Messaggi chiave
- Una serie di studi sta esaminando la fattibilità di una strategia di de-escalation della radioterapia in pazienti con carcinoma mammario precoce (eBC) a basso rischio di recidiva locoregionale (LRR). In questo ambito, è stata effettuata un’analisi esplorativa dello studio MINDACT volta a valutare l’associazione della firma a 70 geni MammaPrint con il rischio di LRR e a stimare l’incidenza cumulativa a 8 anni di LRR in pazienti eBC sottoposte a chirurgia conservativa.
- A un follow-up di 8 anni, 189/6693 pazienti arruolate hanno sviluppato un evento di LRR, per un’incidenza cumulativa pari al 3,2%. Nelle pazienti a basso rischio genomico, l’incidenza cumulativa è risultata pari al 2,7%. Dall’analisi univariata è emersa un’associazione significativa tra punteggio genomico e rischio di LRR, non confermata però nel modello multivariato.
- Nella presente analisi, forse a causa del basso numero di eventi osservati, la firma a 70 geni non è stata un fattore prognostico indipendente di LRR, mentre si è confermato il ruolo prognostico di alcuni fattori clinici convenzionali quali dimensioni e grado del tumore e trattamento sistemico adiuvante.
Abstract
Purpose
- A number of studies are currently investigating de-escalation of radiation therapy in patients with a low risk of in-breast relapses on the basis of clinicopathologic factors and molecular tests.
- We evaluated whether 70-gene risk score is associated with risk of locoregional recurrence (LRR) and estimated 8-year cumulative incidences for LRR in patients with early-stage breast cancer treated with breast conservation.
Methods
- In this exploratory substudy of European Organisation for Research and Treatment of Cancer 10041/BIG 03-04 MINDACT trial, we evaluated women with a known clinical and genomic 70-gene risk score test result and who had breast-conserving surgery (BCS).
- The primary end point was LRR at 8 years, estimated by cumulative incidences.
- Distant metastasis and death were considered competing risks.
Results
- Among 6,693 enrolled patients, 5,470 (81.7%) underwent BCS, of whom 98% received radiotherapy.
- At 8-year follow-up, 189 patients experienced a LRR, resulting in an 8-year cumulative incidence of 3.2% (95% CI, 2.7 to 3.7).
- In patients with a low-risk 70-gene signature, the 8-year LRR incidence was 2.7% (95% CI, 2.1 to 3.3).
- In univariable analysis, adjusted for chemotherapy, five of 12 variables were associated with LRR, including the 70-gene signature.
- In multivariable modeling, adjuvant endocrine therapy and to a lesser extent tumor size and grade remained significantly associated with LRR.
Conclusions
- This exploratory analysis of the MINDACT trial estimated an 8-year low LRR rate of 3.2% after BCS.
- The 70-gene signature was not independently predictive of LRR perhaps because of the low number of events observed and currently cannot be used in clinical decision making regarding LRR.
- The overall low number of events does provide an opportunity to design trials toward de-escalation of local therapy.