1. VOLUME 28 NUMBER 3 JANUARY 20 2010
JOURNAL OF CLINICAL ONCOLOGY C O R R E S P O N D E N C E
Local Control, Survival, and the preting this to mean that local control improves OS. The better inter-
pretation is that some local recurrences are really a manifestation of
Fisher Hypothesis systemic disease, and these cause the subgroup to have inferior sur-
vival. This would explain why in these trials improved local control did
TO THE EDITOR: Rabinovitch and Kavanagh1 seek a middle not improve OS.
ground between the Fisher and Halsted concepts of breast cancer. This leaves these trial results at odds with the meta analysis, but
They report that a meta-analysis showed a highly significant reduction these two large randomized prospective clinical trials tested the same
in annual breast cancer mortality when patients who had undergone hypothesis in two different clinical arenas—B04 was a trial of lymph
lumpectomy also received radiation therapy. Yet the single largest trial node control, B-06 was a trial of breast parenchyma. Both have pro-
evaluating these treatments reported no difference in overall survival vided confirmation of the Fisher hypothesis with 20- and 25-
(OS) out to 20 years.2,3 Should meta-analyses always trump prospec- year follow-up.3,4
tive trials?
Richard G. Margolese
In fact, the B-06 trial can be interpreted as a confirmation of the Department of Oncology, McGill University, Montreal, Quebec, Canada
B-044 trial. Both trials illustrate the lack of effect on OS when local
control is clearly not obtained. In the case of B-04, 39% of the patients
AUTHOR’S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
with clinically negative axillae randomly assigned to radical mastec- The author(s) indicated no potential conflicts of interest.
tomy had histologically positive nodes. Those randomly assigned to
no axillary treatment obviously had the same incidence of histologic REFERENCES
disease, yet only 18% ever developed clinical evidence of recurrence in 1. Rabinovitch R, Kavanagh B: Double helix of breast cancer therapy: Inter-
the axilla. Although that subset had an inferior survival, the overall twining the Halsted and Fisher Hypotheses. J Clin Oncol 27:15:2422-2433, 2008
group of patients with untreated axillae had the same OS as those 2. Fisher B, Bauer M, Margolese RG, et al: Five-year results of a randomized
clinical trial comparing total mastectomy and segmental mastectomy with or
having the Halsted radical mastectomy. without radiation in the treatment of breast cancer. N Engl J Med 312:11:665-
Similarly, after lumpectomy, radiation therapy reduced the local 673, 1985
recurrence rate from 38% to 9%. Although the subsets with local 3. Fisher B, Anderson S, Bryant J, et al: Twenty year follow up of a randomized
recurrence did worse, the overall outcome of the total mastectomy trial comparing total mastectomy, lumpectomy and lumpectomy plus irradiation
for the treatment of invasive breast cancer. N Engl J Med 347:1233-1241, 2002
group or the radiation therapy group was not better than the lumpec- 4. Fisher B, Jeong JH, Anderson S, et al: Twenty-five year follow up of a
tomy alone group. One fairly obvious conclusion is that pathologic randomized trial comparing radical mastectomy, total mastectomy and total
margin sampling does not find all positive margins and it is the mastectomy followed by irradiation. N Engl J Med 75:347-567, 2002
5. Fisher B, Anderson S, Fisher ER, et al: Significance of ipsilateral breast
radiation therapy that helps boost local control, but this does not
tumor recurrence after lumpectomy. Lancet 8763:338 327-331, 1991
translate to better OS.5
In both trials, the group suffering locoregional recurrence does DOI: 10.1200/JCO.2009.24.6520; published online ahead of print at
worse, but there is a danger of confusing cause and effect and inter- www.jco.org on December 14, 2009
■ ■ ■
Journal of Clinical Oncology, Vol 28, No 3 (January 20), 2010: p e39 © 2009 by American Society of Clinical Oncology e39
Downloaded from jco.ascopubs.org on October 7, 2010. For personal use only. No other uses without permission.
Copyright © 2010 American Society of Clinical Oncology. All rights reserved.