Yeokyeong Shin, Soo-Young Lee, Hyehyun Jeong, Jin-Hee Ahn, Kyung Hae Jung, Sung-Bae Kim, Hee Jeong Kim, Jong Won Lee, Byung Ho Son, BeomSeok Ko, Ji Sun Kim, Il Yong Chung, Hee Jin Lee, Gyungyub Gong, Sae Byul Lee, Jae Ho Jeong
Received November 22, 2024 Accepted March 3, 2025 Published online March 5, 2025
Purpose
Although HER2 positivity is prevalent in microinvasive breast cancer (MIBC), data focused on HER2-positive MIBC are limited. We investigated the clinical course and long-term outcomes of HER2-positive MIBC and evaluated the role of adjuvant chemotherapy.
Materials and Methods
The study included patients with curatively resected pT1mi pN0 HER2-positive breast cancer between January 2000 and January 2020. Treatments and survival outcomes, including invasive breast cancer-free survival (IBCFS), distant recurrence-free survival (DRFS), and overall survival (OS) were analyzed.
Results
The analysis included 799 female patients. The median age was 51 years (range, 23–79), and 51.6% (n=412) were premenopausal. Multifocality was confirmed in 17.3% (n=138), and estrogen receptor (ER) positivity in 29.8% (n = 238). Adjuvant chemotherapy was administered to 17.5% (n=140), with doxifluridine in 96.4% of cases. One patient (0.1%) received trastuzumab. With a median follow-up of 119.0 months (95% CI, 114.0–127.0), the 8-year IBCFS, DRFS, and OS were 91.2% (95% CI, 89.1–93.3), 97.5% (95% CI, 96.4–98.7), and 98.8% (95% CI, 98.0–99.6), respectively. No significant differences were observed between patients with and without adjuvant chemotherapy. The lack of differences in IBCFS by chemotherapy was consistent across subgroups, including pre-/postmenopausal patients, grade 1-2/3 tumors, and ER-negative disease.
Conclusion
A clinically meaningful proportion of HER2-positive MIBC patients experience IBCFS events with long-term follow-up. Adjuvant chemotherapy did not improve survival, potentially due to the use of an outdated, ineffective regimen. The role of modern adjuvant regimens, particularly those incorporating HER2-targeted therapy, warrants further exploration.
Purpose This study aimed to investigate the frequency of BRCA testing and related factors among young breast cancer patients (age < 40 years) in South Korea.
Materials and Methods We conducted a nationwide retrospective cohort study using data from the Health Insurance Review and Assessment claims. Newly diagnosed breast cancer patients younger than 40 were included. Annual BRCA testing ratios (number of BRCA test recipients/the number of patients undergoing breast cancer surgery in each year) were analyzed by region and health care delivery system. We investigated the location of breast cancer diagnosis and BRCA testing.
Results From January 2010 to December 2020, there were 25,665 newly diagnosed young breast cancer patients, of whom 12,186 (47.5%) underwent BRCA testing. The BRCA testing ratios increased gradually from 0.084 (154/1,842) in 2010 to 0.961 (1,975/2,055) in 2020. Medical aid (vs. health insurance) and undergoing surgery in metropolitan cities or others (vs. Seoul), general hospitals, and clinics (vs. tertiary hospitals) were associated with a lower likelihood of BRCA testing. While 97.8% of the patients diagnosed in Seoul underwent BRCA testing in Seoul, 22.9% and 29.2% of patients who were diagnosed in metropolitan areas and other regions moved to Seoul and underwent BRCA testing, respectively.
Conclusion The frequency of BRCA testing has increased over time in South Korea, with Seoul showing a particularly high rate of testing. About one-quarter of patients diagnosed with breast cancer outside of Seoul moved to Seoul and underwent BRCA testing.
