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Prognosis of early-onset breast cancer based on BRCA1/2 mutation status in a French population-based cohort and review

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Abstract

Purpose

The debate concerning poorer survival for patients with breast cancer (BC) carrying a BRCA1 germline mutation is unresolved, and requires additional data from population-based studies.

Patients and methods

We followed 232 women with invasive BC under age 46, ascertained prospectively through a French population-based BC registry and tested for BRCA1/2 mutations (median follow-up: 82 months). We compared tumour characteristics and survival rates between 21 BRCA1/2 deleterious mutation carriers and 211 non-carriers.

Results

As compared to sporadic tumours, BRCA1/2 tumours showed higher grade (P = 0.02), fewer ductal carcinoma in situ (P = 0.02), more frequent medullary histology (P = 0.02), more frequent negative oestrogen and progesterone receptors (P = 0.001 each). At 5 years, BC-specific survival, metastasis-free survival, ipsilateral recurrence-free survival and contralateral BC-free survival rates for BRCA1/2 mutation carriers were 95.0%, 94.7%, 100% and 90.0% respectively, compared with 89.6%, 78.2%, 88.8% and 94.4% respectively, for non-carriers (not significant). Rates for women carrying only a BRCA1 mutation were 93.3%, 93.3%, 100%, 86.7%, respectively. 76% of BRCA1/2 carriers received chemotherapy.

Conclusion

Despite unfavourable tumour features, we found no evidence for poorer short-term survival in BRCA1 mutation carriers compared to non-carriers in this prospective population-based cohort. The high rate of BRCA1 carriers who received chemotherapy for their BC should question the positive impact of this treatment, as suggested by preclinical studies showing increased chemosensitivity of BRCA1-associated tumours.

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References

  1. Garber JE, Offit K (2005) Hereditary cancer predisposition syndromes. J Clin Oncol 23:276–292

    Article  PubMed  Google Scholar 

  2. Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W et al (1994) A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 265:1088–2090

    Google Scholar 

  3. Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, Collins N, Gregory S, Gumbs C, Micklem G (1995) Identification of the breast cancer susceptibility gene BRCA2. Nature 378:789–792

    Article  PubMed  CAS  Google Scholar 

  4. Tavtigian SV, Simard J, Rommens J, Couch F, Shattuck Eidens D, Neuhausen S, Merajver S, Thorlacius S, Offit K, Stoppa-Lyonnet D, Belanger C, Bell R, Berry S, Bogden R, Chen Q, Davis T, Dumont M, Frye C, Hattier T, Jammulapati S, Janecki T, Jiang P, Kehrer R, Leblanc JF, Mitchell JT, McArthur-Morrison J, Nguyen K, Peng Y, Samson C, Schroeder M, Snyder SC, Steele L, Stringfellow M, Stroup C, Swedlund B, Swense J, Teng D, Thomas A, Tran T, Tranchant M, Weaver-Feldhaus J, Wong AK, Shizuya H, Eyfjord JE, Cannon-Albright L, Tranchant M, Labrie F, Skolnick MH, Weber B, Kamb A, Goldgar DE (1996) The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds. Nat Genet 12:333–337

    Article  PubMed  CAS  Google Scholar 

  5. Foulkes WD, Wong N, Brunet JS, Begin LR, Zhang JC, Martinez JJ, Rozen F, Tonin PN, Narod SA, Karp SE, Pollak MN (1997) Germ-line BRCA1 mutation is an adverse prognostic factor in Ashkenazi Jewish women with breast cancer. Clin Cancer Res 3:2465–2469

    PubMed  CAS  Google Scholar 

  6. Johannsson OT, Ranstam J, Borg A, Olsson H (1998) Survival of BRCA1 breast and ovarian cancer patients: a population-based study from southern Sweden. J Clin Oncol 16:397–404

    PubMed  CAS  Google Scholar 

  7. Ansquer Y, Gautier C, Fourquet A, Asselain B, Stoppa-Lyonnet D (1998) Survival in early-onset BRCA1 breast-cancer patients. Institut Curie Breast Cancer Group. Lancet 352:541

