A Biological Signature for Breast Ductal Carcinoma In Situ to Predict Radiotherapy Benefit and Assess Recurrence Risk.

Abstract

PURPOSE:

Ductal carcinoma in situ (DCIS) patients and their physicians currently face challenging treatment decisions with limited information about the individual's subsequent breast cancer risk or treatment benefit. The DCISionRT biological signature developed in this study provides recurrence risk and predicts radiotherapy (RT) benefit for DCIS patients following breast-conserving surgery (BCS).

EXPERIMENTAL DESIGN:

A biological signature that calculates an individualized Decision Score (DS) was developed and cross-validated in 526 DCIS patients treated with BCS ± RT. The relationship was assessed between DS and 10-year risk of invasive breast cancer (IBC) or any ipsilateral breast event (IBE), including IBC or DCIS. RT benefit was evaluated by risk group and as a function of DS.

RESULTS:

The DS was significantly associated with IBC and IBE risk, HR (per 5 units) of 4.2 and 3.1, respectively. For patients treated without RT, DS identified a Low Group with 10-year IBC risk of 4% (7% IBE) and an Elevated Risk Group with IBC risk of 15% (23% IBE). In analysis of DS and RT by group, the Elevated Risk Group received significant RT benefit, HR of 0.3 for IBC and IBE. In a clinicopathologically low-risk subset, DS reclassified 42% of patients into the Elevated Risk Group. In an interaction analysis of DS and RT, patients with elevated DS had significant RT benefit over baseline.

CONCLUSIONS:

The DS was prognostic for risk and predicted RT benefit for DCIS patients. DS identified a clinically meaningful low-risk group and a group with elevated 10-year risks that received substantial RT benefit over baseline.

• Authors: Troy Bremer, Pat W Whitworth, Rakesh Patel, Jess Savala, Todd Barry, Stephen Lyle, Glen Leesman, Steven P Linke, Karin Jirström, Wenjing Zhou, Rose-Marie Amini, Fredrik Wärnberg
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 24 Issue 23 Pg. 5895-5901 (12 01 2018) ISSN: 1557-3265 [Electronic] United States
• PMID: 30054280 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2018 American Association for Cancer Research.

Chemical References

• Biomarkers, Tumor

Topics

• Adult
• Aged
• Biomarkers, Tumor
• Breast Neoplasms (diagnosis, mortality, radiotherapy)
• Carcinoma, Intraductal, Noninfiltrating (diagnosis, mortality, radiotherapy)
• Combined Modality Therapy
• Female
• Humans
• Middle Aged
• Neoplasm Grading
• Neoplasm Recurrence, Local
• Prognosis
• Proportional Hazards Models
• Treatment Outcome
• Tumor Burden