1.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 Research and Treatment 2025;57(1):140-149
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.
2.The Incidence of Occult Malignancy in Contralateral Risk Reducing Mastectomy Among Affected Breast Cancer Gene Mutation Carriers in South Korea
Cho Eun LEE ; Dong Seung SHIN ; Ki Jo KIM ; Seok Jin NAM ; Seok Won KIM ; Jonghan YU ; Byung Joo CHAE ; Se Kyung LEE ; Jai Min RYU ; Goo-Hyun MUN ; Jai-Kyong PYON ; Byung-Joon JEON ; Kyongje WOO ; Jeong Eon LEE
Journal of Breast Cancer 2025;28(1):1-10
Purpose:
Breast cancer gene (BRCA) mutation is a well-known risk factor for breast cancer, and clinical interest in prophylactic mastectomy has increased in recent years.We investigated patients who were BRCA mutation carriers and underwent contralateral risk-reducing mastectomy (RRM), focusing on the incidence of occult malignancy after contralateral RRM.
Methods:
Prospectively collected data of patients with breast cancer treated at a single institution were retrospectively reviewed. Patients who underwent RRM with BRCA mutation who underwent RRM between January 2010 and November 2023 were included in this study.Among patients who underwent contralateral RRM, those with a primary cancer diagnosis were included, and those with occult malignancy on the contralateral RRM side were reviewed additionally. The demographics and pathologies of both primary breast cancer and occult malignancies were evaluated.
Results:
In our institution, 925 patients were identified as BRCA mutation carriers, and 320 patients underwent contralateral RRM along with primary breast cancer surgery. BRCA2 mutation occurred more frequently (54.8%) in the overall BRCA mutation cohort. Furthermore, we reviewed 320 patients diagnosed with breast cancer and detected as BRCA mutation carriers who underwent contralateral RRM; high proportion of them were BRCA1 mutation carriers.Interestingly, we found a low incidence of only seven patients (2.2%) with occult malignancy on contralateral RRM side, which is different from that reported in other nations.
Conclusion
The incidence of occult malignancy in the contralateral breast of breast cancer patients with breast cancer with BRCA mutation is significantly low, and may be influenced by several factors. Increased utilization of screening and advancements in diagnostic technologies in South Korea have reduced the chance of occult malignancy in RRM, and a variety of pathologic examination methods may affect the rate of incidence.
3.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 Research and Treatment 2025;57(1):140-149
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.
4.The Incidence of Occult Malignancy in Contralateral Risk Reducing Mastectomy Among Affected Breast Cancer Gene Mutation Carriers in South Korea
Cho Eun LEE ; Dong Seung SHIN ; Ki Jo KIM ; Seok Jin NAM ; Seok Won KIM ; Jonghan YU ; Byung Joo CHAE ; Se Kyung LEE ; Jai Min RYU ; Goo-Hyun MUN ; Jai-Kyong PYON ; Byung-Joon JEON ; Kyongje WOO ; Jeong Eon LEE
Journal of Breast Cancer 2025;28(1):1-10
Purpose:
Breast cancer gene (BRCA) mutation is a well-known risk factor for breast cancer, and clinical interest in prophylactic mastectomy has increased in recent years.We investigated patients who were BRCA mutation carriers and underwent contralateral risk-reducing mastectomy (RRM), focusing on the incidence of occult malignancy after contralateral RRM.
Methods:
Prospectively collected data of patients with breast cancer treated at a single institution were retrospectively reviewed. Patients who underwent RRM with BRCA mutation who underwent RRM between January 2010 and November 2023 were included in this study.Among patients who underwent contralateral RRM, those with a primary cancer diagnosis were included, and those with occult malignancy on the contralateral RRM side were reviewed additionally. The demographics and pathologies of both primary breast cancer and occult malignancies were evaluated.
Results:
In our institution, 925 patients were identified as BRCA mutation carriers, and 320 patients underwent contralateral RRM along with primary breast cancer surgery. BRCA2 mutation occurred more frequently (54.8%) in the overall BRCA mutation cohort. Furthermore, we reviewed 320 patients diagnosed with breast cancer and detected as BRCA mutation carriers who underwent contralateral RRM; high proportion of them were BRCA1 mutation carriers.Interestingly, we found a low incidence of only seven patients (2.2%) with occult malignancy on contralateral RRM side, which is different from that reported in other nations.
