Serum Tumor Marker Levels might have Little Significance in Evaluating Neoadjuvant Treatment Response in Locally Advanced Breast Cancer


Background: To determine the potential value of serum tumor markers in predicting pCR (pathologicalcomplete response) during neoadjuvant chemotherapy. Materials and
Methods: We retrospectively monitoredthe pro-, mid-, and post- neoadjuvant treatment serum tumor marker concentrations in patients with locallyadvanced breast cancer (stage II-III) who accepted pre-surgical chemotherapy or chemotherapy in combinationwith targeted therapy at Fudan University Shanghai Cancer Center between September 2011 and January 2014and investigated the association of serum tumor marker levels with therapeutic effect. Core needle biopsy sampleswere assessed using immunohistochemistry (IHC) prior to neoadjuvant treatment to determine hormone receptor,human epidermal growth factor receptor 2(HER2), and proliferation index Ki67 values. In our study, therapeuticresponse was evaluated by pCR, defined as the disappearance of all invasive cancer cells from excised tissue(including primary lesion and axillary lymph nodes) after completion of chemotherapy. Analysis of variance ofrepeated measures and receiver operating characteristic (ROC) curves were employed for statistical analysisof the data.
Results: A total of 348 patients were recruited in our study after excluding patients with incompleteclinical information. Of these, 106 patients were observed to have acquired pCR status after treatment completion,accounting for approximately 30.5% of study individuals. In addition, 147patients were determined to be Her-2positive, among whom the pCR rate was 45.6% (69 patients). General linear model analysis (repeated measuresanalysis of variance) showed that the concentration of cancer antigen (CA) 15-3 increased after neoadjuvantchemotherapy in both pCR and non-pCR groups, and that there were significant differences between thetwo groups (P=0.008). The areas under the ROC curves (AUCs) of pre-, mid-, and post-treatment CA15-3concentrations demonstrated low-level predictive value (AUC=0.594, 0.644, 0.621, respectively). No significantdifferences in carcinoembryonic antigen (CEA) or CA12-5 serum levels were observed between the pCR andnon-pCR groups (P=0.196 and 0.693, respectively). No efficient AUC of CEA or CA12-5 concentrations wereobserved to predict patient response toward neoadjuvant treatment (both less than 0.7), nor were differencesbetween the two groups observed at different time points. We then analyzed the Her-2 positive subset of ourcohort. Significant differences in CEA concentrations were identified between the pCR and non-pCR groups(P=0.039), but not in CA15-3 or CA12-5 levels (p=0.092 and 0.89, respectively). None of the ROC curves showedunderlying prognostic value, as the AUCs of these three markers were less than 0.7. The ROC-AUCs for theCA12-5 concentrations of inter-and post-neoadjuvant chemotherapy in the estrogen receptor negative HER2positive subgroup were 0.735 and 0.767, respectively. However, the specificity and sensitivity values were at oddswith each other which meant that improving either the sensitivity or specificity would impair the efficiency ofthe other.
Conclusions: Serum tumor markers CA15-3, CA12-5, and CEA might have little clinical significancein predicting neoadjuvant treatment response in locally advanced breast cancer.