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

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Item Type:	Article
Title:	The pathology of familial breast cancer: histological features of cancers in families not attributable to mutations in BRCA1 or BRCA2
Creators Name:	Lakhani, S.R., Gusterson, B.A., Jacquemier, J., Sloane, J.P., Anderson, T.J., Van de Vijver, M.J., Venter, D., Freeman, A., Antoniou, A., McGuffog, L., Smyth, E., Steel, C.M., Haites, N., Scott, R.J., Goldgar, D., Neuhausen, S., Daly, P.A., Ormiston, W., McManus, R., Scherneck, S., Ponder, B.A.J., Futreal, P.A., Peto, J., Stoppa-Lyonnet, D., Bignon, Y.J., Struewing, J.P., Bishop, D.T., Klijn, J.G.M., Devilee, P., Cornelisse, C.J., Lasset, C., Lenoir, G., Barkardottir, R.B., Egilsson, V., Hamann, U., Chang-Claude, J., Sobol, H., Weber, B., Easton, D.F. and Stratton, M.R.
Abstract:	Breast cancers arising in carriers of mutations in the breast cancer susceptibility 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 attributable to these two genes (non-BRCA1/2 families). We have now characterized the pathology of 82 breast cancers from non-BRCA1/2 families. Breast cancers in non-BRCA1/2 families were of lower grade (P = 0.0018), showed fewer mitoses (P < 0.0001), less nuclear pleomorphism (P = 0.0014), less lymphocytic 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 likely 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 tumors 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 cancers unselected for a family history of the disease, non-BRCA1/2 tumors were 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 that non-BRCA1/2 breast cancers differ histologically from both BRCA1 and BRCA2 breast cancers and are overall of lower grade. They also suggest that non-BRCA1/2 breast cancers differ from nonfamilial breast cancers, but these differences may be attributable to various types of bias.
Keywords:	BRCA1 Genes, BRCA2 Protein, Breast Ductal Carcinoma, Breast Neoplasms, Family Health, Lobular Carcinoma, Medullary Carcinoma, Tumor-Infiltrating Lymphocytes, Mitotic Index, Mutation, Neoplasm Proteins, Transcription Factors
Source:	Clinical Cancer Research
ISSN:	1078-0432
Publisher:	American Association for Cancer Research
Volume:	6
Number:	3
Page Range:	782-789
Date:	March 2000
Official Publication:	http://clincancerres.aacrjournals.org/cgi/content/abstract/6/3/782
PubMed:	View item in PubMed

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