Prognostic Factors For Local Control in Breast Cancer After Long-term Follow-up in the EORTC Boost vs No Boost Trial: A Randomized Clinical Trial.

IMPORTANCE Prognostic factors of ipsilateral breast tumor recurrence (IBTR) may change over time following breast-conserving therapy. OBJECTIVE The EORTC "boost no boost" trial showed that young age and high-grade invasive carcinoma were the most important risk factors for IBTR. This study reanalyses pathological prognostic factors related to IBTR using long-term follow-up. DESIGN, SETTING, AND PARTICIPANTS Participants included 5569 early-stage breast cancer patients, treated with breast-conserving surgery (BCS) and whole-breast irradiation (WBI), who were randomized between no boost and a 16-Gy boost in the EORTC phase III "boost no boost" trial (1989-1996). A total of 1616 patients with a microscopically complete resection (according to local pathologists), included in the central pathology review, have been analyzed in this study. Median follow-up was 18.2 years. INTERVENTIONS No further treatment or 16-Gy boost, after BCS and 50-Gy WBI. MAIN OUTCOMES AND MEASURES Time to ipsilateral breast tumor recurrence (IBTR) as first event. RESULTS The 20-year cumulative incidence of IBTR in 1616 patients (160 events observed) was 15%(95% CI, 12%-17%). Young age (P <. 001) and presence of ductal carcinoma in situ (DCIS) (HR, 2.15; 95% CI, 1.36-3.38; P =. 001) were associated with an increased risk of IBTR in multivariable analysis. The cumulative incidence of IBTR at 20 years was 34%(95% CI, 25%-41%), 14%(95% CI, 10%-18%), and 11% (95% CI, 8%-15%), in patients 40 years or younger, 41 to 50 years and 50 years or older, respectively (P <. 001). This incidence was 18% (95% CI, 14%-22%) and 9% (95% CI, 6%-12%) for tumors with and without DCIS (P <. 001). High-grade tumors relapsed more frequently early during follow-up but the relative effect of age and presence of DCIS seemed stable over time. The boost reduced the 20-year IBTR incidence from 31% (95% CI, 22%-39%) to 15%(95% CI, 8%-21%) (HR, 0.37; 95% CI, 0.22-0.62; P <. 001) in high-risk patients (<= 50 years with DCIS present). CONCLUSIONS AND RELEVANCE The association of high-grade invasive tumor with IBTR diminished during follow-up, while the effect of DCIS adjacent to invasive tumor seemed to remain stable. Therefore, patients with high-grade invasive tumors should be monitored closely, especially in the first 5 years, while additional DCIS is an indication for longer follow-up, emphasizing the importance of long-term trial follow-up to estimate absolute effects accurately.