Breast cancer, a global health challenge, exhibits molecular heterogeneity and complex interactions with the tumor microenvironment. We investigated adrenergic modulation in breast cancer spheroids, differentiating between basal-like (MDA-MB-231 and BT549) and luminal-like (T47D and MCF-7) subtypes. Noradrenalin reduced MDA-MB-231 spheroid size, reversed by propranolol, suggesting therapeutic potential. Luminal-like spheroids displayed subtler responses. Proteomic analysis revealed subtype-specific alterations, with TP53 as a consistent regulator affected by noradrenalin. Our study highlights subtype-dependent adrenergic signaling in breast cancer, providing insights for targeted therapies.