Correspondence

Sequencing of Chemotherapy and Radiotherapy in Breast Cancer

N Engl J Med 1996; 335:1240October 17, 1996

Article

To the Editor:

Recht et al. (May 23 issue)1 describe the effect of sequencing of chemotherapy and radiation on the risk of relapse and death in 244 women with early-stage breast cancer. Two points need to be made. First, distant metastases developed in two patients in the radiotherapy-first group while they were receiving therapy. The authors do not state what staging procedures were done before enrollment in the study. Perhaps the authors could recalculate their statistics with these two patients excluded from the analysis, to see whether the two groups still differed from each other. The second point is that the relapse rate in both groups was higher than expected in a group of patients with a median of two positive lymph nodes. Data from the Surveillance, Epidemiology, and End Results Program (SEER)2 suggest that the survival of the group as a whole would have been expected to be better. In the SEER study, remarkable for the size of the retrospective analysis (which involved almost 25,000 patients), patients with one to three positive lymph nodes had a five-year survival of 73 to 87 percent depending on the size of the primary tumor. Furthermore, many of these patients (with disease diagnosed between 1977 and 1982) would have received no chemotherapy. Survival in the study by Recht et al. was similar or slightly inferior to that of the SEER group, raising the question of whether chemotherapy as delivered had any effect on outcome. Are there any other data on the outcome of patients treated with the regimen reported in this paper? It is not widely used in clinical practice.

James J. Stark, M.D.
Mid-Atlantic Hematology and Oncology, Norfolk, VA 23505

2 References

1. 1

   Recht A, Come SE, Henderson IC, et al. The sequencing of chemotherapy and radiation therapy after conservative surgery for early-stage breast cancer. N Engl J Med 1996;334:1356-1361
   Full Text | Web of Science | Medline

2. 2

   Carter CL, Allen C, Henson DE. Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases. Cancer 1989;63:181-187
   CrossRef | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: In response to Dr. Stark's first question, staging with chest radiography, bone scanning, and blood chemical analysis was required before entry into our study. We do not believe it appropriate to exclude patients with early distant failure (during radiotherapy) in analyzing the results of this trial. We have commented elsewhere1 on how exclusion of patients who have local recurrences during chemotherapy, before radiotherapy, might bias an analysis of the effect of the interval between surgery and radiotherapy on rates of local control.

The data quoted by Dr. Stark are relative survival rates, obtained by comparing the observed overall survival rates (which are what we reported) with the expected mortality in a general population with the same age and race distribution.2 Furthermore, the survival rates we reported included patients who had four or more positive axillary nodes (25 percent of our population). Dr. Stark refers to the relative survival rates in patients with one to three positive nodes (Table 3 of the article by Carter et al.),2 which exclude such patients. Both these factors make any detailed comparison between our results and the SEER data misleading.

Although the chemotherapy regimen we employed is not widely used, the results were quite similar to those achieved with other multiagent treatment programs. For example, we previously reported results in a similar population from our institutions treated with more commonly used doxorubicin-based regimens or variations of cyclophosphamide, methotrexate, and fluorouracil.3 In this population, the five-year actuarial rate of distant metastases was 23 percent, as compared with 25 percent among patients who received chemotherapy before radiotherapy in our randomized study.4 For patients with one to three positive nodes, the crude four-year rate of distant metastases (as the first site of failure) was 19 percent in our retrospective study, as compared with a crude five-year rate of 23 percent in our randomized study. Our results are also similar to those found in a meta-analysis of polychemotherapy trials.5 Hence, we do not believe that the particular chemotherapy regimen we used was important in explaining our results.

Abram Recht, M.D.
Steven E. Come, M.D.
Jay R. Harris, M.D.
Harvard Medical School, Boston, MA 02115

5 References

1. 1

   Recht A, Harris JR, Come SE. Sequencing of irradiation and chemotherapy for early-stage breast cancer. Oncology (Huntingt) 1994;8:19-28
   Medline

2. 2

   Carter CL, Allen C, Henson DE. Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases. Cancer 1989;63:181-187
   CrossRef | Web of Science | Medline

3. 3

   Recht A, Come SE, Gelman RS, et al. Integration of conservative surgery, radiotherapy, and chemotherapy for the treatment of early-stage node-positive breast cancer: sequencing, timing, and outcome. J Clin Oncol 1991;9:1662-1667
   Web of Science | Medline

4. 4

   Recht A, Come SE, Henderson IC, et al. The sequencing of chemotherapy and radiation therapy after conservative surgery for early-stage breast cancer. N Engl J Med 1996;334:1356-1361
   Full Text | Web of Science | Medline

5. 5

   Early Breast Cancer Trialists' Collaborative Group. Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy: 133 randomised trials involving 31 000 recurrences and 24 000 deaths among 75 000 women. Lancet 1992;339:1-15, 71
   Web of Science | Medline