title: Effect of multifocality and multicentricity on outcome in early stage breast cancer: a systematic review and meta-analysis.
abstract: Women with multifocal or multicentric breast tumors (multifocality henceforth) have been reported to have greater probability of nodal metastasis and relapse and worse survival than women with unifocal tumors. However, these associations have been inconsistent and multifocality is not taken into account by staging guidelines and prognostic models. A systematic review of electronic databases identified publications exploring the association between multifocality and overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and loco-regional relapse (LRR). The hazard ratios (HRs) for OS and DFS for multifocal compared to unifocal tumors were extracted from multivariable analyses and included in a meta-analysis. For studies not reporting multivariable analyses, odds ratios (OR) were estimated from Kaplan-Meier curves for all endpoints at 5 and 10 years. Twenty-two studies comprising 67,557 women were included. Multifocality was reported in 9.5 % of patients. Classical prognostic factors were well balanced between unifocal and multifocal populations. In multivariable analyses, multifocality was associated with significantly worse OS (HR 1.65; P = 0.02), and a non-significant association with worse DFS (HR 1.96; P = 0.07). In univariable analyses, multifocality was associated with worse OS, DFS, DSS, and LRR at 5 years (OR 1.39, P = 0.02; OR 1.52, P = 0.02; OR 1.56, P = 0.03; and OR 3.23, P = 0.02, respectively). Similar estimates were observed at 10 years, but statistical significance was only reached for DSS and LRR. Mutifocality appears to be associated with a worse prognosis, however, substantial inter-study heterogeneity limits the precise determination of increased risk. Further validation of the independent prognostic impact of multifocality is warranted.
authors.affiliation: Division of Medical Oncology & Hematology, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, ON, M5G 2M9, Canada, Francisco.Vera-Badillo@uhn.ca.
authors.forename: Francisco E
authors.initials: FE
authors.lastname: Vera-Badillo
authors.forename: Marc
authors.initials: M
authors.lastname: Napoleone
authors.forename: Alberto
authors.initials: A
authors.lastname: Ocana
authors.forename: Arnoud J
authors.initials: AJ
authors.lastname: Templeton
authors.forename: Bostjan
authors.initials: B
authors.lastname: Seruga
authors.forename: Mustafa
authors.initials: M
authors.lastname: Al-Mubarak
authors.forename: Hashem
authors.initials: H
authors.lastname: AlHashem
authors.forename: Ian F
authors.initials: IF
authors.lastname: Tannock
authors.forename: Eitan
authors.initials: E
authors.lastname: Amir
mesh_terms: D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000175:diagnosis / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D005260:Female; D006801:Humans; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor