Role of TP53 mutations in triple negative and HER2-positive breast cancer treated with neoadjuvant anthracycline/taxane-based chemotherapy

• Verfasst von: Darb-Esfahani, Silvia [VerfasserIn]
• Verfasst von: Stenzinger, Albrecht [VerfasserIn]
• Verfasst von: Endris, Volker [VerfasserIn]
• Verfasst von: Sinn, Peter [VerfasserIn]
• Titel: Role of TP53 mutations in triple negative and HER2-positive breast cancer treated with neoadjuvant anthracycline/taxane-based chemotherapy
• Verf.angabe: 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 and Sibylle Loibl
• Umfang: 13 S.
• Fussnoten: Gesehen am 03.11.2017
• Titel Quelle: Enthalten in: OncoTarget
• Jahr Quelle: 2016
• Band/Heft Quelle: 7(2016), 42, S. 67686-67698
• ISSN Quelle: 1949-2553
• DOI: doi:10.18632/oncotarget.11891
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1564992152

Abstract

Background TP53 mutations are frequent in breast cancer, however their clinical relevance in terms of response to chemotherapy is controversial. Methods 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. Results 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). Conclusions 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.