title: Multicentric and multifocal versus unifocal breast cancer: is the tumor-node-metastasis classification justified?
abstract: For classification of breast cancer (BC), tumor-node-metastasis (TNM) staging has been considered state of the art for more than 50 years. The T category is well defined, and in multicentric and multifocal tumors, tumor size is assessed by the largest tumor focus. The aim of this study was to compare multicentric/multifocal tumor spread in breast cancer with unifocal disease and to evaluate the diagnostic relevance of multifocality. A retrospective analysis was performed on survival related events in a series of 5,691 breast cancer patients between 1963 and 2007. By matched-pair analysis, patients were entered into two comparable groups of 288 patients after categorizing them as having multifocal/multicentric or unifocal breast cancers. Matching criteria were tumor size, grading, and hormone receptor status, which were equally distributed between both groups (P = 1.000 each). Disease free survival and the occurrence of relapse or of metastatic disease were evaluated. Cox's regression analysis was used for multivariate analysis. In the unifocal group, the mean breast cancer-specific survival time was 221.6 months as opposed to 203.3 months in the multicentric/multifocal group (P < 0.001, log-rank test). The occurrence of local relapse and distant metastasis was significantly increased in the multifocal group in comparison to the unifocal equivalent group (P < 0.001 and P < 0.003, respectively). Cox regression analysis for multivariate analyses demonstrated focality and centricity to be highly significant predictors for reduced overall survival (P = 0.016), local relapse (P = 0.001) and distant metastasis (P = 0.038). Tumor size, histopathological grading, hormone receptor status, and staging of lymph nodes are well-established prognostic parameters. Additionally, the number of foci should be considered as an independent prognostic parameter, which is currently not reflected in the TNM classification. We conclude that multicentric/multifocal BC is an independent BC risk factor and should be included in the risk assessment by re-evaluating the current TNM classification of the UICC.
authors.affiliation: Frauenklinik, Klinikum der Ludwig-Maximilians-Universitaet, Munich, Germany. tobias.weissenbacher@med.uni-muenchen.de
authors.forename: Tobias M
authors.initials: TM
authors.lastname: Weissenbacher
authors.forename: Madeleine
authors.initials: M
authors.lastname: Zschage
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Janni
authors.forename: Udo
authors.initials: U
authors.lastname: Jeschke
authors.forename: Thomas
authors.initials: T
authors.lastname: Dimpfl
authors.forename: Doris
authors.initials: D
authors.lastname: Mayr
authors.forename: Brigitte
authors.initials: B
authors.lastname: Rack
authors.forename: Christian
authors.initials: C
authors.lastname: Schindlbeck
authors.forename: Klaus
authors.initials: K
authors.lastname: Friese
authors.forename: Darius
authors.initials: D
authors.lastname: Dian
mesh_terms: D001943:Breast Neoplasms / Q000145:classification / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000145:classification / Q000401:mortality / Q000473:pathology / Q000556:secondary / Q000628:therapy; D018275:Carcinoma, Lobular / Q000145:classification / Q000401:mortality / Q000473:pathology / Q000556:secondary / Q000628:therapy; D016022:Case-Control Studies; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008593:Menopause; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging / Q000379:methods / Q000592:standards*; D009378:Neoplasms, Multiple Primary / Q000145:classification / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D011379:Prognosis; D016016:Proportional Hazards Models; D047368:Tumor Burden