Genetic variations in triple-negative breast cancers undergoing neo-adjuvant chemotherapy

Miki Mori; Tomoko Watanabe; Sadako Akashi-Tanaka; Kumiko Ueda; Reiko Makino; Yuko Hirota; Seigo Nakamura

doi:10.20517/cdr.2019.44

Genetic variations in triple-negative breast cancers undergoing neo-adjuvant chemotherapy

Cancer Drug Resist. 2019 Sep 19;2(3):877-884. doi: 10.20517/cdr.2019.44. eCollection 2019.

Authors

Miki Mori¹, Tomoko Watanabe¹, Sadako Akashi-Tanaka¹, Kumiko Ueda², Reiko Makino¹, Yuko Hirota³, Seigo Nakamura¹

Affiliations

¹ Department of Breast Surgical Oncology, Showa University, Shinagawaku, Tokyo 142-8666, Japan.
² Clinical Research Laboratory, Showa University, Shinagawaku, Tokyo 142-8666, Japan.
³ Department of Pathology, Showa University, Shinagawaku, Tokyo 142-8666, Japan.

Abstract

Aim: Triple negative breast cancer (TNBC) is known as aggressive subtype and have no identified targeted therapies. We examined the relationship of neoadjuvant chemotherapy response to genetic variations of TNBC. Methods: The tumors used in this study were collected from Showa University Hospital, Japan. Thirteen formalin-fixed paraffin-embedded tumors from Japanese TNBC patients who underwent neoadjuvant chemotherapy were used for analysis. Of these, eight surgically resected tumors showed progressive disease and/or recurrence after treatment (PD/REC), and biopsy tissues from five patients showing pathological complete response (pCR) were analyzed. DNA extracted from tissue sample were analyzed. The Miseq system and Trusight Tumor Sequence panel kit were used to sequence 174 amplicons over 82 exons of 26 cancer-related genes to identify genetic mutations. Results: Seven somatic non-synonymous variants were detected in three genes (FOXL2, PIK3CA, and TP53) in all five pCR patients, and six somatic non-synonymous variants in two genes (PTEN and TP53) were detected in six of eight PD/REC patients. Eight of 13 TNBC tumors were found to have TP53 pathogenic variants, in both pCR and PD/REC cases. Conclusion: Although TP53 variation was detected in both pCR and PD/REC cases, each location and type of the variant were different. We could not identify genetic mutations associated with chemotherapy response and recurrence.

Keywords: TP53 and neo adjuvant chemotherapy; Triple negative breast cancer; next generation sequence.