Liquid biopsy gives new insight into breast cancer prognosis

Liquid biopsy provides an alternative to traditional biopsy

The prognosis of breast cancer has continued to improve in Western countries. In Finland, for example, almost 90% of breast cancer patients are alive after five years of their breast cancer diagnosis. However, there are significant differences in the prognosis of different subtypes of breast cancer, and breast cancer eventually recurs in approximately 20–30% of patients. Identifying patients with a poor prognosis from a large mass of patients earlier and more accurately than before is key to reducing breast cancer mortality.

Liquid biopsy has been proposed as a possible tool for screening breast cancer patients with a poor prognosis. At its best, liquid biopsy utilising circulating markers released by cancer cells can give a more comprehensive picture of the cancer tumour. It can also help to identify characteristics of breast cancer that has a poor prognosis, which would be ignored by traditional analysis methods.

High integrity of circulating DNA is associated with a poor prognosis

The study investigated the integrity of circulating cell-free DNA (cfDNA) in breast cancer patients, and the association of this integrity with breast cancer prognosis.

"High integrity was found to associate with a poor prognosis, and to be a prognostic factor independent of traditional prognostic factors," says Maria Lamminaho, Lic. Med., the first author of the study.

"It has been known that the integrity of cfDNA is higher in breast cancer patients than in healthy controls or in patients with benign breast tumours," says Hanna Peltonen, PhD, one of the authors.

"However, the association of cfDNA integrity with breast cancer prognosis has been studied considerably less, and our study provides much-needed additional evidence of the existence of this association," Peltonen says.

The study used extensive patient data from the Kuopio Breast Cancer Project (KBCP) launched in the 1990s, which enabled a more comprehensive analysis of patients' survival than previous studies.

"Patients in the KBCP have been monitored for almost three decades, which is an exceptionally long follow-up period even by international comparison. It also provides an excellent foundation for assessing patients' long-term survival prognosis," Peltonen says.

Towards a more accurate prognosis at an earlier stage

The findings are particularly interesting because the study focused on breast cancer patients whose prognosis was good when measured on traditional prognostic factors. For example, when analysing the cfDNA integrity of a group of estrogen receptor positive breast cancer patients – whose prognosis is generally considered to be good – the researchers were able to distinguish a group of patients whose prognosis was significantly worse than the rest of the group's.

"Our results show that together with traditional prognostic factors, measuring the integrity of cfDNA can in the future help us to identify breast cancer patients with a poor prognosis earlier and more accurately than before. This would allow patients requiring more intensive care to be placed under intensified care and monitoring earlier," Professor Arto Mannermaa says.