Yoon Ji Choi, Jung Yoon Choi, Ju Won Kim, Ah Reum Lim, Youngwoo Lee, Won Jin Chang, Soohyeon Lee, Jae Sook Sung, Hee-Joon Chung, Jong Won Lee, Eun Joo Kang, Jung Sun Kim, Taekyu Lim, Hye Sook Kim, Yu Jung Kim, Mi Sun Ahn, Young Saing Kim, Ji Hyun Park, Seungtaek Lim, Sung Shim Cho, Jang Ho Cho, Sang Won Shin, Kyong Hwa Park, Yeul Hong Kim
Cancer Res Treat. 2022;54(1):30-39. Published online May 20, 2021
Purpose K-MASTER project is a Korean national precision medicine platform that screened actionable mutations by analyzing next-generation sequencing (NGS) of solid tumor patients. We compared gene analyses between NGS panel from the K-MASTER project and orthogonal methods.
Materials and Methods Colorectal, breast, non–small cell lung, and gastric cancer patients were included. We compared NGS results from K-MASTER projects with those of non-NGS orthogonal methods (KRAS, NRAS, and BRAF mutations in colorectal cancer [CRC]; epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK] fusion, and reactive oxygen species 1 [ROS1] fusion in non–small cell lung cancer [NSCLC], and Erb-B2 receptor tyrosine kinase 2 (ERBB2) positivity in breast and gastric cancers).
Results In the CRC cohort (n=225), the sensitivity and specificity of NGS were 87.4% and 79.3% (KRAS); 88.9% and 98.9% (NRAS); and 77.8% and 100.0% (BRAF), respectively. In the NSCLC cohort (n=109), the sensitivity and specificity of NGS for EGFR were 86.2% and 97.5%, respectively. The concordance rate for ALK fusion was 100%, but ROS1 fusion was positive in only one of three cases that were positive in orthogonal tests. In the breast cancer cohort (n=260), ERBB2 amplification was detected in 45 by NGS. Compared with orthogonal methods that integrated immunohistochemistry and in situ hybridization, sensitivity and specificity were 53.7% and 99.4%, respectively. In the gastric cancer cohort (n=64), ERBB2 amplification was detected in six by NGS. Compared with orthogonal methods, sensitivity and specificity were 62.5% and 98.2%, respectively.
Conclusion The results of the K-MASTER NGS panel and orthogonal methods showed a different degree of agreement for each genetic alteration, but generally showed a high agreement rate.
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Cancer Res Treat. 2019;51(3):1073-1085. Published online November 1, 2018
Purpose
This preliminary study was conducted to evaluate the association between Oncotype DX (ODX) recurrence score and traditional prognostic factors. We also developed a nomogram to predict subgroups with low ODX recurrence scores (less than 25) and to avoid additional chemotherapy treatments for those patients.
Materials and Methods
Clinicopathological and immunohistochemical variables were retrospectively retrieved and analyzed from a series of 485 T1-3N0-1miM0 hormone receptor-positive, human epidermal growth factor 2‒negative breast cancer patients with available ODX test results at Asan Medical Center from 2010 to 2016. One hundred twenty-seven patients (26%) had positive axillary lymph node micrometastases, and 408 (84%) had ODX recurrence scores of ≤25. Logistic regression was performed to build a nomogram for predicting a low-risk subgroup of the ODX assay.
Results
Multivariate analysis revealed that estrogen receptor (ER) score, progesterone receptor (PR) score, histologic grade, lymphovascular invasion (LVI), and Ki-67 had a statistically significant association with the low-risk subgroup. With these variables, we developed a nomogram to predict the low-risk subgroup with ODX recurrence scores of ≤25. The area under the receiver operating characteristic curve was 0.90 (95% confidence interval [CI], 0.85 to 0.96). When applied to the validation group the nomogram was accurate with an area under the curve = 0.88 (95% CI, 0.83 to 0.95).
Conclusion
The low ODX recurrence score subgroup can be predicted by a nomogram incorporating five traditional prognostic factors: ER, PR, histologic grade, LVI, and Ki-67. Our nomogram, which predicts a low-risk ODX recurrence score, will be a useful tool to help select patients who may or may not need additional ODX testing.
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Purpose
Axillary lymph node dissection (ALND) may be avoidable for breast cancer patients with 1-2 positive lymph nodes (LN) after breast-conserving therapy. However, the effects of ALND after mastectomy remain unclear because radiation is not routinely used. Herein, we compared the benefits of post-mastectomy ALND versus sentinel node biopsy (SNB) alone for breast cancer patients with 1-3 metastatic LNs.
