Among women who experience a recurrence after postmastectomy radiation therapy irradiation is not associated with more aggressive local recurrence or reduced survival

Abstract

Recent pre-clinical models suggest that radiation can promote tumor aggressiveness. We hypothesized that if this were occurring clinically, locoregional recurrences (LRRs) after postmastectomy radiation therapy (PMRT) would lead to lower survival than LRR after mastectomy alone. This study used two independent data-sets to compare survival after LRR in women treated with versus without PMRT. Data from 229 LRR cases among 1,500 patients enrolled on prospective trials at the MD Anderson Cancer Center (MDA), and 66 LRR cases among 318 patients enrolled in the British Columbia Cancer Agency (BCCA) PMRT randomized trial were analyzed. In the MDA non-randomized dataset, 189/1031 had LRR after mastectomy alone and 40/469 had LRR after PMRT. In the randomized BC trial dataset, 52/158 had LRR after mastectomy alone and 14/160 had LRR after PMRT. In both datasets, survival was calculated from the time of LRR to death. Analysis of MDA data shows that in all LRR cases regardless of distant metastasis (DM), 5/10-year OS were 50/34% without PMRT and 27/19% after PMRT (P = 0.006). However, PMRT-treated patients had increased risk factors for DM (advanced T and N stages) and more PMRT-treated patients developed DM prior to LRR (63 vs. 34%, P = 0.005). Analyzing only patients will an isolated LRR (without previous or simultaneous DM), there was no OS difference between groups (P = 0.33). Analysis of BCCA data shows that distributions of T and N stages were similar in patients with LRR after mastectomy alone versus after PMRT. DM free survival after any LRR and after isolated LRR were similar in mastectomy alone versus PMRT-treated patients (P = 0.75, P = 0.26, respectively). Overall survival after any LRR and after isolated LRR were also similar in the two groups (P = 0.93, P = 0.28, respectively). Patients who develop LRR after mastectomy alone have high rates of DM and poor OS but these rates are not affected by the use of PMRT at the time of primary treatment. These data do not support the hypothesis that irradiation promotes biologically aggressive local recurrences.

Long-Term Outcomes in Patients With Isolated Supraclavicular Nodal Recurrence After Mastectomy and Doxorubicin-Based Chemotherapy for Breast Cancer

“…In addition, although prior analysis suggests the use of post-mastectomy radiation does not lead to more aggressive LRR (12), the small number of isolated SCV LRR after post-mastectomy radiation make it difficult to generalize to this setting. Indeed, all patients who experience an isolated SCV recurrence after PMRT developed distant disease in less than three years.…”

“…In prior analysis of the British Columbia Cancer Agency randomized data from the post-mastectomy radiation versus none trial (11), we compared outcomes among patients who experienced a LRR after post-mastectomy radiation to those who experienced a LRR after mastectomy alone and demonstrated no difference in overall survival based on prior post-mastectomy radiation (12). The same was observed for isolated LRR in the patient cohort being examined herein in spite of the non-randomized use of post-mastectomy being associated with higher risk characteristics of the presenting disease in these data (12). For this reason, the patients who had prior post-mastectomy radiation and those who did not were combined for this analysis.…”

Risk of locoregional recurrence by receptor status in breast cancer patients receiving modern systemic therapy and post-mastectomy radiation

“…Despite salvage treatment, long-term survival after LRR is poor, with 10-year survival of *30% [1]. Even in women where distant disease does not occur, the onset of LRR is emotionally devastating and results in significant morbidity.…”

Radiation-induced modifications of the tumor microenvironment promote metastasis

“…This effect has been previously termed tumor bed effect [10,11]. A recent study analyzing retrospective datasets, however, reported that recurrences after postmastectomy radiation therapy are not associated with more aggressive local behaviors or reduced survival compared to patients recurring after mastectomy only [12]. Thus, at this point this question remains open and controversial.…”