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

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.

To investigate the impact of metformin on estrogen regulation and prognosis-related nursing outcomes in patients with LABC and T2DM.

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.

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.

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.