Differences within breast tumours and between patients are associated with the risk of metastasis and response to endocrine therapy, according to a new doctoral thesis from Karolinska Institutet. The findings also highlight the importance of long-term follow-up in capturing the full benefit of treatment.
In hormone-sensitive breast cancer, the cancer cells have receptors for the hormone oestrogen, which can stimulate their growth. Patients can therefore be treated with endocrine therapy, but the treatment does not benefit everyone to the same extent. Tumour cells can also remain dormant in the body and begin growing again 10 to 20 years later.
In his thesis, Oscar Danielsson at the Department of Oncology-Pathology investigated how different types of variation in hormone-sensitive breast cancer are associated with the long-term risk of metastasis and the benefit of endocrine therapy.
"Breast cancer can vary both within the tumour and from one patient to another. Our findings show that these differences may be associated with the risk of metastasis and how much patients benefit from treatment," says Oscar Danielsson.
Treatment benefit changed over time
The thesis also examined two common types of hormone-sensitive breast cancer, luminal A and luminal B. Both groups showed long-term benefit from treatment with tamoxifen. For patients with luminal B, much of the benefit was already apparent after five years. For those with luminal A, the benefit was smaller at five years but became greater with longer follow-up.
"For patients with luminal A, a study with only five years of follow-up would have missed much of the later benefit of tamoxifen. This shows why long-term follow-up is important when studying this type of breast cancer," says Oscar Danielsson.
Another part of the thesis looked at variation within individual tumours. Patients whose tumours showed greater variation in progesterone receptor levels had an approximately 40 per cent higher rate of metastasis during follow-up than patients whose tumours showed less variation. Despite this, they still benefited from endocrine therapy.
Two of the studies in the thesis also used artificial intelligence to analyse images of tumour tissue. The analyses identified patterns associated with a higher risk of metastasis. One AI model also identified a group of patients who clearly benefited from treatment with goserelin. However, the findings need to be confirmed in other patient groups before the method can be used in clinical practice.
The thesis work was supervised by docent Linda Lindström at the Department of Oncology-Pathology, Karolinska Institutet.
