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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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]
Cites
Early Breast Cancer Trialists’ Collaborative Group, & Peto, R. (1993) · Recent results in cancer research/Recent Results in Cancer Research · doi:10.1007/978-3-642-84745-5_21 · Cited by 959 · see citing works
Ashkenazi Jewish population frequencies for common mutations in BRCA1 and BRCA2
Roa, B. B., Boyd, A. A., Volcik, K. A., & Richards, C. S. (1996) · Nature Genetics · doi:10.1038/ng1096-185 · Cited by 769 · see citing works
Xu, X., Wagner, K., Larson, D. M., Ohler, Z. W., Li, C., Ried, T., Hennighausen, L. G., Wynshaw-Boris, A. J., & Deng, C. (1999) · Nature Genetics · doi:10.1038/8743 · Cited by 758 · see citing works
Thor, A. D., Moore, D. H., Edgerton, S. M., Kawasaki, E. S., Reihsaus, E., Lynch, H. T., Marcus, J. N., Schwartz, L. H., Chen, L.-C., Mayall, B. H., et al. (1992) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/84.11.845 · Cited by 721 · see citing works
Lakhani, S. R., Jacquemier, J., Sloane, J. P., Gusterson, B. A., Anderson, T. J., van de Vijver, M. J., Farid, L. M., Venter, D., Antoniou, A., Storfer-Isser, A., et al. (1998) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/90.15.1138 · Cited by 707 · see citing works
Struewing, J., Abeliovich, D., Peretz, T., Avishai, N., Kaback, M., Collins, F., & Brody, L. (1995) · Nature Genetics · doi:10.1038/ng1095-198 · Cited by 678 · see citing works
Stratton, M. R. (1997) · The Lancet · doi:10.1016/s0140-6736(96)10109-4 · Cited by 579 · see citing works
Thorlacius, S., Ólafsdóttir, G. H., Tryggvadóttír, L., Neuhausen, S. L., Jonasson, J. G., Tavtigian, S. V., Tulinius, H., Ogmundsdottir, H. M., & Eyfjord, J. E. (1996) · Nature Genetics · doi:10.1038/ng0596-117 · Cited by 523 · see citing works
Survival and tumour characteristics of breast-cancer patients with germline mutations of BRCA1
Verhoog, L., Brekelmans, C., Seynaeve, C., van den Bosch, L., Dahmen, G., van Geel, A., Tilanus-Linthorst, M., Bartels, C., Wagner, A., van den Ouweland, A., et al. (1998) · The Lancet · doi:10.1016/s0140-6736(97)07065-7 · Cited by 452 · see citing works
Hainaut, P. L. (1998) · Nucleic Acids Research · doi:10.1093/nar/26.1.205 · Cited by 446 · see citing works
Warner, E., Foulkes, W., Goodwin, P., Meschino, W., Blondal, J., Paterson, C., Ozçelik, H., Goss, P., Allingham-Hawkins, D., Hamel, N., et al. (1999) · Journal of the National Cancer Institute · doi:10.1093/jnci/91.14.1241 · Cited by 421 · see citing works
Self-citationOddoux, C., Struewing, J. P., Clayton, C. M., Neuhausen, S. L., Brody, L. C., Kaback, M. M., Haas, B. R., Norton, L., Borgen, P. I., Jhanwar, S. C., et al. (1996) · Nature Genetics · doi:10.1038/ng1096-188 · Cited by 381 · see citing works
EARLYBREASTCANCERTRIALISTSCOL (1992) · The Lancet · doi:10.1016/0140-6736(92)90139-t · Cited by 375 · see citing works
Tirkkonen, M., Johannsson, O. T., Agnarsson, B. A., Olsson, H. L., Ingvarsson, S., Karhu, R., Tanner, M., Isola, J. J., Barkardottir, R. B., Borg, Å., et al. (1997) · PubMed · Cited by 354 · see citing works
Frequency of recurrent BRCA1 and BRCA2 mutations in Ashkenazi Jewish breast cancer families
Tonin, P., Weber, B., Offit, K., Couch, F., Rebbeck, T., Neuhausen, S., Godwin, A., Daly, M., Wagner-Costalos, J., Berman, D. B., et al. (1996) · Nature Medicine · doi:10.1038/nm1196-1179 · Cited by 319 · see citing works
Self-citationBRCA-associated breast cancer in young women.
