MRI predicts pathologic complete response in HER2-positive breast cancer after neoadjuvant chemotherapy

Background: Neoadjuvant treatment of HER2-positive breast cancer frequently leads to a pathologic complete response (pCR), which is associated with favourable long-term outcome. Treatment regimens typically consist of 6-9 cycles of trastuzumab-based chemotherapy, although many patients achieve early radiologic complete response (rCR). If rCR accurately predicts pCR, the number of chemotherapy cycles can possibly be reduced.

Methods: We performed a diagnostic accuracy study to determine the association between rCR and pCR in patients with stage II-III HER2-positive breast cancer treated with neoadjuvant trastuzumab-based chemotherapy at the Netherlands Cancer Institute. RCR was defined as the disappearance of pathologic contrast enhancement in the original tumour region on repeated magnetic resonance imaging (MRI). PCR was defined as the absence of invasive tumour cells in the resected breast specimen (ypT0/is). Diagnostic accuracy was estimated in the overall population and in subgroups based on hormone receptor (HR) status. The prognostic value of rCR for recurrence-free interval was evaluated as an exploratory analysis.

Results: We identified 296 eligible patients with 297 HER2-positive tumours (154 HR-negative and 143 HR-positive) treated with neoadjuvant trastuzumab-based chemotherapy between 2004 and 2016. Overall, the rCR rate was 69% (206/297) and the pCR rate was 61% (181/297). Among 206 patients with rCR, 150 also had pCR (negative predictive value [NPV] = 150/206 = 73%). Among 91 patients without rCR, 60 had residual tumour at pathology (positive predictive value [PPV] = 60/91 = 66%). The NPV was better in HR-negative compared to HR-positive tumours (88 vs. 57%), while the PPV was better in HR-positive tumours (50 vs. 78%). Achieving rCR was associated with a 5-year recurrence-free interval of 88% compared to 68% without rCR (hazard ratio 0.34, 95% confidence interval 0.17-0.65, P = 0.001).

Conclusion: Achieving rCR corresponds well with pCR in HER2-positive breast cancer, particularly in the HR-negative subgroup. RCR is also associated with improved long-term outcome.