MULTIFACTORIAL ANALYSIS OF DIFFERENCES BETWEEN SPORADIC BREAST CANCERS AND CANCERS INVOLVING BRCA1 AND BRCA2 MUTATIONS

Background: We have previously demonstrated that breast cancers associ ated with inherited BRCA1 and BRCA2 gene mutations differ from each ot her in their histopathologic appearances and that each of these types differs from breast cancers in patients unselected for family history (i.e., sporadic cancers). We have now conducted a more detailed examin ation of cytologic and architectural features of these tumors. Methods : Specimens of tumor tissue (5-mu m-thick sections) were examined inde pendently by two pathologists, who were unaware of the case or control subject status, for the presence of cell mitosis, lymphocytic infiltr ation, continuous pushing margins, and solid sheets of cancer cells; c ell nuclei, cell nucleoli, cell necrosis, and cell borders were also e valuated. The resulting data mere combined with previously available i nformation on tumor type and tumor grade and further evaluated by mult ifactorial analysis. All statistical tests are two-sided. Results: Can cers associated with BRCA1 mutations exhibited higher mitotic counts ( P = .001), a greater proportion of the tumor with a continuous pushing margin (P<.0001), and more lymphocytic infiltration (P = .002) than s poradic (i.e,, control) cancers. Cancers associated with BRCA2 mutatio ns exhibited a higher score for tubule formation (fewer tubules) (P = .0002), a higher proportion of the tumor perimeter with a continuous p ushing margin (P<.0001), and a lower mitotic count (P = .003) than con trol cancers. Conclusions: Our study has identified key features of th e histologic phenotypes of breast cancers in carriers of mutant BRCA1 and BRCA2 genes. This information may improve the classification of br east cancers in individuals with a family history of the disease and m ay ultimately aid in the clinical management of patients.