Uriel Diaz-Llerenas

Background/Objectives: Orally administered herbal preparations have gained attention as complementary approaches in supportive cancer care; however, their clinical efficacy and safety remain uncertain. This systematic review critically evaluated evidence from randomized clinical trials investigating these interventions in patients with cancer. Methods: The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines and was prospectively registered in PROSPERO. PubMed/MEDLINE, ScienceDirect, Springer Nature Link, CENTRAL, Scopus, LILACS, ClinicalTrials.gov, and WHO ICTRP were searched for English-language studies published from January 1990 through 8 September 2026. Risk of bias was assessed using RoB 2, and outcome-level certainty was evaluated using GRADE. Results: Eight randomized clinical trials met the eligibility criteria and were included in the qualitative synthesis. The studies evaluated Gamiguibi-tang, Rikkunshito, holy basil (Ocimum tenuiflorum), Alcea digitata–Malva sylvestris, Annona muricata, Malva sylvestris–Althaea digitata, Jing Si herbal tea, and Renshen Yangrong Tang across heterogeneous cancer populations. Individual trials reported potentially favorable findings for sleep, fatigue, chemotherapy-induced anorexia, anxiety, salivary function, xerostomia, gastrointestinal symptoms, and quality of life. However, the Jing Si herbal tea trial found no statistically significant between-group differences in fatigue or quality of life, and exploratory ex vivo cytotoxicity findings did not demonstrate clinical antitumor efficacy. Meta-analysis was not feasible because of substantial clinical and methodological heterogeneity. All evaluated outcomes were rated as very-low-certainty evidence, primarily because of risk of bias and serious imprecision. No serious intervention-related adverse events were identified in the published reports, but adverse-event monitoring was inconsistent and no trial was adequately powered to establish safety. Conclusions: The available evidence is insufficient to establish definitive efficacy or safety or to support routine clinical implementation. Adequately powered multicenter trials using botanically authenticated and chemically characterized preparations, clinically meaningful outcomes, interaction assessment, and long-term pharmacovigilance are required.

The widespread use of glyphosate-based herbicides (GBHs) has raised concerns about their potential role in hormone-sensitive cancers such as breast cancer. This systematic review aimed to evaluate preclinical evidence on the effects of glyphosate (pure compound) or glyphosate-based herbicide formulations (GBHs) exposure on breast cancer cell proliferation and related molecular pathways. A structured search was conducted across PubMed, ScienceDirect, and Springer Nature Link, Web of Science databases, covering studies published up to 9 November 2025, following a PROSPERO-registered protocol (ID: CRD42021238350). Eligible studies included original in vitro and in vivo preclinical research using human breast cancer cell lines (e.g., MCF-7, T47D, MDA-MB-231, MCF-12A, and MCF-10A) or relevant animal models. Outcomes assessed included cell viability, proliferation, tumor growth, apoptosis, cell cycle regulation, and molecular markers associated with endocrine signaling. Two reviewers independently screened and extracted data, resolving disagreements via discussion or third-party adjudication. From an initial pool of 699 articles, seven in vitro studies met the inclusion and quality criteria. Glyphosate exposure demonstrated weak estrogenic activity in ER-positive breast cancer cells, primarily via ERα modulation and altered gene expression related to proliferation and DNA repair. GBHs showed greater cytotoxic and epigenetic effects in non-tumorigenic cells, often independent of ER signaling. No included study employed in vivo breast cancer models. Overall, preclinical evidence suggests glyphosate may act as a weak endocrine disruptor under specific conditions, but findings are limited by the short-term in vitro designs, heterogeneous methodologies, and lack of chronic or in vivo data. Further research using long-term exposure and animal models is needed to clarify potential risks and inform regulatory and public health decisions.