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01.12.2014 | Brief Report | Ausgabe 3/2014

Breast Cancer Research and Treatment 3/2014

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

Zeitschrift:
Breast Cancer Research and Treatment > Ausgabe 3/2014
Autoren:
Werner Pfeifer, Anna P. Sokolenko, Olga N. Potapova, Alexandr A. Bessonov, Alexandr O. Ivantsov, Sergey A. Laptiev, Olga A. Zaitseva, Olga S. Yatsuk, Dmitry E. Matsko, Tatiana Yu. Semiglazova, Alexandr V. Togo, Evgeny N. Imyanitov
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1007/​s10549-014-3206-1) contains supplementary material, which is available to authorized users.
Werner Pfeifer and Anna P. Sokolenko have contributed equally to this work.

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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Zusatzmaterial
Supplementary material 1 (DOC 48 kb)
10549_2014_3206_MOESM1_ESM.doc
Supplementary material 2 (XLSX 49 kb)
10549_2014_3206_MOESM2_ESM.xlsx
Supplementary material 3 (DOCX 15 kb)
10549_2014_3206_MOESM3_ESM.docx
Supplementary material 4 (DOCX 20 kb)
10549_2014_3206_MOESM4_ESM.docx
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