Conclusion
The incidence of occult malignancy in the contralateral breast of breast cancer patients with breast cancer with BRCA mutation is significantly low, and may be influenced by several factors. Increased utilization of screening and advancements in diagnostic technologies in South Korea have reduced the chance of occult malignancy in RRM, and a variety of pathologic examination methods may affect the rate of incidence.
5.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 Research and Treatment 2025;57(1):140-149
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.
6.The Incidence of Occult Malignancy in Contralateral Risk Reducing Mastectomy Among Affected Breast Cancer Gene Mutation Carriers in South Korea
Cho Eun LEE ; Dong Seung SHIN ; Ki Jo KIM ; Seok Jin NAM ; Seok Won KIM ; Jonghan YU ; Byung Joo CHAE ; Se Kyung LEE ; Jai Min RYU ; Goo-Hyun MUN ; Jai-Kyong PYON ; Byung-Joon JEON ; Kyongje WOO ; Jeong Eon LEE
Journal of Breast Cancer 2025;28(1):1-10
Purpose:
Breast cancer gene (BRCA) mutation is a well-known risk factor for breast cancer, and clinical interest in prophylactic mastectomy has increased in recent years.We investigated patients who were BRCA mutation carriers and underwent contralateral risk-reducing mastectomy (RRM), focusing on the incidence of occult malignancy after contralateral RRM.
Methods:
Prospectively collected data of patients with breast cancer treated at a single institution were retrospectively reviewed. Patients who underwent RRM with BRCA mutation who underwent RRM between January 2010 and November 2023 were included in this study.Among patients who underwent contralateral RRM, those with a primary cancer diagnosis were included, and those with occult malignancy on the contralateral RRM side were reviewed additionally. The demographics and pathologies of both primary breast cancer and occult malignancies were evaluated.
Results:
In our institution, 925 patients were identified as BRCA mutation carriers, and 320 patients underwent contralateral RRM along with primary breast cancer surgery. BRCA2 mutation occurred more frequently (54.8%) in the overall BRCA mutation cohort. Furthermore, we reviewed 320 patients diagnosed with breast cancer and detected as BRCA mutation carriers who underwent contralateral RRM; high proportion of them were BRCA1 mutation carriers.Interestingly, we found a low incidence of only seven patients (2.2%) with occult malignancy on contralateral RRM side, which is different from that reported in other nations.
Conclusion
The incidence of occult malignancy in the contralateral breast of breast cancer patients with breast cancer with BRCA mutation is significantly low, and may be influenced by several factors. Increased utilization of screening and advancements in diagnostic technologies in South Korea have reduced the chance of occult malignancy in RRM, and a variety of pathologic examination methods may affect the rate of incidence.
7.Oncological outcomes in patients with residual triple-negative breast cancer after preoperative chemotherapy
Hyunki PARK ; Haeyoung KIM ; Won PARK ; Won Kyung CHO ; Nalee KIM ; Tae Gyu KIM ; Young-Hyuck IM ; Jin Seok AHN ; Yeon Hee PARK ; Ji-Yeon KIM ; Seok Jin NAM ; Seok Won KIM ; Jeong Eon LEE ; Jonghan YU ; Byung Joo CHAE ; Sei Kyung LEE ; Jai-Min RYU
Radiation Oncology Journal 2024;42(3):210-217
Purpose:
This study aimed to evaluate the clinical outcomes and prognostic implications of regional nodal irradiation (RNI) after neoadjuvant chemotherapy (NAC) in patients with residual triple-negative breast cancer (TNBC).
Materials and Methods:
We analyzed 152 patients with residual TNBC who underwent breast-conserving surgery after NAC between December 2008 and December 2017. Most patients (n = 133; 87.5%) received taxane-based chemotherapy. Adjuvant radiotherapy (RT) was administered at a total dose of 45–65 Gy in 15–30 fractions to the whole breast, with some patients also receiving RT to regional nodes. Survival was calculated using the Kaplan–Meier method, and prognostic factors influencing survival were analyzed using the Cox proportional-hazards model.
