Oxford University researchers have demonstrated that modern chemotherapy reduces breast cancer mortality by approximately one third in a large number of patients, compared with no chemotherapy. The findings of the meta-analysis of 123 randomized trials, which involved about 100,000 women with breast cancer over the past 4 decades have been published in an article by the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) at the Clinical Trial Service Unit, University of Oxford, UK, which has been published Online First in The Lancet.
The researchers examined trials of several older chemotherapy regimens and discovered that standard 1980s chemotherapy regimens resulted in a reduction of almost a quarter in breast cancer mortality.
During the evaluation of more recent trials regimens compared with the older regimens the researchers found a further reduction of approximately one-sixth in breast cancer mortality.
According to their conclusion, modern chemotherapy reduces breast cancer mortality by approximately one third in a large number of patients, in comparison to patients who received no chemotherapy.
They discovered that standard CMF and standard 4AC chemotherapy, the best regimes amongst the older treatments used in the 1980's, were more or less equal, reducing annual breast cancer mortality rates by 20-25%.
Their findings revealed that other treatments with lower chemotherapy doses were slightly less effective, whilst modern treatments with significantly more chemotherapy than standard 4AC, yet not so intensive as to require stem-cell rescue, proved to be slightly more effective.
The trials also revealed that modern regimen, like CAF and CEF, included higher cumulative doses, and some that consisted of an older 1980's regimen plus a taxane.
The researchers discovered that the reduction of one-third in breast cancer mortality seemed to apply to all women, irrespective of factors, such as tumor size, whether the tumor had spread to local lymph nodes, and whether or not it was estrogen-receptor (ER)-positive.
The reduced mortality rate also appeared to be irrespective of age, although only few women in these trials were older than 70 years.
The mortality risk of ER-positive breast cancer can be significantly reduced with a 5-year endocrine therapy. Endocrine therapy is commonly less toxic than chemotherapy, although, according to the current findings, chemotherapy combined with endocrine therapy in ER-positive cancer patients proved more effective compared with endocrine therapy alone.
The researchers found that achieving an overall reduction of one-third breast cancer mortality depends on the overall risk without chemotherapy. In cases of ER-positive disease, this means the risk remaining with appropriate endocrine treatment.
According to Sir Richard Peto, one of the leaders of this worldwide collaboration:
"Most breast cancers are ER-positive, and for ER-positive disease that appears to have been completely removed by surgery the 10-year risk of recurrence and death from breast cancer can be reduced by at least half by giving a few months of modern chemotherapy plus 5 years of endocrine therapy."
Chemotherapy is only administered in cases that pose a significant risk of cancer recurrence if not given. This is because all chemotherapy treatments can cause severe side effects during treatment, and in some cases they can also potentially cause permanent damage. Some of the recurrence predictors without using chemotherapy are tumor characteristics, such as tumor size and invasiveness, which therefore also help to predict the absolute gain from a one-third reduction in that risk. This was the only way of recording characteristics in these trials that were not able to predict sensitivity to chemotherapy.
Dr Carlo Palmieri, Division of Cancer at the Imperial College London, UK, and Dr Alison Jones, Department of Medical Oncology at the University College Hospital in London, UK say in a linked comment:
"The EBCTCG meta-analyses continue to show that polychemotherapy saves lives (and that it can, on average, reduce breast cancer mortality by about a third). Clearly, the actual benefit and harm of polychemotherapy will be determined by the individual future risk of relapse and coexisting comorbidities.
The challenge now is not only to save more lives, but to reduce the number of women given polychemotherapy unnecessarily. It is with such hope that the results of ongoing oncomolecular trials are awaited. We look forward to the day when treatment of fewer women with a personalized approach achieves more."
Written by Petra Rattue