Primary node negative breast cancer in BRCA1 mutation carriers has a poor outcome

Citation
Wd. Foulkes et al., Primary node negative breast cancer in BRCA1 mutation carriers has a poor outcome, ANN ONCOL, 11(3), 2000, pp. 307-313
Citations number
48
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
ANNALS OF ONCOLOGY
ISSN journal
09237534 → ACNP
Volume
11
Issue
3
Year of publication
2000
Pages
307 - 313
Database
ISI
SICI code
0923-7534(200003)11:3<307:PNNBCI>2.0.ZU;2-3
Abstract
Background: The association between BRCA1 germ-line mutations and breast ca ncer prognosis is controversial. A historical cohort study was designed to determine the prognosis for women with axillary lymph node negative heredit ary 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 t he two common BRCA1 founder mutations, 185delAG and 5382insC. Patients were followed up for a median of 76 months. Somatic TP53 mutations were screene d for by immunohistochemistry, and direct sequencing was performed in the B RCA1-positive tumours. Results: Sixteen breast cancer blocks (13.6%) carried a BRCA1 mutation. You ng age of onset, high nuclear grade, negative estrogen receptor status and over-expression of p53 were highly associated with BRCA1-positive status (P -values all < 0.01). BRCA1 mutation carriers had a higher mortality than no n-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 multivari ate analyses showed that only germ-line BRCA1 mutation status was an indepe ndent prognostic factor for overall survival (P = 0.01). Among nuclear grad e 3 tumours, the BRCA1 mutation carrier status was a significant prognostic factor of death (risk ratio 5.8, 95% confidence interval: 1.5-22, P = 0.00 9). Sequencing of BRCA1-related breast cancers revealed one TP53 missense m utation not previously reported in breast cancer. Conclusions: Using a historical cohort approach, we have identified BRCA1 m utation status as an independent prognostic factor for node negative breast cancer among the Ashkenazi Jewish women. Those managing women carrying a B RCA1 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 BRCA1-related breast cancer, compared to non-hereditary cases.