Multidisciplinary Management of Locoregional Recurrent Breast Cancer.

Abstract

Locoregional recurrence (LRR) from breast cancer represents a heterogeneous class of disease that has significant variation in its prognosis and preferred treatments. Therefore, the optimal management of LRR disease requires multidisciplinary assessment and integration of input from all disciplines involved in breast cancer management. In this review, we identify prognostic variables associated with the treatment outcome of LRR disease; discuss the roles of surgery, radiation, and systemic treatments; and define reasonable treatment algorithms to aid in the evaluation and management of patients. Unfortunately, there are few prospective clinical trials to provide high-level evidence regarding the optimal therapeutic strategy for patients with LRR disease. Such trials are difficult to design and execute because of the heterogeneity of prognostic factors and previous treatments of patients. In addition, LRR is becoming much less common with improvements in diagnostic and therapeutic management of primary disease. For example, the risk of development of LRR in patients with early-stage disease treated with breast-conserving surgery, whole-breast radiation, and appropriate systemic treatments is approximately 0.5% per year.1 This rate is almost half that seen in the first generation of breast-conserving therapy (BCT) trials conducted several decades ago, which averaged LRR rates of approximately 1% per year.2 A number of reasons have contributed to these improved outcomes, including better diagnostic imaging and tumor localization, improved pathologic techniques and attention to surgical margins, more optimal localization of radiation to intended targets, and increased use of effective systemic therapies. These therapeutic advances have also significantly decreased the rates of LRR in patients treated with mastectomy. In one study that focused on LRR for patients with 1-3 positive lymph nodes treated with mastectomy, the LRR rate in a more contemporary cohort who did not receive postmastectomy radiation was 2.8% compared with a rate of 9.5% in a similar staged cohort that was treated approximately 15 years earlier.3 In this study, the era in which the patient was treated was the most significant predictor of the risk of LRR for the cohort of patients who did not receive initial radiation, with an adjusted hazard ratio (HR) of 0.35 for the more recent era (P < .001). Table ​Table11 highlights many of the important prognostic factors for patients with LRR. One of the first considerations for patients with isolated LRR is to determine whether the disease represents a true recurrence versus a new primary, particularly for those with an in-breast recurrence. The following factors suggest a new primary: change in the biomarker profile and/or histopathology of the disease, recurrence is in a different quadrant of the breast compared with the primary tumor, and changes in gene-expression profiles. Investigators from MD Anderson Cancer Center evaluated 397 patients with an in-breast recurrence and classified approximately half as having a new primary and half as having a true recurrence (based on tumor location, histologic subtype, and biomarker profile). The new primary cohort had a better 10-year survival and developed metastatic disease less commonly than patients classified as true recurrence but were more likely to develop contralateral breast carcinoma.4 A similar study from Yale University compared 70 patients classified as having a new primary, with 60 patients classified as having a true recurrence. Again, those with a new primary had a better overall 10-year overall survival (75% v 55%; P < .0001) and distant disease-free survival (DFS; 85% v 41%; P < .0001).5 TABLE 1. Prognostic Factors for Patients With LRR Disease