Metformin and estrogen modulation in LABC with T2DM: A 36-month randomized trial.

Background: Patients with locally advanced breast cancer (LABC) and type 2 diabetes mellitus (T2DM) confront dual challenges: hormone-driven tumor progression and metabolic dysregulation. Although metformin has shown antitumor potential, its effect on estrogen modulation and synergy with nursing care remains unclear in clinical settings. Purpose: To investigate the impact of metformin on estrogen regulation and prognosis-related nursing outcomes in patients with LABC and T2DM. Methods: This multicenter retrospective cohort study with a prospective randomized intervention component evaluated clinical, metabolic, and care-related indicators during the perioperative period. Serum estradiol (E2) was measured at baseline, post-chemotherapy, and 30 days post-surgery. Glucose metabolism was assessed by fasting blood glucose, HbA1c, and CV%, alongside hypoglycemia monitoring. Care quality metrics included wound healing time, infection rate, chemotherapy adherence, and hospital stay length. Survival outcomes (36-month PFS and OS) were analyzed via Kaplan-Meier curves and Cox models adjusted for age, BMI, and tumor stage. Statistical analysis used SPSS 26.0; continuous variables were expressed as mean ± SD, compared with t-tests; HRs and 95% CIs were reported with P < 0.05 considered significant. Results: Metformin led to a 19.3% reduction in E2 levels post-chemotherapy, with sustained suppression, outperforming the control group. Glycemic metrics improved: fasting glucose compliance rose to 83.3%, CV% decreased by 38.2%, and hypoglycemia dropped by 66.7%. Wound healing time was shortened by 3.3 days. Chemotherapy adherence reached 92.8% (vs 73.6%) and self-care scores improved by 25.8% (vs 7.2%). Mechanistic analysis indicated enhanced immune microenvironment regulation and reduced pro-inflammatory cytokines. Conclusion: Metformin, combined with structured nursing care, significantly improves estrogen control, metabolic stability, and survival in LABC patients with T2DM. These findings support its role in integrated pharmaco-nursing management of tumor-metabolic comorbidities.