A Delphi Study of Expert Consensus on Chinese Medicine Syndrome Differentiation and Herbal Use for Early Breast Cancer.

OBJECTIVES: Chinese herbal medicine (CHM) is widely used in breast cancer, but there is no consensus on the Chinese medicine (CM) syndromes in the different conventional treatment stages (preoperative, postoperative, chemotherapy, radiation therapy and endocrine therapy) of early breast cancer. This Delphi study aimed to achieve expert consensus on the CM syndromes, signs and symptoms, and the Chinese herbal formulae for early breast cancer. METHODS: Thirty senior CM clinicians with expertise in managing breast cancer were enrolled. The syndromes selected by ≥50% of experts and the corresponding most common Chinese herbal formulae were considered a consensus. Consensus on signs and symptoms was defined as a median score ≥4 (the item was important or very important) and ≥70% of experts rating the sign or symptom as 4 (important) or 5 (very important) on a 5-point Likert scale. RESULTS: Three survey rounds were conducted from 15 October 2021 to 10 March 2022. Consensus was reached with 3 syndromes confirmed for each treatment stage. Several syndromes, such as dual deficiency of qi and Blood, were considered common to multiple treatment stages. Some important signs and symptoms were presented in multiple treatment stages (eg, shortage of qi in the radiation therapy and endocrine therapy stages). CONCLUSIONS: This Delphi study achieved consensus on the most common CM syndromes, corresponding signs and symptoms, and the most common formulae in each treatment stage of early breast cancer, providing an evidence-based approach for future clinical practice.

Breast cancer prediction model based on clinical and biochemical characteristics: clinical data from patients with benign and malignant breast tumors from a single center in South China.

OBJECTIVE: Breast cancer is the most prevalent cancer and is second leading cause of death from malignancy among women worldwide. In addition to tumor factors, the host characteristics of tumors have been paid more and more attention by the medical community. This study aimed to develop a breast cancer prediction model for the Chinese population using clinical and biochemical characteristics. METHODS: This is a retrospective study. From 2012 to 2021, we selected 19,751 patients with breast diseases from the Guangdong Hospital of Traditional Chinese Medicine, which included 5660 patients with breast cancer and 14,091 patients with benign breast diseases-75% of patients were randomly assigned to the training group and 25% to the test group using a total of 34 clinical and biochemical characteristics. Significant clinical signs were investigated, and logistic regression with recursive feature elimination (RFE) model was used to develop a prediction model for distinguishing benign from malignant breast diseases. The prediction model's accuracy, precision, sensitivity, specificity, and area under the ROC curve (AUC) were calculated. RESULTS: Clinical statistics demonstrated that the prediction model comprised 19 clinical characteristics had statistical separability in both the training group and the test group, as well as good sensitivity and prediction. CONCLUSIONS: This model based on biochemical parameters demonstrates a significant predictive effect for breast cancer and may be useful as a reference for invasive tissue biopsy in patients undergoing BI-RADS 3 and 4A breast imaging.

Astragaloside IV enhances the sensitivity of breast cancer stem cells to paclitaxel by inhibiting stemness.

Background: Chemotherapy is one of the common treatments for breast cancer. The induction of cancer stem cells (CSCs) is an important reason for chemotherapy failure and breast cancer recurrence. Astragaloside IV (ASIV) is one of the effective components of the traditional Chinese medicine (TCM) Astragalus membranaceus, which can improve the sensitivity of various tumors to chemotherapy drugs. Here, we explored the sensitization effect of ASIV to chemotherapy drug paclitaxel (PTX) in breast cancer from the perspective of CSCs. Methods: The study included both in vitro and in vivo experiments. CSCs from the breast cancer cell line MCF7 with stem cell characteristics were successfully induced in vitro. Cell viability and proliferation were detected using the Cell Counting Kit-8 (CCK-8) and colony formation assays, and flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) methods were performed to detect cell apoptosis. Stemness-related protein expression was determined by western blotting (WB) and immunohistochemistry (IHC). Body weight, histopathology, and visceral organ damage of mice were used to monitor drug toxicity. Results: The expression of stemness markers including Sox2, Nanog, and ALDHA1 was stronger in MCF7-CSCs than in MCF7. PTX treatment inhibited the proliferation of tumor cells by promoting cell apoptosis, whereas the stemness of breast cancer stem cells (BCSCs) resisted the effects of PTX. ASIV decreased the stemness of BCSCs, increased the sensitivity of BCSCs to PTX, and synergistically promoted PTX-induced apoptosis of breast cancer cells. Our results showed that the total cell apoptosis rate increased by about 25% after adding ASIV compared with BCSCs treated with PTX alone. The in vivo experiments demonstrated that ASIV enhanced the ability of PTX to inhibit the growth of breast cancer. WB and IHC showed that ASIV reduced the stemness of CSCs. Conclusions: In this study, the resistance of breast cancer to PTX was attributed to the existence of CSCs; ASIV weakened the resistance of MCF7-CSCs to PTX by significantly attenuating the hallmarks of breast cancer stemness and improved the efficacy of PTX.

