Correspondence
Local Therapy and Survival in Breast Cancer
N Engl J Med 2007; 357:1051-1052September 6, 2007
- Article
To the Editor:
One of the shortcomings of the article on local therapy and survival in breast cancer, by Punglia et al. (June 7 issue),1 is the claim that a decrease in breast-cancer mortality and overall mortality as a result of radiation therapy “firmly support[s] a causal link between local control and overall survival in some patients.” Although surgical removal of the breast is the most effective method of local control, the authors' statement that “pooled analyses of randomized trials comparing mastectomy with breast-conserving therapy have shown equivalent survival” is contrary to that thesis. In the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) 2000 overview,2 although radiation therapy appreciably decreased local recurrence, benefits of only 2.1% and 1.2% in overall survival and 3.0% and 4.8% in breast-cancer mortality were noted at 10 and 20 years, respectively. Those modest benefits were partially offset by small disadvantages in deaths not related to breast cancer. Those findings, confirmed by the Cochrane Collaboration,3 support one of the principles of the Fisher hypothesis that “variations in local-regional therapy are unlikely to substantially affect survival.”4 Another EBCTCG meta-analysis showed that systemic therapies not only decreased local and distant disease but also substantially improved survival.5 The claim of a causal relationship between a reduction in local recurrence and improved survival when surgery and radiation therapy are used, either alone or in conjunction with systemic therapy, is tenuous.
5 ReferencesBernard Fisher, M.D.
Stewart J. Anderson, Ph.D.
University of Pittsburgh, Pittsburgh, PA 15213
fisherb2@upmc.edu 1
Punglia RS ,Morrow M ,Winer EP ,Harris JR . Local therapy and survival in breast cancer. N Engl J Med 2007;356:2399-2405
Full Text | Web of Science | Medline2
Early Breast Cancer Trialists' Collaborative Group
CrossRef | Web of Science | Medline3
Early Breast Cancer Trialists' Collaborative Group
Medline4
Fisher B . Laboratory and clinical research in breast cancer -- a personal adventure: the David A. Karnofsky memorial lecture. Cancer Res 1980;40:3863-3874
Web of Science | Medline5
Early Breast Cancer Trialists' Collaborative Group (EBCTCG)
CrossRef | Web of Science | Medline
To the Editor:
Punglia et al. cite the 2005 EBCTCG meta-analysis,1 which showed a 4-to-1 ratio between reduced local recurrences and decreased deaths from cancer with postsurgical radiation therapy. One of Punglia's coauthors and others also advocate universal radiation therapy after breast conservation for ductal carcinoma in situ (DCIS).2
The 2000 EBCTCG meta-analysis3 showed an increase in non–cancer-related deaths caused by radiation that offset the advantage of reduced deaths from breast cancer throughout the 20-year follow-up period, eventuating in an unchanged overall survival. The 2005 EBCTCG report1 noted these increases in deaths from lung cancer (risk ratio, 1.78) and deaths from cardiovascular causes (risk ratio, 1.27) with adjuvant radiation therapy, yet with only a 1% reduction in breast-cancer mortality at 15 years when the reduction in local recurrences was less than 10%.
The review by Punglia et al. and the 2005 EBCTCG meta-analysis fail to extrapolate these data in order to appreciate that, given the minimal risk of death associated with small invasive breast cancers (T1a or T1b) and DCIS, the added risk of death from radiation is still present and may actually reduce overall survival in the current majority of breast cancers with these favorable presentations.
3 ReferencesBlake Cady, M.D.
24 Walnut Pl., Brookline, MA 02445
bcady123@comcast.net 1
Clarke M ,Collins R ,Darby S , et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005;366:2087-2106
Web of Science | Medline2
Buchholz TA ,Haffty BG ,Harris JR . Should all patients undergoing breast conserving therapy for DCIS receive radiation therapy? Yes: radiation therapy, an important component of breast conserving treatment for patients with ductal carcinoma in situ of the breast. J Surg Oncol 2007;95:610-613
CrossRef | Web of Science | Medline3
Early Breast Cancer Trialists' Collaborative Group
CrossRef | Web of Science | Medline
Author/Editor Response
In response to Drs. Fisher and Anderson: we believe that the EBCTCG data1 provide strong evidence of a causal link between the absolute magnitude of the reduction in local recurrence at 5 years and the absolute magnitude of the improvement in 15-year survival. These data are derived from randomized trials in which the only difference between treatment groups was more or less aggressive local therapy, and the linkage is seen consistently across the trials in several different treatment comparisons.
The argument for causality is strengthened by the observed proportionality — that is, the greater the absolute reduction in 5-year local recurrence, the greater the absolute reduction in 15-year mortality. And causality is also supported by the observed time course, such that the reduction in local recurrence is seen during the first 5 years and the improved survival is seen only in the succeeding 10 years. Moreover, the effect is substantial. For example, for the trials randomly assigning patients after breast-conserving surgery to receive radiation therapy or not to receive it, the absolute decrease in breast-cancer mortality was 5.4% at 15 years, which is similar to that seen with adjuvant multiple-agent chemotherapy.2
In the trials comparing breast-conserving therapy and mastectomy, women randomly assigned to breast-conserving surgery also received radiation therapy, whereas those randomly assigned to mastectomy did not. Therefore, the differences in both 5-year local recurrence and 15-year survival were small.
Dr. Cady raises an important point — namely, that radiation therapy can result in increased late, non–breast-cancer mortality. This was seen particularly in the older trials of radiation therapy after mastectomy in which substantial volumes of heart and lung were irradiated, but such effects are much less evident in the more recent trials of radiation therapy after breast-conserving surgery in which the irradiated volumes of heart and lung were much smaller. We have stressed to our radiation oncologist colleagues that computed-tomography–based simulation is critical for patients with left-sided breast cancer so that the volume of irradiated heart can be assessed and minimized. On the basis of the accruing data on cardiac toxicity, in patients with left-sided DCIS in which local radiation therapy would result in substantial heart irradiation, we believe that such radiation therapy should not be used.
2 ReferencesRinaa S. Punglia, M.D., M.P.H.
Dana–Farber and Brigham and Women's Cancer Center, Boston, MA 02115
rpunglia@lroc.harvard. edu Monica Morrow, M.D.
Fox Chase Cancer Center, Philadelphia, PA 19111Jay R. Harris, M.D.
Dana–Farber and Brigham and Women's Cancer Center, Boston, MA 021151
Clarke M ,Collins R ,Darby S , et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005;366:2087-2106
Web of Science | Medline2
Early Breast Cancer Trialists' Collaborative Group (EBCTCG)
CrossRef | Web of Science | Medline
- Citing Articles (1)
Citing Articles
1
Ray Lin, Prabhakar Tripuraneni. (2011) Radiation Therapy in Early-Stage Invasive Breast Cancer. Indian Journal of Surgical Oncology 2:2, 101-111
CrossRef
