Breast cancer and metabolic comorbidities: From epidemiology and molecular mechanisms to precision interventions

Table 1 Clinical implications of metabolic comorbidities throughout the breast cancer care continuum

Clinical dimension	Obesity	Type 2 diabetes	Metabolic syndrome	Cardiovascular disease
Tumour pathology and subtype	Associated with postmenopausal ER+ disease; central obesity linked to luminal B/TNBC in younger[125,127]	Higher incidence of TNBC; lower prevalence of HER2+ disease[54]	Potentially stronger association with poor prognosis in HER2-overexpressing subtypes[61]	-
Treatment delivery and efficacy	Therapeutic decisions: Contributes to treatment de-escalation in older adults[98,132]	Therapeutic decisions: Lower likelihood of receiving chemotherapy[55]	Efficacy: Lower pCR rates after NACT[60,62]	Therapeutic decisions: Contributes to undertreatment, particularly in metastatic HER2+ disease[131]
	Efficacy: Reduced rate of pCR following NACT[42,62]	Safety: Increased risk of postoperative complications[14,49]		Safety: Key predictor of CTRCD; CDK4/6 inhibitors increase risk of hypertension and MACE[71,77,78]
Long-term survival outcomes	Recurrence: Increased risk, especially in HR+ patients on aromatase inhibitors[35,135]	Second primary cancers: Elevated risk of several SPCs (e.g., liver, brain)[16]	Recurrence: Significantly increased risk[12,60]	Mortality: Leading cause of non-cancer death among survivors[67,68]
	Mortality: Elevated breast cancer-specific and all-cause mortality[9,26,136]	Mortality: 20% increased risk of breast cancer-related death; causal evidence exists[10,51]	Mortality: Elevated breast cancer-specific and all-cause mortality[12,60]

ER+: Estrogen receptor-positive; TNBC: Triple-negative breast cancer; pCR: Pathological complete response; HER2: Human epidermal growth factor receptor 2; SPCs: Second primary cancers; pCR: Pathological complete response; NACT: Neoadjuvant chemotherapy; CTRCD: Cancer therapy-related cardiac dysfunction; MACE: Major adverse cardiovascular events.