N1 + HER2 = beam on.

Top Line: We have spent decades defining the role of post-mastectomy radiation (PMRT) in the setting of nodal disease.

The Study: All to have it turned on its head with the arrival of game-changing HER2-targeted systemic therapies. Which is great, albeit somewhat frustrating for data-driven among us. B-51 is a crucial on-going trial designed to clarify the benefit of regional nodal irradiation in the setting of a nodal complete pathologic response to neoadjuvant treatment, but who knows what’ll be on the market by the time it reports. In the meantime, we have this secondary analysis of the HERA trial that established in 2005 the overwhelming benefit of adjuvant HER2-targeted therapy. Among over 5K patients enrolled, over 3400 received adjuvant trastuzumab and over 1600 of those were post-mastectomy (remember this is before the neoadjuvant craze). The primary endpoint was the impact of PMRT, administered on a case-by-case basis, on locoregional control for these 1600 cases—so, as expected, the 58% receiving PMRT had significantly worse disease characteristics. Nevertheless, among those with N1 disease (n=517), survival free from locoregional recurrence was a soaring 97% after PMRT versus 90% otherwise at 10 years. What’s more, death was reduced by one-third with survival measured at 87% after PMRT versus 83% otherwise. There was no distinction seen among those with N0 disease and virtually everyone with N2+ disease received PMRT. Unfortunately, we have no way of knowing which of these women would have achieved a complete response to neoadjuvant therapy and whether this would ameliorate their benefit with PMRT.

TBL: Even with HER2-targeted therapy on board, there is a clear benefit to PMRT for N1 HER2(+) disease, notwithstanding the additional potential treatment discretion afforded with the knowledge of path response. | Jaoude, In J Radiat Oncol Biol Phys 2020