Partial breast irradiation - Is it ready for prime time?

Combining lumpectomy and axillary dissection with breast irradiation (RT) has been established as a safe and effective alternative to mastectomy. More recently, this therapeutic approach has been refined in a number of ways. The importance of margin status has become better appreciated, and adequate margins are now achieved in the vast majority of cases. Surgical management of the axilla has also undergone revolutionary changes with the advent of sentinel lymph node surgery. The RT component of breast-conserving therapy has also improved. The use of three-dimensional treatment planning and multileaf three-dimensional dose compensation has improved the conformity and dose uniformity of radiation delivery. Finally, systemic treatments are now the standard rather than the exception for women with early-stage breast cancer, and it has been demonstrated that the use of systemic therapy significantly decreases the rate of breast recurrence, in addition to providing benefits against metastatic disease. With these improvements, both the rates of breast recurrences after breast conservation and the morbidity of locoregional treatment have decreased. For example, for favorable breast cancer, two recent series have indicated that the 8-year probability of breast recurrence for patients treated with adequate surgery, whole breast RT, and systemic treatment was only 3% (1, 2), and the toxicity associated with locoregional therapy was also quite low. How then can one improve on these outcomes? A natural inclination would be to study whether the “intensity” of the treatment package can be decreased while maintaining the excellent outcome. It is clear that the RT component of breast-conserving therapy is inconvenient, requiring daily treatments for 6–7 weeks. This clearly imposes a hardship for some patients who may not live close to a RT facility. In addition, in Canada and other countries, there is a national shortage of RT facilities, and breast cancer patients may have delays before having access to treatment. The societal costs of breast RT also should be considered, although recent studies have shown that breast RT is a cost-effective therapy (3). The first attempt at decreasing the intensity of treatment was to omit RT completely for subgroups of women with biologically favorable early-stage breast cancer. This attempt has generally been unsuccessful, and currently no subset of women with invasive breast cancer has been identified who is not at a greater risk of cancer recurrence if treated with breast-conserving surgery alone (1, 4). More recent attempts have been aimed at decreasing the overall treatment time. To accomplish this, hypofractionation schedules are required, which potentially decrease the therapeutic ratio and either accept a theoretical increased risk of tumor recurrence or an increased risk of normal tissue complications. Unlike prostate cancer, which has a low / ratio, no biologic rationale exists for testing hypofractionation schedules in breast cancer. Nonetheless, for a number of nonbiologic reasons, this strategy has been studied. A Phase III trial conducted in Canada and the United Kingdom compared a 3-week hypofractionated schedule of whole breast RT with a more conventional 5-week schedule (5). The initial results from this study were successful and indicated equivalence in both tumor control and normal tissue injury. Despite these data, the 3-week schedule has not been widely adopted in the United States. One reason is that the results of this trial have not fully matured, so it remains unclear whether the hypofractionation will result in increased late normal tissue effects. Partial breast treatment is a second new strategy designed to decrease the overall treatment time. In theory, by decreasing the volume of breast treated one may be able to increase the dose per fraction while maintaining a low toxicity profile. Partial breast treatments generally finish the RT in 5 days. Partial breast RT has been delivered using doubleplane brachytherapy implants, Mammosite brachytherapy, intraoperative orthovoltage treatment, intraoperative brachytherapy treatment, and intensity-modulated external beam RT. To date, most of the partial breast RT experience has been with afterloaded brachytherapy. The Radiation Therapy Oncology Group successfully completed a Phase