overexpressing breast cancer patients receiving anti-HER2 targeted therapy. Specifically, omitting regional lymph node irradiation (RNI) after breast-conserving surgery and only performing whole-breast irradiation or omitting postmastectomy radiation therapy.MethodsA retrospective analysis was conducted on 429 patients with stage T1-2N1M0 primary invasive HER2-overexpressing breast cancer from our center between 2004 and 2018. Patients who received anti-HER2 targeted therapy were divided into an RNI group and a no RNI group to assess the role of RNI. The prognostic role of RNI was investigated via the Kaplan-Meier method and Cox proportional hazards modeling.ResultsThe median follow-up time was 46.8 months (range 7.1–225.8 months). In the anti-HER2 targeted therapy group RNI yielded no significant improvements in invasive disease-free survival (IDFS) (p = 0.940), local-regional recurrence-free survival (p = 0.380), distant metastases-free survival (p = 0.698), or overall survival (p = 0.403). Estrogen receptor (ER) status (hazard ratio [HR] 0.105, 95% confidence interval [CI] 0.023–0.749, p = 0.004) and lymph vascular invasion status (LVI) (HR 5.721, 95% CI 1.586–20.633, p = 0.008) were identified as independent prognostic factors for IDFS, and ER-positive and LVI-negative patients exhibited better prognoses.ConclusionOmitting RNI may be a safe option in T1-2N1 HER2-overexpressing breast cancer patients receiving standardized anti-HER2 targeted therapy; particularly in ER-positive or LVI-negative subgroups

Adjuvant radiotherapy and chemotherapy for patients with breast phyllodes tumors: a systematic review and meta-analysis

Abstract Background As the efficacy of radiotherapy and chemotherapy for treatment of phyllodes tumors (PTs) remains unclear, this study aimed to review all available data and evaluate the roles of radiotherapy and chemotherapy in PT treatment. Methods We performed a comprehensive search of databases, including PubMed, Web of Science and the Cochrane Library. The outcomes of interest included the local recurrence (LR) rate, metastasis rate, disease-free survival rate and overall survival rate. Results Seventeen studies enrolling 696 patients were included in this random effect meta-analysis. Subgroup analysis and meta-regression were also conducted to determine study heterogeneity. A pooled local recurrence rate of 8% (95% CI: 1–22%) was observed with a statistical heterogeneity of I2 = 86.6% (p < 0.01) for radiotherapy. This was lower than the recurrence rate of 12% for simple surgical treatment (95% CI: 7–18%). Meta-regression analysis found that surgical margin status was the main source of heterogeneity (p = 0.04). The metastasis rate of 4% (95% CI: 0–11%) for patients receiving radiotherapy without significant heterogeneity was also lower than the rate for the simple surgery group (8, 95% CI: 3–15%). The available data for chemotherapy were too limited to support meta-analysis. Accordingly, we offer a pure review of these data. Conclusion Our findings suggest that radiotherapy is effective in achieving local disease control and preventing metastasis

RecurIndex-Guided postoperative radiotherapy with or without Avoidance of Irradiation of regional Nodes in 1–3 node-positive breast cancer (RIGAIN): a study protocol for a multicentre, open-label, randomised controlled prospective, phase III trial

Introduction Postoperative radiotherapy in patients with breast cancer with one to three lymph node metastases, particularly within the pT1–2N1M0 cohort with a low clinical risk of local–regional recurrence (LRR), has incited a discourse surrounding personalised treatment strategies. Multigene testing for Recurrence Index (RecurIndex) model capably differentiates patients based on their level of LRR risk. This research aims to validate whether a more aggressive treatment approach can enhance clinical outcomes in N1 patients who possess a clinically low risk of LRR, yet a high RecurIndex-determined risk of LRR. Specifically, this entails postoperative whole breast irradiation combined with regional lymph node irradiation (RNI) following breast-conserving surgery or chest wall irradiation with RNI after mastectomy.Methods and analysis The RIGAIN (RecurIndex-Guided postoperative radiotherapy with or without Avoidance of Irradiation of regional Nodes in 1–3 node-positive breast cancer) Study is a multicentre, prospective, randomised, open-label, phase III clinical trial that is being conducted in China. In this study, patients with low clinical LRR risk but high RecurIndex-LRR risk are randomly assigned in a 1:1 ratio to the experimental group or the control group. In the experimental group, RNI is performed and the control group omits RNI. Efficacy and safety analyses will be conducted, enrolling a total of 540 patients (270 per group). The primary endpoint is invasive disease-free survival, and secondary endpoints include any first recurrence, LRR-free survival, distant metastasis-free survival, recurrence-free survival, overall survival, disease-free survival, breast cancer-specific mortality and assessment of patient quality of life. The study began in April 2023 and with a follow-up period of 60 months after the last participant completes radiation therapy.Ethics and dissemination The study was approved by the Ethics Committee of Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University (SYSKY-2022-097-02, V.3.1). It adheres to the Helsinki Declaration and Good Clinical Practice. Research findings will be submitted for publication in peer-reviewed journals.Trial registration number NCT04069884