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The impact of distinct triple-negative breast cancer subtypes on misdiagnosis and diagnostic delay

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Abstract

Background

Triple-negative breast cancer (TNBC) includes mostly aggressive types of breast cancer with poor prognosis. Due to its growth pattern, misinterpretation in clinical imaging is more frequent than in non-TNBC. As the group of TNBC contains heterogeneous types of tumors, marker expression-based subtypes have recently been established. We analyzed clinical features and false-negative imaging findings that could potentially lead to diagnostic delay within the subtypes.

Methods

An exploratory analysis compared the imaging features across the a priori defined subtypes and related these findings to molecular subtype, disease stage, potential diagnostic delay, and patient outcome.

Results

TNBC cases were categorized into basal-like (BL; 38.6%), mesenchymal-like (ML; 19.9%), luminal androgen receptor (LAR; 28.3%), and immunomodulatory (IM; 13.3%) subtype. In almost every third patient, malignant classification was missed in at least one imaging method. Misclassification in mammogram was more frequent in ML, while benign ultrasound features were reported more often in the BL subtype. Diagnostic delay due to misclassification in imaging led to tumor growth and/or upgrading of the tumor stage in 8.9% of BL tumors, which had the lowest overall survivals. Despite misclassification rate was higher in the ML subtype it showed better outcomes. Misdiagnosis of axillary lymph node metastasis was higher in LAR; however, this subtype showed a higher percentage of affected axillary lymph nodes.

Conclusion

TNBC subtypes have different clinical features, benign appearances, and diagnostic delay, which can lead to tumor stage upgrade. Future clinical studies on TNBC outcomes might consider the confounder of clinical delay in the subtypes.

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Authors and Affiliations

  1. Breast-Center Zurich, Seefeldstrasse 214, 8008, Zurich, Switzerland

    C. Elfgen, C. Tausch & U. Güth

  2. Senology Department, Institute of Gynecology and Obstetrics, University of Witten-Herdecke, Witten, Germany

    C. Elfgen & V. Bjelic-Radisic

  3. Institute of Pathology and Molecular Pathology, University Hospital of Zurich, Zurich, Switzerland

    Z. Varga & L. Moskovszky

  4. Biostatistics Department, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland

    K. Reeve

Authors
  1. C. Elfgen
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  2. Z. Varga
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  3. K. Reeve
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  4. L. Moskovszky
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  5. V. Bjelic-Radisic
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  6. C. Tausch
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  7. U. Güth
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Corresponding author

Correspondence to C. Elfgen.

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All authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the Cantonal Ethics Committee of Zurich, Switzerland (BASEC-No. 2017-00219), and in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Elfgen, C., Varga, Z., Reeve, K. et al. The impact of distinct triple-negative breast cancer subtypes on misdiagnosis and diagnostic delay. Breast Cancer Res Treat 177, 67–75 (2019). https://doi.org/10.1007/s10549-019-05298-6

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  • DOI: https://doi.org/10.1007/s10549-019-05298-6

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