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668
COMMENTARY
‘‘One to Three’’ or ‘‘Four or
More’’?
Selecting Patients for Postmastectomy Radiation
Therapy
Lawrence B. Marks, M.D.
Leonard R. Prosnitz, M.D.
Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina.
P
Address for reprints: Lawrence B. Marks, M.D.,
Department of Radiation Oncology, Box 3085,
Duke University Medical Center, Durham, NC
27710.
Received July 24, 1996; revision received October 8, 1996; accepted October 25, 1996.
ostmastectomy radiation therapy (RT) continues to be controversial, but perhaps less so than in the past.1 – 4 Studies convincingly
demonstrate that RT improves locoregional control (LRC) and disease
free survival in lymph node positive patients,5 – 12 and perhaps in
lymph node negative patients as well.9,11,13 Breast carcinoma specific
mortality is also improved with RT.1,4 However, an improvement in
overall survival (OS) has been more difficult to demonstrate.2 In a
1995 overview, a nonstatistically significant improvement in OS was
reported with the addition of RT.2 The inability to convincingly demonstrate an improvement in OS with RT is likely due to excess cardiac
mortality after RT that counteracts the reduction in breast carcinoma
deaths after RT.1,14 The incidence of such RT-induced mortality is
highly dependent on the radiation technique used10,14 – 16 and should
be extremely low with careful modern treatment planning.3,16 – 18
Because RT has a clear impact on LRC but a debatable impact
on OS, many breast oncologists have settled on a ‘‘compromise’’
policy wherein only patients at high risk of locoregional (LR) recurrence are offered RT. Because the LR failure rate increases with the
number of positive axillary lymph nodes,19 RT has been advocated in
patients with four or more, but not one to three, positive axillary
lymph nodes. This is a rational approach as it pertains to LRC, but
might not be appropriate if the goal of RT is to improve OS. Improvements in LRC and OS may not necessarily parallel each other.
The data from six randomized clinical trials can be interpreted to
demonstrate an improvement in OS with RT (Table 1). These studies
enrolled pre- and postmenopausal women, and some used systemic
chemotherapy. In general, only patients with a moderate-to-high risk
of LR relapse were included (either T3 – 4 primary tumors [American
Joint Committee on Cancer, AJCC] or positive axillary lymph nodes).
The Stockholm I and Oslo trials also included lymph node negative
women, but only the data from the lymph node positive patients are
included in Table 1. In some instances, the data in the table are
not precise because they were estimated from graphs and raw data
provided in the publications.
Only two of these six trials meet the strict classic P õ 0.05 statistical criteria.6,12,13 The remaining four studies report ‘‘trends’’ in favor
of the RT. The observations in these four studies should not be disre-
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W: Cancer
Selecting Patients for Postmastectomy RT/Marks and Prosnitz
669
TABLE 1
Postmastectomy Radiation Therapy
Patient
no.
Entry criteria
British Columbia
Cancer
Agency 7,8
Danish Breast
Cancer Group,
Study 6,12
82 b
82 c
Helsinki University13
318
LN /
1473
1202
120
T3-4 or LN/
T3-4 or LN/
T3
Stockholm II10
427
Stockholm I 9,11
Oslo5
238
387
T size ú 3 cm
or LN/
LN /
LN /
Study
%¢
T3
%°3
LN
%¢4
LN
Menopausal
status
Chemotherapy
Data
at (yrs)
Survival
0RT
Survival
/RT
P
value
65
35
Pre
CMF
10a
54
63
0.09
15
12
100
62
57
27
28
34
39
Pre
Post
Pre and post
9
9
6
50
45
60
56
50
80
0.01
0.38
0.01
3
67
23
Post
CMF
TAM
VAC {
levamisole
CMF { TAMb
10
51
63
ns
77
23
Pre and post
Pre and post
10
12
39
É45
45
É55
0.21
0.15
LN: lymph node; RT: radiation therapy; CMF: cyclophosphamide, methotrexate, and 5-fluorouracil; TAM: tamoxifen; VAC: vincristine, doxorubicin, and cyclophosphomide; ns: not significant.
