Adjuvant Chemotherapy Backed for ER-Negative Breast Cancer

By Charles Bankhead
OXFORD, England, Jan. 3 -- For women of any age, adjuvant chemotherapy significantly reduces recurrence of estrogen receptor-negative breast cancer and increases survival, found an updated meta-analysis.
Given that the analysis evaluated trials of older chemotherapy regimens, greater benefits might be expected with newer and future therapies, Richard Peto, Ph.D., of the University of Oxford, and colleagues in the Early Breast Cancer Trialists' Collaborative Group reported in the Jan. 5 issue of The Lancet.
Breast tumors with a minimal volume of estrogen receptors (ER-poor) have a high recurrence rate after surgery, and hormonal therapy has little effect on recurrence, said Dr. Peto. Consequently, the impact of chemotherapy on such tumors has major implications for outcomes.
A single trial of adjuvant chemotherapy usually includes too few ER-poor (or ER-negative) patients for statistical stability, Dr. Peto continued. Treatments in these patients are best examined by periodically updated meta-analyses of all relevant randomized trials.
Since 1984-85, his group has performed meta-analyses every five years of centrally collected data on patients from all randomized trials of early breast cancer therapy. Analyses conducted in 1990 and 1995 showed that the benefits of adjuvant chemotherapy on long-term outcomes were greater in women younger than 50 than in older patients.
Results of the 2000 update demonstrated a greater benefit in older patients but were still insufficient for statistical reliability.
For the 2005-2006 update, the investigators analyzed data on about 6,000 women with ER-poor breast cancer from 46 trials of non-taxane combination chemotherapy and about 14,000 women with ER-poor breast cancer in 50 trials of tamoxifen versus chemotherapy or no adjuvant therapy. The trials had start dates of 1972 to 1993 and a median start date of 1982.
The analysis showed that combination chemotherapy significantly reduced recurrence, breast cancer mortality, and all-cause mortality in women younger than 50 at enrollment and in older patients. In patients younger than 50, combination chemotherapy significantly improved the following 10-year outcomes:
Recurrence, 33% versus 45% (risk ratio: 0.73, P<0.00001)
Breast cancer mortality, 24% versus 32% (RR: 0.73, P=0.0002)
Death from any cause, 25% versus 33% (RR: 0.75, P=0.0003)
Although older women were still underrepresented in the trials, adjuvant chemotherapy also led to significant improvement in 10-year outcomes when patients ages 50 to 59 and 60 to 69 were grouped together:
Recurrence, 42% versus 52% (RR: 0.82, P<0.00001)
Breast cancer mortality, 36% versus 42% (RR: 0.86, P=0.0004)
Death from any cause, 39% versus 45% (RR: 0.87, P=0.0009)
Tamoxifen had little effect on outcomes in women with ER-poor disease and did not significantly modify the effects of adjuvant chemotherapy, the authors said.
In an accompanying commentary, Rinat Yerushalmi, Ph.D., and Karen Gelmon, M.D., of the British Columbia Cancer Agency in Vancouver, said the latest update "further confirms the contribution of chemotherapy to decreasing recurrence of estrogen receptor-negative breast cancer. Efforts should now be directed towards the establishment of finer definitions of subtypes of such cancers, the study of less debilitating but active regimens, and the development of new strategies for those who are not cured by chemotherapy."
Neither the authors of the meta-analysis nor members of the steering committee disclosed any conflicts.
Drs. Yerushalmi and Gelmon declared no conflicts.
Primary source: The LancetSource reference:Early Breast Cancer Trialists' Collaborative Group "Adjuvant chemotherapy in estrogen-receptor-poor breast cancer: patient-level meta-analysis of randomized trials" Lancet 2008; 371: 29-40.