Mori Miki, Watanabe Tomoko, Akashi-Tanaka Sadako, Ueda Kumiko, Makino Reiko, Hirota Yuko, Nakamura Seigo
Department of Breast Surgical Oncology, Showa University, Shinagawaku, Tokyo 142-8666, Japan.
Clinical Research Laboratory, Showa University, Shinagawaku, Tokyo 142-8666, Japan.
Cancer Drug Resist. 2019 Sep 19;2(3):877-884. doi: 10.20517/cdr.2019.44. eCollection 2019.
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. 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. Seven somatic non-synonymous variants were detected in three genes (, , and ) in all five pCR patients, and six somatic non-synonymous variants in two genes ( and ) 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. Although 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.
三阴性乳腺癌（TNBC）是一种侵袭性亚型，目前尚无明确的靶向治疗方法。我们研究了新辅助化疗反应与TNBC基因变异之间的关系。本研究中使用的肿瘤样本来自日本昭和大学医院。选取了13例接受新辅助化疗的日本TNBC患者的福尔马林固定石蜡包埋肿瘤样本进行分析。其中，8例手术切除的肿瘤在治疗后出现疾病进展和/或复发（PD/REC），对5例显示病理完全缓解（pCR）患者的活检组织进行了分析。对从组织样本中提取的DNA进行分析。使用Miseq系统和Trusight Tumor Sequence Panel试剂盒对26个癌症相关基因的82个外显子上的174个扩增子进行测序，以鉴定基因突变。在所有5例pCR患者中，在3个基因（、和）中检测到7个体细胞非同义变异，在8例PD/REC患者中的6例中，在2个基因（和）中检测到6个体细胞非同义变异。在13例TNBC肿瘤中，有8例在pCR和PD/REC病例中均发现有TP53致病变异。虽然在pCR和PD/REC病例中均检测到变异，但变异的位置和类型各不相同。我们未能鉴定出与化疗反应和复发相关的基因突变。
