HER2-overexpressing breast cancer: FDG uptake after two cycles of chemotherapy predicts the outcome of neoadjuvant treatment

Background: Pathologic complete response (pCR) to neoadjuvant treatment (NAT) is associated with improved survival of patients with HER2+ breast cancer. We investigated the ability of interim positron emission tomography (PET) regarding early prediction of pathology outcomes. Methods: During 61 months, consecutive patients with locally advanced or large HER2+ breast cancer patients without distant metastases were included. All patients received NAT with four cycles of epirubicin+cyclophosphamide, followed by four cycles of docetaxel+trastuzumab. 18 F-fluorodeoxyglucose ( 18 F-FDG)-PET/computed tomography (CT) was performed at baseline (PET 1 ) and after two cycles of chemotherapy (PET 2 ). Maximum standardised uptake values were measured in the primary tumour as well as in the axillary lymph nodes. The correlation between pathologic response and SUV parameters (SUV max at PET 1 , PET 2 and ΔSUV max ) was examined with the t -test. The predictive performance regarding the identification of non-responders was evaluated using receiver operating characteristics (ROC) analysis. Results: Thirty women were prospectively included and 60 PET/CT examination performed. At baseline, 22 patients had PET+ axilla and in nine of them 18 F-FDG uptake was higher than in the primary tumour. At surgery, 14 patients (47%) showed residual tumour (non-pCR), whereas 16 (53%) reached pCR. Best prediction was obtained when considering the absolute residual SUV max value at PET 2 (AUC=0.91) vs 0.67 for SUV max at PET 1 and 0.86 for ΔSUV max . The risk of non-pCR was 92.3% in patients with any site of residual uptake >3 at PET 2 , no matter whether in breast or axilla, vs 11.8% in patients with uptake ⩽3 ( P =0.0001). The sensitivity, specificity, PPV, NPV and overall accuracy of this cutoff were, respectively: 85.7%, 93.8%, 92.3%, 88.2% and 90%. Conclusion: The level of residual 18 F-FDG uptake after two cycles of chemotherapy predicts residual disease at completion of NAT with chemotherapy+trastuzumab with high accuracy. Because many innovative therapeutic strategies are now available (e.g., addition of a second HER2-directed therapy or an antiangiogenic), early prediction of poor response is critical.