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.
OBJECTIVE
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.


METHODS
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.


METHODS
No further treatment or 16-Gy boost, after BCS and 50-Gy WBI.


METHODS
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
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.


BACKGROUND
clinicaltrials.gov Identifier: NCT02295033.
Department of Radiation Oncology, Clinique des Grangettes, Geneva, Switzerland.
Conny
C
Vrieling
Department of Biometrics, the Netherlands Cancer Institute, Amsterdam, Netherlands.
Erik
E
van Werkhoven
Department of Radiation Oncology, Centre Georges-François Leclerc, Dijon, France.
Philippe
P
Maingon
Department of Radiation Oncology, Radboud university medical center, Nijmegen, Netherlands.
Philip
P
Poortmans
Department of Radiation Oncology, University Hospitals of Leuven, Leuven, Belgium.
Caroline
C
Weltens
Department of Radiation Oncology, Institut Curie, Paris, France.
Alain
A
Fourquet
Department of Radiation Oncology, Radboud university medical center, Nijmegen, Netherlands.
Dominic
D
Schinagl
Department of Radiation Oncology, Institute Verbeeten, Tilburg, Netherlands.
Bing
B
Oei
Department of Radiation Oncology, Medical Center Utrecht, Utrecht, Netherlands.
Carla C
CC
Rodenhuis
Department of Radiation Oncology, Clinique de Genolier, Genolier, Switzerland.
Jean-Claude
JC
Horiot
Department of Radiation Oncology, Medical Center Utrecht, Utrecht, Netherlands.
Henk
H
Struikmans
Department of Radiation Oncology, University Hospitals of Leuven, Leuven, Belgium.
Erik
E
Van Limbergen
Department of Radiation Oncology, Institut Curie, Paris, France.
Youlia
Y
Kirova
Department of Radiation Oncology, the Netherlands Cancer Institute, Amsterdam, Netherlands.
Paula
P
Elkhuizen
Department of Radiation Oncology, Universitaetsklinikum Köln, Köln, Germany.
Rudolf
R
Bongartz
Division of Radiation Oncology, Hôpitaux Universitaires de Genève, Geneva, Switzerland.
Raymond
R
Miralbell
Department of Clinical Oncology, Nottingham University Hospitals NHS Trust, Nottingham, UK.
David A L
DA
Morgan
Institut Régional du Cancer Montpellier, Montpellier, France.
Jean-Bernard
JB
Dubois
Department of Radiotherapy, Clinique et Maternité Sainte Elisabeth, Namur, Belgium.
Vincent
V
Remouchamps
Department of Radiotherapy, Clinique La Source, Lausanne, Switzerland.
René-Olivier
RO
Mirimanoff
Department of Biometrics, the Netherlands Cancer Institute, Amsterdam, Netherlands.
Guus
G
Hart
EORTC Headquarters, Brussels, Belgium.
Sandra
S
Collette
EORTC Headquarters, Brussels, Belgium.
Laurence
L
Collette
Department of Radiation Oncology, the Netherlands Cancer Institute, Amsterdam, Netherlands.
Harry
H
Bartelink
D000328:Adult; D000359:Aftercare; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015412:Mastectomy, Segmental; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000473:pathology*; D009367:Neoplasm Staging; D011379:Prognosis; D018714:Radiotherapy, Adjuvant