Background
Breast cancer is globally the most common malignancy in women, with about 2.3 million breast cancer diagnoses per year. In Sweden, 10,043 breast cancer diagnoses were reported in women in 2020 and 1,385 women died of breast cancer the same year. Decreasing breast cancer mortality has been recorded in many countries, probably due to the use of various systemic preoperative (neoadjuvant) / adjuvant therapies and partly due to early detection by mammography screening. A key question is why early breast cancer treated in the adjuvant or neoadjuvant situation is increasingly curable, while metastatic breast cancer is rarely cured with current diagnostic and therapeutic agents. Neoadjuvant treatment is now routinely used for Her-2 positive and triple-negative breast cancer; the great advantage is that the treatment can be modified in case of lack of treatment response, this is "never" possible with postoperative (adjuvant) treatment. It is of great importance to understand how the mechanisms of resistance in the macrometastatic environment differ from those in the micrometastatic environment.
Methods
The research includes clinical / translational breast cancer studies with combinations of conventional cancer drugs, targeted drugs and immune-related treatment as well as population-based materials, aiming at better treatment and dosing strategies. The research team performs studies of sequencing and gene signature data, protein data (immunohistochemistry) and the immune microenvironment in primary tumours (ideally with analysis of multiple biopsies over time / during neoadjuvant treatment) to identify and evaluate prognostic and treatment predictive factors. The factors are also studied during tumour progression and in corresponding metastases when tumour material is available for analysis, to investigate changes in the biology of the tumours.
Current projects
- Translational analyses of biopsy material and blood from the completed randomised PANTHER study are ongoing. These include analyses of immunogenomic factors and other biomarkers correlated with clinical parameters. Genotyping data are related to the given dose level, type of toxicity and degree versus outcome, as well as reported quality of life.
- Corresponding translational analyses are performed in the neoadjuvant studies EORTC10994 / BIG1–00, PROMIX, PREDIX HER2.
- Further studies are ongoing and planned in population-based materials as well as registry-based breast cancer data, covering both early and metastatic breast cancer.
Overall, the research aims to design individual-based concepts – precision medicine, to prevent recurrence of breast cancer, and to preserve or improve the patients' quality of life and overall survival.