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Primary node negative breast cancer in BRCA1 mutation carriers has a poor outcome
Open accessAbstract
Background The association between BRCA1 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 BRCA1 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 BRCA1-positive tumours.Results Sixteen breast cancer blocks (13.6%) carried a BRCA1 mutation. Young 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 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 BRCA1 mutation status was an independent prognostic factor for overall survival (P = 0.01). Among nuclear grade 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 = 0.009). Sequencing of BRCA1-related breast cancers revealed one TP53 missense mutation not previously reported in breast cancer.Conclusions Using a historical cohort approach, we have identified BRCA1 mutation status as an independent prognostic factor for node negative breast cancer among the Ashkenazi Jewish women. Those managing women carrying a BRCA1 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.
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BRCA gene mutation might influence response to radiation therapy because tumours in BRCA1/BRCA2 carriers are more sensitive to ionising radiation.
“Several studies suggest that BRCA gene mutation might influence response to radiation therapy because tumours in BRCA1/BRCA2 carriers are more sensitive to ionising radiation [5-12].”
From Is the breast-conserving treatment with radiotherapy appropriate in BRCA1/2 mutation carriers? Long-term results and review of the literature (2010) · cites this paper as [5]
BRCA1 mutation carriers develop tumours of a higher grade and proliferation index, with lower oestrogen receptor levels than patients with no such mutation, and tend to have worse outcomes.
“BRCA1 mutation carriers develop tumours of a higher grade and proliferation index, with lower oestrogen receptor levels than patients with no such mutation, and tend to have worse outcomes [2-5].”
From Is the breast-conserving treatment with radiotherapy appropriate in BRCA1/2 mutation carriers? Long-term results and review of the literature (2010) · cites this paper as [5]
BRCA2 mutation carriers present tumours with pathologic features similar to those of sporadic tumours.
“BRCA2 mutation carriers, on the contrary, present tumours with pathologic features similar to those of sporadic tumours [2-10].”
From Is the breast-conserving treatment with radiotherapy appropriate in BRCA1/2 mutation carriers? Long-term results and review of the literature (2010) · cites this paper as [5]
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Metadata
- Authors
- Foulkes, W. D., Chappuis, P. O., Wong, N., Brunet, J.-S., Vesprini, D., Rozen, F., Yuan, Z. Q., Pollak, M. N., Kuperstein, G., Narod, S. A., & B´gin, L. R.
- Affiliations
- Montreal General Hospital (CA)
- Jewish General Hospital (CA)
- University of Toronto (CA)
- Venue
- Annals of Oncology
- Publisher
- Elsevier BV
- Published
- 2000-03
- Volume
- 11
- Issue
- 3
- Pages
- 307-314
- ISSN
- 0923-7534 (ISSN-L)
- OpenAlex
- W2128784131
- Cited by
- 86
- References
- 50
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2022: 1 · 2021: 2 · 2020: 5 · 2019: 2 · 2018: 4 · 2017: 3 · 2016: 1 · 2015: 2 · 2014: 3 · 2013: 2 · 2012: 2
- FWCI
- 2.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Annals of Oncology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Health Sciences › Medicine › Pathology and Forensic Medicine › Breast Lesions and Carcinomas
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Keywords
- BRCA1 mutation, hereditary breast cancer, node-negative breast cancer, prognosis, overall survival, Ashkenazi Jewish women, TP53 mutation, p53 overexpression, estrogen receptor status, nuclear grade, oncogenic signaling
- MeSH terms
- Adult, Age Factors, Aged, Breast Neoplasms, Female, Humans, Jews, Lymph Nodes, Middle Aged, Neoplasm Proteins, Prognosis, Risk Factors, Transcription Factors, Cohort Studies, Multivariate Analysis, Proportional Hazards Models, Survival Analysis, Genes, p53, Germ-Line Mutation, Genes, BRCA1, BRCA2 Protein
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