Chinese Medicine Syndrome Differentiation for Early Breast Cancer: A Multicenter Prospective Clinical Study.

Background: Chinese medicine (CM) syndrome differentiation is one of the fundamental principles that guide the practice of Chinese herbal medicine (CHM). CHM has been widely used among breast cancer patients. Contemporary literature varies in syndrome diagnosis, and there is a need to standardize syndrome differentiation according to the different stages of breast cancer treatment. This multicenter clinical study aims to identify the CM syndromes and the clinical signs and symptoms in women with early breast cancer. Methods: Participants who met the inclusion and exclusion criteria were interviewed during the five treatment stages: preoperative, postoperative, chemotherapy, radiation therapy, and endocrine therapy. Patient demographic data and CM syndrome (as recorded by the treating CM clinicians in medical records) were gathered. Signs and symptoms were analyzed using descriptive statistics to derive the standardized CM syndromes using hierarchical cluster analysis. Results: The analysis included 964 interviews with 620 participants enrolled between April 29, 2020 and May 30, 2021 from eight participating hospitals in China. The two most frequent syndromes recorded in medical records were dual deficiency of qi and blood, and dual deficiency of qi and yin during all but the preoperative stage. The symptoms of lassitude, lack of strength, and insomnia were common in all but the preoperative stage. Cluster analysis identified two clusters in the preoperative stage that most closely resembled the syndrome diagnoses of liver stagnation with congealing phlegm, and dual deficiency of the liver and kidney. Two clusters-dual deficiency of qi and blood, and dual deficiency of qi and yin-were common to multiple treatment stages. The syndrome cluster of spleen and stomach disharmony existed in both the postoperative and chemotherapy stages. Cluster analysis of the radiation therapy stage identified the unique syndrome of yin deficiency with fire toxin, while the endocrine therapy included the syndromes of liver depression and kidney deficiency. Conclusions: This multicenter clinical study showed consistency between results from cluster analysis and the most common syndromes recorded in the medical records. Findings from this clinical study will be further validated in a Delphi study to standardize CM syndromes for various stages of breast cancer treatment. Clinical Trial Registration: www.chictr.org.cn/index.aspx, identifier ChiCTR2000032497.

Acupuncture for Breast Cancer: A Systematic Review and Meta-Analysis of Patient-Reported Outcomes.

ABSTRACT: The present systematic review and meta-analysis was undertaken to evaluate the effects of acupuncture in women with breast cancer (BC), focusing on patient-reported outcomes (PROs). METHODS: A comprehensive literature search was carried out for randomized controlled trials (RCTs) reporting PROs in BC patients with treatment-related symptoms after undergoing acupuncture for at least four weeks. Literature screening, data extraction, and risk bias assessment were independently carried out by two researchers. RESULTS: Out of the 2, 524 identified studies, 29 studies representing 33 articles were included in this meta-analysis. At the end of treatment (EOT), the acupuncture patients' quality of life (QoL) was measured by the QLQ-C30 QoL subscale, the Functional Assessment of Cancer Therapy-Endocrine Symptoms (FACT-ES), the Functional Assessment of Cancer Therapy-General/Breast (FACT-G/B), and the Menopause-Specific Quality of Life Questionnaire (MENQOL), which depicted a significant improvement. The use of acupuncture in BC patients lead to a considerable reduction in the scores of all subscales of the Brief Pain Inventory-Short Form (BPI-SF) and Visual Analog Scale (VAS) measuring pain. Moreover, patients treated with acupuncture were more likely to experience improvements in hot flashes scores, fatigue, sleep disturbance, and anxiety compared to those in the control group, while the improvements in depression were comparable across both groups. Long-term follow-up results were similar to the EOT results. CONCLUSIONS: Current evidence suggests that acupuncture might improve BC treatment-related symptoms measured with PROs including QoL, pain, fatigue, hot flashes, sleep disturbance and anxiety. However, a number of included studies report limited amounts of certain subgroup settings, thus more rigorous, well-designed and larger RCTs are needed to confirm our results.

