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Molecular Pathology: Sabine Linn

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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

Links

Protocols

Inaugural lecture (Dutch version)

Co-workers

de Boo, Leonora

Leonora de Boo

Ph.D. Student

Experience

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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Bootsma, Sanne

Sanne Bootsma, BSc

Master Student

Experience

I am Sanne Bootsma, a medical student at the University of Amsterdam, currently in the 6th (and last) year of my studies. I will join the group of Sabine Linn for an internship of 6 months.
During these months I will be working on the PARADIGM (PAtients with bReast cAncer DIaGnosed preMenopausally) project, under the supervision of Gwen Dackus.

 

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Gwen Dackus, M.D.

Ph.D. Student

Experience

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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Kruger, Dinja

Dinja Kruger, MD

Ph.D. Student

Experience

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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Mark Opdam, BSc

Technician

Experience

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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Annelot van Rossum, M.D.

Ph.D. Student

Experience

After graduating medical school in 2012 I worked at the Netherlands Cancer Institute as a senior house officer in internal medicine for one year. There I decided I wanted to do research as a next step. The coming years I will be focusing on biomarkers in therapy resistance in breast cancer, concerning both hormonal therapy and chemotherapy.

 

 

 

 

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Experience

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Key publications View All Publications

  • Use of 70-gene signature to predict prognosis of patients with node-negative breast cancer: a prospective community-based feasibility study (RASTER)

    (2007) Lancet Oncol. 8:1079-1087.

    Bueno-de-Mesquita JM, van Harten WH, Retel VP, van't Veer LJ, van Dam FS, Karsenberg K, Douma KF, van Tinteren H, Peterse JL, Wesseling et al.

    Link to PubMed
  • An aCGH classifier derived from BRCA1-mutated breast cancer and benefit of high-dose platinum-based chemotherapy in HER2-negative breast cancer patients

    (2011) Ann Oncol. 22: 1561-70

    Vollebergh MA, Lips EH, Nederlof PM, Wessels LF, Schmidt MK, van Beers EH, Cornelissen S, Holtkamp M, Froklage FE, de Vries EG, Schrama et al.

    Link to PubMed
 
 

Recent publications View All Publications

  • Neoadjuvant Therapy for Breast Cancer: Established Concepts and Emerging Strategies

    (2017) Drugs. Aug;77(12):1313-1336. doi: 10.1007/s40265-017-0774-5. Review

    Steenbruggen TG, van Ramshorst MS, Kok M, Linn SC, Smorenburg CH, Sonke GS

    Link to PubMed
  • Stimulation of the ovaries in women with breast cancer undergoing fertility preservation: Alternative versus standard stimulation protocols; the study protocol of the STIM-trial

    (2017) Contemp Clin Trials. Jul 11;61:96-100. doi: 10.1016/j.cct.2017.07.009.

    Dahhan T, Balkenende EME, Beerendonk CCM, Fleischer K, Stoop D, Bos AME, Lambalk CB, Schats R, van Golde RJT, Schipper I, Louwé LA, ...

    Link to PubMed
 

Contact

  • Office manager

    Suzanne Romijn

  • E-mail

    s.romijn@nki.nl

  • Telephone Number

    +31 20 512 9168

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