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Response to neo-adjuvant chemotherapy in women with BRCA1-positive breast cancers

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

There have been no studies to date which look at the relative effectiveness of different regimens of chemotherapy in women who have breast cancer and who carry a BRCA1 germ-line mutation. We wished to compare rates of response to neo-adjuvant chemotherapy in BRCA1 mutation carriers and non-carrier controls.

Experimental design

From a registry of 3,479 patients, we identified 44 Polish women who carried a BRCA1 founder mutation and who had been treated with neo-adjuvant chemotherapy for breast cancer, and 41 age- and hospital-matched controls.

Results

35 of the 44 BRCA1 mutation carriers (80%) experienced a partial or complete response to neo-adjuvant chemotherapy, compared to 39 of the 41 (95%) non-carriers (P = 0.05). In the hereditary subgroup, response rates differed depending on whether or not a taxane (docetaxel) was given. Six of the 15 BRCA1 carrier women given docetaxel with doxorubicin responded (complete or partial), compared to 29 of 29 given other (DNA-damaging) therapies (P = 0.001). Among the non-carriers, the rates of response to the two categories of chemotherapy were similar.

Conclusions

Breast cancers among BRCA1 carriers frequently do not exhibit sensitivity to docetaxel in the neo-adjuvant setting. It is likely that normal BRCA1 is required for clinical response to mitotic spindle poisons.

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References

  1. Marcus JN, Watson P, Page DL et al (1997) BRCA2 hereditary breast cancer pathophenotype. Breast Cancer Res Treat 44:275–277

    Article  PubMed  CAS  Google Scholar 

  2. Lakhani SR, Jacquemier J, Sloane JP et al (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 

  3. Foulkes WD, Brunet JS, Stefansson IM et al (2004) The prognostic implication of the basal-like (cyclin E high/p27 low/p53+/glomeruloid-microvascular-proliferation+) phenotype of BRCA1-related breast cancer. Cancer Res 64:830–835

    Article  PubMed  CAS  Google Scholar 

  4. Johannsson OT, Idvall I, Anderson C et al (1997) Tumour biological features of BRCA1-induced breast and ovarian cancer. Eur J Cancer 33:362–371

    Article  PubMed  CAS  Google Scholar 

  5. Moynahan ME, Cui TY, Jasin M (2001) Homology-directed DNA repair, mitomycin-c resistance, and chromosome stability is restored with correction of a BRCA1 mutation. Cancer Res 61:4842–4850

    PubMed  CAS  Google Scholar 

  6. Bhattacharyya A, Ear US, Koller BH, Weichselbaum RR, Bishop DK (2000) The breast cancer susceptibility gene BRCA1 is required for subnuclear assembly of Rad51 and survival following treatment with the DNA cross-linking agent cisplatin. J Biol Chem 275:23899–23903

    Article  PubMed  CAS  Google Scholar 

  7. Fedier A, Steiner RA, Schwartz VA et al (2003) The effect of loss of Brca1 on the sensitivity of anticancer agents in p53-deficient cells. Int J Oncol 22:1169–1173

    PubMed  CAS  Google Scholar 

  8. Chabalier C, Lamare C, Racca C et al (2003) BRCA1 down-regulation leads to premature inactivation of spindle checkpoint and confers paclitaxel resistance. Cell Cycle 5:1001–1007

    Google Scholar 

  9. Fisher B, Bryant J, Wolmark N et al (1998) Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol 16:2672–2685

    PubMed  CAS  Google Scholar 

  10. Lubinski J, Gorski B, Huzarski T et al (2006) BRCA1-positive breast cancers in young women from Poland. Breast Cancer Res Treat 99:71–76

    Article  PubMed  CAS  Google Scholar 

  11. Górski B, Byrski T, Huzarski T et al (2000) Founder mutations in BRCA1 gene in Polish families with breast-ovarian cancer. Am J Hum Genet 66:1963–1968

    Article  PubMed  Google Scholar 

  12. Górski B, Jakubowska A, Huzarski T et al (2004) A high proportion of founder BRCA1 mutations in Polish breast cancer families. Int J Cancer 110:683–686

    Article  PubMed  CAS  Google Scholar 

  13. Kennedy RD, Quinn JE, Mullan PB et al (2004) The role of BRCA1 in the cellular response to chemotherapy. J Natl Cancer Inst 96:1659–1668

    Article  PubMed  CAS  Google Scholar 

  14. Zhoue C, Smith JL, Lui J (2003) Role of BRCA1 in cellular resistance to paclitaxel and ionizing radiation in an ovarian cancer cell line carrying a defective BRCA1. Oncogene 22:2396–2404

    Article  CAS  Google Scholar 

  15. Lafarge S, Sulvain V, Ferrara M, Bignon YJ (2001) Inhibition of BRCA1 leads to increased chemoresistance to micotubule-interfering agents, an effect that involves the JNK pathway. Oncogene 20:6597–6606