Robson, M. E., Gilewski, T., Haas, B. R., Levin, D. R., Borgen, P. I., Rajan, P., Hirschaut, Y., Pressman, P., Rosen, P. P., LESSER, M. L., et al. (1998) · Journal of Clinical Oncology · doi:10.1200/jco.1998.16.5.1642 · Cited by 303 · see citing works
Prognostic Factors and Treatment Decisions in Axillary-Node-Negative Breast Cancer
Desforges, J. F., McGuire, W. L., & Clark, G. M. (1992) · New England Journal of Medicine · doi:10.1056/nejm199206253262607 · Cited by 283 · see citing works
Breast cancer outcome and predictors of outcome: are there age differentials?
Albain, K. S., Allred, D. C., & Clark, G. M. (1994) · PubMed · Cited by 264 · see citing works
Prognostic Factors and Therapeutic Decisions in Axillary Node-Negative Breast Cancer
Elledge, R. M., & McGuire, W. L. (1993) · Annual Review of Medicine · doi:10.1146/annurev.me.44.020193.001221 · Cited by 257 · see citing works
Survival of BRCA1 breast and ovarian cancer patients: a population-based study from southern Sweden.
Jóhannsson, O. T., Ranstam, J., Borg, A., & Olsson, H. (1998) · Journal of Clinical Oncology · doi:10.1200/jco.1998.16.2.397 · Cited by 254 · see citing works
Armes, J. E., Trute, L., White, D., Southey, M. C., Hammet, F., Tesoriero, A. A., Hutchins, A., Dite, G. S., McCredie, M. R. E., Giles, G. G., et al. (1999) · PubMed · Cited by 236 · see citing works
Tumor-related prognostic factors for breast cancer
Donegan, W. L. (1997) · CA A Cancer Journal for Clinicians · doi:10.3322/canjclin.47.1.28 · Cited by 228 · see citing works
Inhibition of tumor growth in vivo by hyaluronan oligomers
Zeng, C., Toole, B. P., Kinney, S. D., Kuo, J.-W., & Stamenkovic, I. (1998) · International Journal of Cancer · doi:10.1002/(sici)1097-0215(19980729)77:3 · Cited by 215 · see citing works
Robson, M., Levin, D., Federici, M. G., Satagopan, J. M., Bogolminy, F., Heerdt, A., Borgen, P., Mccormick, B., Hudis, C., Norton, L., et al. (1999) · Journal of the National Cancer Institute · doi:10.1093/jnci/91.24.2112 · Cited by 181 · see citing works
BRCA1 and BRCA2: from molecular genetics to clinical medicine.
Blackwood, M. A., & Weber, B. L. (1998) · Journal of Clinical Oncology · doi:10.1200/jco.1998.16.5.1969 · Cited by 180 · see citing works
Crook, T., Brooks, L. A., Crossland, S., Osin, P., Barker, K. T., Waller, J., Philp, E., Smith, P. D., Yuluğ, I. G., Peto, J., et al. (1998) · Oncogene · doi:10.1038/sj.onc.1202106 · Cited by 179 · see citing works
p53 mutations in BRCA1-associated familial breast cancer
Crook, T., Crossland, S., Crompton, M. R., Osin, P., & Gusterson, B. A. (1997) · The Lancet · doi:10.1016/s0140-6736(05)63327-2 · Cited by 179 · see citing works
Clahsen, P. C., van de Velde, C. J., Duval, C., Pallud, C., Mandard, A. M., Delobelle-Deroïde, A., van den Broek, L., Sahmoud, T., & van de Vijver, M. J. (1998) · Journal of Clinical Oncology · doi:10.1200/jco.1998.16.2.470 · Cited by 171 · see citing works
Germ line mutation at BRCA1 affects the histoprognostic grade in hereditary breast cancer.