Chinese Medicine Syndromes and Stages of Early Breast Cancer: Hierarchical Cluster Analysis and Implication for Clinical Practice.

Background: Chinese medicine (CM) has been widely used for women's health, including those with early breast cancer. Contemporary literature varies in descriptions of the CM syndromes that are critical for determining CM treatment options for breast cancer patients. However, the corresponding syndromes have not been standardized to align with the conventional medicine treatment stages. This review aimed to address this knowledge gap to enhance the quality and consistency of CM interventions for early breast cancer patients. Methods: In total, eight Chinese and English language databases were searched, and textbooks and clinical care documents were gathered. Sources were classified according to five treatment stages: preoperative, postoperative, chemotherapy, radiation therapy, and endocrine therapy. Descriptive statistics were used to examine the syndromes, and hierarchical cluster analysis was conducted to investigate clusters of signs and symptoms. Results: The CM syndrome of dual deficiency of qi and Blood was one of the most common syndromes across all treatment stages, whereas lack of strength and lassitude were the most common clinical presentations throughout all stages, except the preoperative stage. Cluster analyses identify three or four syndromes in each treatment stage. Cluster results for the preoperative stage were: Blood stasis, Liver depression and qi stagnation, and Kidney yin deficiency. Dual deficiency of qi and Blood existed at different stages except for the preoperative stage. In the postoperative stage and chemotherapy stages, some symptoms were categorized into clusters that related to the Spleen and Stomach. Syndromes such as yin deficiency with fire toxin and yin deficiency with fluid depletion were unique to the radiation therapy stage. Clusters for endocrine therapy stage included the dual deficiency of Spleen and Kidney, Liver depression and qi stagnation, and Kidney yin deficiency. Conclusions: Systematic review of the contemporary literature for early breast cancer revealed that the most frequently seen CM syndromes and cluster results have some similarities but some important distinctions. Clinical data are needed to confirm whether the syndromes described in contemporary literature reflect those seen in women with early breast cancer.

Exploring the molecular targets and mechanisms of [10]-Gingerol for treating triple-negative breast cancer using bioinformatics approaches, molecular docking, and in vivo experiments.

BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive among breast cancer subtypes with the worst prognosis. Ginger is widely used in pharmaceuticals and as food. Its anticancer properties are known, but the mechanism is still unclear. [10]-Gingerol is one of the main phenolic compounds isolated from ginger. Studying the biological effects of [10]-Gingerol is of great significance to understand the efficacy of ginger. METHODS: In this study, the therapeutic effects of [10]-Gingerol on TNBC cells were studied using network pharmacology, molecular docking, and in vitro experiments, and the target and mechanism of action were explained. RESULTS: A total of 48 targets of ginger for the treatment of TNBC were found. These targets might interfere with the growth of TNBC by participating in many pathways, such as endocrine resistance, progesterone-mediated oocyte maturation, estrogen signaling pathway, and cellular senescence. Prognostic analyses indicated that the JUN, FASN, ADRB2, ADRA2A, and PGR were the hub genes, while molecular docking predicted the stable binding of ADRB2 protein with drug compounds. Additionally, [10]-Gingerol could induce apoptosis by regulating the caspase activation. CONCLUSIONS: [10]-Gingerol affects the growth of TNBC through multiple action targets and participating in multiple action pathways. ADRB2 and apoptosis pathways might be important target pathways for [10]-Gingerol in the treatment of TNBC.

