Breast cancer research: Per Karlsson Group

Background

In research and clinical practice, the area of specialty is treatment of breast cancer. Over the years, we have conducted many clinical and translational studies in the area of breast cancer. We were, for example, among those who developed Sweden’s national target and technical guidelines for radiation treatment of breast cancer.

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They are standing in front of a linear accelerator at the Oncology Department, in connection with their work on “integration of biological factors in the treatment plan evaluation in breast cancer radiotherapy.”

• We have published many articles based on our Swedish randomized studies in which patients with breast cancer who have undergone breast-preserving surgery were randomly assigned for radiation treatment or not.
• In collaboration with the International Breast Cancer Study Group (IBCSG), we have also been the Swedish principal investigator (PI) for three major randomized trials (SOFT, TEXT, and SOLE) in which patients with hormone receptor-positive breast cancer were randomly assigned for various endocrine treatment options.
• We have also started quality registers following up BRCA carriers in West Sweden.

Some ongoing research projects

• Development of tumor and stromal gene expression profiles and biomarkers that identify whether breast cancer patient need radiation treatment or not.

We carried out a randomized radiation treatment study, in which 1,178 patients with breast cancer who had undergone breast-preserving surgery were assigned randomly to receive radiation treatment or not. From these patients, we extracted RNA from the tumors and analyzed mRNA expression. We were able to identify a genomic profile for radiation resistance.

By studying the stromal area around the tumor, we have also been able to see that the tumor’s local immune response in terms of various measures, including the number of tumor-infiltrating lymphocytes, affects the local recurrence risk and the radiation treatment effect.

We are now working to develop a gene expression profile and biomarker that identify groups of patients with a “treatment omission profile” — that is, who do not need radiation treatment. Research is also underway to understand the importance of the local immunological response for the radiation effect and how it can be modulated for optimal treatment impact.

• Studies of gene expression profiles and biomarkers that identify patients who are sensitive to radiation induction

We have characterized a cohort of children who, long ago, received low doses of ionizing radiation treatment for benign cutaneous hemangioma. We are now studying what characterizes increased sensitivity for induction of breast cancer.

• Monitoring of BRCA carriers

The cancer genetic counselling clinic that has been in existence since the late 1990s has identified numerous BRCA carriers. At an early stage we initiated a quality register, and monitoring of long-term outcomes is under way.

Co-workers in the projects

Zakaria Einbeigi
Khalil Helou
Erik Holmberg
Anikó Kovacs
Dan Lundstedt
Ella Ittner
Axel Stenmark-Tullberg
Toshima Parris
Mats Perman
Elisabeth Werner-Rönnerman
Fredrik Wärnberg
Anna Öfverholm
m.fl.

National and international collaborations

• Mårten Fernö, Per Malmström, Emma Niméus, Fredrika Killander
  Inst för Kliniska Vetenskaper, Lunds Universitet
• Lori Pierce, Correy Speers och Laura Chang
  Ann Arbor, University of Michigan
• Martin Sjöström vid The Quigley Lab,  more about the lab
  University of California San Franscisco
• International breast cancer study group (IBCSG)
  Bern, Milano, Boston Harvard

Publications

Selected publications

Comprehensive Transcriptomic Profiling Identifies Breast Cancer Patients Who May Be Spared Adjuvant Systemic Therapy. Sjöström M, Chang SL, Fishbane N, Davicioni E, Hartman L, Holmberg E, Feng FY, Speers CW, Pierce LJ, Malmström P, Fernö M, Karlsson P. Clin Cancer Res. 2020 (IF 10,1) Jan 1;26(1):171-182. doi: 10.1158/1078-0432. CCR-19-1038. PMID: 31558478

Clinicogenomic Radiotherapy Classifier Predicting the Need for Intensified Locoregional Treatment After Breast-Conserving Surgery for Early-Stage Breast Cancer. Sjöström M, Chang SL, Fishbane N, Davicioni E, Zhao SG, Hartman L, Holmberg E, Feng FY, Speers CW, Pierce LJ, Malmström P, Fernö M, Karlsson P. J Clin Oncol. 2019 (IF 32,9) Dec 10;37(35):3340-3349. doi: 10.1200/JCO.19.00761. PMID: 31618132

Effect of Radiotherapy After Breast-Conserving Surgery Depending on the Presence of Tumor-Infiltrating Lymphocytes: A Long-Term Follow-Up of the SweBCG91RT Randomized Trial. Kovács A, Stenmark Tullberg A, Werner Rönnerman E, Holmberg E, Hartman L, Sjöström M, Lundstedt D, Malmström P, Fernö M, Karlsson P. J Clin Oncol. 2019 (IF 32.9) May 10;37(14):1179-1187. doi: 10.1200/JCO.18.02157. PMID: 30939091

Extended adjuvant intermittent letrozole versus continuous letrozole in postmenopausal women with breast cancer (SOLE): a multicentre, open-label, randomised, phase 3 trial. Colleoni M, Luo W, Karlsson P, Chirgwin J, Aebi S, Jerusalem G, Neven P, Hitre E, Graas MP, Simoncini E, Kamby C, Thompson A, Loibl S, Gavilá J, Kuroi K, Marth C, Müller B, O'Reilly S, Di Lauro V, Gombos A, Ruhstaller T, Burstein H, Ribi K, Bernhard J, Viale G, Maibach R, Rabaglio-Poretti M, Gelber RD, Coates AS, Di Leo A, Regan MM, Goldhirsch A; SOLE Investigators.Lancet Oncol. (IF 35.3) 2018 Jan;19(1):127-138. doi: 10.1016/S1470-2045(17)30715-5. PMID: 29158011 Clinical Trial.

More publications from the research group

To see more publications from the Per Karlsson group, see Per Karlsson’s publication list from Gothenburg University Publications (GUP).