Title |
Role of TP53 mutations in triple negative and HER2-positive breast cancer treated with neoadjuvant anthracycline/taxane-based chemotherapy
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Published in |
Oncotarget, September 2016
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DOI | 10.18632/oncotarget.11891 |
Pubmed ID | |
Authors |
Silvia Darb-Esfahani, Carsten Denkert, Albrecht Stenzinger, Christoph Salat, Bruno Sinn, Christian Schem, Volker Endris, Peter Klare, Wolfgang Schmitt, Jens-Uwe Blohmer, Wilko Weichert, Markus Möbs, Hans Tesch, Sherko Kümmel, Peter Sinn, Christian Jackisch, Manfred Dietel, Toralf Reimer, Sherene Loi, Michael Untch, Gunter von Minckwitz, Valentina Nekljudova, Sibylle Loibl |
Abstract |
TP53 mutations are frequent in breast cancer, however their clinical relevance in terms of response to chemotherapy is controversial. 450 pre-therapeutic, formalin-fixed, paraffin-embedded core biopsies from the phase II neoadjuvant GeparSixto trial that included HER2-positive and triple negative breast cancer (TNBC) were subjected to Sanger sequencing of exons 5-8 of the TP53 gene. TP53 status was correlated to response to neoadjuvant anthracycline/taxane-based chemotherapy with or without carboplatin and trastuzumab/lapatinib in HER2-positive and bevacizumab in TNBC. p53 protein expression was evaluated by immunohistochemistry in the TNBC subgroup. Of 450 breast cancer samples 297 (66.0%) were TP53 mutant. Mutations were significantly more frequent in TNBC (74.8%) compared to HER2-positive cancers (55.4%, P < 0.0001). Neither mutations nor different mutation types and effects were associated with pCR neither in the whole study group nor in molecular subtypes (P > 0.05 each). Missense mutations tended to be associated with a better survival compared to all other types of mutations in TNBC (P = 0.093) and in HER2-positive cancers (P = 0.071). In TNBC, missense mutations were also linked to higher numbers of tumor-infiltrating lymphocytes (TILs, P = 0.028). p53 protein overexpression was also linked with imporved survival (P = 0.019). Our study confirms high TP53 mutation rates in TNBC and HER2-positive breast cancer. Mutations did not predict the response to an intense neoadjuvant chemotherapy in these two molecular breast cancer subtypes. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Portugal | 1 | 1% |
Unknown | 82 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 13 | 16% |
Researcher | 13 | 16% |
Student > Master | 9 | 11% |
Student > Bachelor | 7 | 8% |
Other | 6 | 7% |
Other | 18 | 22% |
Unknown | 17 | 20% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 30 | 36% |
Biochemistry, Genetics and Molecular Biology | 17 | 20% |
Agricultural and Biological Sciences | 6 | 7% |
Pharmacology, Toxicology and Pharmaceutical Science | 4 | 5% |
Economics, Econometrics and Finance | 2 | 2% |
Other | 4 | 5% |
Unknown | 20 | 24% |