Many patients with HER2-positive breast cancer receive trastuzumab emtansine (T-DM1) after surgery when residual disease remains following neoadjuvant treatment, and they are often also offered adjuvant radiotherapy. The safety of giving both treatments together, or in close sequence, had been little studied. A case series from a single centre now describes radiotherapy toxicity that was more intense than expected in ten patients treated with both modalities.
What was already known
The KATHERINE trial showed that T-DM1 improves both relapse-free and overall survival in patients with residual invasive disease after neoadjuvant chemotherapy and HER2-targeted therapy. Many of those patients go on to receive adjuvant radiotherapy, but evidence on combining the two —concurrently or in close sequential proximity— is very limited and comes largely from that same trial.
What this work adds
The authors describe ten cases seen at their institution in which enhanced radiotherapy toxicity was observed when radiotherapy was delivered concurrently with, or in close proximity to, T-DM1. This is a non-consecutive case series: a selection of striking situations rather than a representative sample of all treated patients, so it serves to generate hypotheses, not to quantify risks or establish cause and effect.
Main results
Five patients experienced significant pulmonary toxicity: early-onset radiation pneumonitis, recurrent pneumonitis despite appropriate treatment, and pneumonitis outside the radiation field. Two had more severe skin toxicity than expected: prolonged radiation dermatitis followed by telangiectasia formation in one, and breast cellulitis requiring hospital admission in the other. A further two developed rib fractures, one of which required surgery and hyperbaric oxygen treatment. The final patient developed myositis. Taken together, the findings support the hypothesis that T-DM1 may enhance radiation toxicity, possibly through its emtansine component, a microtubule inhibitor.
What it means
The authors themselves urge caution: this is a small, selected series that cannot establish a causal relationship or estimate how often this occurs. They call for further studies of potential toxicities and, above all, of the optimal sequencing when treatment modalities are combined, and advise clinicians to remain vigilant for unexpected toxicities and to weigh these risks when planning adjuvant radiotherapy in patients receiving T-DM1. For patients, the practical takeaway is to ask about the order and timing of treatments and to report any new respiratory or skin symptom promptly.
A view from the breast unit
This work reinforces coordination between medical oncology and radiation oncology when setting the radiotherapy schedule for patients on T-DM1, and highlights the value of recording and sharing uncommon toxicities in tumour boards.
Reference: Carroll P, Soo J, Byrne K, White M, Antill Y, Taylor K, et al. Acute Toxicity With Trastuzumab Emtansine and Concurrent Radiotherapy: Non-Consecutive Case Series. Asia-Pacific Journal of Clinical Oncology, 2026. https://doi.org/10.1111/ajco.70146
