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

Bremer, Troy ; Whitworth, Pat W ; Patel, Rakesh ; Savala, Jess ; Barry, Todd ; Lyle, Stephen ; Leesman, Glen ; Linke, Steven P ; Jirström, Karin LU orcid and Zhou, Wenjing , et al. (2018) In Clinical cancer research : an official journal of the American Association for Cancer Research 24(23). p.5895-5901
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Adult, Aged, Biomarkers, Tumor, Breast Neoplasms/diagnosis, Carcinoma, Intraductal, Noninfiltrating/diagnosis, Combined Modality Therapy, Female, Humans, Middle Aged, Neoplasm Grading, Neoplasm Recurrence, Local, Prognosis, Proportional Hazards Models, Treatment Outcome, Tumor Burden
in
Clinical cancer research : an official journal of the American Association for Cancer Research
volume
24
issue
23
pages
5895 - 5901
publisher
American Association for Cancer Research
external identifiers
  • scopus:85053419668
  • pmid:30054280
ISSN
1078-0432
DOI
10.1158/1078-0432.CCR-18-0842
language
English
LU publication?
yes
additional info
©2018 American Association for Cancer Research.
id
75ddae82-2d1d-487e-be51-2386a5b232e9
date added to LUP
2023-09-13 07:27:22
date last changed
2024-04-20 03:08:26
@article{75ddae82-2d1d-487e-be51-2386a5b232e9,
  abstract     = {{<p>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).</p><p>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.</p><p>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.</p><p>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.</p>}},
  author       = {{Bremer, Troy and Whitworth, Pat W and Patel, Rakesh and Savala, Jess and Barry, Todd and Lyle, Stephen and Leesman, Glen and Linke, Steven P and Jirström, Karin and Zhou, Wenjing and Amini, Rose-Marie and Wärnberg, Fredrik}},
  issn         = {{1078-0432}},
  keywords     = {{Adult; Aged; Biomarkers, Tumor; Breast Neoplasms/diagnosis; Carcinoma, Intraductal, Noninfiltrating/diagnosis; Combined Modality Therapy; Female; Humans; Middle Aged; Neoplasm Grading; Neoplasm Recurrence, Local; Prognosis; Proportional Hazards Models; Treatment Outcome; Tumor Burden}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{23}},
  pages        = {{5895--5901}},
  publisher    = {{American Association for Cancer Research}},
  series       = {{Clinical cancer research : an official journal of the American Association for Cancer Research}},
  title        = {{A Biological Signature for Breast Ductal Carcinoma In Situ to Predict Radiotherapy Benefit and Assess Recurrence Risk}},
  url          = {{http://dx.doi.org/10.1158/1078-0432.CCR-18-0842}},
  doi          = {{10.1158/1078-0432.CCR-18-0842}},
  volume       = {{24}},
  year         = {{2018}},
}