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Breast cancer sensitivity to neoadjuvant therapy in BRCA1 and CHEK2 mutation carriers and non-carriers

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Abstract

Breast carcinomas caused by inheritance of cancer-predisposing germ-line mutations have specific bioclinical features. This study aimed to analyze the efficacy of conventional cytotoxic treatment in BRCA1 and CHEK2 mutation carriers and non-carriers. The study included 415 Russian breast cancer patients aged 50 years or younger, who were subjected to various standard schemes of neoadjuvant therapy. The choice of therapy was done without the knowledge of the mutations status, because DNA testing was performed retrospectively using the archival tissue samples. 19 BRCA1 (4.6 %) and 8 CHEK2 (1.9 %) heterozygous genotypes were identified. BRCA1 mutation carriers achieved pathological complete response more frequently than non-carriers [6/19 (31.6 %) vs. 46/388 (11.9 %), p = 0.024]; this effect was limited to women treated by anthracycline-based therapy without taxanes [5/9 (55.6 %) vs. 28/247 (11.3 %), p = 0.002] and was not observed in any of 7 BRCA1 carriers receiving taxane-containing regimens. CHEK2 heterozygotes did not experience pathological complete response and showed lower frequency of objective clinical responses as compared to mutation non-carriers [4/8 (50 %) vs. 333/388 (85.5 %), p = 0.020]; the efficacy of neoadjuvant therapy was particularly poor in CHEK2 carriers receiving anthracyclines without taxanes. This study provides evidence for distinct sensitivity of BRCA1 and CHEK2 mutation-driven breast carcinomas to standard chemotherapeutic schemes.

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Abbreviations

BC:

Breast cancer

ER:

Estrogen receptor

LOH:

Loss-of-heterozygosity

OR:

Objective response

pCR:

Pathological complete response

PgR:

Progesterone receptor

RECIST:

Response Evaluation In Solid Tumors

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Acknowledgments

This work was supported by the Russian Scientific Fund (Grant Number 14-25-00111). We cordially thank Prof. Vladimir F. Semiglazov and Prof. William R. Miller for stimulating discussions. We also thank Tatiana P. Kutilova for her technical assistance. Werner Pfeifer was a recipient of a Marie-Curie Fellowship (contract PITN-GA-2009-238132).

Conflict of interest

None.

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Authors and Affiliations

  1. Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, Pesochny-2, 197758, Saint Petersburg, Russia

    Werner Pfeifer, Anna P. Sokolenko, Olga N. Potapova, Alexandr O. Ivantsov, Sergey A. Laptiev, Olga A. Zaitseva, Olga S. Yatsuk, Dmitry E. Matsko, Tatiana Yu. Semiglazova, Alexandr V. Togo & Evgeny N. Imyanitov

  2. St.-Petersburg State Pediatric Medical University, Saint Petersburg, Russia

    Anna P. Sokolenko & Evgeny N. Imyanitov

  3. City Cancer Center, Saint Petersburg, Russia

    Alexandr A. Bessonov

  4. I.P. Pavlov Medical University, Saint Petersburg, Russia

    Sergey A. Laptiev

  5. I.I. Mechnikov North-Western Medical University, Saint Petersburg, Russia

    Tatiana Yu. Semiglazova & Evgeny N. Imyanitov

Authors
  1. Werner Pfeifer
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  2. Anna P. Sokolenko
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  3. Olga N. Potapova
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  4. Alexandr A. Bessonov
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  5. Alexandr O. Ivantsov
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  6. Sergey A. Laptiev
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  7. Olga A. Zaitseva
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  8. Olga S. Yatsuk
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  9. Dmitry E. Matsko
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  10. Tatiana Yu. Semiglazova
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  11. Alexandr V. Togo
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  12. Evgeny N. Imyanitov
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Corresponding author

Correspondence to Evgeny N. Imyanitov.

Additional information

Werner Pfeifer and Anna P. Sokolenko have contributed equally to this work.

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Pfeifer, W., Sokolenko, A.P., Potapova, O.N. et al. Breast cancer sensitivity to neoadjuvant therapy in BRCA1 and CHEK2 mutation carriers and non-carriers. Breast Cancer Res Treat 148, 675–683 (2014). https://doi.org/10.1007/s10549-014-3206-1

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  • DOI: https://doi.org/10.1007/s10549-014-3206-1

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