Radiation therapy for invasive breast cancer: not just for local control.

Some of the earliest randomized trials in all of clinical medicine, conducted in the1950s, tested theuseof 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 comparedwithmastectomywerestarted.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 thefieldon the statusofRT in invasivebreast cancer. Two of these reviews summarize the latest information (primarily from randomized clinical trials) on the use of RT aftermastectomy 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 inpatientswith 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 tomakeRTmore 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 distantmetastases 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), 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 theDanish 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 ofRT is proportional, as is seenwithmost therapies inbreast 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. Anothermajor theme in these reviews is theneed tobalance the benefits of RT against its costs, complications, and inconvenience. One of the most serious complications seen withRT for breast cancer, particularly for left-sided cancers, is increased late cardiac mortality. Early techniques of breast cancer RT, especially those techniques which intended to treat the internal mammary nodes, resulted in substantial doses of RT to the heart. It is fortunate that improved RT techniques, especially with the use of computed tomography–based simulation, allow for exclusion of the VOLUME 23 d NUMBER 8 d MARCH 1