[Intertumoral heterogeneity of molecular phenotype and analysis of prognosis in multifocal and multicentric breast cancer].

ABSTRACT

Objective: This study was designed to investigate the prognostic implications of the intertumoral heterogeneity of molecular phenotype in multifocal and multicentric breast cancer (MMBC). Methods: The clinical and follow-up data of 146 patients with MMBC from Jan.2009 to Dec. 2009 treated in Tumor Hospital Affiliated to Zhengzhou University were retrospectively analyzed. We used Kaplan-Meier curves to compare the survivals of patients who had tumors with molecular phenotypic heterogeneity and patients who had multifocal homogeneous tumors in molecular phenotype, and the survivals of patients who had heterogeneous tumor type and grade and who had homogeneous tumor type and grade.The corresponding hazard ratio was calculated by Cox proportional-hazards regression. Results: Intertumoral heterogeneity in histological type and grade of multiple breast cancer was detected in 16 of 146 patients (11.0%) and in 10 of 146 patients (6.8%), respectively. Interfocal heterogeneous molecular phenotype of multiple breast cancer was detected in 24 of 146 patients (16.4%). There was no significant difference in 5-year disease-free survival in multifocal cancer patients who had heterogeneous histological type and grade and who had homogeneous type and grade tumors (75.0% vs. 77.3%, P=0.808). Multifocal cancers patients who had heterogeneous tumorsin molecular phenotype compared with those with homogeneous tumors in molecular phenotype had worse 5-year disease-specific survival (78.7% vs. 58.3%, P=0.037), and had a greater risk of recurrence (HR=2.130, 95%CI=1.027-4.420; P=0.042). Phenotyping the additional cancer foci influenced the therapeutic decision in up to 16 patients(11.0%). Conclusions: Multifocal breast cancer patients who had heterogeneous tumors in molecular phenotype have a statistically significantly shorter disease-free survival. Phenotyping the additional cancer foci and managing with proper therapeutic decision may reduce the risk of recurrence or metastasis, and improve the outcomes of the patients.