Cancer Research and Treatment

Original Articles

Breast cancer

Endoxifen Concentration Is Associated with Recurrence-Free Survival in Hormone-Sensitive Breast Cancer Patients: Beomki Lee, Seok Jin Nam, Seok Won Kim, Jonghan Yu, Byung-Joo Chae, Se Kyung Lee, Jai Min Ryu, Jeong Eon Lee, Soo-Youn Lee; Cancer Res Treat. 2025;57(1):140-149. Published online June 18, 2024; DOI: https://doi.org/10.4143/crt.2023.1285

Abstract PDF PubReader ePub: Purpose
The metabolism of tamoxifen is influenced by various cytochrome p450 enzymes, including CYP2D6 and CYP2C19, leading to variations in the levels of endoxifen, even with the same tamoxifen dose. However, the clinical significance of endoxifen for the prognosis of breast cancer patients remains controversial. This study aimed to elucidate the relevance of endoxifen level to recurrence-free survival censored with tamoxifen discontinuation (RFSt), representing the RFS for tamoxifen itself, of breast cancer patients and determine a suitable cutoff for prognostication.
Materials and Methods
The study included 478 breast cancer patients. Tamoxifen and its metabolites, including endoxifen, were measured using liquid chromatography-tandem mass spectrometry. An optimal cutoff was determined with maximally selected rank statistics. Survival analysis and Cox regression were conducted based on this cutoff.
Results
An endoxifen level of 21.00 ng/mL was the optimal cutoff for prognostication. Survival analysis revealed a statistically significant difference in RFSt between the low endoxifen group (≤ 21.00 ng/mL) and the high endoxifen group (> 21.00 ng/mL) (log-rank test, p=0.032). The 10-year probability of RFSt was 83.2% (95% confidence interval [CI], 77.0 to 89.9) and 88.3% (95% CI, 83.3 to 93.5) in the low and high endoxifen groups, respectively. Multivariable Cox proportional hazards regression indicated endoxifen concentration as a significant factor associated with prognosis.
Conclusion
Endoxifen could serve as a marker for appropriate tamoxifen treatment with a cutoff of 21.00 ng/mL. Based on this cutoff, therapeutic drug monitoring would benefit patients displaying suboptimal endoxifen concentrations.

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Clinicopathological Characterization of Double Heterozygosity for BRCA1 and BRCA2 Variants in Korean Breast Cancer Patients: Yoon Ju Bang, Won Kyung Kwon, Seok Jin Nam, Seok Won Kim, Byung-Joo Chae, Se Kyung Lee, Jai Min Ryu, Jong-Won Kim, Jonghan Yu, Jeong Eon Lee; Cancer Res Treat. 2022;54(3):827-833. Published online October 13, 2021; DOI: https://doi.org/10.4143/crt.2021.791

Abstract PDF Supplementary Material PubReader ePub

Purpose
Double heterozygosity (DH) for BRCA1 and BRCA2 variant is very rare with only a few cases reported, and most those in Caucasians. In this article, we present seven unrelated cases of DH for BRCA1/2 identified from a single institution in Korea, and describe the characteristics and phenotype of DH individuals compared to those with a single BRCA variant.
Materials and Methods
This study included 27,678 patients diagnosed with breast cancer and surgically treated at Samsung Medical Center (SMC) between January 2008 and June 2020. In total, 4,215 high-risk breast cancer patients were tested for the BRCA1/2 genes, and electronic medical records from 456 cases with pathogenic/likely pathogenic variants (PVs/LPVs) were reviewed.
Results
A younger mean age at diagnosis was associated with DH than a single variant of BRCA1/2. More triple-negative breast cancer (TNBC) and higher nuclear and histologic grade cancer occurred with DH than BRCA2 variant. All 7 cases of DH were unrelated, and their mutation combinations were different. There were no Ashkenazi founder variants detected.
Conclusion
We suggest that patients with DH for BRCA1/2 variants develop breast cancer at a younger age, but the histopathologic features are similar to those of BRCA1.

Citations

Citations to this article as recorded by

Multi-locus inherited neoplasia alleles syndromes in cancer: implications for clinical practice
Jeanette Yuen, Siqin Zhou, Rebecca Caeser, Mallika Venkatramani, Diana Nur Bte Ishak, Shao-Tzu Li, Zewen Zhang, Jianbang Chiang, Sock Hoai Chan, Joanne Ngeow
European Journal of Human Genetics.2025;[Epub] CrossRef
Cost-effectiveness of talazoparib for patients with germline BRCA1/2 mutated HER2-negative advanced breast cancer in China and the US
Junjie Pan, Ning Ren, Lanqi Ren, YiBei Yang, Qiaoping Xu
Scientific Reports.2024;[Epub] CrossRef
Characteristics of Chinese breast cancer patients with double heterozygosity for BRCA1 and BRCA2 germline pathogenic variants
Song Wen, Meng Zhang, Jiuan Chen, Li Hu, Jie Sun, Lu Yao, Ye Xu, Juan Zhang, Yuntao Xie
Breast Cancer Research and Treatment.2024; 208(1): 155. CrossRef
Discovery of BRCA1/BRCA2 founder variants by haplotype analysis
Won Kyung Kwon, Hyeok-Jae Jang, Jeong Eon Lee, Yeon Hee Park, Jai Min Ryu, Jonghan Yu, Ja-Hyun Jang, Jong-Won Kim
Cancer Genetics.2022; 266-267: 19. CrossRef

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