Enabling DCIS subtyping: leveraging foundation models for robust grading and molecular biomarker scoring

npj Breast Cancer, vol. 12

Abstract

Ductal Carcinoma In Situ (DCIS) is a non-obligate precursor of invasive breast cancer. Due to a lack of reliable prognostic markers, nearly all women with DCIS undergo intensive treatment-often unnecessarily. The LORD trial addresses this by offering active surveillance to women with screen-detected, ER-positive, HER2-negative, grade 1 or 2 DCIS, aiming to reduce overtreatment. To support this, we developed a deep learning pipeline based on foundation models to predict grade, ER, and HER2 status directly from H&E-stained digitized pathology slides. Models were trained and tested on a Dutch multicenter dataset (n = 887) and externally validated on a UK dataset (n = 259). On the Dutch data, the models achieved mean AUROCs of 0.90 (ER), 0.84 (HER2), and 0.86 (grade); external validation yielded 0.80, 0.74, and 0.75, respectively. Using these outputs, we stratified patients according to active surveillance criteria, reaching balanced accuracies of 0.81 (Dutch) and 0.64 (UK), with corresponding NPVs of 0.86 and 0.76. Our models generalize across cohorts and reliably predict key biomarkers, supporting the identification of DCIS patients eligible for less aggressive management.

Authors 37

1. S. Doyle

   The Netherlands Cancer Institute · University of Amsterdam

   Affiliation as printed

   Division of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands

   Informatics Institute, University of Amsterdam, Amsterdam, the Netherlands

2. M. A. Oerlemans

   The Netherlands Cancer Institute

   Affiliation as printed

   Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands

   Division of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands

3. J. Brunekreef

   The Netherlands Cancer Institute · University of Amsterdam

   Affiliation as printed

   Division of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands

   Informatics Institute, University of Amsterdam, Amsterdam, the Netherlands

4. E. Marcus

   The Netherlands Cancer Institute · University of Amsterdam

   Affiliation as printed

   Division of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands

   Informatics Institute, University of Amsterdam, Amsterdam, the Netherlands

5. L. Mulder

   The Netherlands Cancer Institute

   Affiliation as printed

   Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands

6. Y. Liu

   The Netherlands Cancer Institute

   Affiliation as printed

   Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands

7. I. Bouybayoune

   King's College London

   Affiliation as printed

   School of Cancer & Pharmaceutical Sciences, King's College London, London, UK

8. E.J. Sawyer

   King's College London

   Affiliation as printed

   King's College London, London, UK

   School of Cancer & Pharmaceutical Sciences, King's College London, London, UK

9. A. M. Thompson

   Baylor College of Medicine

   Affiliation as printed

   Baylor College of Medicine, Houston, TX, USA

   Department of Surgery, Baylor College of Medicine, Houston, TX, USA

10. S. E. Pinder

    King's College London

    Affiliation as printed

    School of Cancer & Pharmaceutical Sciences, King's College London, London, UK

11. Jelle Wesseling Aachen Department of Pathology, Leiden University Medical Center

    Leiden University Medical Center · The Netherlands Cancer Institute

    Affiliation as printed

    Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands

    Department of Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands

    Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands

    Netherlands Cancer Institute, Amsterdam, the Netherlands

12. Alastair M. Thompson

    Baylor College of Medicine

    Affiliation as printed

    Baylor College of Medicine, Houston, TX, USA

    Department of Surgery, Baylor College of Medicine, Houston, TX, USA

13. Serena Nik-Zainal

    University of Cambridge

    Affiliation as printed

    University of Cambridge, Cambridge, UK

14. Elinor J. Sawyer

    King's College London

    Affiliation as printed

    King's College London, London, UK

    School of Cancer & Pharmaceutical Sciences, King's College London, London, UK

15. Helen Davies

    University of Cambridge

    Affiliation as printed

    University of Cambridge, Cambridge, UK

16. Andrew Futreal

    The University of Texas MD Anderson Cancer Center

    Affiliation as printed

    MD Anderson Cancer Center, Houston, TX, USA

17. Nicholas Navin

    The University of Texas MD Anderson Cancer Center

    Affiliation as printed

    MD Anderson Cancer Center, Houston, TX, USA

18. E. Shelley Hwang

    Duke University

    Affiliation as printed

    Duke University School of Medicine, Durham, NC, USA

19. Jos Jonkers

    The Netherlands Cancer Institute

    Affiliation as printed

    Netherlands Cancer Institute, Amsterdam, the Netherlands

20. Jacco van Rheenen

    The Netherlands Cancer Institute

    Affiliation as printed

    Netherlands Cancer Institute, Amsterdam, the Netherlands

21. Fariba Behbod

    University of Kansas Medical Center

    Affiliation as printed

    Kansas University Medical Center, Kansas City, KS, USA

22. Esther H. Lips corresponding

    The Netherlands Cancer Institute

    Affiliation as printed

    Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands. e.lips@nki.nl

    Netherlands Cancer Institute, Amsterdam, the Netherlands

23. Esther H. Lips

    The Netherlands Cancer Institute

    Affiliation as printed

    Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands. e.lips@nki.nl

    Netherlands Cancer Institute, Amsterdam, the Netherlands

24. Marjanka Schmidt

    The Netherlands Cancer Institute

    Affiliation as printed

    Netherlands Cancer Institute, Amsterdam, the Netherlands

25. Lodewyk F.A. Wessels

    The Netherlands Cancer Institute

    Affiliation as printed

    Netherlands Cancer Institute, Amsterdam, the Netherlands

26. Daniel Rea

    University of Birmingham

    Affiliation as printed

    University of Birmingham, Birmingham, UK

27. Proteeti Bhattacharjee

    The Netherlands Cancer Institute

    Affiliation as printed

    Netherlands Cancer Institute, Amsterdam, the Netherlands

28. Hilary Stobart
    Affiliation as printed

    Independent Cancer Patients' Voice, London, UK

29. Deborah Collyar
    Affiliation as printed

    Patient Advocates in Research, New York, NY, USA

30. Donna Pinto
    Affiliation as printed

    DCIS411, Houston, TX, USA

31. Ellen Verschuur

    Borstkankervereniging Nederland

    Affiliation as printed

    Borstkanker Vereniging Nederland, Utrecht, the Netherlands

32. Marja van Oirsouw

    Borstkankervereniging Nederland

    Affiliation as printed

    Borstkanker Vereniging Nederland, Utrecht, the Netherlands

33. Nicholas E. Navin

    The University of Texas MD Anderson Cancer Center

    Affiliation as printed

    MD Anderson Cancer Center, Houston, TX, USA

34. C. I. Sánchez

    University of Amsterdam

    Affiliation as printed

    Informatics Institute, University of Amsterdam, Amsterdam, the Netherlands

35. J. Teuwen

    Radboud University Nijmegen · The Netherlands Cancer Institute

    Affiliation as printed

    Department of Medical Imaging, Radboud University Nijmegen, Nijmegen, the Netherlands

    Division of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands

36. J. Wesseling Aachen Department of Pathology, Leiden University Medical Center

    Leiden University Medical Center · The Netherlands Cancer Institute

    Affiliation as printed

    Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands

    Department of Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands

    Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands

    Netherlands Cancer Institute, Amsterdam, the Netherlands

37. EH Lips

    The Netherlands Cancer Institute

    Affiliation as printed

    Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands. e.lips@nki.nl

    Netherlands Cancer Institute, Amsterdam, the Netherlands