MetaFemina: development and evaluation of a large language model-assisted platform for automated meta-analysis of nutritional exposures and breast, ovarian, and uterine cancer risk

Objective To develop and evaluate an automated large language model (LLM)-based framework for conducting meta-analyses of nutrition-related exposures and the risk of breast, ovarian, and uterine cancers. Design We developed MetaFemina, an automated evidence-synthesis pipeline for women's cancers that integrates keyword-based literature retrieval, LLM-assisted evidence extraction, and random-effects meta-analysis. We evaluated its performance against two recently published peer-reviewed meta-analyses and compared exposure-outcome associations across the three cancer types. Data sources PubMed articles identified through keyword-based searches of titles and abstracts. Methods MetaFemina was developed as a web platform that identifies relevant scientific articles, automatically extracts relevant information using LLMs, and synthesizes extracted evidence using random-effects meta-analysis. Additional analyses included assessment of heterogeneity, publication bias, and leave-one-out sensitivity analyses. The platform also provides sample size calculations based on synthesized effect sizes and generates visual summaries and plain-language interpretations. Results Compared with two recent peer-reviewed meta-analyses of folate and vitamin E intake in relation to breast cancer risk, MetaFemina demonstrated high sensitivity (81.82% and 80%, respectively) in identifying eligible studies and additionally retrieved relevant articles that had been missed by manual screening (27 and 13, respectively). Among 226 exposures considered, lutein and beta-carotene were significantly associated with lower risks of breast, ovarian, and uterine cancers. Vitamin D, antioxidants, and soy were significantly associated with lower risks of both breast and ovarian cancers, whereas calcium and folic acid were significantly associated with lower risks of both breast and uterine cancers. In contrast, iron, red meat, and copper were significantly associated with higher risks of both breast and uterine cancers. omega-6 fatty acids showed contrasting associations, being significantly associated with higher breast cancer risk but lower ovarian cancer risk. After restriction to dietary-intake studies, these cross-cancer significant associations remained statistically significant except for copper, which no longer met the two-study threshold for either breast or uterine cancer. Additionally, calcium became significantly associated with lower ovarian cancer risk, resulting in significant negative associations across all three cancer types, while vitamin E became significantly associated with lower breast cancer risk and remained significantly associated with lower ovarian cancer risk. Conclusions MetaFemina demonstrated high sensitivity for identifying relevant scientific literature, extracts key evidence, and performs statistically rigorous automated meta-analyses. The framework may facilitate more rapid evidence synthesis in nutritional epidemiology and may support researchers in study design, hypothesis generation, and interpretation of emerging evidence.