    CAS  Google Scholar 

  8. Robson M, Levin D, Federici M, Satagopan J, Bogolminy F, Heerdt A, Borgen P, McCormick B, Hudis C, Norton L, Boyd J, Offit K (1999) Breast conservation therapy for invasive breast cancer in Ashkenazi women with BRCA gene founder mutations. J Natl Cancer Inst 91:2112–2117

    Article  PubMed  CAS  Google Scholar 

  9. Foulkes WD, Chappuis PO, Wong N, Brunet JS, Vesprini D, Rozen F, Yuan ZQ, Pollak MN, Kuperstein G, Narod SA, Begin LR (2000) Primary node negative breast cancer in BRCA1 mutation carriers has a poor outcome. Ann Oncol 11:307–313

    Article  PubMed  CAS  Google Scholar 

  10. Stoppa-Lyonnet D, Ansquer Y, Dreyfus H, Gautier C, Gauthier-Villars M, Bourstyn E, Clough KB, Magdelenat H, Pouillart P, Vincent-Salomon A, Fourquet A, Asselain B (2000) Familial invasive breast cancers: worse outcome related to BRCA1 mutations. J Clin Oncol 18:4053–4059

    PubMed  CAS  Google Scholar 

  11. Eerola H, Vahteristo P, Sarantaus L, Kyyronen P, Pyrhonen S, Blomqvist C, Pukkala E, Nevanlinna H, Sankila R (2001) Survival of breast cancer patients in BRCA1, BRCA2, and non-BRCA1/2 breast cancer families: a relative survival analysis from Finland. Int J Cancer 93:368–372

    Article  PubMed  CAS  Google Scholar 

  12. Moller P, Borg A, Evans DG, Haites N, Reis MM, Vasen H, Anderson E, Steel CM, Apold J, Goudie D, Howell A, Lalloo F, Maehle L, Gregory H, Heimdal K (2002) Survival in prospectively ascertained familial breast cancer: analysis of a series stratified by tumour characteristics, BRCA mutations and oophorectomy. Int J Cancer 101:555–559

    Article  PubMed  CAS  Google Scholar 

  13. Robson ME, Chappuis PO, Satagopan J, Wong N, Boyd J, Goffin JR, Hudis C, Roberge D, Norton L, Begin LR, Offit K, Foulkes WD (2004) A combined analysis of outcome following breast cancer: differences in survival based on BRCA1/BRCA2 mutation status and administration of adjuvant treatment. Breast Cancer Res 6:R8–R17

    Article  PubMed  CAS  Google Scholar 

  14. Breast Cancer Linkage Consortium (BCLC) (1997) Pathology of familial breast cancer: differences between breast cancers in carriers of BRCA1 or BRCA2 mutations and sporadic cases. Lancet 349:1505–1510

    Article  Google Scholar 

  15. Lakhani SR, Jacquemier J, Sloane JP, Gusterson BA, Anderson TJ, van de Vijver MJ, Farid LM, Venter D, Antoniou A, Storfer-Isser A, Smyth E, Steel CM, Haites N, Scott RJ, Goldgar D, Neuhausen S, Daly PA, Ormiston W, McManus R, Scherneck S, Ponder BA, Ford D, Peto J, Stoppa-Lyonnet D, Bignon YJ, Struewing JP, Spurr NK, Bishop DT, Klijn JG, Devilee P, Cornelisse CJ, Lasset C, Lenoir G, Barkardottir RB, Egilsson V, Hamann U, Chang-Claude J, Sobol H, Weber B, Stratton MR, Easton DF (1998) Multifactorial analysis of differences between sporadic breast cancers and cancers involving BRCA1 and BRCA2 mutations. J Natl Cancer Inst 90:1138–1145

    Article  PubMed  CAS  Google Scholar 

  16. Lakhani SR, van de Vijver MJ, Jacquemier J, Anderson TJ, Osin PP, McGuffog L, Easton (2002) The pathology of familial breast cancer: predictive value of immunohistochemical markers estrogen receptor, progesterone receptor, HER-2, and p53 in patients with mutations in BRCA1 and BRCA2. J Clin Oncol 20:2310–2308