Eisinger, F., Stoppa‐Lyonnet, D., Longy, M., Kerangueven, F., Noguchi, T., Bailly, C., Vincent‐Salomon, A., Jacquemier, J. D., Birnbaum, D., & Sobol, H. (1996) · PubMed · Cited by 171 · see citing works
Founder BRCA1 and BRCA2 Mutations in French Canadian Breast and Ovarian Cancer Families
Tonin, P. N., Mes‐Masson, A., Futreal, P. A., et al. (1998) · The American Journal of Human Genetics · doi:10.1086/302099 · Cited by 168 · see citing works
BRCA2 and p53 mutations in primary breast cancer in relation to genetic instability.
Grétarsdóttir, S., Thorlacius, S., Valgardsdottir, R., Gudlaugsdottir, S., Sigurðsson, S., Steinarsdóttir, M., Jonasson, J. G., Anamthawat‐Jónsson, K., & Eyfjörd, J. E. (1998) · PubMed · Cited by 131 · see citing works
Porter, D., Cohen, B. B., Wallace, M. R., Smyth, E., Chetty, U., Dixon, J. M., Steel, C. M., & Carter, D. C. (1994) · British journal of surgery · doi:10.1002/bjs.1800811038 · Cited by 122 · see citing works
Foulkes, W. D., Wong, N., Brunet, J., Bégin, L. R., Zhang, J. C., Martinez, J. J., Rozen, F., Tonin, P. N., Narod, S. A., Karp, S. E., et al. (1997) · PubMed · Cited by 122 · see citing works
Self-citationSurvival after breast cancer in Ashkenazi Jewish BRCA1 and BRCA2 mutation carriers.
Lee, J. S., Wacholder, S., Struewing, J., McAdams, M., Pee, D., Brody, L., Tucker, M. A., & Hartge, P. (1999) · Journal of the National Cancer Institute · doi:10.1093/jnci/91.3.259 · Cited by 113 · see citing works
Frequency of p53 mutations in breast carcinomas from Ashkenazi Jewish carriers of BRCA1 mutations.
Phillips, K., Nichol, K., Ozçelik, H., Knight, J., Done, S., Goodwin, P., & Andrulis, I. (1999) · Journal of the National Cancer Institute · doi:10.1093/jnci/91.5.469 · Cited by 111 · see citing works
Functions of the BRCA1 and BRCA2 genes
Bertwistle, D., & Ashworth, A. (1998) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(98)80056-7 · Cited by 110 · see citing works
Response to radiation therapy and prognosis in breast cancer patients with BRCA1 and BRCA2 mutations
Gaffney, D. K., Brohet, R. M., Lewis, C. M., et al. (1998) · Radiotherapy and Oncology · doi:10.1016/s0167-8140(98)00023-1 · Cited by 110 · see citing works
A phase I clinical trial of immunotherapy with interferon-? gene-modified autologous melanoma cells
Abdel-Wahab, Z., Weltz, C., Hester, D., Pickett, N., Vervaert, C. E., Barber, J. R., Jolly, D. J., & Seigler, H. F. (1997) · Cancer · doi:10.1002/(sici)1097-0142(19970801)80:3 · Cited by 107 · see citing works
Phillips, K., Andrulis, I., & Goodwin, P. J. (1999) · Journal of Clinical Oncology · doi:10.1200/jco.1999.17.11.3653 · Cited by 103 · see citing works
BRCA-associated breast cancer: absence of a characteristic immunophenotype.
Robson, M. E., Rajan, P., Rosen, P., Gilewski, T., Hirschaut, Y., Pressman, P., Haas, B. R., Norton, L., & Offit, K. (1998) · PubMed · Cited by 88 · see citing works
Mammary tumor formation in p53- and BRCA1-deficient mice.
Cressman, V. L., Backlund, D. C., Hicks, E., Gowen, L. C., Godfrey, V., & Koller, B. H. (1999) · PubMed · Cited by 84 · see citing works
Survival in early-onset BRCA1 breast-cancer patients
Ansquer, Y., Gautier, C., Fourquet, A., Asselain, B. J. R., & Stoppa‐Lyonnet, D. (1998) · The Lancet · doi:10.1016/s0140-6736(05)79248-5 · Cited by 80 · see citing works
The influence of familial and hereditary factors on the prognosis of breast cancer.
