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Post-Mastectomy Chest Wall Irradiation: An Ongoing Controversy
-Allen S. Lichter, M.D. and Lori J. Pierce, M.D.
For more than 50 years, clinical researchers have been studying
the role of post-mastectomy chest wall irradiation in the
management of patients with local/regional breast cancer.
The impetus for these studies is relatively straightforward.
In some patients, especially those with positive axillary
nodes, mastectomy is followed months to years later with a
local recurrence on the chest wall. The risk of such an event
is, over time, somewhere in the range of 10 to 30 percent
(1). The risk of chest wall recurrence increases with the
number of positive lymph nodes and also with the size of the
primary tumor. Thus patients with T3 primary tumors (greater
than 5 cm) who have positive nodes have a risk of local recurrence
that is 30 percent or more.
Effectiveness of Radiation
When radiation is utilized in the post-mastectomy setting,
the risk of chest wall recurrence decreases substantially
to around 5 percent. This effect of decreased chest wall recurrence
has been seen in every trial of chest wall radiation ever
In some trials, disease-free survival is increased in radiated
patients and meta-analysis suggest that the risk of dying
from breast cancer is also reduced (2). Many practitioners
would argue that chest wall radiation is worth using in high-risk
populations - typically for women with large primaries or
four or more positive axillary lymph nodes - solely on the
basis of reduced local recurrence and increased disease-free
Most practitioners would agree that a local chest wall recurrence
is a psychologically devastating event for most patients and,
if the disease cannot be controlled with a combination of
surgery and radiation, can be a devastating physical event
as well. Clinical experience indicates that half or fewer
of local chest wall failures ultimately can be controlled,
thus giving way to the argument that preventing such failures
is superior to attempting to treat them when they occur (3).
New Clinical Trial Evidence
However, many investigators have insisted that chest wall
radiation should not be routinely employed in high-risk women
unless it could be shown to increase overall survival. Until
recently, evidence for overall survival benefit stemming from
irradiation was elusive. Technical factors, especially those
associated with treating the internal mammary lymph nodes
and the attendant increased radiation to the heart, led to
an increase in cardiac mortality that canceled any survival
benefit that might have been a by-product of radiation (4).
However, two recent trials were published in October 1997,
which show clear survival benefits with the use of chest wall
irradiation. The trials, one from Denmark (5) and one from
Canada (6), are summarized in Table 1.
Both trials treated node positive patients who were premenopausal
(the Danish trial had about 10 percent of its patients who
were T3, N0). All women in the trial received CMF chemotherapy
and half were randomized to receive chest wall radiation.
The results of the studies are shown in Figure
1. The results are strikingly similar with a 7 to 8 percent
increase in overall survival at 10 to 15 years following treatment.
Critique of the Trials
There have been many criticisms leveled at these two trials,
and certainly no trial is free from all methodological concerns.
Probably the most serious critique concerns the high rate
of local failure seen in these studies. The axillary lymph
node dissection, especially in the Danish trial, was limited,
and the number of nodes recovered was far less than the typical
lymph node dissection done in the United States. Consequently,
nearly half the local failures were in the axilla, whereas
in this country an axillary failure is uncommon after a level
I, II axillary dissection.
Thus, there is concern that chest wall and regional irradiation
in both of these studies simply made up for less than ideal
surgery, and some investigators speculate that if a more complete
surgical procedure was performed, the results of these trials
would have been negative. Nonetheless, one thing is clearly
shown by these two trials: a reduction in local failures can
lead to a reduction in breast cancer metastasis and an improvement
in overall survival. This is an extremely important concept
Since post-mastectomy chest wall irradiation in high-risk
patients has added to the local effectiveness of surgery in
every trial ever done, one might speculate that even if more
complete surgery were performed and the local failure rate
in the control group was lowered, radiation would still add
to the outcome of these patients, albeit, not to the extent
that it did in these trials. In order to clarify this point
more completely, a new study of post-mastectomy chest wall
irradiation has been proposed by the authors. While it will
take some additional time to develop the results from this
study, a well-performed trial in the United States should
go a long way towards finally ending all controversy concerning
the effectiveness of chest wall irradiation in the treatment
of breast cancer.
In the meantime, what shall we recommend for patients who
are treated prior to the activation of the national study
or who refuse entry into the study once it is activated? At
the University of Michigan, patients with four or more positive
axillary lymph nodes are routinely treated with radiation
therapy post mastectomy (8). This is true for pre- and post-menopausal
patients and is based on the increased local control that
radiation can offer, to say nothing of the possible increase
in overall survival stemming from this therapy.
All patients who have T3 or T4 primaries receive radiation,
as well as those patients with positive margins following
mastectomy. In pre-menopausal patients, we consider radiation
to the chest wall for those women with one to three positive
nodes because of the increase in survival seen in this subset
of patients in the Vancouver study cited previously. Virtually
all women who are candidates for chest wall radiation will
also be receiving systemic chemotherapy. Our own style of
treatment is to deliver all the chemotherapy up front and
then follow with the chest wall radiation as the final therapeutic
In summary, chest wall radiation adds to the local
control in high-risk patients, namely those with four or more
positive lymph nodes and/or large primary tumors. Studies
from Canada and Denmark indicate that this therapy may also
be associated with a survival advantage, especially in pre-menopausal
patients. Additional clinical research proposed by our group
will help further clarify the role of post-mastectomy chest
wall irradiation. An excellent summary of this subject is
written by Recht et al in the August 1998, Journal of Clinical
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1. Fowble B. Postmastectomy radiation: then and
now. Oncology. 11: 213-239, 1997.
2. Early Breast Cancer Trialists' Collaborative Group. Effects
of radiotherapy and surgery in early breast cancer. N Engl
J Med. 333: 1444-1455, 1995.
3. Stadler B, Kogelnik H. Local control and outcome of patients
irradiated for isolated chest wall recurrences of breast cancer.
Radiotherapy and Oncology. 8: 105-111, 1987.
4. Cuzick J, Stewart H, Rutqvist L, et al. Cause-specific
mortality in long term survivors of breast cancer who participated
in trials of radiotherapy. J Clin Oncol. 12: 447-453, 1994.
5. Overgaard M, Hansen P, Overgaard J, et al. Postoperative
radiotherapy in high-risk premenopausal women with breast
cancer who receive adjuvant chemotherapy. N Engl J Med. 237:
6. Ragaz J, Jackson S, Ian N, et al. Adjuvant radiotherapy
and chemotherapy in node-positive premenopausal women with
breast cancer. N Engl J Med. 337: 956-962, 1997.
7. Hellman S. Stopping metastases at their source. N Engl
J Med. 337: 996-997, 1997.
8. Pierce L. Defining the role of post-mastectomy radiotherapy:
the new evidence. Oncology. 10: 991-1002, 1996.
9. Recht A, Bartelink H, Fourquet A, Fowble B, et al. Postmastectomy
radiotherapy: Questions for the twenty-first century. J Clin
Oncol. 16(8): 2886-2895, 1998.
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Post-Mastectomy Radiotherapy Trials
||British Columbia (6)
|Year of Accrual
|Number of Patients Randomized
||TM + AXD
|Locoregional failure with
|Disease-free Survival with
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Overall survival in the Danish Breast Cancer Cooperative
Group Trial. (5)
Overall survival in the British Columbia Trial. (6)
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