Extracapsular tumor spread and the risk of local, axillary and supraclavicular recurrence in node-positive, premenopausal patients with breast cancer.
BACKGROUND
Extracapsular tumor spread (ECS) has been identified as a possible risk factor for breast cancer recurrence, but controversy exists regarding its role in decision making for regional radiotherapy. This study evaluates ECS as a predictor of local, axillary, and supraclavicular recurrence.


METHODS
International Breast Cancer Study Group Trial VI accrued 1475 eligible pre- and perimenopausal women with node-positive breast cancer who were randomly assigned to receive three to nine courses of classical combination chemotherapy with cyclophosphamide, methotrexate, and fluorouracil. ECS status was determined retrospectively in 933 patients based on review of pathology reports. Cumulative incidence and hazard ratios (HRs) were estimated using methods for competing risks analysis. Adjustment factors included treatment group and baseline patient and tumor characteristics. The median follow-up was 14 years.


RESULTS
In univariable analysis, ECS was significantly associated with supraclavicular recurrence (HR = 1.96; 95% confidence interval 1.23-3.13; P = 0.005). HRs for local and axillary recurrence were 1.38 (P = 0.06) and 1.81 (P = 0.11), respectively. Following adjustment for number of lymph node metastases and other baseline prognostic factors, ECS was not significantly associated with any of the three recurrence types studied.


CONCLUSIONS
Our results indicate that the decision for additional regional radiotherapy should not be based solely on the presence of ECS.
Gruber
G
G
Institut für Radiotherapie, Klinik Hirslanden and Swiss Group for Clinical Cancer Research (SAKK), Zurich, Switzerland. Electronic address: guenther.gruber@hirslanden.ch.
Cole
B F
BF
International Breast Cancer Study Group Statistical Center, Boston, MA and Department of Mathematics and Statistics, University of Vermont, Burlington, USA.
Castiglione-Gertsch
M
M
International Breast Cancer Study Group (IBCSG) Coordinating Center, Bern, Switzerland.
Holmberg
S B
SB
Department of Surgery, Sahlgrenska University Hospital, Göteborg, Sweden.
Lindtner
J
J
The Institute of Oncology, Ljubljana, Slovenia.
Golouh
R
R
The Institute of Oncology, Ljubljana, Slovenia.
Collins
J
J
Department of Surgery, The Royal Melbourne Hospital, Melbourne, Australia.
Crivellari
D
D
Centro di Riferimento Oncologico, Aviano, Italy.
Thürlimann
B
B
Senology Center of Eastern Switzerland, Kantonsspital and SAKK, St Gallen, Switzerland.
Simoncini
E
E
Oncologia Medica-Spedali Civili, Brescia, Italy.
Fey
M F
MF
Department of Medical Oncology, Inselspital and SAKK, Bern, Switzerland.
Gelber
R D
RD
IBCSG Statistical Center, Dana-Farber Cancer Institute, Frontier Science and Technology Research Foundation, Harvard School of Public Health, Boston, MA, USA.
Coates
A S
AS
International Breast Cancer Study Group, Bern, Switzerland and University of Sydney, Sydney, Australia.
Price
K N
KN
IBCSG Statistical Center, Frontier Science and Technology Research Foundation, Boston, MA, USA.
Goldhirsch
A
A
Oncology Institute of Southern Switzerland, Lugano, Switzerland and European Institute of Oncology, Milan, Italy.
Viale
G
G
Division of Pathology and Laboratory Medicine, European Institute of Oncology and University of Milan, Milan, Italy.
Gusterson
B A
BA
Division of Cancer Sciences and Molecular Pathology, Faculty of Medicine, Glasgow University, Glasgow, UK.
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000532:radiotherapy; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008727:Methotrexate / Q000008:administration & dosage; D009364:Neoplasm Recurrence, Local / Q000473:pathology*; D009367:Neoplasm Staging; D017697:Premenopause; D012189:Retrospective Studies; D016896:Treatment Outcome
D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate