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Molecular Pathology: Sabine Linn


Sabine Linn, Ph.D. M.D. professorGroupleader

About Sabine Linn

Research interest: Biomarker research

I have a long-standing interest in mechanisms of anticancer drug resistance and sensitivity, and how to translate these fundamental insights into clinically meaningful diagnostic tests in order to deliver personalized medicine.
Although breast cancer survival has improved substantially over the past decade, still 1 out of 4 women die of the disease. In order to further improve breast cancer survival better adjuvant systemic therapies are needed. For this, we need predictive biomarkers that tell us how to treat a particular patient. In addition, overtreatment, especially considering adjuvant systemic therapy, should be reduced.  For this we need prognostic biomarkers that tell us who should receive additional systemic therapy after locoregional therapy for breast cancer.
I am a medical oncologist specialized in breast cancer and have three major research lines: 1) Diagnostics and therapeutics for BRCAness in breast cancer, 2) diagnostics and therapeutics for endocrine therapy resistance in breast cancer, 3) prognostic tests to reduce overtreatment of breast cancer patients.

Together with my group I have made important contributions to the field of multidrug resistance, and to the field of gene expression profiling, including the introduction of the MammaPrint® prognostic gene expression classifier into daily clinical practice. I am principle investigator of several multicenter randomized clinical trials in early breast cancer in the Netherlands (e.g. RASTER study (ISRCTN71917916), MATADOR study (ISRCTN61893718), TEAM IIb study (ISRCTN17633610)). Over 2,000 breast cancer patients have been accrued onto those trials. Fresh frozen or RNAlater preserved primary breast cancer tissue is available for over 1,000 patients with clinical follow-up data and can be used to develop predictive and prognostic tests for personalized medicine.

The NKI-AVL has excellent facilities to support these studies, including a DNA microarray and next-generation sequencing facility, a surgical pathology department with a large tissue bank, an internationally recognized datacenter, an encoded patient registry for clinical research purposes, animal pathology, and a large animal facility. Since 1984, frozen tissue is available for virtually all primary breast cancers treated at the NKI-AVL at the Department of Pathology. Clinical follow-up data of these patients has been stored in a coded database. Most of these patients have been treated in the context of a clinical trial.

The research in the Linn lab is supported by grants from the Dutch Cancer Society, A Sister's Hope, BBMRI, Pink Ribbon, NWO-ZonMw, TI Pharma, Life Sciences Center Amsterdam (LSCA) Validation Fund, KWF, the Seventh Framework Programme (FP7) of the European Commission, generous gifts from individuals, and unrestricted research grants from Sanofi-Aventis, Amgen, Pfizer, Roche and AstraZeneca.


Former colleagues Sabine Linn

Inaugural lecture (Dutch version)




de Boo, Leonora

Leonora de Boo

Ph.D. Student


In September 2017 I interrupted my residency IN internal medicine to join the research group of Sabine Linn (Dept ofMolecular Pathology). Understanding the behavior of cancer and the effect of different treatment modalities are my interests and I strive for expanding knowledge in this field.

As a PhD student my main focus is to evaluate predictive biomarkers in breast cancer which may in the end lead to individualized therapy. One of the projects I will focus on is the Triple-B study, a biomarker discovery, randomized phase IIb strial with carboplatin-cyclophosphamide versus paclitaxel with or without atezolizumab as first-line treatment in advanced Tiple negative breast cancer.'  

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Dactus, Gwen.jpg

Gwen Dackus, M.D.

Ph.D. Student


After finishing my medical training I joined the lab of Sabine Linn as a PhD student in the spring of 2012.

I work on a collaborative project with the Netherlands Cancer Registry called the Netherlands Breast Cancer Project (NBCP), investigating the presumed equal effectiveness of different drugs in specific breast cancer subtypes.

My main focus is on assessing the true prognosis of very young breast cancer patients by developing a genomic based test that can separate patients with a long-term good prognosis from those patients who have a poor prognosis.

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Jong, Vincent de

Vincent de Jong

Ph.D. Student


After graduating medical school (VUmc) in 2016, I worked as a senior house officer in internal medicine for two years, during which I grew an interest in medical oncology.  

During my PhD, I put most emphasis on the SUBITO-trial, in which intensified Alkylating chemotherapy is compared to conventional therapy extended with one year of PARPi (olaparib) therapy in stage III HER2-negative BRCA1-like breast cancer. Besides the SUBITO-trail I aim to detect associations between genomic profiles and specific outcomes (e.g. metastasis, mortality) of premenopausal women with early-stage breast cancer.

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Kruger, Dinja

Dinja Kruger, MD

Ph.D. Student


After graduating medical school in 2013, I started as a PhD student in the VU University Medical Center at the department of Medical Oncology. Part of this research project is in cooperation with the NKI and therefore, I joined the group of Sabine Linn.

