title: Prediction of nodal metastasis and prognosis of breast cancer by ANN-based assessment of tumour size and p53, Ki-67 and steroid receptor expression.
abstract: BACKGROUND
  Tumour stage and the appropriate course of treatment in patients with breast cancer are primarily characterized by the state of metastasis in the axillary lymph nodes. In recent years, substantial research has focused on the prediction of lymph node status based on various pathological and molecular markers in order to obviate the necessity to carry out axillary dissection. In the present study, artificial neural network (ANN) is employed as the analysis platform to examine the prognostic significance of a group of well-established prognostic markers for breast cancer outcome prediction in terms of nodal status. Furthermore, we investigated existing interactions between these markers.
  
  
  METHODS
  The data set contained 66 patient records, where 5 pathological and molecular markers including tumour size, oestrogen receptor status (ER), progesterone receptor status (PR), Ki-67 and p53 expression had been assessed for each patient. The spread of metastasis to the axillary lymph nodes was clinically diagnosed and patients were accordingly categorized into node-positive and node-negative groups. The aforementioned markers were analyzed using a probabilistic neural network (PNN) for nodal status prediction which was considered as the network output. Furthermore, the interactions between these markers were evaluated using different marker combinations as the network input for finding the best marker arrangement for nodal predication.
  
  
  RESULTS
  The best prediction accuracy was obtained by a 3-marker combination including tumour size, PR and p53 with 71% accuracy for nodal prediction. Leaving out ER and PR from the full marker set showed approximately the same variations in the results, which is an indication of the direct correlation of these two markers. Furthermore, tumour size was proved to be the most significant individual marker for predicting nodal metastasis. However, when used in combination with Ki-67 the prediction results drop significantly.
  
  
  CONCLUSIONS
  The results presented here indicate that molecular and pathological markers can provide useful information for early-stage prognosis. However, the interactions between these markers must be considered in order to achieve accurate and reliable prediction.
authors.affiliation: School of Electrical, Electronic and Computer Engineering, University of Newcastle upon Tyne, Newcastle upon Tyne, England, U.K. gajanan.sherbet@newcastle.ac.uk.
authors.forename: Shirin
authors.initials: S
authors.lastname: Mojarad
authors.forename: Barbara
authors.initials: B
authors.lastname: Venturini
authors.forename: Patrizia
authors.initials: P
authors.lastname: Fulgenzi
authors.forename: Renata
authors.initials: R
authors.lastname: Papaleo
authors.forename: Massimo
authors.initials: M
authors.lastname: Brisigotti
authors.forename: Franco
authors.initials: F
authors.lastname: Monti
authors.forename: Debora
authors.initials: D
authors.lastname: Canuti
authors.forename: Alberto
authors.initials: A
authors.lastname: Ravaioli
authors.forename: Lok
authors.initials: L
authors.lastname: Woo
authors.forename: Satnam
authors.initials: S
authors.lastname: Dlay
authors.forename: Gajanan V
authors.initials: GV
authors.lastname: Sherbet
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008207:Lymphatic Metastasis; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53
keywords: Artificial neural networks; cancer prognosis; ki-67; oestrogen/progesterone receptors; p53; prediction of nodal status