The impact of breast cancer morphology on the prediction of a BRCA1 mutation.

22125 Background: Since tailored therapeutic strategies are currently being developed, it would be useful to know at the time of diagnosis whether a BRCA1 or BRCA2 mutation is causatively related to an individual breast cancer. The aim of this study was to determine in an unselected hospital-based series of breast cancer patients, whether morphological features can improve the prediction of a BRCA1 mutation.,In a retrospective approach, histopathological results of tumours from 897 women previously diagnosed with breast cancer were re-evaluated regarding the age at diagnosis, subtype of cancer, tumour grade, estrogen (ER), progesterone (PR) and the Her2/neu receptor status as well as the p53 and Ki67 status. 142 tumours fulfilled the morphologic criteria indicative of a BRCA1 mutation. Out of 59 women who were willing to participate in this study, 26 concomitantly showed a positive family history.,Pathogenic BRCA1 germline mutations were detected in seven out of the 18 women (39%). None of these women carried a BRCA2 mutation. All BRCA1-associated tumours were of high grade, of invasive-ductal subtype, PR and Her2/neu-negative, 91% were negative for ER. 60% of the tumours showed a high expression of p53 and 60% showed a high expression of Ki67. In particular, there was a highly significant difference between BRCA1-associated tumours and other familial tumours with respect to grading (p=0.001 for G3), ER negativity (p=0.0075), Ki67 ≥ 65% (p=0.0039) and "triple (ER-, PR-, Her2/neu-) negativity" (p=0.0019).,This study more clearly defines the histopathological criteria, i.e. triple negative, high expression of Ki67 and p53, that may help to improve the prediction of a BRCA1 mutation in breast cancer patients. No significant financial relationships to disclose.