Potential value of tumor stiffness and sE-cadherin in predicting the response to neoadjuvant therapy in HER2-positive breast cancers

Plain language summary HER2 positivity in breast cancer is associated with a poor prognosis and shortened overall survival. For patients with HER2-positive early breast cancer, the standard neoadjuvant treatment consists of trastuzumab and pertuzumab plus docetaxel, and produces high response rates. In spite of the success of neoadjuvant therapy, some patients show no response due to drug resistance. An accurate prediction of the response of early HER2-positive breast cancer to neoadjuvant therapy would allow the modification of treatment with a response-guided strategy, thereby improving overall survival. Shear wave elastography and serum soluble E-cadherin may provide useful data on responsiveness to neoadjuvant therapy in breast cancers. This study was conducted to compare the diagnostic value of tumor stiffness and soluble E-cadherin expression for predicting the response to neoadjuvant therapy in HER2-positive breast cancers. Although these results will require further verification with larger studies, this study may promote noninvasive prediction of neoadjuvant therapy responses and help personalize the treatment regimen. Background: This prospective study compared the diagnostic value of tumor stiffness and serum soluble E-cadherin (sE-cadherin) expression for predicting response to neoadjuvant therapy in HER2-positive breast cancers. Methods: 112 patients with early or locally advanced HER2-positive breast cancer were enrolled. Maximum stiffness (Emax), mean stiffness (Emean) and their relative changes were assessed at t0 and t2. sE-cadherin levels were analyzed using ELISA. Pathological complete response was defined as no invasive disease in the breast and axilla (ypT0/is, ypN0) after surgery. The ability of tumor stiffness, sE-cadherin and the combination of Delta Emean (the relative change in Emean after the second cycle of neoadjuvant therapy) and sE-cadherin in predicting tumor responses was assessed using receiver operating characteristic curves and the Z-test. Results: Tumor stiffness and sE-cadherin decreased during neoadjuvant therapy. Delta Emean and sE-cadherin revealed the best predictive performance, with areas under the curve (AUCs) of 0.843 and 0.857, respectively. No significant differences in AUCs were reported between Delta Emean and sE-cadherin (p = 0.795). The combined use of Delta Emean and sE-cadherin showed the highest sensitivity and specificity (93.22 and 90.57%, respectively), with an AUC of 0.937. Conclusion: The combination of Delta Emean and sE-cadherin may improve the predictive power of each single factor. Although further verification is required, this study may promote noninvasive prediction of neoadjuvant therapy responses and help personalize the treatment regimen.