title: Serum Tumor Marker Levels might have Little Significance in Evaluating Neoadjuvant Treatment Response in Locally Advanced Breast Cancer.
abstract: BACKGROUND
  To determine the potential value of serum tumor markers in predicting pCR (pathological complete response) during neoadjuvant chemotherapy.
  
  
  METHODS
  We retrospectively monitored the pro-, mid-, and post- neoadjuvant treatment serum tumor marker concentrations in patients with locally advanced breast cancer (stage II-III) who accepted pre-surgical chemotherapy or chemotherapy in combination with targeted therapy at Fudan University Shanghai Cancer Center between September 2011 and January 2014 and investigated the association of serum tumor marker levels with therapeutic effect. Core needle biopsy samples were 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, therapeutic response 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 of repeated measures and receiver operating characteristic (ROC) curves were employed for statistical analysis of the data.
  
  
  RESULTS
  A total of 348 patients were recruited in our study after excluding patients with incomplete clinical 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-2 positive, among whom the pCR rate was 45.6% (69 patients). General linear model analysis (repeated measures analysis of variance) showed that the concentration of cancer antigen (CA) 15-3 increased after neoadjuvant chemotherapy in both pCR and non-pCR groups, and that there were significant differences between the two groups (P=0.008). The areas under the ROC curves (AUCs) of pre-, mid-, and post-treatment CA15-3 concentrations demonstrated low-level predictive value (AUC=0.594, 0.644, 0.621, respectively). No significant differences in carcinoembryonic antigen (CEA) or CA12-5 serum levels were observed between the pCR and non-pCR groups (P=0.196 and 0.693, respectively). No efficient AUC of CEA or CA12-5 concentrations were observed to predict patient response toward neoadjuvant treatment (both less than 0.7), nor were differences between the two groups observed at different time points. We then analyzed the Her-2 positive subset of our cohort. 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 showed underlying prognostic value, as the AUCs of these three markers were less than 0.7. The ROC-AUCs for the CA12-5 concentrations of inter-and post-neoadjuvant chemotherapy in the estrogen receptor negative HER2 positive subgroup were 0.735 and 0.767, respectively. However, the specificity and sensitivity values were at odds with each other which meant that improving either the sensitivity or specificity would impair the efficiency of the other.
  
  
  CONCLUSIONS
  Serum tumor markers CA15-3, CA12-5, and CEA might have little clinical significance in predicting neoadjuvant treatment response in locally advanced breast cancer.
authors.affiliation: Department of Breast Surgery, Fudan University Shanghai Cancer Center, and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China E-mail : drxiaoyanhuang@aliyun.com.
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Wang
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Huang
authors.forename: Miao
authors.initials: M
authors.lastname: Mo
authors.forename: Jian-Wei
authors.initials: JW
authors.lastname: Li
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Jia
authors.forename: Zhi-Min
authors.initials: ZM
authors.lastname: Shao
authors.forename: Zhen-Zhou
authors.initials: ZZ
authors.lastname: Shen
authors.forename: Jiong
authors.initials: J
authors.lastname: Wu
authors.forename: Guang-Yu
authors.initials: GY
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D012372:ROC Curve; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human