    Article  PubMed  CAS  Google Scholar 

  16. Quinn JE, Kennedy RD, Mullan PB et al (2003) BRCA1 functions as a diferential modulator of chemotherapy-induced apoptosis. Cancer Res 63:6221–6228

    PubMed  CAS  Google Scholar 

  17. Tassone P, Tagliaferri P, Perricelli A et al (2003) BRCA1 expression modulates chemosensitivity of BRCA1-defective HCC1937 human breast cancer cells. Br J Cancer 88:1285–1291

    Article  PubMed  CAS  Google Scholar 

  18. Chappuis PO, Goffin J, Wong N et al (2002) A significant response to neoadjuant chemotherapy in BRCA1/2 related breast cancer. J Med Genet 39:608–610

    Article  PubMed  CAS  Google Scholar 

  19. Delaloge S, Kloos I et al (2002) BRCA1-linked breast cancer is highly more chemosensitive than its BRCA2-linked or sporadic counterparts. Program and abstracts of the 27th Congress of the European Society for Medical Oncology 2002

  20. Rouzier R, Perou CM, Symmans WF et al (2005) Breast cancer molecular subtypes respond differently to pre-operative chemotherapy. Clin Cancer Res 11:5678–5685

    Article  PubMed  CAS  Google Scholar 

  21. Foulkes WD, Stefansson IM, Chappuis PO et al (2003) Germline BRCA1 mutations and a basal epithelial phenotype in breast cancer. J Natl Cancer Inst 95:1482–1485

    PubMed  CAS  Google Scholar 

  22. Kennedy RD, Quinn JR, 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 

  23. Turner N, Tutt A, Ashworth A (2005) Targeting the DNA repair defect of BRCA tumours. Curr Opin Pharmacol 5:338–393

    Article  CAS  Google Scholar 

  24. Garber JE, Richardson A, Harris LN et al (2006) Neo-adjuvant cisplatin (CDPP) in “triple-negative” breast cancer. Abstract of the San Antonio Breast Cancer Symposium, San Antonio

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Acknowledgements

This study was funded by the Polish Ministry of Science 04/p05/11. Supported by the Canadian Breast Cancer Research Alliance. We thank William Foulkes for helpful comments.

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Authors and Affiliations

  1. Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland

    T. Byrski, J. Gronwald, T. Huzarski & J. Lubinski

  2. Department of Tumor Biology, Centre of Oncology, Maria Sklodowska-Curie Memorial Institute, Gliwice, Poland

    E. Grzybowska & M. Budryk

  3. Prophylactic and Epidemiology Center, Poznan, Poland

    M. Stawicka

  4. Regional Oncology Hospital, Bydgoszcz, Poland

    T. Mierzwa

  5. Regional Oncology Center, Opole, Poland

    M. Szwiec

  6. Regional Oncology Hospital, Bielsko Biala, Poland

    R. Wiśniowski

  7. Holy Cross Oncology Center, Kielce, Poland

    M. Siolek

  8. Women’s College Research Institute, University of Toronto, 790 Bay Street, 7th Floor, Toronto, ON, Canada, M5G1N8

    S. A. Narod

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  1. T. Byrski
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  2. J. Gronwald
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  3. T. Huzarski
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  4. E. Grzybowska
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  5. M. Budryk
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  6. M. Stawicka
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  7. T. Mierzwa
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  8. M. Szwiec
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  9. R. Wiśniowski
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  10. M. Siolek
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  11. S. A. Narod
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  12. J. Lubinski
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Consortia

the Polish Hereditary Breast Cancer Consortium

Corresponding author

Correspondence to S. A. Narod.

Additional information

Other members of the Polish Hereditary Breast Cancer Consortium: M. Foszczynska-Kloda, P. Serrano-Fernández, M. Chosia, M. Uciński, D. Lange, B. Mika, A. Mackiewicz, A. Karczewska, J. Breborowicz, K. Lamperska, S. Gozdecka-Grodecka, M. Bębenek, D. Sorokin, A. Wojnar, O. Haus, J. Sir, S. Niepsuj, K. Gugała, S. Goźdź, J. Sygut, B. Kozak-Klonowska, M. Musiatowicz, R. Posmyk, M. Kordek, O. Morawiec, B. Zambrano, L. Waśko, D. Fudali, D. Surdynka, K. Urbański, J. Mituś, J. Ryś, A. Rozmiarek, I. Dziuba, P. Wandzel, C. Szczylik, A. Kozak, A. Kozłowski.

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Byrski, T., Gronwald, J., Huzarski, T. et al. Response to neo-adjuvant chemotherapy in women with BRCA1-positive breast cancers. Breast Cancer Res Treat 108, 289–296 (2008). https://doi.org/10.1007/s10549-007-9600-1

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  • DOI: https://doi.org/10.1007/s10549-007-9600-1

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