    Article  PubMed  CAS  Google Scholar 

  17. Foulkes WD, Metcalfe K, Hanna W, Lynch HT, Ghadirian P, Tung N, Olopade O, Weber B, McLennan J, Olivotto IA, Sun P, Chappuis PO, Begin LR, Brunet JS, Narod SA (2003) Germline BRCA1 mutations and a basal epithelial phenotype in breast cancer. J Natl Cancer Inst 95:1482–1485

    PubMed  CAS  Google Scholar 

  18. Lakhani SR, Reis-Filho JS, Fulford L, Penault-Llorca F, van der Vijver M, Parry S, Bishop T, Benitez J, Rivas C, Bignon YJ, Chang-Claude J, Hamann U, Cornelisse CJ, Devilee P, Beckmann MW, Nestle-Kramling C, Daly PA, Haites N, Varley J, Lalloo F, Evans G, Maugard C, Meijers-Heijboer H, Klijn JG, Olah E, Gusterson BA, Pilotti S, Radice P, Scherneck S, Sobol H, Jacquemier J, Wagner T, Peto J, Stratton MR, McGuffog L, Easton DF (2005) Breast Cancer Linkage Consortium.: Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype. Clin Cancer Res 11:5175–5180

    Article  PubMed  CAS  Google Scholar 

  19. Brenton JD, Carey LA, Ahmed AA, Caldas C (2005) Molecular classification and molecular forecasting of breast cancer: ready for clinical application? J Clin Oncol 23:7350–7360

    Article  PubMed  CAS  Google Scholar 

  20. Verhoog LC, Brekelmans CT, Seynaeve C, van den Bosch LM, Dahmen G, van Geel AN, Tilanus-Linthorst MM, Bartels CC, Wagner A, van den Ouweland A, Devilee P, Meijers-Heijboer EJ, Klijn JG (1998) Survival and tumour characteristics of breast-cancer patients with germline mutations of BRCA1. Lancet 351:316–21

    Article  PubMed  CAS  Google Scholar 

  21. Gaffney DK, Brohet RM, Lewis CM, Holden JA, Buys SS, Neuhausen SL, Steele L, Avizonis V, Stewart JR, Cannon-Albright LA (1998) Response to radiation therapy and prognosis in breast cancer patients with BRCA1 and BRCA2 mutations. Radiother Oncol 47:129–136

    Article  PubMed  CAS  Google Scholar 

  22. Hamann U, Sinn HP (2000) Survival and tumor characteristics of German hereditary breast cancer patients. Breast Cancer Res Treat 59:185–192

    Article  PubMed  CAS  Google Scholar 

  23. El Tamer M, Russo D, Troxel A, Bernardino LP, Mazziotta R, Estabrook A, Ditkoff BA, Schnabel F, Mansukhani M (2004) Survival and recurrence after breast cancer in BRCA1/2 mutation carriers. Ann Surg Oncol 11:157–164

    Article  PubMed  Google Scholar 

  24. Brekelmans CTM, Seynaeve C, Menke-Pluymers M et al (2005) Survival and prognostic factors in BRCA1-associated breast cancer. Ann Oncol doi:10.1093/annonc/mdj095

  25. Loman N, Johannsson O, Bendahl P, Dahl N, Einbeigi Z, Gerdes A, Borg A, Olsson H (2000) Prognosis and clinical presentation of BRCA2-associated breast cancer. Eur J Cancer 36:1365–1373

    Article  PubMed  CAS  Google Scholar 

  26. Chappuis PO, Kapusta L, Begin LR, Wong N, Brunet JS, Narod SA, Slingerland J, Foulkes WD (2000) Germline BRCA1/2 mutations and p27(Kip1) protein levels independently predict outcome after breast cancer. J Clin Oncol 18:4045–4052

    PubMed  CAS  Google Scholar 

  27. Haffty BG, Harrold E, Khan AJ, Pathare P, Smith TE, Turner BC, Glazer PM, Ward B, Carter D, Matloff E, Bale AE, Alvarez-Franc M (2002) Outcome of conservatively managed early-onset breast cancer by BRCA1/2 status. Lancet 359:1471–1477