a
Interval is not stated in recent abstract but is 10 years in prior abstract.
b
Some patients received noncyclophosphamide, methotrexate, and 5-flurorouracil chemotherapy.
garded, given their statistical limitations. The number
of patients needed to demonstrate an approximately
5% improvement in OS at the P Å 0.05 level is approximately 3000. These studies had the statistical power
to detect larger differences in OS but were inadequate
to detect small differences. Thus, the nonstatistically
significant P values might be more a measure of inadequate study size rather than the absence of a clinically
meaningful difference.20
The majority of patients in these studies had one
to three positive axillary lymph nodes. Only a minority
of the patients had four or more positive lymph nodes.
The results in the one to three versus four or more
positive lymph nodes subgroups are not generally
available. The Danish Breast Cancer Study did comment that most of the survival benefit was observed
in younger patients with four or more lymph nodes,
although the exact data were not given.6,12 In the British Columbia study, an improvement in distant disease free survival was noted in both the one to three
and four or more positive lymph node groups (P Å
0.06). Although the magnitude of the difference was
greater in the group with four or more positive lymph
nodes, the relative systemic recurrence rate was reduced by É30% in both groups (from 46% to 32% in
the group with one to three positive lymph nodes and
81% to 59% in the group with four or more positive
lymph nodes).7,8
Because patients with one to three positive lymph
nodes represented the majority of patients in the studies that suggest an improvement in OS with RT, it
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appears reasonable to recommend RT in these patients as well. If a 5% improvement in OS for the overall
group was derived entirely from approximately onethird of patients in the subgroup with four or more
positive lymph nodes, an approximate 15% improvement in OS would need to be achieved in that subgroup. In light of the available data, we recommend
that postmastectomy RT can be prescribed for all node
positive breast cancer patients. Locoregional RT
clearly improves LRC and appears to provide an approximately 5 – 10% improvement in overall survival,
a benefit quite similar to that provided by adjuvant
systemic therapy. Final resolution of the controversy
regarding the survival impact of postmastectomy RT
would require a very large prospective trial with thousands of patients such that clinically meaningful differences could be detected and appropriate patient subsets analyzed.
REFERENCES
1.
2.
3.
4.
Cuzick J, Steward H, Rutqvist L, Houghton J, Edwards R,
Redmond C, et al. Cause-specific mortality in long-term survivors of breast cancer who participated in trials of radiotherapy. J Clin Oncol 1994;12:447–53.
Early Breast Cancer Trialists’ Collaborative Group. Effects of
radiotherapy and surgery in early breast cancer. N Engl J
Med 1995;333:1444–55.
Pierce L. Editorial. Postmastectomy radiotherapy: more than
locoregional control. J Clin Oncol 1994;12:444–6.
Recht A. Editorial. The return (?) of postmastectomy radiotherapy. J Clin Oncol 1995;13:2861–4.
W: Cancer
670
CANCER February 15, 1997 / Volume 79 / Number 4
5.
Host H, Brennhovd IO, Loeb M. Postoperative radiotherapy
in breast cancer—long-term results from the Oslo Study.
Int J Radiat Oncol Biol Phys 1986;12:727–32.
6. Overgaard M, Christensen JJ, Johansen H, Nybo-Rasmussen
A., Rose C, van der Kooy P, et al. Evaluation of radiotherapy
in high-risk breast cancer patients: report from the Danish
Breast Cancer Cooperative Group (DBCG 82) Trial. Int J Radiat Oncol Biol Phys 1990;19:1121–4.
7. Ragaz J, Jackson SM, Plenderleith IH, Wilson K, Basco V,
Knowling M, et al. Can adjuvant radiotherapy (XRT) improve
the overall survival (OS) of breast cancer (BR CA) patients
in the presence of adjuvant chemotherapy (CT)? 10 Year
analysis of the British Columbia Randomized Trial [abstract]. Proc ASCO 1993;12:60.
