Isolated loco-regional recurrence of breast cancer after mastectomy represents several clinical challenges. The current staging system has no mechanism to categorize these patients and treatment approaches are not standardized. Furthermore, these patients are more likely to develop additional loco-regional recurrences, as well as distant metastases, despite the best available therapy. Complete surgical resection has typically been associated with improved local control and overall survival [3, 7, 8, 13], as has post-operative radiation therapy [7, 9, 14]. Systemic therapy is controversial, with at least one study showing no benefit to the addition of chemotherapy . However, many studies appear to show improved outcomes with the addition of systemic chemotherapy [16, 17] or hormonal therapy [10, 18] in this setting. In the same vein, with improved chemotherapeutic options and patient selection, some patients will have a complete response (CR) to neoadjuvant systemic therapy. In these patients, data from this study suggest that the addition of surgical excision, with its concomitant morbidity, may not be necessary, adding another layer of clinical complexity in an already challenging disease.
Multi-modality therapy including systemic therapy, surgery and radiation has the potential to cure selected patients. In this study, which represents the largest single institutional study to date, we observed a 77% locoregional control rate and a 55% overall survival rate at 5 years. This again highlights that aggressive local-regional therapy is appropriate and compares favorably to the most recent experience in a similar group of patients . We observed that the most important predictor for any outcome, including LRC, was the presence of residual gross disease at the time of radiation. Local failure was high at 38% in patients with clinically apparent residual disease and neither debulking surgery nor radiation dose escalation appeared to result in improved local control. Conversely, patients who achieved a complete response to chemotherapy and those with surgically resected disease had higher rates of loco-regional control.
We were dissatisfied with the overall loco-regional control rate in patients with isolated loco-regional recurrence from our last analysis of this patient cohort  and we speculated that dose escalation could be useful, as we had shown its value in inflammatory carcinoma . However, in this study we could not demonstrate a benefit to a 10% dose escalation for isolated LRR in breast cancer. LRC rates in both the standard and dose escalated groups were similar with no specific subset of patients exhibiting a benefit.
Our strategy in treating patients with isolated loco-regionally recurrent breast cancer involves comprehensive – as opposed to involved field – post-operative radiotherapy in addition to systemic therapy. At least one study of LRR in breast cancer specifically comparing treatment of the tumor only compared to elective nodal radiation showed a significant improvement in local control with comprehensive irradiation . In that study, multiple recurrences after radiation occurred outside the original area of recurrence. Here, however in our study all recurrences were in-field or at the field edge suggesting the appropriateness of the field selection and that intrinsic resistance is the primary cause for failure to control the disease.
In regards to the patient population as a whole, a number of indicators of poor prognosis were seen on univariate analysis, including nodal stage at the initial presentation as well as time to LRR after initial diagnosis. These factors are similar to those seen by ourselves and others [2, 6], and thus provide further verification of their adverse effect on local control and survival outcomes. As in primary breast cancer, lower tumor and nodal stage, ER positivity, and smaller size of the recurrent tumor were all prognostic of better outcomes.
However, by far, the most significant prognostic factor in this study was residual, clinically detectable or gross disease at the time of radiation. Patients with gross disease at the time of radiation had dramatically poorer locoregional control and survival outcomes than those patients with either a complete surgical excision or a CR to chemotherapy and dose escalation had no significant effect on outcome. Interestingly, in patients with a CR to chemotherapy, locoregional control rates were similar to those in patients who were treated with a complete excision, implying surgical resection might be optional after complete response to chemotherapy. If further surgical resection is not an option, additional systemic therapies including targeted agents and radiation sensitizers represent the most promising approach for those that did not respond to chemotherapy and had gross residual disease at the time of radiation, especially since failure to achieve local control virtually guarantees that the patient will subsequently develop systemic metastasis.
This study is limited by several factors inherent in all retrospective reviews. Although the standard and dose escalated groups were well balanced in regards to most known factors, confounding factors may have influenced the total dose selection. In addition, only 159 total patients were reviewed. While this represents that largest study of its kind, this number may not allow the current study to detect small differences in the outcomes measured. Further, the difference in total dose between the two schedules is not profound. These results must be considered hypothesis generating; however given the unlikelihood of a randomized trial in this setting the high rates of local failure among patients with gross residual disease at the time of radiation certainly demonstrate room for improvement in treatment approach.