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Results of Randomized Clinical Trials Translate to Improved Survival in Early Breast Cancer

Goodman, Alice

doi: 10.1097/01.COT.0000287834.32348.1e

A study presented at the San Antonio Breast Cancer Symposium provides reassurance that the results of randomized controlled trials showing benefit for adjuvant therapy have filtered down to the general community.

The magnitude of risk reduction in 10-year risk of death from breast cancer in a geographically defined cohort of patients with Stages I/II breast cancer was similar to what could be predicted from the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) meta-analyses of randomized trials of adjuvant chemotherapy and hormonal therapy, reported Ivo Olivotto, MD, Head of the Breast Cancer Outcomes Unit for the British Columbia Cancer Agency.

Figure. Iv

Figure. Iv

The outcomes were better with adjuvant therapy than what would have been predicted without adjuvant therapy. The anticipated risk reduction was calculated using a Web-based decision-making tool for selecting adjuvant therapy called Adjuvant! (

“The mortality and breast cancer recurrence in the population we defined seem to be similar to what could be anticipated from Adjuvant!,” Dr. Olivotto said.

“The findings suggest that a significant part of the decline in breast cancer mortality since 1990 is due to the implementation of adjuvant systemic therapies—about 30% for younger women and about 15% for older women.”

Since only about 3% of women in North America with newly diagnosed breast cancer enroll in randomized clinical trials of adjuvant therapies, participants in randomized controlled trials are different from non-participants and do not represent unselected patients, he said.

The 10-year outcomes were studied in 4,721 cases of breast cancer. Adjuvant chemotherapy, mainly CMF or AC x 4, was offered to patients with node-positive breast cancer and for node-negative breast cancer if lymphatic invasion was present or if the tumor was larger than 2 cm and was estrogen-receptor negative.

At that time, Dr. Olivotto noted, the policy was to give tamoxifen for three years, although it is now clear that five years is the optimal duration of therapy.

No systemic therapy was administered in 2,091 patients; 1,427 received tamoxifen alone (only 3% were under age 50); 743 were treated with chemotherapy alone; 460 patients received both chemotherapy and tamoxifen.

Few older women were treated with chemotherapy alone, and few younger women had tamoxifen alone. Untreated patients generally had node-negative tumors that were 2 cm or smaller, although approximately 5% were unfit for or declined to have the indicated systemic therapy.

“In British Columbia, we looked at what would have happened to our patients had they not been treated, based on the assumption that Adjuvant! could predict the outcome of untreated patients,” he said.

Dr. Olivotto added that several months earlier at the most recent ASCO Annual Meeting, a validation was presented showing that Adjuvant! predicted overall survival, breast cancer-specific, and event-free survival “quite well” for a variety of different subgroups based on prognosis and treatment received.

Based on the specific disease characteristics of the 2,091 untreated patients from British Columbia, the tool predicted that 10-year overall survival would be 90.1% and event-free survival would be 76.6%, which was remarkably similar to the 90.2% 10-year overall survival and 76.0% 10-year event-free survival actually observed.

“This reassured us that Adjuvant! would perform as well in treated cohorts, and we could look at the relative proportional reductions,” Dr. Olivotto said.

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Treated Patients

For women under age 50 treated with polychemotherapy, the relative reduction in mortality of 29.5% was remarkably similar to the 27.3% observed in the EBCTCG meta-analysis for similar patients. Risk reduction for recurrence was also remarkably similar—32.4% in British Columbia vs 34% in the EBCTCG data.

Looking at treatment with tamoxifen, the researchers saw an average reduction of 15% in the 10-year risk of breast cancer death, similar to the 17% reduction in the EBCTCG data for patients receiving two years of tamoxifen but inferior to the 26% reduction in the EBCTCG data for ER-positive patients receiving five years of tamoxifen.

The risk of recurrence for patients treated on average with three years of tamoxifen in British Columbia was 34%, intermediate between the EBCTCG observations of 29% with two years of tamoxifen and 47% with five years.

“The results of this study confirm that the benefits of adjuvant systemic therapy for early stage breast cancer can be translated into population-based gains for women treated in community practice,” Dr. Olivotto said.

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Affirmative Study

Asked to comment on the study, Clifford Hudis, MD, Chief of the Breast Cancer Medical Service at Memorial Sloan-Kettering Cancer Center, said that the answer to the question the researchers asked of whether results of randomized controlled trials showing the benefits of adjuvant therapy have been translated to clinical practice, is “yes,—which is reassuring to us and the population we treat.”

Dr. Hudis noted that the same group of researchers had previously reported similar results with trials of chemotherapy and that this study extends those benefits to adjuvant hormonal therapy.

When asked whether results of this trial can be extrapolated to the United States, Dr. Hudis said, “I would think so. British Columbia has centralized databases and is equipped to handle such data, but I have no reason to doubt that this is occurring in the US as well.

“Data on improved survival in breast cancer patients over the past decade suggest that the benefits of randomized controlled trials are accruing across the board.”

© 2005 Lippincott Williams & Wilkins, Inc.
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