The Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) was established in 1983. The purpose of this group, based primarily at Oxford University in the UK, was to compile together data on early-stage breast cancer from hundreds of clinical trials that have been conducted on that disease. The consequence has been a highly influential series of analyses and publications over the ensuing decades that have provided information on tens of thousands of patients with localized breast cancer and given outstanding summary conclusions on the effects of surgery, radiation therapy, chemotherapy and hormonal therapy under various circumstances for such patients. Much of our current practices derive from the conclusions and results that have been presented in these studies promulgated by the EBCTCG.
Therefore, one always reacts with interest when a new study is published from this group. One such study was published in October in The Lancet. The purpose of this paper was to assess recent trends in the probability of late recurrence for women with early-stage breast cancer who have undergone adjuvant therapy. Earlier studies by the EBCTCG had demonstrated that, for women with hormone-receptor positive breast cancer who underwent resection, that five years of hormonal therapy with either tamoxifen or an aromatase inhibitor would reduce the rate of distant recurrence or breast cancer death by approximately 40%. However, they also found that the risks of distant recurrence persisted for 20 years or more afterwards, varying as a function of the woman’s initial stage at diagnosis, and persisting as long as 30 years. To my mind, this is one of the great negatives of breast cancer—that no matter how well a woman appears to be doing with localized disease and its treatment, she can never rest easy.
Of course, the observation of recurrences after an interval of 30 years requires that we be evaluating therapies that were prescribed and administered around 1990, many years ago, and may not represent very well the potential results with the newer available approaches to breast cancer screening, diagnosis and treatment that are currently extant.
The current study from the EBCTCG was an effort to evaluate these more recent approaches and their outcomes. This was undertaken by using the database of the EBCTCG on more than 650,000 women who were enrolled in clinical trials between 1990 and 2009 for early-stage breast cancer. Women with tumors greater than 5 cm in size or with more than 10 positive lymph nodes were excluded from these analyses. Thus, this assessment is really for women with better prognosis localized breast cancers.
There were 114,811 women with hormone receptor positive disease and 40,935 women who were hormone receptor negative included in these analyses. They observed a strong trend towards lower risk tumors since 1990. This was driven both by smaller tumors and by fewer positive lymph nodes.
For estrogen receptor negative breast cancers, 80% of the recurrences occurred in the first five years after diagnosis regardless of the time period. For both estrogen receptor positive and estrogen receptor negative tumors, there was a substantial reduction in the risk of distant tumor recurrence for the first 10 years after surgery for those women diagnosed after the year 2000 as compared to those diagnosed between 1990 and 1999. As a general finding, the overall rates of distant recurrence were reduced by approximately 25% for those with hormone receptor positive disease and by 19% for those with estrogen receptor negative disease when those diagnosed after 2000 were compared to those diagnosed between 1990 and 1999.
What factors led to these significant and dramatic improvements in outcomes in the more recently diagnosed women? One finding was that the more recent cohort had a higher proportion of node-negative breast cancer. The investigators estimated that this accounted for one-third to one-half of the improvement in outcomes. This improvement probably resulted from more widespread utilization of screening mammography and earlier diagnosis of breast cancer. Another possibility was that improvements in diagnosis, such as improved approaches to sentinel lymph node sampling, could have had some effect as well.
The authors also hypothesize that one-third to one-half of the improvement in outcomes may have resulted from actual improvements in the therapies themselves. The use of anthracyclines, such as doxorubicin (Adriamycin) with taxanes, such as Taxotere (docetaxel), or the more widespread use of dose-intense chemotherapy regimens may have also played a role. While hormonal therapy was previously used for a duration of five years, the more recent trend has been towards a duration of treatment of 10 years, and this has become commonplace. Treatment for the fraction of women with HER2 positive disease (perhaps 15-20% of patients) has also played a significant role in improving outcomes.
We should bear in mind, however, that despite improvements, those with, for example, four to nine positive lymph nodes still remain at considerably elevated risk of recurrence, and we must continue to address efforts to further improve outcomes for this disease. Furthermore, this report did not address those with stage III, IV or metastatic disease, all of whom have also had dramatic improvements and prolongations in survival outcomes. We must await reports from other sources to appreciate and quantify exactly how large these improvements have been.
Alfred I. Neugut, MD, PhD, is a medical oncologist and cancer epidemiologist at Columbia University Irving Medical Center/New York Presbyterian and Mailman School of Public Health in New York. Email: [email protected].
This article is for educational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment, and does not constitute medical or other professional advice. Always seek the advice of your qualified health provider with any questions you may have regarding a medical condition or treatment.