During the upcoming years, I will investigate in postmenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer, whether biomarkers can be identified in the PI3K-Akt-mTOR pathway that predict which patients will benefit from treatment with everolimus and exemestane.


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Opdam, Mark.jpg

Mark Opdam, BSc



I perform most immunostaining for tumors and tissues of interest for the Linn lab. In addition, I contribute to a multitude of projects including the MATADOR trial (ISRCTN61893718).

The aim of this project is to assess whether we can use gene expression profiling to determine the most effective adjuvant chemotherapy for breast cancer patients. In addition, pharmacogenomic analyses will be carried out in this project to correlate chemotherapy toxicity and efficacy with patients' genotypes. The ultimate goal is to contribute knowledge that can be used to individualize therapy.


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Vliek, Sonja

Sonja Vliek

Ph.D. Student


I'm a medical oncologist in training and PhD student since 2016. I coordinate the SUBITO-trial, which compares Intensified Alkylating  chemotherapy to conventional therapy added with one year PARPi (olaparib) in stage III HER2-negative BRCA1-like breast cancer (BC) and the ABC-trial which evaluates the potential efficacy of PARPi (niraparib) in metastatic BRCA1-like BC.

Secondly I'm involved in the neoTN trial (Intensified Alkylating  chemotherapy in BRCA1-like BC), TEAM IIB trial (adjuvant bisphosphonates in postmenopausal women with ER+ early BC), RASTER (observational trial concerning the MammaPrint in early BC) and follow-up and additional analysis of the IKA-tamoxifen trial.

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Key publications View All Publications

  • Immune induction strategies in metastatic triple-negative breast cancer to enhance the sensitivity to PD-1 blockade: the TONIC trial

    (2019) Nat Med. Jun;25(6):920-928. doi: 10.1038/s41591-019-0432-4. Epub 2019 May 13.

    Voorwerk L, Slagter M, Horlings HM, Sikorska K, van de Vijver KK, de Maaker M, Nederlof I, Kluin RJC, Warren S, Ong S, Wiersma TG, Russell NS, Lalezari F, Schouten PC, Bakker NAM, Ketelaars SLC, Peters D, Lange CAH, van Werkhoven E, van Tinteren H, Mandjes IAM, Kemper I, Onderwater S, Chalabi M, Wilgenhof S, Haanen JBAG, Salgado R, de Visser KE, Sonke GS, Wessels LFA, Linn SC, Schumacher TN, Blank CU, Kok M.

    Link to PubMed
  • Neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2 blockade for HER2-positive breast cancer (TRAIN-2): a multicentre, open-label, randomised, phase 3 trial

    (2018) Lancet Oncol. Dec;19(12):1630-1640. doi: 10.1016/S1470-2045(18)30570-9. Epub 2018 Nov 6.

    van Ramshorst MS, van der Voort A, van Werkhoven ED, Mandjes IA, Kemper I, Dezentjé VO, Oving IM, Honkoop AH, Tick LW, van de Wouw AJ, Mandigers CM, van Warmerdam LJ, Wesseling J, Vrancken Peeters MT, Linn SC, Sonke GS; Dutch Breast Cancer Research Group (BOOG).

    Link to PubMed

Recent publications View All Publications

  • POSEIDON Trial Phase 1b Results: Safety, Efficacy and Circulating Tumor DNA Response of the Beta Isoform-Sparing PI3K Inhibitor Taselisib (GDC-0032) Combined with Tamoxifen in Hormone Receptor Positive Metastatic Breast Cancer Patients

    (2019) Clin Cancer Res. Nov 15;25(22):6598-6605. doi: 10.1158/1078-0432.CCR-19-0508. Epub 2019 Aug 22.

    Baird RD, van Rossum AGJ, Oliveira M, Beelen K, Gao M, Schrier M, Mandjes IAM, Garcia-Corbacho J, Vallier AL, Dougall G, van Werkhoven E, Linossi C, Kumar S, van Tinteren H, Callari M, Beddowes E, Perez-Garcia JM, Rosing H, Platte E, Nederlof P, Schot M, de Vries Schultink A, Bernards R, Saura C, Gallagher W, Cortès J, Caldas C, Linn SC.

    Link to PubMed
  • IGF-1R pathway activation as putative biomarker for linsitinib therapy to revert tamoxifen resistance in ER-positive breast cancer

    (2019) Int J Cancer. Sep 6. doi: 10.1002/ijc.32668. [Epub ahead of print]

    Kruger DT, Alexi X, Opdam M, Schuurman K, Voorwerk L, Sanders J, van der Noort V, Boven E, Zwart W, Linn SC

    Link to PubMed


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