Results:
During a median follow-up of 66 months (range, 9 to 179 months), the 5-year disease-free survival (DFS) rate was 68.0%. The 5-year locoregional recurrence-free survival, distant metastasis-free survival, and overall survival rates were 83.6%, 72.6%, and 78.7%, respectively. In the univariate analysis, the cN stage, ypT stage, ypN stage, axillary operation type, and RT field were associated with DFS. Multivariate analysis revealed that higher ypT stage (hazard ratio [HR] = 2.0; 95% confidence interval [CI] 1.00–3.82; p = 0.049) and ypN stage (HR = 4.7; 95% CI 1.57–14.24; p = 0.006) were associated with inferior DFS. Among clinically node-positive patients, those who received RT to the breast only had a 5-year DFS of 73.7%, whereas those who received RNI achieved a DFS of 59.6% (p = 0.164). There were no differences between the DFS and RNI.
Conclusion
In patients with residual TNBC, higher ypT and ypN stages were associated with poorer outcomes after NAC. RNI did not appear to improve DFS. More intensive treatments incorporating systemic therapy and RT should be considered for these patients.
8.Oncological outcomes in patients with residual triple-negative breast cancer after preoperative chemotherapy
Hyunki PARK ; Haeyoung KIM ; Won PARK ; Won Kyung CHO ; Nalee KIM ; Tae Gyu KIM ; Young-Hyuck IM ; Jin Seok AHN ; Yeon Hee PARK ; Ji-Yeon KIM ; Seok Jin NAM ; Seok Won KIM ; Jeong Eon LEE ; Jonghan YU ; Byung Joo CHAE ; Sei Kyung LEE ; Jai-Min RYU
Radiation Oncology Journal 2024;42(3):210-217
Purpose:
This study aimed to evaluate the clinical outcomes and prognostic implications of regional nodal irradiation (RNI) after neoadjuvant chemotherapy (NAC) in patients with residual triple-negative breast cancer (TNBC).
Materials and Methods:
We analyzed 152 patients with residual TNBC who underwent breast-conserving surgery after NAC between December 2008 and December 2017. Most patients (n = 133; 87.5%) received taxane-based chemotherapy. Adjuvant radiotherapy (RT) was administered at a total dose of 45–65 Gy in 15–30 fractions to the whole breast, with some patients also receiving RT to regional nodes. Survival was calculated using the Kaplan–Meier method, and prognostic factors influencing survival were analyzed using the Cox proportional-hazards model.
Results:
During a median follow-up of 66 months (range, 9 to 179 months), the 5-year disease-free survival (DFS) rate was 68.0%. The 5-year locoregional recurrence-free survival, distant metastasis-free survival, and overall survival rates were 83.6%, 72.6%, and 78.7%, respectively. In the univariate analysis, the cN stage, ypT stage, ypN stage, axillary operation type, and RT field were associated with DFS. Multivariate analysis revealed that higher ypT stage (hazard ratio [HR] = 2.0; 95% confidence interval [CI] 1.00–3.82; p = 0.049) and ypN stage (HR = 4.7; 95% CI 1.57–14.24; p = 0.006) were associated with inferior DFS. Among clinically node-positive patients, those who received RT to the breast only had a 5-year DFS of 73.7%, whereas those who received RNI achieved a DFS of 59.6% (p = 0.164). There were no differences between the DFS and RNI.
Conclusion
In patients with residual TNBC, higher ypT and ypN stages were associated with poorer outcomes after NAC. RNI did not appear to improve DFS. More intensive treatments incorporating systemic therapy and RT should be considered for these patients.
9.Oncological outcomes in patients with residual triple-negative breast cancer after preoperative chemotherapy
Hyunki PARK ; Haeyoung KIM ; Won PARK ; Won Kyung CHO ; Nalee KIM ; Tae Gyu KIM ; Young-Hyuck IM ; Jin Seok AHN ; Yeon Hee PARK ; Ji-Yeon KIM ; Seok Jin NAM ; Seok Won KIM ; Jeong Eon LEE ; Jonghan YU ; Byung Joo CHAE ; Sei Kyung LEE ; Jai-Min RYU
Radiation Oncology Journal 2024;42(3):210-217
Purpose:
This study aimed to evaluate the clinical outcomes and prognostic implications of regional nodal irradiation (RNI) after neoadjuvant chemotherapy (NAC) in patients with residual triple-negative breast cancer (TNBC).
