Breast cancer is a type of cancer frequently encountered in women, and there is a need for more efficient and safer therapeutic approaches. Letrozole is an aromatase inhibitor that suppresses the growth of estrogen-dependent tumors, but its metabolic stability at high temperatures may restrict its therapeutic activity. In the present theoretical work, based on quantum calculations using the Gaussian software package, we examine the thermodynamic properties of the letrostructure alone and in combination with lead-free perovskite (CaTiO₃)₂ structure. The compatibility of the perovskite was further examined in terms of its biosafety in relation to the hemoglobin molecule. The obtained difference in Gibbs free energy (ΔG) values and displacement of enthalpy (ΔH) towards the more stable side, as well as higher deformation and binding energies of perovskite, were found when combined with letrozole. These signs suggest that more spontaneous tumor growth and tight binding to the cancerous formation were achieved, which did not present any apparent hematotoxicity. Then, lead-free perovskites may serve as a potential mediator for enhancing the efficacy of letrozole in breast cancer treatment.