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Prognostic Biomarkers in Triple-Negative Breast Cancer Treated With Adjuvant Doxorubicin/Cyclophosphamide


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As reported in the Journal of Clinical Oncology by Priyanka Sharma, MD, and colleagues, biomarker analysis among women with triple-negative breast cancer treated with adjuvant doxorubicin/cyclophosphamide in the SWOG 9313c trial has confirmed a 44-gene DNA damage immune response signature and density of stromal tumor-infiltrating lymphocytes (sTIL) as prognostic markers.

Priyanka Sharma, MD

Priyanka Sharma, MD

Study Details

In the trial, patients with early-stage, high-risk, node-negative or node-positive disease were randomly assigned to one of two equivalent dose schedules of adjuvant doxorubicin/cyclophosphamide given sequentially or concurrently. No significant differences in progression-free or overall survival were observed between sequential and concurrent groups. The current analysis included 425 women with triple-negative breast cancer; of these, 33% had node-positive disease.

Biomarker Performance

DNA damage immune response was successfully tested in 381 patients (90%); of these, 62% had a positive DNA damage immune response signature. In analysis adjusting for treatment arm, nodal status, and tumor size, DNA damage immune response signature–positive status vs -negative status was associated with improved disease-free survival (hazard ratio [HR] = 0.67, P = .015) and overall survival (HR = 0.61, P = .010); 5-year rates were 79% vs 66% and 86% vs 78%. At 3 years, disease-free survival and overall survival rates in a subgroup of patients with DNA damage immune response positivity and T1c/T2N0 disease were 88% and 94%.

KEY POINTS

  • Positive status on the 44-gene DNA damage immune response signature was associated with improved disease-free and overall survival.
  • sTIL density ≥ 20% was associated with improved disease-free and overall survival.

sTIL density assessment was available for 423 patients (99%); of these, 43% had sTIL density ≥ 20%. In adjusted analysis, sTIL density ≥ 20% vs < 20% was associated with improved disease-free survival (HR = 0.70, P = .026) and overall survival (HR = 0.59, P = .004); 5-year rates were 80% vs 70% and 89% vs 78%.

DNA damage immune response signature score and sTIL density were only moderately correlated, precluding statistical significance for disease-free survival in a model including both markers.

The investigators concluded, “The prognostic role of sTILs and DNA damage immune response in early-stage [triple-negative breast cancer] was confirmed. DNA damage immune response signature conferred improved prognosis in two thirds of patients with [triple-negative breast cancer] treated with adjuvant doxorubicin/cyclophosphamide. DNA damage immune response signature has the potential to stratify outcome and to identify patients with less projected benefit after [adjuvant] chemotherapy.”

Priyanka Sharma, MD, of the Division of Medical Oncology, University of Kansas Medical Center, Westwood, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by grants from the National Cancer Institute and National Clinical Trials Network, an ASCO Advanced Clinical Cancer Research Award, and others. For full disclosures of the study authors, visit jco.ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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