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PMID: 19720911 Published · ppublish English Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Prediction of local recurrence, distant metastases, and death after breast-conserving therapy in early-stage invasive breast cancer using a five-biomarker panel.

Millar EK, Graham PH, O'Toole SA, McNeil CM, Browne L, Morey AL, Eggleton S, Beretov J, Theocharous C, Capp A, Nasser E, Kearsley JH, Delaney G, Papadatos G, Fox C, Sutherland RL

Abstract

To determine the clinical utility of intrinsic molecular phenotype after breast-conserving therapy (BCT) with lumpectomy and whole-breast irradiation with or without a cavity boost. Four hundred ninety-eight patients with invasive breast cancer were enrolled into a randomized trial of BCT with or without a tumor bed radiation boost. Tumors were classified by intrinsic molecular phenotype as luminal A or B, HER-2, basal-like, or unclassified using a five-biomarker panel: estrogen receptor, progesterone receptor, HER-2, CK5/6, and epidermal growth factor receptor. Kaplan-Meier and Cox proportional hazards methodology were used to ascertain relationships to ipsilateral breast tumor recurrence (IBTR), locoregional recurrence (LRR), distant disease-free survival (DDFS), and death from breast cancer. Median follow-up was 84 months. Three hundred ninety-four patients were classified as luminal A, 23 were luminal B, 52 were basal, 13 were HER-2, and 16 were unclassified. There were 24 IBTR (4.8%), 35 LRR (7%), 47 distant metastases (9.4%), and 37 breast cancer deaths (7.4%). The overall 5-year disease-free rates for the whole cohort were: IBTR 97.4%, LRR 95.6%, DDFS 92.9%, and breast cancer-specific death 96.3%. A significant difference was observed for survival between subtypes for LRR (P = .012), DDFS (P = .0035), and breast cancer-specific death (P = .0482), but not for IBTR (P = .346). The 5-year and 10-year survival rates varied according to molecular subtype. Although this approach provides additional information to predict time to IBTR, LRR, DDFS, and death from breast cancer, its predictive power is less than that of traditional pathologic indices. This information may be useful in discussing outcomes and planning management with patients after BCT.

MeSH Terms
Adult Aged Aged, 80 and over Biomarkers, Tumor/genetics,metabolism Breast Neoplasms/genetics,metabolism,therapy Combined Modality Therapy ErbB Receptors/metabolism Female Humans Immunohistochemistry In Situ Hybridization, Fluorescence Kaplan-Meier Estimate Keratin-5/metabolism Keratin-6/metabolism Middle Aged Neoplasm Invasiveness Neoplasm Metastasis Neoplasm Recurrence, Local Neoplasm Staging Predictive Value of Tests Prognosis Receptor, ErbB-2/genetics,metabolism Receptors, Estrogen/metabolism Receptors, Progesterone/metabolism Young Adult
Chemicals
Biomarkers, Tumor Keratin-5 Keratin-6 Receptors, Estrogen Receptors, Progesterone ErbB Receptors Receptor, ErbB-2
Authors & Affiliations
16 authors, click to expand affiliations / ORCID
Millar Ewan K A
Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia. e.millar@garvan.org.au
Graham Peter H
O'Toole Sandra A
McNeil Catriona M
Browne Lois
Morey Adrienne L
Eggleton Sarah
Beretov Julia
Theocharous Constantine
Capp Anne
Nasser Elias
Kearsley John H
Delaney Geoff
Papadatos George
Fox Christopher
Sutherland Robert L
Article Info
Journal
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Abbr.
J Clin Oncol
ISSN
1527-7755
Published
2009-10-01
Epub
2009-00-31
Pages
4701-8
Language
English
Region
United States
NLM ID
8309333
Subset
IM
Databases
ClinicalTrials.gov
NCT00138814
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