Materials and Methods
A total of 1,697 patients with pN1 disease who underwent mastectomy during 2000-2015 were identified from an institutional database. Outcomes were compared using the inverse probability of treatment weighted method.
Results
Patients who underwent SNB tended to have smaller tumors, a lower histology grade, a lower number of positive LNs, and better immunohistochemical findings. After correcting all confounding factors regarding patient, tumor, and adjuvant treatment, the SNB and ALND groups did not differ in terms of overall survival (OS) and disease-free survival (DFS), distant metastasis and locoregional recurrence. The 10-year DFS and OS rates were 83% and 84%, respectively, during a median follow-up period of 93 months.
Conclusion
ALND did not improve post-mastectomy survival outcomes among patients with N1 breast cancer, even after adjusting for all histopathologic and treatment-related factors.
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Cancer Res Treat. 2018;50(1):275-282. Published online April 14, 2017
Purpose
We evaluated the effect of positive superficial and/or deep margin status on local recurrence (LR) in invasive breast cancer treated with breast-conserving surgery (BCS) followed by radiotherapy.
Materials and Methods
In total, 3,403 stage 1 and 2 invasive breast cancer patients treated with BCS followed by radiotherapy from January 2000 to December 2008 were included in this study. These patients were divided into three groups according to margin status: clear resection margin status for all sections (group 1, n=3,195); positive margin status in superficial and/or deep sections (group 2, n=121); and positive peripheral parenchymal margin regardless of superficial and/or deep margin involvement (group 3, n=87). The LR-free survival between these three groups was compared and the prognostic role of margin status was analyzed.
Results
Across all groups, age, tumor size, nodal status, and human epidermal growth factor receptor 2 status did not significantly differ. High grade, positive extensive intraductal component, hormone receptor positivity, hormone therapy received, and chemotherapy not received were more prevalent in groups 2 and 3 than in group 1. Five-year LR rates in groups 1, 2, and 3 were 1.9%, 1.7%, and 7.7%, respectively. Multivariate analysis revealed that group 3 was a significant predictor for LR (hazard ratio [HR], 4.78; p < 0.001), but that positive superficial and/or deep margin was not (HR, 0.66; p=0.57).
Conclusion
Superficial and/or deep margin involvement following BCS is not an important predictor for LR.
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Impact of Oncotype DX Recurrence Score on the Patterns of Locoregional Recurrence in Breast Cancer (Korean Radiation Oncology Group 19-06) Kyubo Kim, Jinhong Jung, Kyung Hwan Shin, Jin Ho Kim, Ji Hyun Chang, Su Ssan Kim, Haeyoung Kim, Won Park, Yong Bae Kim, Jee Suk Chang Journal of Breast Cancer.2020; 23(3): 314. CrossRef
Magnetic resonance imaging based 3-dimensional printed breast surgical guide for breast-conserving surgery in ductal carcinoma in situ: a clinical trial Zhen-Yu Wu, Aisha Alzuhair, Heejeong Kim, Jong Won Lee, Il Yong Chung, Jisun Kim, Sae Byul Lee, Byung Ho Son, Gyungyub Gong, Hak Hee Kim, Joon Beom Seo, Sei Hyun Ahn, Namkug Kim, BeomSeok Ko Scientific Reports.2020;[Epub] CrossRef
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Purpose
The purpose of this study was to compare treatment outcomes between combined gonadotropin-releasing hormone agonist and tamoxifen (GnRHa+T) and sequential adriamycin and cyclophosphamide chemotherapy and tamoxifen (AC->T) in premenopausal patients with hormone-responsive, lymph-node–negative breast cancer.
Materials and Methods
In total, 994 premenopausal women with T1-T2, lymph-node–negative, hormone-receptor-positive, HER2-negative breast cancer between January 2003 and December 2008 were included in this retrospective cohort study. GnRHa+T and AC->T were administered to 608 patients (61.2%) and 386 patients (38.8%), respectively. Propensity score matching and inverse probability weighting were applied to the original cohort, and 260 patients for each treatment arm were included in the final analysis. Recurrence-free, cancer-specific, and overall survival was compared between the two treatment groups.
