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 patients.
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 breast cancer.
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 all.