Should Surgery Referral be Standard Practice in Metastatic Inflammatory Breast Cancer

There is no doubt that the level of evidence desired to define practice in any disease is high and that the limitations of retrospective studies place them appropriately in the category of hypothesis generation. Randomized studies may be an unrealistic bar, however, in some uncommon diseases where patient numbers or national infrastructure are inadequate to facilitate randomized, controlled trials. Such is likely in the case of inflammatory breast cancer (IBC), although increasing development of dedicated IBC specialized centers may ultimately increase future feasibility of randomized trials. In this issue, Warren et al. (2015) have examined the case for locoregional therapy in the setting of metastatic IBC as well as documenting local recurrence rates in the postmastectomy setting. Setting aside the controversial question of whether local therapy influences survival in the setting of metastatic breast cancer, there remains a compelling argument, unique to IBC, for local therapy in the metastatic setting. That argument is that there is a propensity for high rates of morbid local regional disease progression in patients treated with systemic therapy alone, which could be prevented or reduced with local therapy. In the nonmetastatic IBC setting, there are not many studies of patients who do not receive postmastectomy radiation, from which to determine the locoregional recurrence rates (LRR) in the absence of radiation therapy. The Early Breast Cancer Trialists’ Collaborative Group examining numerous studies of radiation versus no radiation concluded that in general, radiation reduced the risk of LRR by approximately two-thirds. Therefore, one could estimate the LRR expected without postmastectomy radiation by multiplying the LRR after trimodality therapy by three. One might then speculate the expected rate of local progression or recurrence after response in metastatic IBC patients without surgery would be higher than this and that the rate of LRR after mastectomy in the metastatic setting would be similar. Warren et al. reviewed the LRR for nonmetastatic patients treated with standard trimodality therapy and report a 3-year cumulative LRR of 21 %. A weighted average of 5-year LRR from published series, including 613 patients similarly treated with trimodality therapy (summarized in,) yields a 5-year LRR of 20 %. Tripling this rate, one might expect LRR after surgery in the absence of radiation to be 60 % at 3–5 years and the rate of progression without surgery to be higher than this. In this ballpark, among the 54 IBC patients with metastatic disease in the Warren study, the crude LRR/progressive recurrence rate among women who did not receive local therapy was 57 %. These patients had a median 2-year follow-up after local therapy and the 1-year cumulative LRR was 17.6 % with local therapy and 48.3 % without local therapy. Convincingly, this high rate of locoregional recurrence or progression without local therapy is a clinical problem that could merit preventive therapy in some cases. The authors find that the presence of an involved nonlocoregional lymph node was the only significant independent predictor of local recurrence or progression prompting the further question of the potential role to include these in the radiation targeting when it can be done safely and the decision to deliver postmastectomy radiation has been made. These new data are consistent with a previous study of local therapy in metastatic IBC patients. In a similar analysis of 172 patients with metastatic IBC, Akay et al. reported that local control was significantly higher at last Society of Surgical Oncology 2015