Risk of breast cancer recurrence and contralateral breast cancer in relation to BRCA1 and BRCA2 mutation status following breast-conserving surgery and radiotherapy
Abstract
BRCA1 and BRCA2 germline mutations are associated with a strong risk of breast cancer, which may preclude breast-conserving treatment in carriers. This study examined whether mutation status influenced the rate of breast cancer recurrence following breast-conserving treatment. BRCA1 and BRCA2 genes were screened for germline mutations in 131 patients with a family history of breast and/or ovarian cancer, who had been treated with breast-conserving surgery and radiotherapy. The 131 patients with familial history were matched to 261 patients without, according to age at diagnosis and year of treatment. The follow-up of controls was at least equal to the time-interval between diagnosis and genetic testing in familial cases. Matched cohorts were compared according to rates of breast cancer recurrence as first event and contralateral breast cancer using log-rank tests. BRCA1/2 mutations were found in 20.6% patients with a family history. Nineteen patients had a BRCA1 mutation and 8 had a BRCA2 mutation. Breast cancers in mutation carriers were more often grade III (p<10-4) and oestrogen receptor negative (p=0.005) than tumours in both non-carriers and controls. Median follow-up for all 392 patients was 8.75 years. No significant differences in breast cancer recurrence as first event were seen between BRCA1/2 tumours and controls (p=0.47), carriers and non-carriers with a family history (p=0.96), or non-carriers and controls (p=0.10). On multivariate analysis, age was the most important factor significantly predicting for breast cancer recurrence. The rate of contralateral breast cancer was significantly increased in all patients with a family history: BRCA1/2 carriers versus controls (p=0.0003), non-carriers versus controls (p=0.0034) and carriers versus non-carriers (p=0.02). At a 9-year median follow-up, the rate of ipsilateral breast cancer recurrence was not higher in BRCA1 and BRCA2 mutation carriers than in non-carriers with a family history or sporadic cases. These results support the hypothesis that breast tumours in BRCA carriers are more sensitive to radiation. Therefore, breast-conserving treatment can be offered to these patients. However, longer follow-up is needed to ensure that the rate of new primary cancer in the treated breast does not increase in the long-term.
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?
The recurrence rate in BRCA1/BRCA2 carriers is not increased in this population of patients.
“We and other authors demonstrated that the recurrence rate in BRCA1/BRCA2 carriers is not increased in this population of patients [28-32].”
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 [28]
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 [28]
Young age rather than BRCA status is a strong predictive factor for local relapse in hereditary breast cancer patients.
“In this study and also in other series, age was a significant predictor of recurrence, supporting the observation that young age rather than BRCA status is a strong predictive factor for local relapse in hereditary breast cancer patients [28, 32].”
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 [28]
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 [28]
Cites
Nonparametric Estimation from Incomplete Observations
Kaplan, E. L., & Meier, P. (1992) · Springer series in statistics · doi:10.1007/978-1-4612-4380-9_25 · Cited by 45,232 · see citing works
Regression Models and Life-Tables
Cox, D. R. (1972) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1972.tb00899.x · Cited by 39,793 · see citing works
Nonparametric Estimation from Incomplete Observations
Kaplan, E. L., & Meier, P. (1958) · Journal of the American Statistical Association · doi:10.1080/01621459.1958.10501452 · Cited by 39,158 · see citing works
Regression Models and Life-Tables
Cox, D. R. (1992) · Springer Series in Statistics · doi:10.1007/978-1-4612-4380-9_37 · Cited by 26,297 · see citing works
Evaluation of survival data and two new rank order statistics arising in its consideration.
