The BRCA1/BRCA2/Rad51 complex is a prognostic and predictive factor in early breast cancer.
OBJECTIVE
The breast cancer susceptibility genes BRCA1 and BRCA2 interact with Rad51, one of the central components in the homologous recombination repair pathway. This study evaluates the prognostic and predictive role of BRCA1, BRCA2 and Rad51, individually and as a complex, in breast cancer.


METHODS
Expression of BRCA1, BRCA2 and Rad51 was investigated using immunohistochemistry in tumours from 224 women with early breast cancer, who were randomised to receive postoperative radiotherapy or adjuvant chemotherapy (CMF).


RESULTS
Fifty-three percent (112/212) of the tumours had reduced expression of the BRCA1/BRCA2/Rad51 complex. Low expression correlated to high histologic grade (p=0.05). Patients with low expression of the complex developed significantly more local recurrences as compared to patients with high expression (RR=3.20, 95% CI 1.48-6.88, p=0.003). Expression of the BRCA1/BRCA2/Rad51 complex was an independent prognostic factor in multivariate analysis (p=0.03). Patients with low expression of the complex responded well to radiotherapy (RR=0.31, 95% CI 0.14-0.70, p=0.005), whereas patients with high expression had few local recurrences and no additional benefit from radiotherapy (RR=1.08, 95% CI 0.40-2.90, p=0.88).


CONCLUSIONS
Low expression of the BRCA1/BRCA2/Rad51 complex is a marker of poor prognosis, but predicts good response to radiotherapy in patients with early breast cancer.
Söderlund
Karin
K
Department of Biomedicine and Surgery, Linköping University, Linköping, Sweden. karin.soderlund@ibk.liu.se
Skoog
Lambert
L
Fornander
Tommy
T
Askmalm
Marie Stenmark
MS
D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000532:radiotherapy*; D005260:Female; D015870:Gene Expression; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D007150:Immunohistochemistry; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D051135:Rad51 Recombinase / Q000235:genetics*
C495153:RAD51 protein, human; D051135:Rad51 Recombinase