    Article  PubMed  Google Scholar 

  28. Verhoog LC, Brekelmans CT, Seynaeve C, Dahmen G, van Geel AN, Bartels CC, Tilanus-Linthorst MM, Wagner A, Devilee P, Halley DJ, van den Ouweland AM, Meijers-Heijboer EJ, Klijn JG (1999) Survival in hereditary breast cancer associated with germline mutations of BRCA2. J Clin Oncol 17:3396–3402

    PubMed  CAS  Google Scholar 

  29. Pierce LJ, Strawderman M, Narod SA, Oliviotto I, Eisen A, Dawson L, Gaffney D, Solin LJ, Nixon A, Garber J, Berg C, Isaacs C, Heimann R, Olopade OI, Haffty B, Weber BL (2000) Effect of radiotherapy after breast-conserving treatment in women with breast cancer and germline BRCA1/2 mutations. J Clin Oncol 18:3360–3369

    PubMed  CAS  Google Scholar 

  30. Robson M, Gilewski T, Haas B, Levin D, Borgen P, Rajan P, Hirschaut Y, Pressman P, Rosen PP, Lesser ML, Norton L, Offit K (1998) BRCA-associated breast cancer in young women. J Clin Oncol 16:1642–1649

    PubMed  CAS  Google Scholar 

  31. Phillips KA, Andrulis IL, Goodwin PJ (1999) Breast carcinomas arising in carriers of mutations in BRCA1 or BRCA2: are they prognostically different? J Clin Oncol 17:3653–3663

    PubMed  CAS  Google Scholar 

  32. Robson M (2000) Are BRCA1- and BRCA2- associated breast cancers different? Prognosis of BRCA1-associated breast cancer. J Clin Oncol 18:113s–118s

    PubMed  CAS  Google Scholar 

  33. Evans DG, Howell A (2004) Are BRCA1- and BRCA2- related breast cancers associated with increased mortality ? Breast Cancer Res 6:E7

    Article  PubMed  CAS  Google Scholar 

  34. Bonadona V, Sinilnikova OM, Chopin S, Antoniou AC, Mignotte H, Mathevet P, Brémond A, Martin A, Bobin JY, Romestaing P, Raudrant D, Rudigoz RC, Léoné M, Chauvin F, Easton DF, Lenoir GM, Lasset C (2005) Contribution of BRCA1 and BRCA2 germline mutations to the incidence of breast cancer in young women: results from a prospective population-based study in France. Genes Chromosomes Cancer 43:404–413

    Article  PubMed  CAS  Google Scholar 

  35. Davison AC, Hinkley DV (1997) Bootstrap methods and their application. Cambridge University Press

  36. Weber BL (2005) Genetic testing for BRCA1 and BRCA2: a paradigm for personalized medicine. Plenary Session III, ASCO Annual meeting, Orlando, May 13–17

  37. Foulkes WD, Metcalfe K, Hanna W, Lynch HT, Ghadirian P, Tung N, Olopade O, Weber B, McLennan J, Olivotto IA, Sun P, Chappuis PO, Begin LR, Brunet JS, Narod SA (2003) Disruption of the expected positive correlation between breast tumor size and lymph node status in BRCA1-related breast carcinoma. Cancer 98:1569–1577

    Article  PubMed  Google Scholar 

  38. Kennedy RD, Quinn JE, Mullan PB, Johnston PG, Harkin DP (2004) The role of BRCA1 in the cellular response to chemotherapy. J Natl Cancer Inst 96:1659–1668

    Article  PubMed  CAS  Google Scholar 

  39. Venkitaraman AR (2002) Cancer susceptibility and the functions of BRCA1 and BRCA2. Cell 108:171–182

    Article  PubMed  CAS  Google Scholar 

  40. Kennedy RD, Quinn JE, Johnston PG, Harkin DP (2002) BRCA1: mechanisms of inactivation and implications for managements of patients. Lancet 360:1007–1014

    Article  PubMed  CAS  Google Scholar 

  41. Metcalfe K, Lynch HT, Ghadirian P, Tung N, Olivotto I, Warner E, Olopade OI, Eisen A, Weber B, McLennan J, Sun P, Foulkes WD, Narod SA (2004) Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. J Clin Oncol 22:2328–2335

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by grants from the « Fondation de France », the « Comité départemental du Rhône de la Ligue Contre le Cancer » and the « Fédération Nationale des Groupements des Entreprises Françaises dans la lutte contre le cancer ».