8. Ragaz J, Jackson S, Le N, Plenderleith IH, Spinelli J, Wilson K,
et al. Can adjuvant locoregional radiotherapy (XRT) reduce
systemic recurrences in stage I–II breast cancer patients?
Recurrence analysis of the British Columbia Randomized
Trials [abstract]. Proc ASCO 1996;15:121.
9. Rutqvist LE, Cedermark B, Glas U, Johansson H, Rotstein S,
Skoog L, et al. Radiotherapy, chemotherapy, and tamoxifen
as adjuncts to surgery in early breast cancer: a summary of
three randomized trials. Int J Radiat Oncol Biol Phys
1989;16:629–39.
10. Rutqvist LE. Cedermark B. Glas U, Johansson H, Rotstein
S, Skoog L, et al. Randomized trial of adjuvant tamoxifen
combined with postoperative radiation therapy or adjuvant
chemotherapy in postmenopausal breast cancer. Cancer
1990;66:89–96.
11. Wallgren A, Arner O, Bergström J, Blomstedt B, Granberg P,
Räf L, et al. Radiation therapy in operable breast cancer:
results from the Stockholm trial on adjuvant radiotherapy.
Int J Radiat Oncol Biol Phys 1986;12:533–7.
12. Overgaard, M. The role of postmastectomy radiotherapy in
high-risk breast cancer patients receiving adjuvant systemic
therapy. In: Kogelnik HD, editor. Proceedings of the 5th In-
/ 7b4c$$0879
01-27-97 07:32:14
cana
13.
14.
15.
16.
17.
18.
19.
20.
ternational Meeting on Progress in Radio-Oncology, Salzburg, Austria, May 10–14, 1995. Bologna, Italy: Monduzzi
Editore.
Klefström P, Gröhn P, Heinonen E, Hosti L, Holsti P. Adjuvant postoperative radiotherapy, chemotherapy, and immunotherapy in Stage III breast cancer. Cancer 1987;60:936–
42.
Rutqvist LE, Lax I, Fornander T, Johansson H. Cardiovascular mortality in a randomized trial of adjuvant radiation therapy versus surgery alone in primary breast cancer. Int J Radiat Oncol Biol Phys 1992;22:887–96.
Haybittle JL, Brinkley D, Houghton J, A’Hern RP, Baum M.
Postoperative radiotherapy and late mortality: evidence
from the Cancer Research Campaign trial for early breast
cancer. BMJ 1989;298:1611–4.
Levitt SH, Fletcher GH. Trials and tribulations: do clinical
trials prove that irradiation increases cardiac and secondary
cancer mortality in the breast cancer patient? Int J Radiat
Oncol Biol Phys 1991;20:523–7.
Levitt SH. Editorial. Cardiac damage following radiation
treatment of primary breast cancer: assessing the risk, exploring the cause. Int J Radiat Oncol Biol Phys 1992;22:1157–
8.
Marks LB, Hebert ME, Bentel G, Spencer DP, Sherouse GW,
Prosnitz LR. To treat or not to treat the internal mammary
nodes: a possible compromise. Int J Radiat Oncol Biol Phys
1994;29:903–9.
Fowble B, Gray R, Gilchrist K, Goodman RL, Taylor S, Tormey DC. Identification of a subgroup of patients with breast
cancer and histologically positive axillary nodes receiving
adjuvant chemotherapy who may benefit from postoperative radiotherapy. J Clin Oncol 1988;6:1107–17.
Simon R. Design and conduct of clinical trials. In: DeVita
VT Jr., Hellman S, Rosenberg A, editors. Cancer: principles
and practice of oncology. 4th edition. Philadelphia: J.B. Lippincott Co., 1993:418–40.
W: Cancer
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