The pathology of familial breast cancer: Histological features of cancers in families not attributable to mutations in BRCA1 or BRCA2

Breast cancers arising in carriers of mutations in the breast cancer suscep tibility genes, BRCA1 and BRCA2, differ histologically from each other and from breast cancers unselected for a family history. However, a substantial proportion of families with multiple cases of breast cancer is not attribu table to these two genes (non-BRCA1/2 families). We have now characterized the pathology of 82 breast cancers from non-BRCA1/2 families. Breast cancer s in non-BRCA1/2 families were of lo,ver grade (P = 0.0018), showed fewer m itoses (P < 0.0001), less nuclear pleomorphism (P = 0.0014), less lymphocyt ic infiltrate (P < 0.0001), a lesser extent of the tumor with a continuous pushing margin (P = 0.004), a lesser extent of the tumor composed of solid sheets of cells (P = 0.0047), less necrosis (P = 0.002), and were more like ly to be of invasive lobular type (P = 0.0003) than breast cancers arising in BRCA1 mutation carriers. In comparison with BRCA2 tumors, non-BRCA1/2 tu mors were lower grade (P = 0.017) and exhibited less pleomorphism (P = 0.01 ) and more tubule formation (P = 0.05). In comparison with control breast c ancers unselected for a family history of the disease, non-BRCA1/2 tumors w ere of significantly lower grade (P = 0.001), showed less pleomorphism (P = 0.0002), and had a lower mitotic count (P = 0.003). The results indicate t hat non-BRCA1/2 breast cancers differ histologically from both BRCA1 and BR CA2 breast cancers and are overall of lower grade. They also suggest that n on-BRCA1/2 breast cancers differ from nonfamilial breast cancers, but these differences may be attributable to various types of bias.