Barcelona, Spain: Fragments of tumour DNA circulating in the bloodstream of patients with breast cancer can predict whether they are likely to relapse, especially when samples are taken after the patients have received treatments prior to surgery.
The study, presented at the 15th European Breast Cancer Conference (EBCC15) in Barcelona today (Friday), included the largest number of events reported so far for circulating tumour DNA (ctDNA) in individual patients. Events could include the tumour starting to grow again, cancer cells spreading to other parts of the body (metastasising), death or a new tumour in the same or the second breast.
The findings mean that doctors could analyse ctDNA in patients when they complete neoadjuvant therapy – anti-cancer treatments such as chemotherapy, radiotherapy or hormone therapy, given before surgery. The results could help the doctors to assess the risk of relapse and plan appropriate, individualised treatments after surgery.
Dr Elisa Agostinetto, a medical oncologist and researcher at the Institut Jules Bordet in Brussels, Belgium, worked with colleagues from her institute and researchers coordinated by Dr Serena Di Cosimo at the Instituto Nazionale dei Tumori in Milan, Italy, to analyse ctDNA in blood plasma samples taken from 81 patients with early breast cancer enrolled in two prospective studies, one at each centre.
The women's ages ranged from 27-75 years (median age 48 years), and most had tumours smaller than 5cms that had spread to the lymph nodes, and more than half (60%) had a type of cancer called 'triple negative', which often occurs in young women and is less responsive to treatment.
The researchers took ctDNA samples at three time points: when the patients entered the studies and before they started neoadjuvant treatment; at the end of the treatment and before surgery; and during the follow-up period (median of approximately seven years). During this time, one patient died without their cancer recurring, 21 patients experienced a recurrence and four patients died after a recurrence.
Dr Agostinetto said: "The results from this large, prospective study, conducted in a real-world setting, showed that finding ctDNA was linked to a higher chance of breast cancer coming back, especially when ctDNA was detected at the end of pre-surgery treatment. These results suggest that ctDNA could be useful in identifying patients at higher risk after neoadjuvant therapy, and to guide additional treatment if needed."
The researchers found ctDNA in 57% of plasma samples at the start of the studies, but at the end of neoadjuvant treatment this dropped to 17%. There was a trend towards cancer recurring in patients who had ctDNA in their blood at the start of treatment, but this was not statistically significant. However, patients who had ctDNA in their blood at the end of their neoadjuvant treatment were 3.5 times more likely to have their cancer return during the follow-up period, even after adjusting for variables that could affect the analyses, such as tumour size, age and hormone receptor status.
Even if there was no sign of the tumour after the neoadjuvant treatment – known as pathological complete response – ctDNA still predicted whether or not the cancer would recur.
The presence of ctDNA, both at the start of the two studies and after neoadjuvant treatment, was significantly associated with women who had a type of breast cancer called hormone receptor negative (HR-), which is often more aggressive and harder to treat successfully. Sixty-four percent of patients had HR- disease at the beginning of the studies and 36% had HR+ disease.
Dr Agostinetto said: "We know already that ctDNA has prognostic relevance, and its detection is consistently associated with a higher risk of recurrence and a worse survival, often anticipating clinical relapse by months. It is good at reflecting minimal residual disease and tumour burden. However, until now there has been limited evidence about its usefulness in the neoadjuvant setting, mainly due to small numbers of patients in available clinical studies. Our analysis includes the largest number of events following neoadjuvant treatment, and shows that ctDNA can be useful in guiding further treatments. At present, it is not used as a standard clinical practice for prognosis outside of clinical trials."
She said the use of ctDNA in the neoadjuvant setting should be tested in prospective clinical trials where treatments decisions were guided by ctDNA results, to show whether intervening early in ctDNA-positive patients actually improved outcomes.
Strengths of the study include the long follow-up period and the inclusion of consecutive series of patients in more than one cancer centre.
"This is the only way that biomarker research is truly feasible, and I would like to thank all the colleagues involved in this collaboration between Institut Jules Bordet and Istituto Nazionale dei Tumori for their efforts," she concluded.
Dr Javier Cortés is chair of the EBCC15 national organising committee, and co-director of the International Breast Cancer Center (IBCC) in Barcelona and of IOB in Madrid. He was not involved with the research. He commented: "The analysis presented today at EBCC15 adds to the growing evidence that ctDNA in breast cancer has prognostic relevance and can help us to choose the most appropriate treatment for individual patients. Clinical trials should investigate this further to see if treatment decisions guided by ctDNA results actually improve outcomes. We also need to know if the presence of ctDNA has the same implications across all the different sub-types of breast cancer."
