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BRCA‐ related breast carcinoma can be prevented through prophylactic surgery and an intensive follow‐up regimen. However,  BRCA  genetic tests cannot be routinely performed, and some  BRCA  mutations could not be defined as deleterious mutations or normal variants. Therefore, an easy functional assay of BRCA will be useful to evaluate  BRCA  status. As it has been reported that BRCA functions in the regulation of centrosome number, we focused on centrosome number in cancer tissues. Here, 70 breast cancer specimens with known  BRCA  status were analyzed using immunofluorescence of γ‐tubulin (a marker of centrosome) foci. The number of foci per cell was higher in cases with  BRCA  mutation compared to wild‐type cases, that is, 1.9 (95% confidence interval [CI], 1.5‐2.3) vs 0.5 (95% CI, 0.2‐0.8) ( P  < .001). Specifically, foci numbers per cell in  BRCA1  and  BRCA2  mutation cases were 1.2 (95% CI, 0.6‐1.8) and 2.2 (95% CI, 1.7‐2.6), respectively, both higher than those in wild‐type cases ( P  = .042 and  P  < .0001, respectively). The predictive value of γ‐tubulin foci as determined by area under the curve (AUC = 0.86) for  BRCA  status was superior to BRCAPRO (AUC = 0.69), Myriad Table (AUC = 0.61), and KOHBRA BRCA risk calculator (AUC = 0.65) pretest values. The use of γ‐tubulin foci to predict  BRCA  status had sensitivity = 83% (19/23), specificity = 89% (42/47), and positive predictive value = 77% (20/26). Thus, γ‐tubulin immunofluorescence, a functional assessment of BRCA, can be used as a new prospective test of  BRCA  status.

Increased centrosome number in BRCA ‐related breast cancer specimens determined by immunofluorescence analysis