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

Abstract

PURPOSE:

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.

PATIENTS AND METHODS:

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.

RESULTS:

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).

CONCLUSION:

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.

• Authors: Ewan K A Millar, Peter H Graham, Sandra A O'Toole, Catriona M McNeil, Lois Browne, Adrienne L Morey, Sarah Eggleton, Julia Beretov, Constantine Theocharous, Anne Capp, Elias Nasser, John H Kearsley, Geoff Delaney, George Papadatos, Christopher Fox, Robert L Sutherland
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 27 Issue 28 Pg. 4701-8 (Oct 01 2009) ISSN: 1527-7755 [Electronic] United States
• PMID: 19720911 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Keratin-5
• Keratin-6
• Receptors, Estrogen
• Receptors, Progesterone
• ErbB Receptors
• Receptor, ErbB-2

Topics

• 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