What is the long-term impact of prognostic factors on ipsilateral breast tumor recurrence (IBTR) in patients treated with breast-conserving therapy?
Young age and the presence of ductal carcinoma in situ (DCIS) adjacent to the invasive tumor were associated with an increased incidence of IBTR at long-term follow-up, whereas high-grade tumors relapsed more frequently only during the first 5 years.
Patients with high-grade invasive tumors should be monitored closely, especially in the first 5 years. The impact of DCIS remained constant over time, indicating that long-term follow-up is necessary. The boost significantly reduced IBTR in these patients.
Prognostic factors of ipsilateral breast tumor recurrence (IBTR) may change over time following breast-conserving therapy.
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.
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.
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.
clinicaltrials.gov Identifier: NCT02295033
Vrieling C, van Werkhoven E, Maingon P, Poortmans P, Weltens C, Fourquet A, Schinagl D, Oei B, Rodenhuis CC, Horiot J, Struikmans H, Van Limbergen E, Kirova Y, Elkhuizen P, Bongartz R, Miralbell R, Morgan DAL, Dubois J, Remouchamps V, Mirimanoff R, Hart G, Collette S, Collette L, Bartelink H, for the European Organisation for Research and Treatment of Cancer, Radiation Oncology and Breast Cancer Groups. Prognostic Factors for Local Control in Breast Cancer After Long-term Follow-up in the EORTC Boost vs No Boost TrialA Randomized Clinical Trial. JAMA Oncol. 2017;3(1):42-48. doi:10.1001/jamaoncol.2016.3031