Traditional Chinese Medicine Extract from Huaier Increases the Expression of Duffy Antigen Receptor for Chemokines and Reduces the Expression of Its Ligands.

AIMS: The aim of the present study is to investigate whether the aqueous extract from Huaier, a traditional Chinese medicine (TCM), can affect the expression of Duffy antigen receptor for chemokines (DARC) and its ligands. Moreover, we compare the status of DARC in primary and metastatic breast cancer tissues from the same patient. METHODS: Immunohistochemistry was used to detect the expression of DARC in primary and metastatic focuses in 30 patients with breast cancer. The effect of Huaier aqueous extract on the expression of DARC and its ligands was investigated by quantitative real-time polymerase chain reaction, Western blotting, and enzyme-linked immunosorbent assay. RESULTS: The expression score of DARC in primary focuses was significantly higher than that in metastatic focuses, while changes of ER, PR, and HER2 receptors were not significantly different between primary and metastatic focuses. Huaier aqueous extract promoted the expression of DARC and reduced the secretion of CC chemokine ligand 2 (CCL-2), CXC chemokine ligand 8 (CXCL-8, IL-8), matrix metalloproteinase 2 (MMP-2), and CXC chemokine ligand 1 (CXCL-1). CONCLUSION: The present study demonstrates that difference in expression level of DARC between primary and metastatic focuses of breast cancer was significant, while differences in expression of ER, PR, and HER2 between primary and metastatic focuses were not significant. DARC may play a negative role in the metastasis of breast cancer. Traditional Chinese medicine extract from Huaier can increase DARC expression and reduce the expression of its ligands such as CCL-2, IL-8, MMP-2, and CXCL-1.

Effect of Jianpi Bushen formula on aromatase-inhibitor-associated bone loss after menopause.

OBJECTIVE: To investigate the effect of Jianpi Bushen (JPBS) formula on aromatase inhibitor (AI)-associated bone loss after menopause. METHODS: Six-month-old female rats were randomly divided into 6 groups: a sham group, an ovariectomized (OVX) group, an OVX treated with exemestane and 3 OVX groups each treated with a different dose of JPBS formula. Bone mineral density (BMD) at the lumbar vertebrae, histology, bone markers and serum levels of estrogen were assessed. Furthermore, a cohort study was conducted in 130 postmenopausal women with breast cancer that had undergone treatment with AIs. The subjects were given JPBS + caltrate D or caltrate D only, administered orally. BMD at the lumbar vertebrae and femoral neck and bone markers were evaluated in both control and herbal treatment groups at baseline and 12 months. RESULTS: Experimental results indicated that a high dose of JPBS significantly increased the trabecular bone area percentage (Tb.Ar %) and broadened the trabecular thickness (Tb.Th). The JPBS formula enriched the carboxyterrninal propeptide of type ipmcollagen and increased serum estrogen level significantly. The clinical investigation revealed that bone loss was decreased in the group treated with JPBS vs control (BMD T score at lumbar vertebrae, 3.9% increased vs 14.58% decreased, respectively, P = 0.004 and BMD T score on femoral neck, 1.8% decreased vs 22.45% decreased, respectively, P = 0.008). Besides, JPBS formula elevated N- middle osteocalcin and decreased type I collagen cross-linked C-terminal telopeptide. CONCLUSION: JPBS formula prevented aromatase-inhibitor-associated bone loss after menopause by inhibiting bone resorption and promoting bone formation.

Standardization of Syndrome Differentiation Defined by Traditional Chinese Medicine in Operative Breast Cancer: A Modified Delphi Study.

