Fig. 3: The puzzling timing of metastatic relapse in breast cancer patients.

Two different models are shown, based on disparate growth rates observed among breast tumours. a The first model is based on fast-growing breast tumours (i.e., non-luminal), which can take ~1 year to give rise to clinically detectable neoplasms (~1 cm in diameter). Assuming comparable proliferative indices for distant lesions, direct metastatic outgrowth of early (parallel progression) or late (linear progression) DTCs could justify cases of early metastatic recurrence. Alternatively, tumour dormancy might be responsible for late relapses of fast-proliferating tumours. b The second model is based on slow-growing breast tumours (i.e., luminal), which can take up to 50 years to become clinically detectable. Assuming comparable proliferative indices for distant lesions, direct metastatic outgrowth of DTCs without dormancy could explain both early and late cases of recurrence, regardless of the timing of DTC spread. DTC disseminated tumour cell, LP linear progression, PP parallel progression, T tumour stage, YRS years. Figure created with BioRender.com.