Radiation Therapy for Invasive Breast Cancer: Not Just for Local Control

Some of the earliest randomized trials in all of clinical medicine, conducted in the 1950s, tested the use of radiation therapy (RT) in patients with invasive breast cancer treated with mastectomy. Subsequently, beginning in the 1960s, trials of breast-conserving surgery combined with RT compared with mastectomy were started. Over time, considerable information has been accumulated on the use of RT in patients with invasive breast cancer, both after mastectomy and after breast-conserving surgery.

In this issue of the Journal of Clinical Oncology, there are three timely reviews by experts in the field on the status of RT in invasive breast cancer. Two of these reviews summarize the latest information (primarily from randomized clinical trials) on the use of RT after mastectomy and after breast-conserving surgery. The third review summarizes the latest information on the promising innovative approach of accelerated partial breast irradiation. All the reviews discuss the current state of the art and identify areas of opportunities.

There are a couple of major themes in these reviews.

One is the important issue of assessing the value of RT separately when used in the absence of, or in conjunction with, adjuvant systemic therapy. Given the demonstrated value of adjuvant systemic therapy in improving relapse-free and overall survival, systemic therapy (hormonal therapy and/or chemotherapy) is now typically used in patients with invasive breast cancer. In the absence of systemic therapy, RT reduces local recurrence after either mastectomy or breast-conserving surgery by about 70%.

Theoretically, the use of adjuvant systemic therapy by itself might lower local recurrence (lessening the need for RT), interact with RT to make RT more or less effective, and/or provide spatial complementarity (RT for local and systemic therapy for systemic disease) to improve survival when both are used. What has, in fact, been serendipitous, is that these systemic therapies—hormonal therapy more than chemotherapy—interact with RT to substantially improve local tumor control. More important is the finding that RT, when used with systemic therapy, decreases distant metastases and improves survival. For those of us who grew up in the early "Fisherian" Era (circa National Surgical Adjuvant Breast and Bowel Project Trial B-04),11 where systemic therapy was not used and RT was found not to influence survival, this new finding is a dramatic one. It suggests that when systemic therapy is effective at controlling micrometastatic disease, it is important to obtain local tumor control. Eventually, it is anticipated that systemic therapy will advance in its effectiveness so that no local therapy is needed; however, until now, the use of systemic therapy has increased the role of local therapy.

Of note in the Danish postmastectomy trials testing RT in patients treated with adjuvant systemic therapy, there was about a 30% rate of local recurrence in the absence of RT, and RT resulted in a 10% absolute improvement in survival. If the benefit of RT is proportional, as is seen with most therapies in breast cancer, and acts through its reduction in local recurrence, it would suggest that patients with a 15% rate of local recurrence would have a 5% absolute improvement in survival. Unfortunately, given the failure to accrue to the large randomized trial of postmastectomy RT in patients with one to three positive nodes treated with adjuvant systemic therapy (a group with an anticipated local recurrence rate of about 15%), this extrapolation remains conjectural.