Jonas Bergh's Group

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Our research aims to identify the best breast cancer treatment for each individual based on analyses of prognostic and treatment predictive markers, and also by identifying mechanisms implicated in metastasis. Based on our results and studies by others we carry out randomized studies in the adjuvant, neoadjuvant (including predefined switch-strategies) and metastatic setting and use population based materials  to further explore and verify our working hypotheses.

Breast cancer is the most common malignancy in women, the global incidence has increased almost threefold during the last 30 years and the estimated annual incidence in 2012 was 1.67 million with rapid increases in Asia. Some of the therapy options have been investigated in the adjuvant setting resulting in a 20-40% drop in the risk of dying from breast cancer by reducing micrometastases, extrapolated from clinical studies and population based data, but the results in the metastatic setting have not improved to the same extent. It has been taken for granted that metastatic breast cancer should be characterized by the same biomarker/mutation profile as the matching primary tumour, despite lack of proper data. This may have contributed to worse outcome in the relapse situation, while therapy choices were made on the primary cancer characteristics.

Our biomarker and sequencing analyses of both the primary cancer and the corresponding relapse in the same individual have shown that metastatic breast cancer is frequently characterized by different biomarker and mutation profile compared with the matching primary breast cancer. Studies by us and others have resulted in that biopsies from recurrences are now recommended in international guidelines (ASCO: http://www.breastcancer. org/research-news/guidelinesissued-on-biomarkers-for-mets). To address the complex seeding and spreading patterns in breast cancer, we perform evolutionary analyses using exome-sequencing data of matched primary breast cancer/local relapses and metastatic lesions. Our research also focuses on gene expression analyses, including studies of different immune related gene signatures. In a collaboration project we make use of the novel Cellular Thermal Shift Assay (CETSA) for drug target engagement analyses, aiming to adapt new strategies for drug development and monitoring of used breast cancer drugs and therapeutic efficacy in breast cancer.

Our clinical studies aim to predict the response and resistance to different treatment modalities by performing molecular characterization on biopsies and blood. Further, the aim is to carry out studies of pharmacokinetics with the utilization of individual drug dose adaptions based on recorded toxicities. Present standard dosing of cytostatic aiming at a similar dose for each individual based on body surface calculations is not well correlated with how the patient metabolizes and excretes cytostatics, accordingly resulting in underdosing and overdosing.

For future breast cancer treatment strategies, better understanding of the individual breast cancer biology and markers/genetic-clonal alterations during tumour progression will be required in order to more readily match the right treatment to the right patient in optimized dosage.

Research teams

RESEARCH TEAM KENNY RODRIGUEZ-WALLBERG

Infertility as sequela of cancer treatment has a recognized negative impact in quality of survival and performance of procedures aimed at fertility preservation are thus increasing in the population of young patients with cancer. My clinical research projects aim at evaluate and increase the safety and efficacy of fertility preservation in patients. My experimental research is conducted at the Laboratory of Translational Fertility Preservation at Cancer Center Karolinska and it is oriented to the investigation of gonadal damage due to cancer treatment.

Group members

Jonas Bergh, Professor, Group leader
Susanne Agartz, Lab Engineer
Amandine Anastácio, PhD, Postdoc

Helen Eriksson, Personal Administrator
Louise Eriksson-Bergman, MD, PhD

Claudette Falato, MD, PhD student
Theodoros Foukakis, MD, Associate Professor
Karthik Govindasamy Muralidharan, MSc, PhD student
Xia Hao, MSc, PhD student

Johan Hartman, MD, Associate Professor
Thomas Hatschek, MD, Associate Professor
Elham Hedayati, MD, Postdoc
Gry Johansen, MD, PhD student
Luisa Kessler, MD, PhD student

Johanna Klinge, PhD, Research Engineer
Elisabet Lidbrink, MD, PhD
Arian Lundberg, PhD student

John Lövrot, Bioinformatician
Ran Ma, PhD
Anna Marklund, MD, PhD student
Alexios Matikas, MD, Postdoc
Antroula Papakonstantinou, MD, PhD student
Stephanie Robertson, MD, PhD student

Per Rydberg, PhD, Researcher
Emmanouil Sifakis, PhD, Bioinformatician
Gustav Stålhammar, MD, PhD student

Nick Tobin, PhD, Assistant Professor
Ikram Ullah, PhD, Bioinformatician

Lisa Viberg, Research Coordinator
Birgitta Wallberg, MD, PhD

Nils Wilking, MD, Associate Professor
Ulla Wilking, PhD, Postdoc
Kenny Rodriguez-Wallberg, MD, Associate Professor
Ioannis Zerdes, MD, PhD student

Selected publications

Complete sequencing of the p53 gene provides prognostic information in breast cancer patients, particularly in relation to adjuvant systemic therapy and radiotherapy.
Bergh J, Norberg T, Sjögren S, Lindgren A, Holmberg L
Nat. Med. 1995 Oct;1(10):1029-34

Positron emission tomography studies in patients with locally advanced and/or metastatic breast cancer: a method for early therapy evaluation?
Jansson T, Westlin J, Ahlström H, Lilja A, Långström B, Bergh J
J. Clin. Oncol. 1995 Jun;13(6):1470-7

Tailored fluorouracil, epirubicin, and cyclophosphamide compared with marrow-supported high-dose chemotherapy as adjuvant treatment for high-risk breast cancer: a randomised trial. Scandinavian Breast Group 9401 study.
Bergh J, Wiklund T, Erikstein B, Lidbrink E, Lindman H, Malmström P, et al
Lancet 2000 Oct;356(9239):1384-91

Growth-inhibitory and tumor- suppressive functions of p53 depend on its repression of CD44 expression.
Godar S, Ince T, Bell G, Feldser D, Donaher J, Bergh J, et al
Cell 2008 Jul;134(1):62-73

TP53 status for prediction of sensitivity to taxane versus non-taxane neoadjuvant chemotherapy in breast cancer (EORTC 10994/BIG 1-00): a randomised phase 3 trial.
Bonnefoi H, Piccart M, Bogaerts J, Mauriac L, Fumoleau P, Brain E, et al
Lancet Oncol. 2011 Jun;12(6):527-39

Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials.
, Peto R, Davies C, Godwin J, Gray R, Pan H, et al
Lancet 2012 Feb;379(9814):432-44

Clinically used breast cancer markers such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 are unstable throughout tumor progression.
Lindström L, Karlsson E, Wilking U, Johansson U, Hartman J, Lidbrink E, et al
J. Clin. Oncol. 2012 Jul;30(21):2601-8

Thyroid hormone inactivation in gastrointestinal stromal tumors.
Foukakis T, Lövrot J, Bergh J
N. Engl. J. Med. 2014 Jul;371(1):84-5

Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials.

Lancet 2015 Oct;386(10001):1353-1361

Effect of Tailored Dose-Dense Chemotherapy vs Standard 3-Weekly Adjuvant Chemotherapy on Recurrence-Free Survival Among Women With High-Risk Early Breast Cancer: A Randomized Clinical Trial.
Foukakis T, von Minckwitz G, Bengtsson N, Brandberg Y, Wallberg B, Fornander T, et al
JAMA 2016 11;316(18):1888-1896

Full list of publications 2016-12-06