Response evaluation after primary systemic therapy of Her2 positive breast cancer - an observational cross-sectional study

Abstract

Aim: To evaluate (I) trastuzumab-containing primary systemic therapy (PST) in human epidermal growth factor receptor 2 (Her2) overexpressing breast carcinomas.; (II) compare the patients who achieved and those who did not achieve pathological complete remission (pCR), and (III) analyze the accuracy of different clinical-imaging modalities in tumor response monitoring. Methods: 188 patients who received PST between 2008 and 2014 were reviewed and 43 Her2 overexpressing breast cancer patients (28 Luminal B/Her2-positive and 15 Her2-positive) were enrolled. 26 patients received mostly taxane-based PST without trastuzumab (Group 1) and 17 patients received trastuzumab- containing PST (Group 2). We compared the concordance between pCR and complete remission (CR) defined by breast-ultrasound, CR defined by standard 18F-fluoro-deoxy- glucose positron emission tomography and computerized tomography (FDG-PET/CT) criteria (Method 1) and CR defined by a novel, breast cancer specific FDG-PET/CT criteria (Method 2). Sensitivity (sens), specificity (spec), and positive (PPV) and negative predictive values (NPV) were calculated. Results: Ten patients (38.5%) in Group 1 and eight (47%) in Group 2 achieved pCR. pCR was significantly more frequent in Her2-positive than in Luminal B/Her2-positive tumors in both Group 1: (P = 0.043) and Group 2: (P = 0.029). PET/CT evaluated by the breast cancer specific criteria (Method 2) differentiated pCR from non-pCR more accurately in both groups (Group 1: sens = 77.8%, spec = 100%, PPV = 100%, NPV = 71.4%; Group 2: sens = 87.5%, spec = 62.5%, PPV = 70%, NPV = 83.3%) than standard PET/CT criteria (Method 1) (Group 1: sens = 22.2% spec = 100% PPV = 100% NPV = 41.7%; in Group 2: sens = 37.5%, spec = 87.5%, PPV = 75% NPV = 58.3%) or breast ultrasound (Group 1, sens = 83.3% spec = 25% PPV = 62.5% NPV = 50%; Group 2, sens = 100% spec = 12.5% PPV = 41.6% NPV = 100%). Conclusion: The benefit of targeted treatment with trastuzumab-containing PST in Her2 overexpressing breast cancer was defined in terms of pCR rate. Luminal B/Her2-positive subtype needs further subdivision to identify patients who would benefit from PST. Combined evaluation of tumor response by our novel, breast cancer specific FDG-PET/CT criteria accurately differentiated pCR from non-pCR patients.