Advertisement

Medical Oncology

, 31:850 | Cite as

Should BRCA2 mutation carriers avoid neoadjuvant chemotherapy?

  • J. RaphaelEmail author
  • C. Mazouni
  • O. Caron
  • M. Ferchiou
  • S. Delaloge
Short Communication

Abstract

BRCA2 mutation carriers typically develop luminal B breast cancers. Data on the effectiveness of neoadjuvant chemotherapy in these patients are limited because of small patient numbers and lack of prospective studies. We used our 15-year genetic clinic database to compare retrospectively the pathological complete response rates (pCR) and rates of post-chemotherapy nodal involvement among BRCA2 carriers and BRCA1/2-negative (WT) patients with luminal B tumours, all treated with neoadjuvant anthracyclines ± taxanes-based chemotherapy. Twenty-nine BRCA2 carriers and 67 WT patients fulfilled the inclusion criteria and were analysed. Patients and treatment characteristics were represented. A pCR occurred in 3 (10 %) BRCA2 patients and 13 (19 %) WT patients (p = 0.43). Twenty (69 %) BRCA2 carriers and 34 (51 %) WT patients remained node-positive at surgery (p = 0.17). BRCA2 germline mutations are associated with a low probability of pCR and a high risk of axillary invasion. Alternative treatments are highly expected, and clinical trials are needed to set the best treatment regimen in this population.

Keywords

Breast cancer BRCA2 Neoadjuvant chemotherapy pCR Response rate 

Notes

Conflict of interest

The authors declare they have no conflict of interest.

References

  1. 1.
    Risch HA, McLaughlin JR, Cole DE, et al. Population BRCA1 and BRCA2 mutation frequencies and cancer penetrances: a KIN-cohort study in Ontario, Canada. J Natl Cancer Inst. 2006;98(23):1694–706.PubMedCrossRefGoogle Scholar
  2. 2.
    Ford D, Easton DF, Bishop DT, Narod SA, Goldgar DE. Risks of cancer in BRCA1-mutation carriers. Breast cancer linkage consortium. Lancet. 1994;343(8899):692–5.PubMedCrossRefGoogle Scholar
  3. 3.
    Melchor L, Honrado E, Garcia MJ, et al. Distinct genomic aberration patterns are found in familial breast cancer associated with different immunohistochemical subtypes. Oncogene. 2008;27(22):3165–75.PubMedCrossRefGoogle Scholar
  4. 4.
    Arun B, Bayraktar S, Liu DD, et al. Response to neoadjuvant systemic therapy for breast cancer in BRCA mutation carriers and noncarriers: a single-institution experience. J Clin Oncol. 2011;29(28):3739–46.PubMedCrossRefGoogle Scholar
  5. 5.
    Vargas AC, Reis-Filho JS, Lakhani SR. Phenotype-genotype correlation in familial breast cancer. J Mammary Gland Biol Neoplasia. 2011;16(1):27–40.PubMedCrossRefGoogle Scholar
  6. 6.
    Goodwin PJ, Phillips KA, West DW, et al. Breast cancer prognosis in BRCA1 and BRCA2 mutation carriers: an International Prospective Breast Cancer Family Registry population-based cohort study. J Clin Oncol. 2012;30(1):19–26.PubMedCrossRefGoogle Scholar
  7. 7.
    Farmer H, McCabe N, Lord CJ, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434(7035):917–21.PubMedCrossRefGoogle Scholar
  8. 8.
    Bryant HE, Schultz N, Thomas HD, et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature. 2005;434(7035):913–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Byrski T, Huzarski T, Dent R, et al. Response to neoadjuvant therapy with cisplatin in BRCA1-positive breast cancer patients. Breast Cancer Res Treat. 2009;115:359–63.PubMedCrossRefGoogle Scholar
  10. 10.
    Chappuis PO, Goffin J, Wong N, et al. A significant response to neoadjuvant chemotherapy in BRCA1/2 related breast cancer. J Med Genet. 2002;39:608–10.PubMedCrossRefGoogle Scholar
  11. 11.
    Rennert G, Bisland-Naggan S, Barnett-Griness O, et al. Clinical outcomes of breast cancer in carriers of BRCA1 and BRCA2 mutations. N Engl J Med. 2007;357(2):115–23.PubMedCrossRefGoogle Scholar
  12. 12.
    Edge SB, Byrd DR, Compton CC, et al. AJCC cancer staging manual. 7th ed. New York: Springer; 2010.Google Scholar
  13. 13.
    Balaton AL, Coindre JM, Collin F, et al. Recommendations for the immunohistochemical evaluation of hormone receptors on paraffin sections of breast cancer. Study Group on Hormone Receptors using Immunohistochemistry FNCLCC/AFAQAP. National Federation of Centres to Combat Cancer/French Association for Quality Assurance in Pathology. Ann Pathol. 1996;16(2):144–8.PubMedGoogle Scholar
  14. 14.
    Cortazar P, Zhang L, Untch M, et al. Meta-analysis results from the collaborative trials in neoadjuvant breast cancer. 2012 San Antonio Breast Cancer Symposium. Abstract S1-11. Presented December 5, 2012.Google Scholar
  15. 15.
    Kriege M, Seynaeve C, Meijers-Heijboer H, et al. Sensitivity to first-line chemotherapy for metastatic breast cancer in BRCA1 and BRCA2 mutation carriers. J Clin Oncol. 2009;27(23):3764–71. doi: 10.1200/JCO.2008.19.9067.PubMedCrossRefGoogle Scholar
  16. 16.
    Von Minckwitz G, Untch M, Blohmer JU, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012;30:1796–804.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • J. Raphael
    • 1
    Email author
  • C. Mazouni
    • 2
  • O. Caron
    • 3
  • M. Ferchiou
    • 4
  • S. Delaloge
    • 1
  1. 1.Breast Cancer Group, Department of MedicineGustave RoussyVillejuifFrance
  2. 2.Breast Cancer Group, Department of SurgeryGustave RoussyVillejuifFrance
  3. 3.Breast Cancer Group, Department of OncogeneticsGustave RoussyVillejuifFrance
  4. 4.Breast Cancer Group, Department of BiopathologyGustave RoussyVillejuifFrance

Personalised recommendations