Materials and Methods:
We analyzed 152 patients with residual TNBC who underwent breast-conserving surgery after NAC between December 2008 and December 2017. Most patients (n = 133; 87.5%) received taxane-based chemotherapy. Adjuvant radiotherapy (RT) was administered at a total dose of 45–65 Gy in 15–30 fractions to the whole breast, with some patients also receiving RT to regional nodes. Survival was calculated using the Kaplan–Meier method, and prognostic factors influencing survival were analyzed using the Cox proportional-hazards model.
Results:
During a median follow-up of 66 months (range, 9 to 179 months), the 5-year disease-free survival (DFS) rate was 68.0%. The 5-year locoregional recurrence-free survival, distant metastasis-free survival, and overall survival rates were 83.6%, 72.6%, and 78.7%, respectively. In the univariate analysis, the cN stage, ypT stage, ypN stage, axillary operation type, and RT field were associated with DFS. Multivariate analysis revealed that higher ypT stage (hazard ratio [HR] = 2.0; 95% confidence interval [CI] 1.00–3.82; p = 0.049) and ypN stage (HR = 4.7; 95% CI 1.57–14.24; p = 0.006) were associated with inferior DFS. Among clinically node-positive patients, those who received RT to the breast only had a 5-year DFS of 73.7%, whereas those who received RNI achieved a DFS of 59.6% (p = 0.164). There were no differences between the DFS and RNI.
Conclusion
In patients with residual TNBC, higher ypT and ypN stages were associated with poorer outcomes after NAC. RNI did not appear to improve DFS. More intensive treatments incorporating systemic therapy and RT should be considered for these patients.
10.Oncological outcomes in patients with residual triple-negative breast cancer after preoperative chemotherapy
Hyunki PARK ; Haeyoung KIM ; Won PARK ; Won Kyung CHO ; Nalee KIM ; Tae Gyu KIM ; Young-Hyuck IM ; Jin Seok AHN ; Yeon Hee PARK ; Ji-Yeon KIM ; Seok Jin NAM ; Seok Won KIM ; Jeong Eon LEE ; Jonghan YU ; Byung Joo CHAE ; Sei Kyung LEE ; Jai-Min RYU
Radiation Oncology Journal 2024;42(3):210-217
Purpose:
This study aimed to evaluate the clinical outcomes and prognostic implications of regional nodal irradiation (RNI) after neoadjuvant chemotherapy (NAC) in patients with residual triple-negative breast cancer (TNBC).
Materials and Methods:
We analyzed 152 patients with residual TNBC who underwent breast-conserving surgery after NAC between December 2008 and December 2017. Most patients (n = 133; 87.5%) received taxane-based chemotherapy. Adjuvant radiotherapy (RT) was administered at a total dose of 45–65 Gy in 15–30 fractions to the whole breast, with some patients also receiving RT to regional nodes. Survival was calculated using the Kaplan–Meier method, and prognostic factors influencing survival were analyzed using the Cox proportional-hazards model.
Results:
During a median follow-up of 66 months (range, 9 to 179 months), the 5-year disease-free survival (DFS) rate was 68.0%. The 5-year locoregional recurrence-free survival, distant metastasis-free survival, and overall survival rates were 83.6%, 72.6%, and 78.7%, respectively. In the univariate analysis, the cN stage, ypT stage, ypN stage, axillary operation type, and RT field were associated with DFS. Multivariate analysis revealed that higher ypT stage (hazard ratio [HR] = 2.0; 95% confidence interval [CI] 1.00–3.82; p = 0.049) and ypN stage (HR = 4.7; 95% CI 1.57–14.24; p = 0.006) were associated with inferior DFS. Among clinically node-positive patients, those who received RT to the breast only had a 5-year DFS of 73.7%, whereas those who received RNI achieved a DFS of 59.6% (p = 0.164). There were no differences between the DFS and RNI.
Conclusion
In patients with residual TNBC, higher ypT and ypN stages were associated with poorer outcomes after NAC. RNI did not appear to improve DFS. More intensive treatments incorporating systemic therapy and RT should be considered for these patients.

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