TRAIN-3 reports early experience with an investigational MRI-guided approach to chemotherapy duration in HER2-positive breast cancer.

Evidence before this study

We performed a comprehensive literature search using PubMed, reviewing clinical trial publications in English from database inception to March 21, 2025. Our search focused on two main areas: first, pathological complete response rates and long-term survival outcomes following neoadjuvant chemotherapy regimens of different durations in early-stage HER2-positive breast cancer. Second, the accuracy of breast MRI and other imaging modalities for detecting complete responders to neoadjuvant chemotherapy. Search terms were “response”, “HER2-positive breast cancer”, “de-escalation”, “neoadjuvant”, AND “MRI” OR “PET”.

Previous evidence indicates that patients with stage II–III HER2-positive breast cancer have high pathological complete response rates and favourable long-term survival following six to nine cycles of anti-HER2 based chemotherapy. However, this approach is associated with substantial toxicity. A subgroup of patients show an early complete pathological response after only one to three cycles. Therefore, we designed the current study to evaluate whether MRI-guided tailoring of chemotherapy duration based on radiological complete response could maintain favourable outcomes while reducing treatment-related toxicity.

At the first planned analysis, we showed that an early pathological complete response after three cycles of chemotherapy was observed in approximately a third of patients with hormone receptor-negative tumours and a sixth of patients with hormone receptor-positive tumours. The negative predictive value of the MRI to predict a pathological complete response was 87% in hormone receptor-negative tumours and 53% in hormone receptor-positive tumours.

Added value of this study

To our knowledge, TRAIN-3 is the first trial using breast MRI to tailor neoadjuvant chemotherapy duration in patients with stage II–III HER2-positive breast cancer. Our findings show favourable 3-year event-free survival outcomes with MRI-guided treatment optimisation. Notably, patients with a rapid response after only one to three chemotherapy cycles had high event-free survival rates compared with clinical practice. This image-guided approach was associated with reduced treatment-related toxicity without compromising clinical efficacy.

Implications of all the available evidence

Seven clinical trials have now shown that a substantial proportion of patients with early-stage HER2-positive breast cancer have a pathological complete response with six or fewer chemotherapy cycles (NeoSphere, WSG-TP-II, WSG-ADAPT-HER2+/HR-, PHERGain, TRYPHAENA, KRISTINE, and TRAIN-3). Considering the event-free survival results from TRAIN-3, chemotherapy duration could be individualised by using breast MRI to identify complete responders, especially in hormone receptor-negative, HER2-positive breast cancer. These results support adopting MRI-guided chemotherapy duration as a novel approach in daily clinical practice. However, for patients with hormone receptor-positive disease, better monitoring tools remain necessary.

Source: The Lancet Oncology