Correspondence
Radical and Simple Mastectomy
N Engl J Med 2002; 347:2170-2171December 26, 2002
- Article
To the Editor:
Fisher et al. (Aug. 22 issue)1 report that radical mastectomy and total mastectomy are equally effective in terms of survival (equipotent) and interpret the small differences between the groups in their study as insignificant. We believe, however, that the trial in women with a clinically negative axilla was grossly undersized and that equipotency cannot be determined. A meta-analysis of trials addressing treatment of the axilla has shown a 5.4 percent (95 percent confidence interval, 2.7 to 8.0 percent) absolute benefit in survival.2
The authors state that a 5 percent difference is insignificant. The recent National Institutes of Health consensus3 on breast-cancer treatment confirms that a 2.3 percent difference in survival in patients with node-positive breast cancer after adjuvant chemotherapy is a clinically important benefit and that the use of anthracycline-based chemotherapy, as compared with cyclophosphamide, methotrexate, and fluorouracil, improves survival by 2.7 percent.4
4 ReferencesRajendra A. Badwe, M.D.
Mangesh A. Thorat, M.D.
Rohini W. Havaldar, B.Sc.
Tata Memorial Hospital, 400012 Mumbai, India
tmhcrs@vsnl.com 1
Fisher B ,Jeong J-H ,Anderson S ,Bryant J ,Fisher ER ,Wolmark N . Twenty-five-year follow-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation. N Engl J Med 2002;347:567-575
Full Text | Web of Science | Medline2
Orr RK . The impact of prophylactic axillary node dissection on breast cancer survival -- a Bayesian meta-analysis. Ann Surg Oncol 1999;6:109-116
CrossRef | Web of Science | Medline3
Adjuvant therapy for breast cancer. NIH consensus statement. Vol. 17. No. 4. Bethesda, Md.: Office of Medical Applications of Research, November 2000:1-23.
4
Early Breast Cancer Trialists' Collaborative Group
CrossRef | Web of Science | Medline
To the Editor:
The Halsted radical mastectomy still has a role in modern breast-cancer surgery. We use the Halsted procedure in patients with breast cancer that infiltrates the pectoral muscles. Radical mastectomy in these cases is the only treatment that offers a wide, clear surgical margin.1 We therefore wonder whether patients with tumors invading the pectoral muscles but not invading the chest wall (i.e., not of stage T4a) were included in the study by Fisher et al. The same question applies to patients with breast cancer located just below the clavicle, for whom the Halsted radical mastectomy is also advocated.
1 ReferencesAndrzej L. Komorowski, M.D.
Wojciech Wysocki, M.D.
Cancer Center, Krakow 31-115, Poland
alkomorowski@wp.pl To the Editor:
Table 1 of the article by Fisher et al. indicates that there was no significant difference in relapse-free survival among the treatment groups. This finding depends on the authors' definition of “recurrence”: ipsilateral lymph-node recurrence is not counted as a recurrence in women with clinically negative nodes who had undergone only total mastectomy. If a more standard definition is applied, the rate of regional recurrence in this group would be a substantial 24.6 percent, as compared with 4 percent for the others.
The odds of five-year relapse-free and overall survival among women with four or more involved axillary nodes remain unfavorable.1,2 Although not every woman with breast cancer needs to undergo axillary-node dissection,3 decisions about whether to abandon such a procedure will have to be based on the results of ongoing randomized trials specifically designed to address this important issue.
3 ReferencesGeorge Somlo, M.D.
City of Hope National Medical Center, Duarte, CA 91010-3000
gsomlo@coh.org 1
Bonadonna G ,Zambetti M ,Valagussa P . Sequential or alternating doxorubicin and CMF regimens in breast cancer with more than three positive nodes: ten-year results. JAMA 1995;273:542-547
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Somlo G ,Simpson JF ,Frankel P , et al. Predictors of long-term outcome following high-dose chemotherapy in high-risk primary breast cancer. Br J Cancer 2002;87:281-288
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Edge SB ,Gold K ,Berg CD , et al. Patient and provider characteristics that affect the use of axillary dissection in older women with stage I-II breast carcinoma. Cancer 2002;94:2534-2541
CrossRef | Web of Science | Medline
To the Editor:
Fisher and colleagues conclude, on the basis of their 25-year follow-up study comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation, that there was no significant survival advantage from radiation therapy. This conclusion is based on somewhat shaky ground. Specifically, significantly fewer patients in the irradiated group than in the nonirradiated groups were treated according to protocol, and there was a significantly greater rate of major protocol violations in the irradiated group than in the other groups. In addition, the dose of radiation was below protocol in 20 percent of the areas treated, and in 70 percent of the patients with axilla-positive disease, the dose to the axilla was below protocol.1 Finally, the power of the study with respect to the patients randomly assigned to irradiation was not adequate to determine statistical significance.2
Fisher and colleagues have made, and continue to make, important contributions to the treatment of breast cancer. Our concern is about the possible inferences that could be made on the basis of a study in which the power is too small to determine whether irradiation is, or is not, of benefit.