Mantel, N. (1966) · PubMed · Cited by 7,516 · see citing works
Fisher, B., Anderson, S., Bryant, J., Margolese, R. G., Deutsch, M., Fisher, E. R., Jeong, J.-H., & Wolmark, N. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa022152 · Cited by 6,249 · see citing works
Fisher, B., Costantino, J. P., Wickerham, D. L., Redmond, C. K., Kavanah, M. T., Cronin, W. M., Vogel, V. G., Robidoux, A., Dimitrov, N. S., Atkins, J. N., et al. (1998) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/90.18.1371 · Cited by 5,478 · see citing works
Veronesi, U., Cascinelli, N., Mariani, L., Greco, M., Saccozzi, R., Luini, A., Aguilar, M., & Marubini, E. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa020989 · Cited by 4,450 · see citing works
Tamoxifen for early breast cancer: an overview of the randomised trials
Abe, O., Bartholomeus, S., & Piccart-Gebhart, M. (1998) · The Lancet · doi:10.1016/s0140-6736(97)11423-4 · Cited by 4,118 · see citing works
Cancer Susceptibility and the Functions of BRCA1 and BRCA2
Venkitaraman, A. R. (2002) · Cell · doi:10.1016/s0092-8674(02)00615-3 · Cited by 1,713 · see citing works
Prophylactic Oophorectomy in Carriers of BRCA1 or BRCA2 Mutations
Rebbeck, T. R., Lynch, H. T., Neuhausen, S. L., Narod, S. A., Veer, L. V., Garber, J. E., Evans, D. G., Isaacs, C. J., Daly, M. B., Matloff, E. T., et al. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa012158 · Cited by 1,462 · see citing works
van Dongen, J. A. (2000) · Journal of the National Cancer Institute · doi:10.1093/jnci/92.14.1143 · Cited by 1,271 · see citing works
Risk-Reducing Salpingo-oophorectomy in Women with aBRCA1orBRCA2Mutation
Kauff, N. D., Satagopan, J. M., Robson, M. E., Scheuer, L., Hensley, M. L., Hudis, C. A., Ellis, N. A., Boyd, J. A., Borgen, P. I., Barakat, R. R., et al. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa020119 · Cited by 1,250 · see citing works
Easton, D. F., Bishop, D. T., Ford, D., & Crockford, G. P. (1993) · Europe PMC (PubMed Central) · Cited by 1,243 · see citing works
Cortez, D., Wang, Y., Qin, J., & Elledge, S. J. (1999) · Science · doi:10.1126/science.286.5442.1162 · Cited by 1,020 · see citing works
Gene-expression profiles in hereditary breast cancer.
Hedenfalk, I., Duggan, D., Chen, Y.-D., Radmacher, M., Bittner, M., Simon, R., Meltzer, P., Gusterson, B., Esteller, M., Raffeld, M., et al. (2001) · New England Journal of Medicine · doi:10.1056/nejm200102223440801 · Cited by 978 · see citing works
Genetic analysis of breast cancer in the cancer and steroid hormone study.
Claus, E. B., RISCH, N. J., & Thompson, W. D. (1991) · PubMed · Cited by 911 · see citing works
Dynamic changes of BRCA1 subnuclear location and phosphorylation state are initiated by DNA damage
Scully, R., Chen, J., Ochs, R. L., Keegan, K., Hoekstra, M., Feunteun, J., & Livingston, D. M. (1997) · Cell · doi:10.1016/s0092-8674(00)80503-6 · Cited by 900 · see citing works
Jacobson, J. A., Danforth, D. N., Cowan, K. H., d'Angelo, T., Steinberg, S. M., Pierce, L., Lippman, M. E., Lichter, A. S., Glatstein, E., & Okunieff, P. (1995) · New England Journal of Medicine · doi:10.1056/nejm199504063321402 · Cited by 892 · cited 1× · see citing works
“Numerous randomised trials have proven the equivalence in survival between breast-conserving surgery with radiotherapy and mastectomy in early stage breast cancer [1–8].”
BackgroundClarke, M. J., Collins, R., Davies, C., Godwin, J., Gray, R. G., & Peto, R. (2000) · The Lancet · Cited by 824 · see citing works
Xu, X., Ohler, Z. W., Linke, S. P., Li, C., Gotay, J., Wang, X. W., Harris, C. C., Ried, T., & Deng, C. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80466-9 · Cited by 819 · 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
Self-citationStratton, M. R. (1997) · The Lancet · doi:10.1016/s0140-6736(96)10109-4 · Cited by 579 · see citing works
Narod, S., Brunet, J., Ghadirian, P., Robson, M., Heimdal, K., Neuhausen, S., Stoppa-Lyonnet, D., Lerman, C., Pasini, B., Ríos, P. D. L., et al. (2000) · The Lancet · doi:10.1016/s0140-6736(00)03258-x · Cited by 557 · see citing works
Self-citationSchrag, D., Kuntz, K. M., Garber, J. E., & Weeks, J. C. (1997) · New England Journal of Medicine · doi:10.1056/nejm199705153362022 · Cited by 457 · 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
Clark, R. M., McCulloch, P. B., Levine, M. N., Lipa, M., Wilkinson, R. H., Mahoney, L. J., Basrur, V. R., Nair, B. D., McDermot, R. S., Wong, C. S., et al. (1992) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/84.9.683 · Cited by 395 · see citing works
Powell, S. N., & Kachnic, L. A. (2003) · Oncogene · doi:10.1038/sj.onc.1206678 · Cited by 364 · see citing works
Presymptomatic DNA testing and prophylactic surgery in families with a BRCA1 or BRCA2 mutation.
