Top Line: For bulky, HER2 positive breast cancer that’s inoperable at presentation, what benefit might there be to moving radiation to the preoperative setting?
The Study: The standard sequence (neoadjuvant chemo plus HER2 blockade, surgery, adjuvant RT) quietly assumes the tumor will be resectable once systemic therapy is done. That’s not always a given, though. The case for preoperative RT is mechanical as much as biologic as an intact target is more reliably delineated with less geometric uncertainty and smaller volumes, and downstaging is the whole point when the problem is margins rather than micrometastases. NEOTRAC randomized 126 women with inoperable stage III HER2-positive breast cancer to neoadjuvant chemotherapy and HER2 targeted therapy alone or with concurrent 46 Gy to the breast and regional nodes during the paclitaxel/trastuzumab component of therapy. This was followed by mastectomy. The primary endpoint of pathologic complete response was not significantly higher with neoadjuvant RT (50.9% v 46.6%). Granted, surgery took place 4-6 weeks after RT, so there was limited time for additional RT response to occur. Three-year EFS was also similar (76.8% vs 79.8%) and there was no difference in OS. The rate of grade 3 dermatitis was 5.5%, and there was a numerically higher rate (though not significant) of wound morbidity after surgery with RT (16.4% vs 6.9%). The positive takeaway was a significant reduction in total treatment time where neoadjuvant RT shaved over 60 days from treatment duration.
TBL: Concurrent chemoradiation with trastuzumab in the neoadjuvant setting didn’t increase pathologic complete response rate, though all patients in the RT arm converted to operable disease and there was a significant reduction in total treatment time. | Iyer, Int J Radiat Oncol Biol Phys 2026
The Study: The standard sequence (neoadjuvant chemo plus HER2 blockade, surgery, adjuvant RT) quietly assumes the tumor will be resectable once systemic therapy is done. That’s not always a given, though. The case for preoperative RT is mechanical as much as biologic as an intact target is more reliably delineated with less geometric uncertainty and smaller volumes, and downstaging is the whole point when the problem is margins rather than micrometastases. NEOTRAC randomized 126 women with inoperable stage III HER2-positive breast cancer to neoadjuvant chemotherapy and HER2 targeted therapy alone or with concurrent 46 Gy to the breast and regional nodes during the paclitaxel/trastuzumab component of therapy. This was followed by mastectomy. The primary endpoint of pathologic complete response was not significantly higher with neoadjuvant RT (50.9% v 46.6%). Granted, surgery took place 4-6 weeks after RT, so there was limited time for additional RT response to occur. Three-year EFS was also similar (76.8% vs 79.8%) and there was no difference in OS. The rate of grade 3 dermatitis was 5.5%, and there was a numerically higher rate (though not significant) of wound morbidity after surgery with RT (16.4% vs 6.9%). The positive takeaway was a significant reduction in total treatment time where neoadjuvant RT shaved over 60 days from treatment duration.
TBL: Concurrent chemoradiation with trastuzumab in the neoadjuvant setting didn’t increase pathologic complete response rate, though all patients in the RT arm converted to operable disease and there was a significant reduction in total treatment time. | Iyer, Int J Radiat Oncol Biol Phys 2026