Originally published as JCO Early Release 10.1200/JCO.2008.21.7075 on August 31 2009

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Prediction of Local Recurrence, Distant Metastases, and Death After Breast-Conserving Therapy in Early-Stage Invasive Breast Cancer Using a Five-Biomarker Panel

From the Cancer Research Program, Garvan Institute of Medical Research, and Department of Pathology (SydPath), St Vincent's Hospital, Darlinghurst; Department of Anatomical Pathology, South Eastern Area Laboratory Service, and Department of Radiation Oncology, Cancer Care Centre, St George Hospital, Kogarah; Department of Medical Oncology, University of Sydney, Westmead Hospital, Westmead; Department of Radiation Oncology, Liverpool Hospital, Liverpool; Department of Radiation Oncology, Wollongong Hospital, Wollongong; St Vincent's Clinical School, University of New South Wales, and University of Western Sydney, Sydney; and Department of Anatomical Pathology, Royal Prince Alfred Hospital, Camperdown, Australia.

Corresponding author: Ewan K.A. Millar, MD, Cancer Research Program, Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, New South Wales 2010, Australia; e-mail: e.millar{at}garvan.org.au.

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.

Supported by grants from the National Health and Medical Research Council of Australia, the Cancer Institute New South Wales, the Petre Foundation, and the R.T. Hall Trust.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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