title: Intensive post-operative follow-up of breast cancer patients with tumour markers: CEA, TPA or CA15.3 vs MCA and MCA-CA15.3 vs CEA-TPA-CA15.3 panel in the early detection of distant metastases.
abstract: BACKGROUND
  In breast cancer current guidelines do not recommend the routine use of serum tumour markers. Differently, we observed that CEA-TPA-CA15.3 (carcinoembryonic (CEA) tissue polypeptide (TPA) and cancer associated 115D8/DF3 (CA15.3) antigens) panel permits early detection and treatment for most relapsing patients. As high sensitivity and specificity and different cut-off values have been reported for mucin-like carcinoma associated antigen (MCA), we compared MCA with the above mentioned tumour markers and MCA-CA15.3 with the CEA-TPA-CA15.3 panel.
  
  
  METHODS
  In 289 breast cancer patients submitted to an intensive post-operative follow-up with tumour markers, we compared MCA (cut-off values, > or = 11 and > or = 15 U/mL) with CEA or CA15.3 or TPA for detection of relapse. In addition, we compared the MCA-CA15.3 and CEA-TPA-CA15.3 tumour marker panels.
  
  
  RESULTS
  Distant metastases occurred 19 times in 18 (6.7%) of the 268 patients who were disease-free at the beginning of the study. MCA sensitivity with both cut-off values was higher than that of CEA or TPA or CA15.3 (68% vs 10%, 26%, 32% and 53% vs 16%, 42%, 32% respectively). With cut-off > or = 11 U/mL, MCA showed the lowest specificity (42%); with cut-off > or = 15 U/mL, MCA specificity was similar to TPA (73% vs 72%) and lower than that of CEA and CA15.3 (96% and 97% respectively). With > or = 15 U/mL MCA cut-off, MCA sensitivity increased from 53% to 58% after its association with CA15.3. Sensitivity of CEA-TPA-CA15.3 panel was 74% (14 of 19 recurrences). Eight of the 14 recurrences early detected with CEA-TPA-CA15.3 presented as a single lesion (oligometastatic disease) (5) or were confined to bony skeleton (3) (26% and 16% respectively of the 19 relapses). With > or = 11 U/mL MCA cut-off, MCA-CA15.3 association showed higher sensitivity but lower specificity, accuracy and positive predictive value than the CEA-TPA-CA15.3 panel.
  
  
  CONCLUSIONS
  At both the evaluated cut-off values serum MCA sensitivity is higher than that of CEA, TPA or CA15.3 but its specificity is similar to or lower than that of TPA. Overall, CEA-TPA-CA15.3 panel is more accurate than MCA-CA15.3 association and can "early" detect a few relapsed patients with limited metastatic disease and more favourable prognosis. These findings further support the need for prospective randomised clinical trial to assess whether an intensive post-operative follow-up with an appropriate use of serum tumour markers can significantly improve clinical outcome of early detected relapsing patients.
authors.affiliation: Department of Internal Medicine, University of Pisa, Pisa, Italy. a.nicolini@int.med.unipi.it
authors.forename: Andrea
authors.initials: A
authors.lastname: Nicolini
authors.forename: Gianna
authors.initials: G
authors.lastname: Tartarelli
authors.forename: Angelo
authors.initials: A
authors.lastname: Carpi
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Metelli
authors.forename: Paola
authors.initials: P
authors.lastname: Ferrari
authors.forename: Loretta
authors.initials: L
authors.lastname: Anselmi
authors.forename: Massimo
authors.initials: M
authors.lastname: Conte
authors.forename: Piero
authors.initials: P
authors.lastname: Berti
authors.forename: Paolo
authors.initials: P
authors.lastname: Miccoli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D001859:Bone Neoplasms / Q000097:blood / Q000175:diagnosis / Q000556:secondary*; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000601:surgery*; D002272:Carcinoembryonic Antigen / Q000097:blood*; D042241:Early Diagnosis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood*; D011182:Postoperative Care / Q000379:methods; D012680:Sensitivity and Specificity; D019396:Tissue Polypeptide Antigen / Q000097:blood*
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D018396:Mucin-1; D019396:Tissue Polypeptide Antigen; C057387:mucinous carcinoma-associated antigen