Jonas Bergh's Group
Our research aims to improve breast cancer treatments, without increasing serious treatment related toxcity. We conduct and analyse prospective and randomised clinical studies and perform analyses of prognostic and treatment predictive markers; we analyse/validate these in population derived patient materials in both primary and metastatic breast cancer. We will further develop the strategies with tailored treatments, aiming to identify markers for individualised treatment selections within the concept of ”Precision Medicine”.
Globally, 2.1 million women were estimated to be diagnosed with breast cancer during 2018, the mortality was estimated to be around 626,679 breast cancer deaths in 2018. In Sweden, 10,319 women were diagnosed with breast cancer during 2017, and 1,407 women died from breast cancer in 2018. For Swedish breast cancer patients the survival is among the best in Europe. (Neo)adjuvant therapies and early diagnostics have significantly improved the prognosis. The combination of chemotherapy, endocrine therapy and anti-HER2 therapies results in an at least 50% reduced risk of dying, and there are currently clear indications that immune therapy in addition to standard HER2 therapy appears to have a potential added value primarily in triple negative breast cancer, but also in HER2-positive disease. Patients with metastatic breast cancer have a much worse prognosis and the median surival vary between 1.5-3 years; we have demonstrated that the survival after loco-regional failure of breast cancer has improved over time, especially in younger women.
Our research includes analyses of sequencing data, gene expression data and protein expression, and we investigate how these differ between primary tumours and recurrences. The results are related to various clinical data. Our exome sequencing data show considerable intra-/intermetastasis heterogeneity and alterations over time, supporting our previous findings demonstrating marked discrepancy of ER and PR in primary tumours/metastases. Immune signatures/TILs in tumours seem to be implicated in the effect of chemotherapy. Randomised clinical studies are conducted based on the recent findings. Several prospective randomised studies are conducted, aiming to improve relapse-free survival and overall survival in breast cancer; we evaluate alternatives to /improvements of current standard treatments. Chemotherapy, endocrine therapy and anti-HER2 therapies in different sequences and combinations are used for neoadjuvant and adjuvant treatments, depending on the biology of the disease and the risk of recurrence. Molecular characterisation of biopsies and blood is carried out in the studies, as well as comparisons of individualised doses of drugs based on registered toxicities. There is a major advantage of neoadjuvant treatment compared with adjuvant treatment; patients not responding to treatment can be offered an optional pre- or post-surgical treatment and thus achieve a better outcome; in an ongoing prospective randomised study we have used cross-over strategies in practice. A surrogate marker for neoadjuvant therapy is pathologic complete response (pCR).
The overarching aim of our strategies is to provide the best possible primary treatment aiming for cure, and in the recurrent setting to optimise the applied treatments ad modum precision cancer medicine, for prolonged survival and improved life quality.
Infertility as sequela of cancer treatment has a recognized negative impact in quality of survival and performance of procedures aimed at fertility preservation are increasing in the population of young patients with cancer. My clinical research projects aim to evaluate and increase the safety and efficacy of fertility preservation and to find predictors of success for treatments using assisted reproductive technologies. My experimental research is conducted at our Laboratory of Translational Fertility Preservation at KI and Cancer Center Karolinska and it is oriented to the investigation of gonadal damage due to cancer treatment and ovarian transplantation.
Jonas Bergh, Professor, Group leader
Susanne Agartz, Lab Engineer
Amandine Anastácio, PhD, Postdoc
Aafke Duinmeijer, Student
Helen Eriksson, Personal Administrator
Louise Eriksson-Bergman, MD, PhD
Theodoros Foukakis, MD, PhD, Associate Professor
Johanna Furuhjelm, PhD, Adminstrative Director Cancer Research KI
Alaa Haidar, MD
Xia Hao, MSc, PhD student
Thomas Hatschek, MD, PhD, Associate Professor
Elham Hedayati, MD, PhD
Gry Johansen, MD, PhD student
Luisa Kessler, MD, PhD student
Johanna Klinge, PhD, Research Engineer
Elisabet Lidbrink, MD, PhD
Anna Marklund, MD, PhD student
Alexios Matikas, MD, PhD
Antroula Papakonstantinou, MD, PhD student
Kenny Rodriguez-Wallberg, MD, PhD, Associate Professor
Per Rydberg, PhD, Researcher
Emmanouil Sifakis, PhD, Bioinformatician
Nick Tobin, PhD, Associate Professor
Birgitta Wallberg, MD, PhD
Nils Wilking, MD, PhD, Associate Professor
Ulla Wilking, PhD
Hanjing Xie, MD, PhD, Associate Professor
Ioannis Zerdes, MD, PhD student
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 JE, 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 TA, Bell GW, Feldser D, Donaher JL, 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.
Early Breast Cancer Trialists' Collaborative Group (EBCTCG), Peto R, Davies C, Godwin J, Gray R, Pan HC, Clarke M, Cutter D, Darby S, McGale P, Taylor C, Wang YC, Bergh J, Di Leo A, Albain K, Swain S, Piccart M, Pritchard K.
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 LS, Karlsson E, Wilking UM, Johansson U, Hartman J, Lidbrink EK, et al
J. Clin. Oncol. 2012 Jul;30(21):2601-8
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 NO, Brandberg Y, Wallberg B, Fornander T, et al
JAMA 2016 11;316(18):1888-1896
20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years.
Pan H, Gray R, Braybrooke J, Davies C, Taylor C, McGale P, et al
N. Engl. J. Med. 2017 11;377(19):1836-1846
Evolutionary history of metastatic breast cancer reveals minimal seeding from axillary lymph nodes.
Ullah I, Karthik GM, Alkodsi A, Kjällquist U, Stålhammar G, Lövrot J, et al
J. Clin. Invest. 2018 04;128(4):1355-1370
Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials.
Early Breast Cancer Trialists' Collaborative Group* (EBCTCG)(*Jonas Bergh member of Steering Committee & co-Chairman for EBCTCG & writing commettee.
Lancet, 393:1440-1452, 2019
An HIF-1α/VEGF-A Axis in Cytotoxic T Cells Regulates Tumor Progression.
Palazon A, Tyrakis PA, Macias D, Veliça P, Rundqvist H, Fitzpatrick S, et al
Cancer Cell 2017 11;32(5):669-683.e5
Chemoresistance Evolution in Triple-Negative Breast Cancer Delineated by Single-Cell Sequencing.
Kim C, Gao R, Sei E, Brandt R, Hartman J, Hatschek T, et al
Cell 2018 05;173(4):879-893.e13