Chappuis, P. O., Rosenblatt, J., & Foulkes, W. (1999) · Annals of Oncology · doi:10.1023/a:1008301314812 · Cited by 74 · see citing works
Self-citationBRCA1 and BRCA2 hereditary breast carcinoma phenotypes
Marcus, J. N., Page, D. L., Watson, P. A., Narod, S. A., Lenoir, G., & Lynch, H. T. (1997) · Cancer · doi:10.1002/(sici)1097-0142(19970801)80:3+ · Cited by 53 · see citing works
Self-citationThe Functions of Breast Cancer Susceptibility Gene 1 (BRCA1) Product and Its Associated Proteins
Irminger‐Finger, I., Siegel, B., & Leung, W.-C. (1999) · Biological Chemistry · doi:10.1515/bc.1999.019 · Cited by 53 · see citing works
Is p53 a protein that predicts the response to chemotherapy in node negative breast cancer?
Degeorges, A., de Roquancourt, A., Extra, J. M., Espié, M., Bourstyn, E., de Crémoux, P., Soussi, T., & Marty, M. E. (1998) · Breast Cancer Research and Treatment · doi:10.1023/a:1005824216444 · Cited by 40 · see citing works
Germ-line BRCA1 mutations in women with sporadic breast cancer: clinical correlations.
Garcia-Patiño, E., Gomendio, B., Provencio, M., et al. (1998) · Journal of Clinical Oncology · doi:10.1200/jco.1998.16.1.115 · Cited by 37 · see citing works
p53 mutations in BRCA1-associated familial breast cancer
Schlichtholz, B., Bouchindhomme, B., Pagés, S., Martin, E., Liva, S., Magdelénat, H., Sastre‐Garau, X., Stoppa‐Lyonnet, D., & Soussi, T. (1998) · The Lancet · doi:10.1016/s0140-6736(05)79576-3 · Cited by 27 · see citing works
BRCA1-p53 relationship in hereditary breast cancer
Sobol, H., Stoppa‐Lyonnet, D., Paillerets, B. B., Peyrat, J. P., Guinebretière, J., Jacquemier, J. D., Eisinger, F., & Birnbaum, D. (1997) · International Journal of Oncology · doi:10.3892/ijo.10.2.349 · Cited by 25 · see citing works
Yuan, Z., Bégin, L. R., Wong, N., et al. (1999) · British Journal of Cancer · doi:10.1038/sj.bjc.6690775 · Cited by 12 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Malone, K. E., Begg, C. B., Haile, R. W., Borg, A., Concannon, P., Tellhed, L., Xue, S., Teraoka, S., Bernstein, L., Capanu, M., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.24.2495 · Cited by 191 · see citing works
Prognosis of BRCA-associated breast cancer: a summary of evidence
Bordeleau, L., Panchal, S., & Goodwin, P. (2010) · Breast Cancer Research and Treatment · doi:10.1007/s10549-009-0566-z · Cited by 135 · see citing works
Kirova, Y. M., Stoppa-Lyonnet, D., Savignoni, A., Sigal-Zafrani, B., Fabre, N., & Fourquet, A. (2005) · European Journal of Cancer · doi:10.1016/j.ejca.2005.02.037 · Cited by 129 · see citing works
van den Broek, A. J., van ’t Veer, L. J., Hooning, M. J., Cornelissen, S., Broeks, A., Rutgers, E. J., Smit, V. T. H. B. M., Cornelisse, C. J., van Beek, M., Janssen-Heijnen, M. L., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2015.62.3942 · Cited by 104 · see citing works
Kirova, Y. M., Savignoni, A., Sigal-Zafrani, B., de La Rochefordiere, A., Salmon, R. J., This, P., Asselain, B., Stoppa-Lyonnet, D., & Fourquet, A. (2010) · Breast Cancer Research and Treatment · doi:10.1007/s10549-009-0685-6 · Cited by 102 · see citing works
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
