Recurrence of breast cancer after more than 10 years is an important factor in survival

Dr Sven Mieog, MD, a research fellow at Leiden University Medical Centre (Leiden, The Netherlands) told the conference that in women treated with breast conserving treatment for early stage breast cancer, a locoregional recurrence remained the most important prognostic factor after a disease-free interval of five years. Moreover, after a disease-free interval of ten years, locoregional recurrence remained the sole independent prognostic factor.

"In patients who were free of disease for more than ten years after primary treatment, locoregional recurrence had a significant impact on both disease-free survival and overall survival," he said. "The increased risk of metastases after a recurrence was approximately four times higher than if there had been no recurrence, and the risk of dying after a recurrence was around eight times higher. However, these levels of increased risk need to be treated with caution because, with the longer time interval between the primary cancer and the recurrence, the number of events goes down, making these calculations less certain, although they remain important for clinicians when deciding on the best treatments."

Dr Mieog and his colleagues pooled data from 7,749 early stage breast cancer patients taking part in four trials run by the European Organisation for Research and Treatment of Cancer (EORTC). The average length of follow-up was 10.9 years and three different analyses looked at: 1) all the patients, 2) only patients without further cancer after at least five years, and, 3) patients without further cancer after at least 10 years.

In the analysis of all patients, locoregional recurrence, tumour size, whether the cancer had spread to the lymph nodes, young age, oestrogen receptor status and treatment with chemotherapy were all independent prognostic factors with a significant impact on long-term outcome, with locoregional recurrence being the strongest factor.

In the second analysis looking at patients who were disease-free after at least five years, locoregional recurrence was the strongest independent prognostic factor for overall survival and metastases-free survival. In the third analysis looking at patients who were disease-free after at least ten year, locoregional recurrence was the only independent prognostic factor.

Dr Mieog said: "These findings suggest that even after a long, event-free interval, locoregional recurrence seems to be associated with distant disease rather than a cause of subsequent distant disease."

Dr Jos A. van der Hage, MD PhD, a surgical oncologist at The Netherlands Cancer Institute (Amsterdam, The Netherlands) who collaborated with Dr Mieog but was unable to attend EBCC7, explained: "Locoregional recurrence is a well-known risk factor for subsequent distant disease and death. The nature of this relationship is not clear. However, most recurrences are not causes of subsequent disease spread but rather a symptom of disease progression, associated with a high likelihood of simultaneous metastases.

"On the other hand, approximately 25% of all local recurrences are believed to be able to induce further disease progression themselves. This rationale is based upon the fact that radiotherapy trials demonstrate a decrease in local recurrence rates as well as improved long-term outcome in patients receiving adjuvant radiotherapy after breast surgery.

"The fact that locoregional recurrence is still a very strong prognostic factor, even after a long disease-free interval suggests that it probably is a symptom of (and therefore associated with) distant disease occurring at the same time, and not the instigator of disease progression in the majority of cases."

However, he said that further research on locoregional recurrences was needed. "To date, it remains difficult to assess whether a locoregional recurrence is a true recurrence or a second primary. This is of significant importance for clinicians when they assess the indications for giving adjuvant systemic therapy. There are not many large-scale studies, which address this clinical feature of breast cancer disease. Since breast cancer may recur even after 15 years of follow-up, studies demonstrating the prognostic impact of events that happen after primary treatment are very important."

The research provides further information for the ongoing debates about how long women who have been treated successfully for breast cancer should be followed up by doctors. While not giving any definitive answers on this, the study does show that breast cancer can recur and progress even after a long time disease free. "Therefore, clinicians and patients should consider adjuvant systemic, both for the treatment of the primary cancer and in the event of any recurrence," said Dr van der Hage.