2 ReferencesSeymour H. Levitt, M.D., D.Sc.
University of Minnesota School of Medicine, Minneapolis, MN 55455
levit002@umn.edu 1
Levitt SH . Is there a role for post-operative adjuvant radiation in breast cancer? Beautiful hypothesis versus ugly facts: 1987 Gilbert H. Fletcher lecture. Int J Radiat Oncol Biol Phys 1988;14:787-796
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Potish RA ,Boen J ,Levitt SH . Statistical inference in the analysis of radiation compliance and its relation to treatment outcome. Cancer Clin Trials 1981;4:475-481
Medline
Author/Editor Response
The authors reply:
To the Editor: Contrary to the contention of Badwe and colleagues, in our report we never state that a 5 percent difference in survival — a benefit that we did not observe in the B-04 clinical trial — is or is not significant or clinically important, nor do we claim equivalency of survival (equipotency) among the treatment groups. We explicitly state that because of the size of our trial, we could not have ascertained the significance of small differences, such as those observed in the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) meta-analyses.1
In response to Komorowski and Wysocki: the B-04 protocol required that tumors be movable in relation to the underlying muscle and chest wall; women with tumors located “below” the clavicle were eligible.
Somlo is concerned about our failure to include delayed axillary-node involvement as an event in the determination of relapse-free survival in patients who underwent total mastectomy without removal of the axillary nodes. Our decision not to include such events was made when the B-04 trial was designed, because treatment of the axilla in the radical-mastectomy group precluded the occurrence of such events in that group, rendering meaningless a comparison of the incidence of lymph-node involvement among the various groups. Somlo has apparently missed the significance of our finding that, even though the “rate of regional recurrence in [the total-mastectomy] group [was] a substantial 24.6 percent, as compared with 4 percent for the others,” there was no commensurate decrease in survival in that group.
Levitt challenges the quality of the radiation therapy used in the B-04 trial, even though the study was planned, monitored, and administered by many of the most eminent radiation therapists of the time as well as by the staff of the Radiation Physics Center at the M.D. Anderson Cancer Center. Our detailed report on radiation compliance refutes the contention that the failure to demonstrate a significant survival advantage in the trial was related to inadequate treatment.2 An acceptable dose was delivered to the axilla in patients with axillary-node–positive disease but without the use of an additional boost.
Finally, when the B-04 trial was begun, it was thought that deviation from Halsted surgery was likely to have catastrophic effects on the outcome. Thus, regardless of whether or not the trial had the power to establish equivalency, it produced findings consistent with the results of the EBCTCG meta-analysis3 — that is, a reduction of 2±7 percent in the odds of death when simple mastectomy is compared with radical mastectomy (P=0.8). A total of 56 percent of the patients and 49 percent of the deaths in this comparison in the EBCTCG overview were from the B-04 trial.
3 ReferencesBernard Fisher, M.D.
Stewart Anderson, Ph.D.
John Bryant, Ph.D.
National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA 15212-5234
bernard.fisher@nsabp. org 1
Early Breast Cancer Trialists' Collaborative Group
CrossRef | Web of Science | Medline2
Fisher B ,Montague E ,Redmond C , et al. Findings from the NSABP Protocol No. B-04: comparison of radical mastectomy with alternative treatments for primary breast cancer. I. Radiation compliance and its relation to treatment outcome. Cancer 1980;46:1-13
CrossRef | Web of Science | Medline3
Early Breast Cancer Trialists' Collaborative Group
Full Text | Web of Science | Medline
