Abstract P6-06-30: Are synchronous and metachronous bilateral breast cancers different? An immunohistochemical analysis aimed at intrinsic tumor phenotype

Abstract

Abstract Background: The biology and pathomechanism of bilateral breast cancers is not fully understood: the risk of developing second (metachronous) breast cancer is 4-6 times higher than that of first primary in general population, whereas for synchronous breast cancers the number of cases is about 100 times higher than could be expected by chance alone. We compared the morphological and immunohistochemical characteristics of primary synchronous (sBBC) vs. metachronous (mBBC) bilateral breast cancers), with special focus on intrinsic tumor phenotype. Methods: Tumor morphology and expression of 8 immunohistochemical markers were assessed in tissue microarrays containing primary breast tumor cores from 113 mBBC and 61 sBBC. Analyzed markers included hormone receptors (estrogen receptor, progesterone receptor), HER2, Ki67, cytokeratin 5/6, E-cadherin, vimentin and epidermal growth factor receptor. Surrogate intrinsic phenotypes were determined according to St Gallen 2011 criteria. Results: mBBChad higher incidence of ductal histology (p = 0.037), lower estrogen receptor expression (p = 0.047), and higher expression of cytokeratin 5/6 (p = 0.017) and of vimentin (p = 0.008); in multivariate analysis only vimentin retained the significance (p = 0.01). Ten (13%) and 11 (26%) of mBBCand sBBC, respectively, had luminal A phenotype, 39 (50%) and 15 (36%) were luminal B HER2-negative, 13 (17%) and 12 (28%) - luminal B HER2-positive, 3 (4%) and 2 (5%) - HER2-positive (not luminal), and 12 (16%) and 2 (5%) had triple negative phenotype (p = 0.07). Characteristics of mBBC and sBBCFeaturemBBC (%)sBBC (%)p valueDuctal histology98 (87)47 (77)0.037Grade 346 (41)17 (28)0.09Extensive intraductal component26 (23)18 (29)0.42Strong ER expression73 (67)48 (81)0.047Strong PR expression55 (49)38 (63)0.07HER2 positivity (2+, 3+)51 (46)29 (50)0.6Ki76 ≤14%24 (22)21 (35)0.06Surrogate intrinsic phenotype luminal A10 (13)11 (26) luminal B HER2-39 (50)15 (36) luminal B HER2+13 (17)12 (28)0.07triple negative12 (16)2 (5) HER2+ (non luminal)3 (4)2 (5) CK5/6 >10%28 (26)6 (11)0.017Vimentin >10%25 (23)4 (7)0.008E-cadherin (+)88 (83)49 (83)0.99EGFR (+)35 (32)11 (19)0.07 Conclusion: mBBC, compared to sBBC, are characterized by more aggressive phenotype, expressed by lower expression of estrogen receptor and stronger expression of cytokeratin /6 and vimentin; this does not, however, translate into substantial differences in the proportion of intrinsic tumor phenotypes. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-06-30.