We thank Cécile Giraud for collecting follow-up data and Sandrine Handallou for technical assistance.

We thank Margaret Haugh for her help with the preparation of this manuscript.

We thank the investigators participating in this study: Ardiet JM, Ardisson P, Audra P, Aussavis F, Barbier B, Barrier PY, Berard P, Berland M, Berlier JL, Dargent D, Bernard M, Blondet R, Bobin JY, Bolsigner L, Bonardel C, Bonnevie R, Boue P, Boulet S, Bouzid D, Bremond A, Broussard, Buatois F, Canat EP, Carrie C, Catimel G, Cauvin I, Chabert, Champion F, Chassagnard F, Chauvot P, Cognat M, Coquard R, Coste JD, Courtieu G, Cousin C, Crozet B, De Roissard, De saint Hilaire P, Dumas AM, Gaucherand P, Gelas M, Gerard JP, Gillion, Golfier F, Goncalves M, Gratadour AC, Guastalla JP, Ingels J, Jacquot D, Jaussaud D, Labrosse H, Lafont A, Lagoutte J, Lambert J, Laville, Le Maout G, Mallecourt P, Marsaud H, Martin A, Martin JP, Martin P, Mathevet P, Mayer B, Mellier G, Mignotte H, Montvernay C, Palayer C, Papillon M, Pasquier J, Pegaz M, Piacenza JM, Pic JC, Raudrant D, Raymaud, Romestaing P, Rondelet O, Rudigoz RC, Salles B, Seligmann G, Servajean F, Tairraz JP, Thevenot-Rivoire D, Thome Saint Paul M, Victoria J, Vidal M, Villard, Watrelot A, Zinzindouhe C, Zlatoff␣P.

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Authors and Affiliations

  1. Centre Léon Bérard, Unit of Prevention and Genetic Epidemiology, 28 rue Laënnec, 69 373, Lyon cedex 08, France

    Valérie Bonadona, Sophie Dussart-Moser, Nicolas Voirin & Christine Lasset

  2. International Agency for Research on Cancer, Lyon, France

    Olga M Sinilnikova

  3. Plate-forme mixte de génétique constitutionnelle des cancers fréquents, Hospices Civils de Lyon/Centre Léon Bérard, Lyon, France

    Olga M Sinilnikova

  4. Department of Surgical Oncology, Centre Léon Bérard, Lyon, France

    Hervé Mignotte & Alain Brémond

  5. Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France

    Patrice Mathevet

  6. ADEMAS, Breast Cancer Rhône Registry, Lyon, France

    Alain Brémond

  7. Department of Pathology, Centre Léon Bérard, Lyon, France

    Isabelle Treilleux

  8. Clinique Jeanne d’Arc, Lyon, France

    Alain Martin

  9. Department of Radiotherapy and Oncology, Lyon-Sud Hospital Center, Hospices Civils de Lyon, Pierre-Benite, France

    Pascale Romestaing

  10. Hôtel Dieu Hospital, Hospices Civils de Lyon, Lyon, France

    Daniel Raudrant

  11. Croix Rousse Hospital, Hospices Civils de Lyon, Lyon, France

    René-Charles Rudigoz

  12. CNRS - UMR 8125, Institut Gustave Roussy, Villejuif, France

    Gilbert M. Lenoir

  13. Laboratoire d’Epidémiologie et de Santé Publique, Université Claude Bernard Lyon I, Lyon, France

    Christine Lasset

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  1. Valérie Bonadona
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  2. Sophie Dussart-Moser
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  3. Nicolas Voirin
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  4. Olga M Sinilnikova
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  13. Gilbert M. Lenoir
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  14. Christine Lasset
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Correspondence to Valérie Bonadona.

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Bonadona, V., Dussart-Moser, S., Voirin, N. et al. Prognosis of early-onset breast cancer based on BRCA1/2 mutation status in a French population-based cohort and review. Breast Cancer Res Treat 101, 233–245 (2007). https://doi.org/10.1007/s10549-006-9288-7

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