OBJECTIVE: The aim of this study was to establish the standardization of syndrome differentiation of operative breast cancer treated with Traditional Chinese Medicine (TCM) by the modified Delphi method. METHOD: A literature search for standardization of syndrome differentiation of operative breast cancer was conducted and eligible articles were identified in indexed databases from 1982 to 2013. We carried out two rounds of investigation between March and October 2013 and organized 20 experts who focused on TCM or integrative medicine in breast cancer research. Experts' judgments were collected via posted questionnaires or e-mail. A final evaluation was carried out after the end of both rounds. RESULT: The response ratio of the 1st round investigation reached 100%, and two experts were excluded due to the uncompleted questionnaire. The 2nd round investigation was completed by 18 experts in the 1st round panel board. In both rounds, the experts agreed that the stage of breast cancer defined by TCM could be divided into the perioperation period, the perichemotherapy period, the periradiotherapy period, and the consolidation period. CONCLUSION: We identified the feasibility and reasonability to establish the standardization of syndrome differentiation of operative breast cancer. According to the suggestions from experts in our Delphi study, we preliminarily established the TCM standard of syndrome differentiation based on different treatment stages of operative breast cancer.

[Standardization of syndrome differentiation based on stages for breast cancer: a significant and updating topic on mastology of traditional Chinese medicine].

The incidence of breast cancer increased rapidly in recent years. Breast cancer has become the most frequent malignant tumor of female especially in the developed regions. Traditional Chinese medicine (TCM) is effective in treating breast cancer, but its theories appear hysteretic, restricting the progress in clinical practice, teaching and research of TCM in the treatment of breast cancer. This article described the significance and urgency to work out the standardization of syndrome differentiation based on stages for breast cancer and put it into practice. It also analyzed the foundations, ideas and approaches of the research of standardization of syndrome differentiation based on stages for breast cancer in light of the changes of spectrum of diseases, the weaknesses of modern medicine in treating breast cancer, and the existed problems in the update clinical practice.

[Discussion of some problems about use of traditional Chinese medicine in perioperative management of breast cancer].

The study on use of traditional Chinese medicine in perioperative management of breast cancer is still in the beginning phase. With the emergence of new understanding about the biological characteristics of breast cancer, the concept of treatment has changed. For instance, the resection extent is tending to be narrower, large doses of radiotherapy may be adopted during the operation, and early use of adjuvant chemotherapy is advocated after the operation. These have bought about changes to the intervention factors in the perioperative period for breast cancer. Some related problems about the participation of traditional Chinese medicine in perioperative management of breast cancer are discussed in this article, so as to make the perioperative management perfect.

[Effects of Runing Recipe II on expressions of p53 and ras oncogene proteins and cell cycle of the transplanted Ca761 breast cancer in mice].

OBJECTIVE: To explore the mechanisms of Runing Recipe II (a recipe composed of traditional Chinese herbs) in inhibiting the growth of breast cancer by observing its effects on the expressions of p53 and ras oncogene proteins and cell cycle of the transplanted Ca761 breast cancer in mice. METHODS: We established the breast cancer model by transplanting Ca761 cells in mice. The mice were randomly divided into 4 groups: normal saline control group, CTX-treated group, Runing Recipe II-treated group, and Runing Recipe II and CTX-treated group, with 12 mice in each group. We detected the cell cycle of the cancer cells in the mice's transplanted tumor with flow cytometry and measured the expressions of p53 and ras oncogene proteins in the transplanted tumor with immunohistochemical methods. RESULTS: The percentages of tumor cells in S-phase of the Runing Recipe II treated group, CTX-treated group and Runing Recipe II and CTX-treated group were significantly lower than that of the normal saline control group respectively (P<0.05). The percentage of tumor cells in G(0)-G(1) phase of the Runing Recipe II treated group was lower than that of the CTX-treated group (P<0.05), while the percentage of tumor cells in G(2)-M phase was higher than that of the CTX-treated group. The immunoreactive scores (IRSs) of p53 in the Runing Recipe II treated group and Runing Recipe II and CTX-treated group were significantly lower than that in the normal saline control group respectively (P<0.05). The effect of CTX on the expression of p53 was not significant. The IRSs of ras oncogene protein in the Recipe II-treated group, CTX-treated group and Runing Recipe II and CTX-treated group were lower than that in the normal saline control group respectively (P<0.05). CONCLUSION: Runing Recipe II can inhibit the growth of Ca761 breast cancer in mice by controlling the cell cycle of the transplanted tumor. This may be related to its effect on the gene expressions of p53 and ras in the tumor tissue.