The impact of loco-regional recurrences on metastatic progression in early-stage breast cancer: a multistate model

G. H. Bock (1) , H. Putter (2) , J. Bonnema (3) , J. A. Hage (4) , H. Bartelink (5) , C. J. Velde (4)

1 University of Groningen [Groningen]
2 Department of Medical Statistics
3 Department of Surgery
4 Department of Surgery, D6-43
5 Department of Radiotherapy

To study whether the effects of prognostic factors associated with the occurrence of distant metastases (DM) at primary diagnosis change after the incidence of loco-regional recurrences (LRR) among women treated for invasive stage I or II breast cancer. The study population consisted of 3,601 women, enrolled in EORTC trials 10801, 10854, or 10902 treated for early-stage breast cancer. Data were analysed in a multivariate, multistate model by using multivariate Cox regression models, including a state-dependent covariate. The presence of a LRR in itself is a significant prognostic risk factor (HR: 3.64; 95%-CI: 2.02–6.5) for the occurrence of DM. Main prognostic risk factors for a DM are young age at diagnosis (≤40: HR: 1.79; 95%-CI: 1.28–2.51), larger tumour size (HR: 1.58; 95%-CI: 1.35–1.84) and node positivity (HR: 2.00; 95%-CI: 1.74–2.30). Adjuvant chemotherapy is protective for a DM (HR: 0.66; 95%-CI: 0.55–0.80). After the occurrence of a LRR the latter protective effect has disappeared ( = 0.009). The presence of LRR in itself is a significant risk factor for DM. For patients who are at risk of developing LRR, effective local control should be the main target of therapy.

Mots clés: Breast cancer; Follow-up studies; Women; Local recurrences; Distant metastasis; Prognostic factors; Survival analysis; Meta-analysis; Multistate model

G. H. Bock, H. Putter, J. Bonnema, J. A. Hage, H. Bartelink, et al.. The impact of loco-regional recurrences on metastatic progression in early-stage breast cancer: a multistate model. Breast Cancer Research and Treatment, 2009, 117 (2), pp.401-408. ⟨10.1007/s10549-008-0300-2⟩. ⟨hal-00535330⟩