91̽��

Image

ANNA THULIN
Dissertation defense: 6 September 2024 (click for details)
Doctoral thesis:
Research area: Oncology
Sahlgrenska Academy, The Institute of Clinical 91̽��s

Even though as many as nine out of ten breast cancer patients are cured, it remains the deadliest cancer for women in Sweden and globally.

Disseminated breast cancer has spread from the breast to other parts of the body. In this setting cure is almost impossible but treatments may prolong a patient’s life. Treatment selection is based on the subgroup of breast cancer the patient has been diagnosed with.

“The treatments currently given to prevent relapse and prolong life, unfortunately are not reducing brain metastases from breast cancer. Brain metastases have not been as thoroughly researched as other metastatic sites. This may be due to the condition not being as common previously, and that there were very few effective treatments for brain metastases,” says Anna Thulin, an oncology resident at Sahlgrenska University Hospital and a doctoral student at the Institute of Clinical 91̽��s.

Studying cancer’s transformation

What is your research about?
“We compared patients’ breast cancer with a brain metastasis from the same patient. By comparing the cancer cells and surrounding tissue, the adaptations in cancer cells as it spreads from breast to brain may be studied. We used mutation analyses, gene expression analyses, and protein level studies using immunohistochemistry. We also added clinical data such as number of patients diagnosed over time.”

Increasing number of patients affected

What are the key findings of your research?
“We found that the number of patients developing brain metastases increased over time. This knowledge is crucial in evaluating whether we should screen for brain metastases, and to increase the number of patients with brain metastases included in clinical trials.”

What did the comparisons between tissue samples from primary breast tumors and brain metastases reveal?
“We found that the subtype of breast cancer changes in 25% of patients. This is about the same proportion as in other metastatic locations. The brain is a difficult location for biopsy but this highlights the need for new methods such as liquid biopsy.”

Suppressed immune system in metastases

“We have studied both gene mutations, expression of genes, and also stained immune cells in the matched material. There we see that gene expression changes, particularly those genes related to the immune system,” explains Anna Thulin, adding:

“We found that both immune cells and genes involved in the immune response were significantly lower in brain metastases than in primary breast tumors. This could explain why immunotherapy is not very effective against brain metastases from breast cancer.”

What practical benefits could your research provide?
“My results might contribute to an increased understanding of the biology of brain metastases, which has previously been quite limited. I now hope for better characterization of brain metastases with new methods, but above all for new medications to better prevent brain metastasization.”

“Learned things I never thought possible”

What has been rewarding and challenging about your doctoral project?
“I have learned a lot that I didn’t think was possible. For example, I now feel relatively confident with statistics. For a doctor who is used to clinical work, it is challenging to take on more preclinical methods, as well as methods from other specialties,” says Anna Thulin, and continues:

“It has required collaboration with others and delving into topics that initially felt too difficult. Doing research also makes one better at evaluating research by others, benefitting clinical work.”

Text: Jakob Lundberg