A combined analysis of outcome following breast cancer: differences in survival based on BRCA1/BRCA2 mutation status and administration of adjuvant treatment
Open accessAbstract
BACKGROUND: The prognostic significance of germline mutations in BRCA1 and BRCA2 in women with breast cancer remains unclear. A combined analysis was performed to address this uncertainty. METHODS: Two retrospective cohorts of Ashkenazi Jewish women undergoing breast-conserving treatment for invasive cancer between 1980 and 1995 (n = 584) were established. Archived tissue blocks were used as the source of DNA for Ashkenazi Jewish BRCA1/BRCA2 founder mutation analysis. Paraffin-embedded tissue and follow-up information was available for 505 women. RESULTS: Genotyping was successful in 496 women, of whom 56 (11.3%) were found to carry a BRCA1/BRCA2 founder mutation. After a median follow-up period of 116 months, breast cancer specific survival was worse in women with BRCA1 mutations than in those without (62% at 10 years versus 86%; P < 0.0001), but not in women with the BRCA2 mutation (84% versus 86% at 10 years; P = 0.76). Germline BRCA1 mutations were an independent predictor of breast cancer mortality in multivariate analysis (hazard ratio 2.4, 95% confidence interval 1.2-4.8; P = 0.01). BRCA1 status predicted breast cancer mortality only among women who did not receive chemotherapy (hazard ratio 4.8, 95% confidence interval 2.0-11.7; P = 0.001). The risk for metachronous ipsilateral cancer was not greater in women with germline BRCA1/BRCA2 founder mutations than in those without mutations (P = 0.68). CONCLUSION: BRCA1 mutations, but not BRCA2 mutations, are associated with reduced survival in Ashkenazi women undergoing breast-conserving treatment for invasive breast cancer, but the poor prognosis associated with germline BRCA1 mutations is mitigated by adjuvant chemotherapy. The risk for metachronous ipsilateral disease does not appear to be increased for either BRCA1 or BRCA2 mutation carriers, at least up to 10 years of follow up.
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Four studies including selected patients and accounting for competing risks reported higher 10-year contralateral breast cancer risk estimates (21%-27%), similar to the risk observed in this study for mutation carriers with a family history of breast cancer (25%).
“Four studies including”
From Impact of Age at Primary Breast Cancer on Contralateral Breast Cancer Risk in <i>BRCA1/2</i> Mutation Carriers (2016) · cites this paper as [31]
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 [9]
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 [9]
The results of the two non-matched cohort studies in Table 4 are contradictory: no significant difference was found in the Robson et al. study, unlike in the Haffty et al. study of a subgroup of 127 patients under 42 years of age.
“The results of the two non-matched cohort studies in Table 4 are contradictory, no significant difference being found in the Robson et al. study unlike in the Haffty et al. study of a subgroup of 127 patients under 42 years of age [9, 37].”
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 [9]
All studies of BRCA1 and/or BRCA2 mutation carriers so far have reported an increased incidence of contralateral breast cancer.
“All studies of BRCA1 and/or BRCA2 mutation carriers so far have reported an increased incidence of contralateral breast cancer [9, 15, 28-30, 37, 38, 40].”
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 [9]
The safety of BCT in BRCA mutation carriers is a matter of debate.
“However, its safety in BRCA mutation carriers is a matter of debate, and several studies have compared ipsilateral tumour recurrence after breast-conserving treatment (BCT) in BRCA1 and BRCA2 mutation carriers and patients with sporadic cancers [9, 28-32, 37-41].”
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 [9]
Robson et al. reported a 27% risk of contralateral breast cancer in carriers versus 8% in non-carriers (P = 0.002) after 10 years of follow-up.
“Robson et al. [9] reported a 27% risk in carriers versus an 8% risk in non-carriers ( P = 0.002) after 10 years of follow-up.”
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 [9]
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References 41 · Cited by 307
- Authors
- Robson, M. E., Chappuis, P. O., Satagopan, J., Wong, N., Boyd, J., Goffin, J. R., Hudis, C., Roberge, D., Norton, L., Bégin, L. R., Offit, K., & Foulkes, W. D.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Tufts University (US)
- Jewish General Hospital (CA)
- McGill University (CA)
- McGill University Health Centre (CA)
- Corresponding author
- Foulkes, William D
- ORCID
- Venue
- Breast Cancer Research
- Published
- 2003-10-24
- Volume
- 6
- Issue
- 1
- Pages
- R8-R17
- ISSN
- 1465-5411 (ISSN-L)
- 1465-542X
- PMC
- PMC314444
- OpenAlex
- W1945350395
- Cited by
- 307
- References
- 41
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 16 · 2023: 2 · 2022: 8 · 2021: 11 · 2020: 11 · 2019: 10 · 2018: 9 · 2017: 14 · 2016: 10 · 2015: 14 · 2014: 22 · 2013: 18 · 2012: 7
- FWCI
- 8.98
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Breast Cancer Research (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, other-oa)
- PubMed (publishedVersion)
- eScholarship@McGill (McGill) (submittedVersion)
- Funders
- Breast Cancer Research Foundation
- Susan G. Komen
- Hôpitaux Universitaires de Genève
- Medical Research and Materiel Command
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Keywords
- BRCA1 mutation, BRCA2 mutation, Ashkenazi Jewish women, breast cancer survival, breast-conserving therapy, adjuvant chemotherapy, prognosis, invasive breast cancer
- MeSH terms
- Adult, Breast Neoplasms, Follow-Up Studies, Humans, Jews, Male, Middle Aged, Risk Factors, Time Factors, Multivariate Analysis, Survival Analysis, Treatment Outcome, Chemotherapy, Adjuvant, Germ-Line Mutation, BRCA1 Protein, BRCA2 Protein
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