Meijers-Heijboer, E. J., Verhoog, L., Brekelmans, C., Seynaeve, C., Tilanus-Linthorst, M., Wagner, A., Dukel, L., Devilee, P., van den Ouweland, A. V. D., van Geel, A. V., et al. (2000) · The Lancet · doi:10.1016/s0140-6736(00)02347-3 · Cited by 328 · see citing works
Robson, M. E., Chappuis, P. O., Satagopan, J., Wong, N., Boyd, J., Goffin, J. R., Hudis, C., Roberge, D., Norton, L., Bégin, L. R., et al. (2003) · Breast Cancer Research · doi:10.1186/bcr658 · Cited by 307 · see citing works
Outcome of conservatively managed early-onset breast cancer by BRCA1/2 status
Haffty, B. G., Harrold, E., Khan, A. J., Pathare, P., Smith, T. E., Turner, B. C., Glazer, P. M., Ward, B., Carter, D., Matloff, E., et al. (2002) · The Lancet · doi:10.1016/s0140-6736(02)08434-9 · Cited by 307 · see citing works
Pierce, L., Strawderman, M., Narod, S., Oliviotto, I., Eisen, A., Dawson, L., Gaffney, D., Solin, L., Nixon, A., Garber, J., et al. (2000) · Journal of Clinical Oncology · doi:10.1200/jco.2000.18.19.3360 · Cited by 270 · see citing works
Familial invasive breast cancers: worse outcome related to BRCA1 mutations.
Stoppa-Lyonnet, D., Ansquer, Y., Dreyfus, H., Gautier, C., Gauthier-Villars, M., Bourstyn, E., Clough, K., Magdelénat, H., Pouillart, P., Vincent-Salomon, A., et al. (2000) · Journal of Clinical Oncology · doi:10.1200/jco.2000.18.24.4053 · Cited by 224 · see citing works
Self-citationDenaturing High-Performance Liquid Chromatography Detects Reliably BRCA1 and BRCA2 Mutations
Wagner, T. M. U., Stoppa‐Lyonnet, D., Fleischmann, E., Muhr, D., Pagès-Berhouet, S., Sandberg, T., Caux‐Moncoutier, V., Möslinger, R., Langbauer, G., Borg, Å., et al. (1999) · Genomics · doi:10.1006/geno.1999.6026 · Cited by 224 · see citing works
Self-citationBrodie, S. G., Xu, X., Qiao, W., Li, W.-M., Cao, L., & Deng, C. (2001) · Oncogene · doi:10.1038/sj.onc.1204929 · Cited by 188 · see citing works
Arriagada, R., Lê, M. G., Guinebretière, J.-M., Dunant, A., Rochard, F., & Tursz, T. (2003) · Annals of Oncology · doi:10.1093/annonc/mdg452 · Cited by 179 · see citing works
Stoppa‐Lyonnet, D., Laurent‐Puig, P., Essioux, L., et al. (1997) · PubMed · Cited by 143 · see citing works
Self-citationBaeyens, A., Thierens, H., Claes, K., Poppe, B., Messiaen, L., De Ridder, L., & Vral, A. (2002) · British Journal of Cancer · doi:10.1038/sj.bjc.6600628 · Cited by 136 · cited 1× · see citing works
“It was shown that tumours in BRCA1/BRCA2 carriers are more sensitive to ionising radiation [48,49].”
BackgroundTurner, B. C., Harrold, E., Matloff, E., Smith, T., GUMBS, A., Beinfield, M., Ward, B., Skolnick, M., Glazer, P., Thomas, A., et al. (1999) · Journal of Clinical Oncology · doi:10.1200/jco.1999.17.10.3017 · Cited by 118 · see citing works
Ipsilateral breast tumour recurrence in hereditary breast cancer following breast-conserving therapy
Seynaeve, C., Verhoog, L. C., van de Bosch, L. M. C., van Geel, A. N., Menke-Pluymers, M., Meijers-Heijboer, E. J., van den Ouweland, A. M. W., Wagner, A., Creutzberg, C. L., Niermeijer, M. F., et al. (2004) · European Journal of Cancer · doi:10.1016/j.ejca.2004.01.017 · Cited by 92 · see citing works
Haber, D. A. (2002) · New England Journal of Medicine · doi:10.1056/nejmed020044 · Cited by 86 · see citing works
Primary node negative breast cancer in BRCA1 mutation carriers has a poor outcome
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., et al. (2000) · Annals of Oncology · doi:10.1023/a:1008340723974 · Cited by 86 · see citing works
Adem, C., Reynolds, C. A., Soderberg, C. L., Slezak, J. M., McDonnell, S. K., Sebo, T. J., Schaid, D. J., Myers, J. L., Sellers, T. A., Hartmann, L. C., et al. (2002) · Cancer · doi:10.1002/cncr.11048 · Cited by 84 · see citing works
Low expression of bcl-2 in Brca1-associated breast cancers
Fréneaux, P., Stoppa‐Lyonnet, D., Mouret, E., Kambouchner, M., Nicolas, A., Sigal‐Zafrani, B., Vincent‐Salomon, A., Fourquet, A., Magdelénat, H., & Sastre‐Garau, X. (2000) · British Journal of Cancer · doi:10.1054/bjoc.2000.1438 · Cited by 51 · see citing works
Self-citationRobson, M. E. (2002) · Cancer Control · doi:10.1177/107327480200900602 · Cited by 38 · see citing works
Genes implicated in hereditary breast cancer syndromes.