Results
A total of 994 patients were followed up for a median of 7.4 years (range, 0.5 to 11.4 years). The 5-year follow-up rate was 98.7%, and 13 patients were lost to follow-up. In propensity=matched cohorts (n=520), there was no difference in recurrence-free, cancer-specific, and overall survival rates between the two treatment groups (p=0.306, p=0.212, and p=0.102, respectively), and this was maintained after applying inverse probability weighting.
Conclusion
GnRHa+T is a reasonable alternative to AC-> T in patients with premenopausal, hormoneresponsive, HER2-negative, lymph-node–negative, T1-T2 breast cancer.
Citations
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Effectiveness of a 6-Month 22.5-mg Leuprolide Acetate Depot Formulation With Tamoxifen for Postoperative Premenopausal Estrogen Suppression in Hormone Receptor-Positive Breast Cancer Zhen-Yu Wu, Young-jin Lee, Heejeong Kim, Jongwon Lee, Il Yong Chung, Jisun Kim, Saebyeol Lee, Byung-Ho Son, Sung-Bae Kim, Jae Ho Jeong, Gyungyub Gong, Sei-Hyun Ahn, BeomSeok Ko Frontiers in Oncology.2021;[Epub] CrossRef
Changes in bone mineral density during 5 years of adjuvant treatment in premenopausal breast cancer patients Minsung Kim, Hanna Kim, Sei Hyun Ahn, Vafa Tabatabaie, Sung Wook Choi, Guiyun Sohn, Sae Byul Lee, Beom Seok Ko, Il Yong Chung, Jisun Kim, Jong Won Lee, Byung Ho Son, Hee Jeong Kim Breast Cancer Research and Treatment.2020; 180(3): 657. CrossRef
Change in Estradiol Levels among Premenopausal Patients with Breast Cancer Treated Using Leuprolide Acetate 11.25 Milligrams 3-Month Depot and Tamoxifen Young-jin Lee, Zhen-Yu Wu, Hee jeong Kim, Jong Won Lee, Il Yong Chung, Jisun Kim, Sae Byul Lee, Byung Ho Son, Sung-Bae Kim, Jae Ho Jung, Gyungyub Gong, Sei-Hyun Ahn, BeomSeok Ko Journal of Breast Cancer.2020; 23(5): 553. CrossRef
Survival outcome of combined GnRH agonist and tamoxifen is comparable to that of sequential adriamycin and cyclophosphamide chemotherapy plus tamoxifen in premenopausal patients with early breast cancer Doonyapat Sa‑Nguanraksa, Thitikon Krisorakun, Wanee Pongthong, Pornchai O‑Charoenrat Molecular and Clinical Oncology.2019;[Epub] CrossRef
Purpose
The 21-gene (Oncotype DX) recurrence score (RS) assay is useful in predicting the benefits of adjuvant chemotherapy for early breast cancer patients and is widely used in Western countries. However, to date, it has not gained much popularity in East Asia. We analyzed the results from five institutions’ experience from using the 21-gene assay and examined the impact of assay results on decision making of chemotherapy in Korean breast cancer patients and the associations between RS and clinicopathologic characteristics.
Materials and Methods
The 21-gene assay was performed on 212 patients with estrogen receptor-positive early breast cancer in five institutions. Each center made systemic treatment decisions both before and after the knowledge of assay results.
Results
Among the 212 patients, 132 (62.3%) had a low RS of < 18, 60 (28.3%) had an intermediate RS of 18-30, and 20 (9.4%) had a high RS of ≥ 31. Histologic grade, presence of micrometastases, Ki-67, and presence of lymphatic invasion were statistically associated with the RS results. Treatment decisions were changed in 115 of 212 patients (54.2%) in 109 of 212 (51.4%) from chemotherapy plus hormone therapy to hormone therapy, and in six of 212 (2.8%) from hormone therapy to chemotherapy plus hormone therapy.
Conclusion
The 21-gene breast cancer assay proved to have a significant impact on treatment decision- making. The test reduces chemotherapy use in more than 50% of Korean estrogen receptor-positive, early breast cancer patients.
Citations
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