Fig. 1

Long-term oestrogen deprivation therapy as a clinical model to investigate breast cancer dormancy and acquired resistance. a Extended (4–45 months) letrozole treatment was exploited as a clinical model of breast cancer dormancy and acquired resistance. Sequential clinical samples from the same patient with no surgery and extended treatment were used to model clinical breast cancer dormancy and resistance. Before (pre, ≤ 0 days), early-on (early, 13–120 days) and long-term (long, > 120 days) neoadjuvant aromatase inhibitor therapy with letrozole. b Dynamic change in tumour size by ultrasound scan (USS) and mean expression of proliferation markers MKI67, PCNA, and MCM2 were used to classify patients into two categories: dormant (blue) and resistant (red). Overall comparisons of classifications per patient based on USS and mean change in proliferation markers with final classification are shown. c The duration of letrozole treatment (days) for samples from dormant (blue) and resistant (red) patients. Each bar represents a sample. Samples are ordered by time on treatment. d Intrinsic subtype classification by PAM50 of samples at each time point. Stacked bar graphs on the right show the percentage of each subtype of samples from dormant and resistant patients. e Kaplan-Meier plot showing disease-free survival probability in patients with dormant versus resistant tumours (log-rank test). Disease-free survival was defined from time of surgery. f Density plot showing the distribution of time to recurrence (in years; defined from time of surgery) in patients with dormant and resistant tumours. CI confidence interval, HR hazard ratio, LumA luminal A, LumB luminal B