Germline Pathogenic Variants and Clinical Outcomes in Asian Patients With Breast Cancer

Despite the importance of genetic testing for risk assessment and treatment in breast cancer, the prognostic impact of germline pathogenic variants (PVs), especially in Asian populations, is unclear. We assessed the impact of germline PVs in patients with early-stage breast cancer. This study included 7278 Japanese multihospital registry patients. PVs of ATM, BRCA1, BRCA2, CDH1, CHEK2, NBN, NF1, PALB2, PTEN, STK11, and TP53 were evaluated. PV and non-PV carriers were matched by age, histology, and stage. Associations between PVs and survival were assessed. The primary outcome was invasive disease-free survival (IDFS). Secondary outcomes included relapse-free survival (RFS), overall survival, and breast cancer-specific survival. We identified 320 (4.4%) patients with BRCA1/2 PVs and 79 (1.1%) with PVs other than BRCA1/2 (non-BRCA1/2). A total of 360 patients (BRCA1/2, n = 289; non-BRCA1/2, n = 71) were matched to 720 noncarriers. Patients with BRCA1/2 PVs had significantly shorter 10-year IDFS (adjusted hazard ratio (aHR) = 2.15; 95% confidence interval (CI), 1.61-2.86; p < 0.001); and RFS (aHR = 1.74; 95% CI, 1.25-2.44; p = 0.001) than noncarriers. Among patients with hormone receptor-positive HER2-negative breast cancer, BRCA1/2 PV carriers exhibited significantly shorter 10-year IDFS than noncarriers, even those with stage I/II disease (total, aHR = 2.23; 95% CI, 1.55-3.23; p < 0.001, Stage I/II, aHR = 2.22; 95% CI, 1.43-3.44; p < 0.001). There was no significant difference in 10-year IDFS between the non-BRCA1/2 PV carrier and noncarrier groups (aHR = 1.40; 95% CI, 0.67-2.93; p = 0.37). Asian patients with breast cancer carrying germline BRCA1/2 PV, even those with a low recurrence risk, have significantly shorter 10-year IDFS than noncarriers.

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Publication Details

Journal
Cancer Science
Published
2025-02-10
DOI
https://doi.org/10.1111/cas.70002
Citations
1
Primary Topic
BRCA gene mutations in cancer
Type
article
Field-Weighted Citation Impact
1.82

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article

Germline Pathogenic Variants and Clinical Outcomes in Asian Patients With Breast Cancer

Takeshi Murata, Kenichi Harano, Yosuke Hirotsu, Yukihide Momozawa et al.
1 citations
Cancer Science
BRCA gene mutations in cancer
1.82
article

Germline Pathogenic Variants and Clinical Outcomes in Asian Patients With Breast Cancer

Takeshi Murata, Kenichi Harano, Yosuke Hirotsu, Yukihide Momozawa, Chikako Shimizu, Ryuji Hamamoto, Rui Kitadai, Shu Yazaki, Tatsunori Shimoi, Akihiko Shimomura, Kan Yonemori, Kouya Shiraishi, Akihiko Suto, Takashi Kohno, Masao Omata, Tohru Ohtake, Yohei Miyagi, Hisaki Aiba, Aya Kuchiba, Yuki Kojima, Takashi Yamanaka, Hiroshi Nakagomi, Megumi Hori, Sho Shiino, Yoichi Naito, Takahiro Kogawa, Kazuki Sudo, Tatsuya Onishi, Kuniko Sunami, Chisako Yamauchi, Kota Katanoda, Motonobu Saito, Saori Fujiwara, Teruhiko Yoshida, Masayuki Yoshida, Yoko Shimada, Toshinari Yamashita, Yuji Yamashita, Kazunoshin Tachibana
article en
1 citations

Abstract

Despite the importance of genetic testing for risk assessment and treatment in breast cancer, the prognostic impact of germline pathogenic variants (PVs), especially in Asian populations, is unclear. We assessed the impact of germline PVs in patients with early-stage breast cancer. This study included 7278 Japanese multihospital registry patients. PVs of ATM, BRCA1, BRCA2, CDH1, CHEK2, NBN, NF1, PALB2, PTEN, STK11, and TP53 were evaluated. PV and non-PV carriers were matched by age, histology, and stage. Associations between PVs and survival were assessed. The primary outcome was invasive disease-free survival (IDFS). Secondary outcomes included relapse-free survival (RFS), overall survival, and breast cancer-specific survival. We identified 320 (4.4%) patients with BRCA1/2 PVs and 79 (1.1%) with PVs other than BRCA1/2 (non-BRCA1/2). A total of 360 patients (BRCA1/2, n = 289; non-BRCA1/2, n = 71) were matched to 720 noncarriers. Patients with BRCA1/2 PVs had significantly shorter 10-year IDFS (adjusted hazard ratio (aHR) = 2.15; 95% confidence interval (CI), 1.61-2.86; p < 0.001); and RFS (aHR = 1.74; 95% CI, 1.25-2.44; p = 0.001) than noncarriers. Among patients with hormone receptor-positive HER2-negative breast cancer, BRCA1/2 PV carriers exhibited significantly shorter 10-year IDFS than noncarriers, even those with stage I/II disease (total, aHR = 2.23; 95% CI, 1.55-3.23; p < 0.001, Stage I/II, aHR = 2.22; 95% CI, 1.43-3.44; p < 0.001). There was no significant difference in 10-year IDFS between the non-BRCA1/2 PV carrier and noncarrier groups (aHR = 1.40; 95% CI, 0.67-2.93; p = 0.37). Asian patients with breast cancer carrying germline BRCA1/2 PV, even those with a low recurrence risk, have significantly shorter 10-year IDFS than noncarriers.

Cancer ScienceVol. 116(4)
Fukushima Medical University (JP), University of Shizuoka (JP), Kanagawa Prefectural Hospital Organization (JP), National Center for Global Health and Medicine (JP), RIKEN Center for Advanced Intelligence Project (JP), The Cancer Institute Hospital (JP), National Cancer Center Hospital East (JP), RIKEN Center for Integrative Medical Sciences (JP), Tokyo National Hospital (JP), Yamanashi Prefectural Central Hospital (JP), Japanese Foundation For Cancer Research (JP), Kanagawa Cancer Center, The University of Tokyo (JP), Teikyo University (JP)
Japan Agency for Medical Research and Development, Japan Society for the Promotion of Science, RIKEN
Good health and well-being
Openalex Percentile: Top 18%
BRCA gene mutations in cancer
1.82
DOIOpen Access PDFOpenAlex
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