Postmastectomy radiotherapy has been used since the early part of the
20th century in an effort to decrease local recurrences and potentially
improve survival. It clearly reduces the rate of local chest-wall failure
following mastectomy, increases relapse-free survival, leads to a reduction
in distant metastases, and decreases the number of deaths from breast cancer.
Despite all of these beneficial effects, however, we still do not know
for certain how best to employ this therapy in the management of patients
with primary operable breast cancer.
In the current article, Dr. Fowble provides a comprehensive, scholarly
review of postmastectomy radiotherapy and makes recommendations for its
use. She thoroughly discusses the sizable literature on this subject and
also summarizes it for us in tabular form. I believe that this work will
be a major reference for students of this field.
Why the Confusion and Contentiousness?
Why has there been such confusion and contentiousness regarding the
use of postmastectomy radiotherapy? A good part of the problem relates
to the design of the numerous studies described by Dr. Fowble. For the
first 2 to 3 decades of study of this subject, clinical trials were performed
without systemic chemotherapy. These trials used inconsistent and, at times,
inadequate radiotherapy techniques. They often mixed node-positive and
node-negative patients and liberally allowed the use of hormonal manipulation,
typically ovarian ablation. The vast majority of trials accrued small numbers
of patients, and thus, had little statistical power to show a survival
difference with the use of postmastectomy radiotherapy should one exist.
We recognize today that survival improvement in breast cancer will come
in small steps, not in large leaps. To look for statistical survival differences
of 5% to 10% requires large studies, which today usually are performed
through the collaboration of multiple national cooperative groups. Studies
of 100 to 300 patients per arm are not of sufficient size to reveal small
survival differences. Yet, when one pools these multiple trials, the reduction
in local recurrences and the increase in relapse-free survival are clearly
demonstrated. Furthermore, a reduction in deaths from breast cancer is
seen. Although meta-analyses do not reveal increases in overall survival
with the use of post-mastectomy radiotherapy, some of the difference may
be obscured due to an increase in late cardiac mortality among irradiated
Modern radiotherapy techniques, including CT-based treatment planning,
can allow for chest-wall irradiation to be performed without radiating
large volumes of the heart. It is certainly a reasonable hypothesis that
with excellent radiotherapy technique that may reduce or eliminate late
cardiac mortality, coupled with high-quality systemic chemotherapy, postmastectomy
chest-wall radiation could result in a survival advantage for women with
node-positive breast cancer. This hypothesis could and should be tested
in a large randomized prospective trial.
Should the Internal Mammary Nodes Be Treated?
One of the interesting radiotherapy issues is whether the internal mammary
lymph nodes should be treated in these node-positive patients. Dr. Fowble
states that radiation to the internal mammary chain (IMC) is not indicated.
She bases this conclusion on the facts that radiating the IMC field would
increase cardiac morbidity and mortality, and that these nodes are an infrequent
site of local failure. Yet, in series of axillary node-positive patients
in whom the internal mammary lymph nodes were biopsied, they contained
identifiable metastases approximately 30% of the time. Subset analysis
of some post-mastectomy chest-wall irradiation trials indicates that patients
with medial tumors, coincidentally those with the highest likelihood of
having IMC involvement, derived the biggest survival benefit from postmastectomy
chest- wall irradiation that included the IMC within the radiotherapy fields.[2,3]
It seems to me that if the goal of postmastectomy chest wall irradiation
is to increase survival through the elimination of residual locoregional
breast cancer cells, ignoring the IMC is perilous. If the goal of the treatment
is just to reduce the incidence of locoregional chest-wall failure, then
I agree with Dr. Fowble that treating the IMC is not indicated. Using sophisticated
treatment planning and concentrating on the superior portion of the internal
mammary lymph node chain, the region most likely to contain metastatic
disease, should allow IMC treatment to be given safely by those practitioners
who feel that such treatment is warranted.
Time for a National Cooperative Trial
Dr. Fowble concludes with a recommendation that high-risk patients,
ie, those with primary tumors greater than 5 cm in size and four or more
positive axillary lymph nodes, deserve careful consideration for postmastectomy
chest-wall irradiation. This year in the United States, approximately 25,000
such patients will present with breast cancer. It seems a shame that after
decades of study of postmastectomy chest-wall irradiation, we still do
not know the definitive place of this therapy in the treatment of operable
This is clearly an important question that deserves to be answered.
Ample numbers of patients need this information, and they deserve our best
efforts in securing an answer to this straightforward clinical question.
The time is clearly ripe for a national cooperative trial testing post-mastectomy
chest-wall irradiation so that we may learn its proper role once and for
1. Veronesi U, Cascinelli N, Bufalino R, et al: Risk of internal mammary
lymph node metastases and its relevance on prognosis of breast cancer patients.
Ann Surg 198:681-684, 1983.
2. Host H, Brennhovd IO, Loeb M, et al: Postoperative radiotherapy in
breast cancer--long-term results from the Oslo study. Int J Radiat Oncol
Biol Phys 12:727-732, 1986.
3. Rutqvist LE, Pettersson D, Johansson H: Adjuvant radiation therapy
vs. surgery alone in operable breast cancer: Long-term follow-up of a randomized
clinical trial. Radiother Oncol 26:104-110, 1993.