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Annals of Oncology 11:307-313, 2000
© 2000 European Society for Medical Oncology

research-article

Primary node negative breast cancer in BRCAI mutation carriers has a poor outcome

W. D. Foulkes1,2,, P. O. Chappuis1,2, N. Wong1, J.-S. Brunet3, D. Vesprini3, F. Rozen1, Z. Q. Yuan1, M. N. Pollak1, G. Kuperstein3, S. A. Narod3 and L. R. B{acute}gin1

1Departments of Medicine, Oncology, Pathology, Surgery and Cancer Prevention Research Unit Sir M. B. Davis-Jewish General Hospital, Canada
2Departments of Medicine, Human Genetics and Oncology, Montreal General Hospital, McGill University Montreal, Quebec, Canada
3Centre for Research in Women's Health, University of Toronto Toronto, Ontario, Canada

Correspondence to: W. D. Foulkes, MD Sir Mortimer B. Davis-Jewish General Hospital, Room A-803 3755 ch. de la Côte te Catherine Montreal H3T 1E2, Quebec, Canada. E-mail: MDWF{at}musica.mcgill.ca

Background: The association between BRCAI germ-line mutations and breast cancer prognosis is controversial. A historical cohort study was designed to determine the prognosis for women with axillary lymph node negative hereditary breast cancer.

Patients and methods: We tested pathology blocks from 118 Ashkenazi Jewish women with axillary lymph node negative breast cancer for the presence of the two common BRCAI founder mutations, 185delAG and 5382insC. Patients were followed up for a median of 76 months. Somatic TP53 mutations were screened for by immunohistochemistry, and direct sequencing was performed in the BRCAI-positive tumours.

Results; Sixteen breast cancer blocks (13.6%) carried a BRCAI mutation. Young age of onset, high nuclear grade, negative estrogen receptor status and over-expression of p53 were highly associated with BRCAI-positive status (P-values all < 0.01). BRCAI mutation carriers had a higher mortality than non-carriers (five-year overall survival, 50% and 89.6%, respectively, P = 0.0001). Young age of onset, estrogen receptor negative status, nuclear grade 3, and over-expression of p53 also predicted a poor outcome. Cox multivariate analyses showed that only germ-line BRCAI mutation status was an independent prognostic factor for overall survival (P = 0.01). Among nuclear grade 3 tumours, the BRCAI mutation carrier status was a significant prognostic factor of death (risk ratio 5.8, 95% confidence interval: 1.5–22, P = 0.009). Sequencing of BRCAI-related breast cancers revealed one TP53 missense mutation not previously reported in breast cancer.

Conclusions: Using a historical cohort approach, we have identified BRCAI mutation status as an independent prognostic factor for node negative breast cancer among the Ashkenazi Jewish women. Those managing women carrying a BRCAI mutation may need take these findings into consideration. Additionally, our preliminary results, taken together with the work of others suggest a different carcinogenic pathway in BRCAI-related breast cancer, compared to non-hereditary cases.

BRCAI, breast cancer, p53, survival


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