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Original Investigation
January 2017

Prognostic Factors for Local Control in Breast Cancer After Long-term Follow-up in the EORTC Boost vs No Boost TrialA Randomized Clinical Trial

Author Affiliations
  • 1Department of Radiation Oncology, Clinique des Grangettes, Geneva, Switzerland
  • 2Department of Biometrics, the Netherlands Cancer Institute, Amsterdam, Netherlands
  • 3Department of Radiation Oncology, Centre Georges-François Leclerc, Dijon, France
  • 4Department of Radiation Oncology, Radboud university medical center, Nijmegen, Netherlands
  • 5Department of Radiation Oncology, University Hospitals of Leuven, Leuven, Belgium
  • 6Department of Radiation Oncology, Institut Curie, Paris, France
  • 7Department of Radiation Oncology, Institute Verbeeten, Tilburg, Netherlands
  • 8Department of Radiation Oncology, Medical Center Utrecht, Utrecht, Netherlands
  • 9Department of Radiation Oncology, Clinique de Genolier, Genolier, Switzerland
  • 10Department of Radiation Oncology, the Netherlands Cancer Institute, Amsterdam, Netherlands
  • 11Department of Radiation Oncology, Universitaetsklinikum Köln, Köln, Germany
  • 12Division of Radiation Oncology, Hôpitaux Universitaires de Genève, Geneva, Switzerland
  • 13Department of Clinical Oncology, Nottingham University Hospitals NHS Trust, Nottingham, UK
  • 14Institut Régional du Cancer Montpellier, Montpellier, France
  • 15Department of Radiotherapy, Clinique et Maternité Sainte Elisabeth, Namur, Belgium
  • 16Department of Radiotherapy, Clinique La Source, Lausanne, Switzerland
  • 17EORTC Headquarters, Brussels, Belgium
JAMA Oncol. 2017;3(1):42-48. doi:10.1001/jamaoncol.2016.3031
Key Points

Question  What is the long-term impact of prognostic factors on ipsilateral breast tumor recurrence (IBTR) in patients treated with breast-conserving therapy?

Findings  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.

Meaning  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.


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.

Trial Registration  clinicaltrials.gov Identifier: NCT02295033