Prognostic value of extracapsular tumor spread for locoregional control in premenopausal patients with node-positive breast cancer treated with classical cyclophosphamide, methotrexate, and fluorouracil: long-term observations from International Breast Cancer Study Group Trial VI.

Abstract

PURPOSE:

We sought to determine retrospectively whether extracapsular spread (ECS) might identify a subgroup that could benefit from radiotherapy after mastectomy, especially patients with 1 to 3 positive lymph nodes (LN1-3+).

PATIENTS AND METHODS:

We randomized 1,475 premenopausal women with node-positive breast cancer to three, six, or nine courses of "classical" CMF (cyclophosphamide, methotrexate, and fluorouracil). After a review of all pathology forms, 933 patients (63%) had information on the presence or absence of ECS. ECS was present in 49.5%. The median follow-up was 10 years.

RESULTS:

In univariate analyses, ECS was associated with worse disease-free survival (DFS) and overall survival (OS). In multivariate analyses adjusting for tumor size, vessel invasion, surgery type, and age group, ECS remained significant (DFS: hazard ratio, 1.61; 95% CI, 1.34 to 1.93; P < .0001; OS: 1.67; 95% CI, 1.34 to 2.08; P < .0001). However, ECS was not significant when the number of positive nodes was added. The locoregional failure rate +/- distant failure (LRF +/- distant failure) within 10 years was estimated at 19% (+/- 2%) without ECS, versus 27% (+/- 2%) with ECS. The difference was statistically significant in univariate analyses, but not after adjusting for the number of positive nodes. No independent effect of ECS on DFS, OS, or LRF could be confirmed within the subgroup of 382 patients with LN1-3+ treated with mastectomy without radiotherapy.

CONCLUSION:

Our results do not support an independent prognostic value of ECS, nor its use as an indication for irradiation in premenopausal patients with LN1-3+ treated with classical CMF. However, we could not examine whether extensive ECS is of prognostic importance.

• Authors: Günther Gruber, Marco Bonetti, M Laura Nasi, Karen N Price, Monica Castiglione-Gertsch, Carl-Magnus Rudenstam, Stig B Holmberg, Jurij Lindtner, Rastko Golouh, John Collins, Diana Crivellari, Antonino Carbone, Beat Thürlimann, Edda Simoncini, Martin F Fey, Richard D Gelber, Alan S Coates, Aron Goldhirsch, International Breast Cancer Study Group
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 23 Issue 28 Pg. 7089-97 (Oct 01 2005) ISSN: 0732-183X [Print] United States
• PMID: 16192592 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Cyclophosphamide
• Fluorouracil
• Methotrexate

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, therapeutic use)
• Breast Neoplasms (drug therapy, pathology, radiotherapy)
• Cyclophosphamide (administration & dosage)
• Disease-Free Survival
• Female
• Fluorouracil (administration & dosage)
• Humans
• Lymph Nodes (pathology)
• Lymphatic Metastasis
• Mastectomy
• Methotrexate (administration & dosage)
• Middle Aged
• Neoplasm Invasiveness
• Neoplasm Recurrence, Local
• Neoplasm Staging
• Postmenopause
• Prognosis
• Retrospective Studies