Translational Oncology (Oct 2024)
TP53 signature predicts pathological complete response after neoadjuvant chemotherapy for breast cancer: Observational and confirmational study using prospective study cohorts
- Shin Takahashi,
- Nobuaki Sato,
- Kouji Kaneko,
- Norikazu Masuda,
- Masaaki Kawai,
- Hisashi Hirakawa,
- Tadashi Nomizu,
- Hiroji Iwata,
- Ai Ueda,
- Takashi Ishikawa,
- Hiroko Bando,
- Yuka Inoue,
- Takayuki Ueno,
- Shinji Ohno,
- Makoto Kubo,
- Hideko Yamauchi,
- Masahiro Okamoto,
- Eriko Tokunaga,
- Shunji Kamigaki,
- Kenjiro Aogi,
- Hideaki Komatsu,
- Masahiro Kitada,
- Yasuaki Uemoto,
- Tatsuya Toyama,
- Yutaka Yamamoto,
- Toshinari Yamashita,
- Takehiro Yanagawa,
- Hiroko Yamashita,
- Yoshiaki Matsumoto,
- Masakazu Toi,
- Minoru Miyashita,
- Takanori Ishida,
- Fumiyoshi Fujishima,
- Satoko Sato,
- Takuhiro Yamaguchi,
- Fumiaki Takahashi,
- Chikashi Ishioka
Affiliations
- Shin Takahashi
- Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan; Department of Clinical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan
- Nobuaki Sato
- Department of Breast Oncology, Niigata Cancer Center Hospital, Niigata, Japan
- Kouji Kaneko
- Department of Breast Oncology, Niigata Cancer Center Hospital, Niigata, Japan
- Norikazu Masuda
- Department of Breast and Endocrine Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan; Department of Surgery, Breast Oncology, National Hospital Organization Osaka National Hospital, Osaka, Japan
- Masaaki Kawai
- Department of Breast Surgery, Miyagi Cancer Center Hospital, Miyagi, Japan; Department of Surgery I, Yamagata University Graduate School of Medical Science, Yamagata, Japan
- Hisashi Hirakawa
- Department of Surgery, Tohoku Kosai Hospital, Sendai, Japan
- Tadashi Nomizu
- Department of Surgery, Hoshi General Hospital, Fukushima, Japan
- Hiroji Iwata
- Department of Breast Oncology, Aichi Cancer Center Hospital, Nagoya, Japan
- Ai Ueda
- Department of Breast Oncology and Surgery, Tokyo Medical University Hospital, Tokyo, Japan
- Takashi Ishikawa
- Department of Breast Oncology and Surgery, Tokyo Medical University Hospital, Tokyo, Japan
- Hiroko Bando
- Breast and Endocrine Surgery, Institute of Medicine, University of Tsukuba, Ibaraki, Japan
- Yuka Inoue
- Breast Oncology Center, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
- Takayuki Ueno
- Breast Oncology Center, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
- Shinji Ohno
- Breast Oncology Center, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
- Makoto Kubo
- Department of Breast Surgical Oncology, Kyushu University Hospital, Kyushu University, Fukuoka, Japan
- Hideko Yamauchi
- Department of Breast Surgical Oncology, St. Luke's International Hospital, Tokyo, Japan
- Masahiro Okamoto
- Department of Breast Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
- Eriko Tokunaga
- Department of Breast Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
- Shunji Kamigaki
- Department of Surgery, Sakai Municipal Hospital, Sakai, Japan
- Kenjiro Aogi
- Department of Breast Oncology, National Hospital Organization Shikoku Cancer Center, Ehime, Japan
- Hideaki Komatsu
- Department of Surgery, Iwate Medical University School of Medicine, Shiwa, Japan
- Masahiro Kitada
- Breast Disease Center, Asahikawa Medical University Hospital, Asahikawa, Japan
- Yasuaki Uemoto
- Department of Breast Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
- Tatsuya Toyama
- Department of Breast Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
- Yutaka Yamamoto
- Department of Breast and Endocrine Surgery, Kumamoto University Hospital, Kumamoto, Japan
- Toshinari Yamashita
- Department of Breast Surgery and Oncology, Kanagawa Cancer Center, Yokohama, Japan
- Takehiro Yanagawa
- Department of Breast Surgery, Kansai Rosai Hospital, Amagasaki, Japan
- Hiroko Yamashita
- Department of Breast Surgery, Hokkaido University Hospital, Sapporo, Japan
- Yoshiaki Matsumoto
- Breast Cancer Unit, Kyoto University Hospital, Graduate School of Medicine, Kyoto, Japan
- Masakazu Toi
- Breast Cancer Unit, Kyoto University Hospital, Graduate School of Medicine, Kyoto, Japan
- Minoru Miyashita
- Department of Breast and Endocrine Surgical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan
- Takanori Ishida
- Department of Breast and Endocrine Surgical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan
- Fumiyoshi Fujishima
- Department of Pathology, Tohoku University Hospital, Sendai, Japan
- Satoko Sato
- Department of Pathology, Tohoku University Hospital, Sendai, Japan
- Takuhiro Yamaguchi
- Division of Biostatistics, Tohoku University Graduate School of Medicine, Sendai, Japan
- Fumiaki Takahashi
- Division of Medical Engineering, Department of Information Science, Iwate Medical University, Yahaba, Japan
- Chikashi Ishioka
- Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan; Department of Clinical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan; Corresponding author at: 4-1 Seiryo-machi, Aobaku, Sendai 980-8575, Japan.
- Journal volume & issue
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Vol. 48
p. 102060
Abstract
The TP53 signature is considered a predictor of neoadjuvant chemotherapy (NAC) response and prognostic factor in breast cancer. The objective of this study was to confirm TP53 signature can predict pathological complete response (pCR) and prognosis in cohorts of breast cancer patients who received NAC in prospective studies.Development cohorts (retrospective [n = 37] and prospective [n = 216] cohorts) and validation cohorts (NAC administered prospective study cohorts [n = 407] and retrospective perioperative chemotherapy (PC)-naïve, hormone receptor (HrR)-positive cohort [PC-naïve_HrR+ cohort] [n = 322]) were used. TP53 signature diagnosis kit was developed using the development cohorts. TP53 signature predictability for pCR and the relationship between recurrence-free survival (RFS), overall survival (OS), and the TP53 signature were analyzed.The pCR rate of the mutant (mt) signature group was significantly higher than that of the wild-type (wt) signature group (odds ratio, 5.599; 95 % confidence interval = 1.876–16.705; P = 0.0008). The comparison of the RFS and OS between the HrR+ and HER2− subgroup of the NAC cohort and of the PC-naïve_HrR+ cohort indicated that the RFS and OS benefit of NAC was greater in the mt signature group than in the wt signature group. From post hoc analyses, the RFS and OS benefit from adding capecitabine to FEC+T as NAC might be observed only in the mt signature group.The TP53 signature can predict the pCR after NAC, and the RFS and OS benefit from NAC may be greater in the mt signature group than in the wt signature group.
