Predictors of Distant Metastases in Triple-Negative Breast Cancer Without Pathologic Complete Response After Neoadjuvant Chemotherapy

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William R. KennedyDepartment of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri;

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Christopher TricaricoDepartment of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri;

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Prashant GabaniDepartment of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri;

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Ashley A. WeinerDepartment of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina; and

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Michael B. AltmanDepartment of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri;

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Laura L. OchoaDepartment of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri;

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Maria A. ThomasDepartment of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri;

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Julie A. MargenthalerDepartment of Surgery,

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Souzan SanatiDepartment of Pathology, and

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Lindsay L. PetersonDivision of Oncology, Washington University School of Medicine, St. Louis, Missouri.

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Cynthia X. MaDivision of Oncology, Washington University School of Medicine, St. Louis, Missouri.

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Foluso O. AdemuyiwaDivision of Oncology, Washington University School of Medicine, St. Louis, Missouri.

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Imran ZoberiDepartment of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri;

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Background: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) for triple-negative breast cancer (TNBC) predicts decreased distant metastasis. However, most patients do not experience pCR, and other risk factors for distant metastasis after NAC are poorly characterized. This study investigated factors predictive of distant metastasis in TNBC without pCR after NAC. Methods: Women with TNBC treated with NAC, surgery, and radiation therapy in 2000 through 2013 were reviewed. Freedom from distant metastasis (FFDM) was compared between patients with and without pCR using the Kaplan-Meier method. In patients without pCR, univariate and multivariable Cox analyses were used to determine factors predictive of distant metastasis. Results: We identified 153 patients with median follow-up of 4.0 years (range, 0.5–14.0 years). After NAC, 108 had residual disease (pCR, 29%). Five-year FFDM was 98% and 55% in patients with and without pCR, respectively (P<.001). Factors independently predicting FFDM in patients without pCR were pathologic nodal positivity (hazard ratio, 3.08; 95% CI, 1.54–6.14; P=.001) and lymphovascular space invasion (hazard ratio, 1.91; 95% CI, 1.07–3.43; P=.030). Patients with a greater number of factors had worse FFDM; 5-year FFDM was 76.5% for patients with no factors (n=38) versus 54.9% and 27.5% for patients with 1 (n=44) and 2 factors (n=26), respectively (P<.001). Conclusions: Lack of pCR after NAC resulted in worse overall survival and FFDM, despite trimodality therapy. In patients with residual disease after NAC, pathologic lymph node positivity and lymphovascular space invasion predicted worse FFDM.

Submitted April 10, 2019; accepted for October 3, 2019.

Author contributions: All authors listed contributed significantly to warrant authorship of the present work.

Disclosures: The authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Correspondence: Imran Zoberi, MD, Department of Radiation Oncology, Center for Advanced Medicine, Washington University School of Medicine, 4921 Parkview Place, Lower Level, St. Louis, MO 63110. Email: izoberi@wustl.edu
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