Tonin, P. (2000) · Seminars in surgical oncology · doi:10.1002/(sici)1098-2388(200006)18:4 · Cited by 35 · see citing works
Should prophylactic surgery be used in women with a high risk of breast cancer?
Klijn, J. G. M. (1997) · European Journal of Cancer · doi:10.1016/s0959-8049(97)00360-2 · Cited by 34 · see citing works
Radiotherapy for breast cancer in BRCA1/BRCA2 carriers: clinical issues and management dilemmas.
Pierce, L. (2002) · Seminars in Radiation Oncology · doi:10.1053/srao.2002.35254 · Cited by 17 · see citing works
Salmon, R.-J., Asselain, B., Gal, M. L., et al. (1997) · The Breast · doi:10.1016/s0960-9776(97)90574-9 · Cited by 9 · see citing works
EUSOMA guidelines on the management of familial breast cancer risk
Blamey, R. W., Mackay, J., & Macmillan, D. R. (2004) · European Journal of Cancer Supplements · doi:10.1016/s1359-6349(04)90939-1 · Cited by 4 · see citing works
Prophylactic mastectomy in high risk women
Klijn, J. G. M. (2004) · European Journal of Cancer Supplements · doi:10.1016/s1359-6349(04)90943-3 · Cited by 1 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Brekelmans, C. T. M., Tilanus-Linthorst, M. M. A., Seynaeve, C., vd Ouweland, A., Menke-Pluymers, M. B. E., Bartels, C. C. M., Kriege, M., van Geel, A. N., Burger, C. W., Eggermont, A. M. M., et al. (2007) · European Journal of Cancer · doi:10.1016/j.ejca.2006.12.009 · Cited by 233 · see citing works
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
Heemskerk-Gerritsen, B. A. M., Brekelmans, C. T. M., Menke-Pluymers, M. B. E., van Geel, A. N., Tilanus-Linthorst, M. M. A., Bartels, C. C. M., Tan, M., Meijers-Heijboer, H. E. J., Klijn, J. G. M., & Seynaeve, C. (2007) · Annals of Surgical Oncology · doi:10.1245/s10434-007-9449-x · Cited by 153 · 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
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
Self-citationBreast-Conserving Surgery in BRCA1/2 Mutation Carriers: Are We Approaching an Answer?
Garcia-Etienne, C. A., Barile, M., Gentilini, O. D., Botteri, E., Rotmensz, N., Sagona, A., Farante, G., Galimberti, V., Luini, A., Veronesi, P., et al. (2009) · Annals of Surgical Oncology · doi:10.1245/s10434-009-0638-7 · Cited by 100 · see citing works
- Authors
- Kirova, Y. M., Stoppa-Lyonnet, D., Savignoni, A., Sigal-Zafrani, B., Fabre, N., & Fourquet, A.
- Affiliations
- Institut Curie (FR)
- Corresponding author
- Kirova, Youlia M.
- Venue
- European Journal of Cancer
- Publisher
- Elsevier BV
- Published
- 2005-10
- Volume
- 41
- Issue
- 15
- Pages
- 2304-2311
- ISSN
- 0959-8049 (ISSN-L)
- OpenAlex
- W2013945615
- Cited by
- 129
- References
- 52
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 5 · 2020: 8 · 2019: 3 · 2018: 4 · 2017: 6 · 2016: 1 · 2015: 11 · 2014: 6 · 2013: 8 · 2012: 7
- FWCI
- 5.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Cancer (publishedVersion)
- PubMed (publishedVersion)
- 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 › Epidemiology › Multiple and Secondary Primary Cancers
- Keywords
- breast cancer recurrence, contralateral breast cancer, BRCA1 mutation, BRCA2 mutation, germline mutations, breast-conserving surgery, adjuvant radiotherapy, hereditary breast cancer, radiosensitivity, estrogen receptor status, tumor grade, age as risk factor, genetic testing, family history of cancer, ovarian cancer risk
- MeSH terms
- Adult, Aged, Breast Neoplasms, Epidemiologic Methods, Female, Heterozygote, Humans, Middle Aged, Neoplasm Recurrence, Local, Mastectomy, Segmental, Polymerase Chain Reaction, Germ-Line Mutation, Genes, BRCA1, Genes, BRCA2
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
