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.
Chang Min Kim, Kyong Hwa Park, Yun Suk Yu, Ju Won Kim, Jin Young Park, Kyunghee Park, Jong-Han Yu, Jeong Eon Lee, Sung Hoon Sim, Bo Kyoung Seo, Jin Kyeoung Kim, Eun Sook Lee, Yeon Hee Park, Sun-Young Kong
Cancer Res Treat. 2024;56(4):1113-1125. Published online May 10, 2024
Purpose Triple-negative breast cancer (TNBC) is a particularly challenging subtype of breast cancer, with a poorer prognosis compared to other subtypes. Unfortunately, unlike luminal-type cancers, there is no validated biomarker to predict the prognosis of patients with early-stage TNBC. Accurate biomarkers are needed to establish effective therapeutic strategies.
Materials and Methods In this study, we analyzed gene expression profiles of tumor samples from 184 TNBC patients (training cohort, n=76; validation cohort, n=108) using RNA sequencing.
Results By combining weighted gene expression, we identified a 10-gene signature (DGKH, GADD45B, KLF7, LYST, NR6A1, PYCARD, ROBO1, SLC22A20P, SLC24A3, and SLC45A4) that stratified patients by risk score with high sensitivity (92.31%), specificity (92.06%), and accuracy (92.11%) for invasive disease-free survival. The 10-gene signature was validated in a separate institution cohort and supported by meta-analysis for biological relevance to well-known driving pathways in TNBC. Furthermore, the 10-gene signature was the only independent factor for invasive disease-free survival in multivariate analysis when compared to other potential biomarkers of TNBC molecular subtypes and T-cell receptor β diversity. 10-gene signature also further categorized patients classified as molecular subtypes according to risk scores.
Conclusion Our novel findings may help address the prognostic challenges in TNBC and the 10-gene signature could serve as a novel biomarker for risk-based patient care.
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Significance of Multi-Cancer Genome Profiling Testing for Breast Cancer: A Retrospective Analysis of 3326 Cases from Japan’s National Database Kyoka Kawabata, Hinano Nishikubo, Saki Kanei, Rika Aoyama, Yuki Tsukada, Tomoya Sano, Daiki Imanishi, Takashi Sakuma, Koji Maruo, Yurie Yamamoto, Qiang Wang, Zhonglin Zhu, Canfeng Fan, Masakazu Yashiro Genes.2024; 15(6): 792. CrossRef
Purpose We evaluated the association between changes in social support after cancer treatment and recurrence-free survival (RFS) in such patients using a prospective cohort study.
Materials and Methods Data were obtained from a prospective cohort study (NCT03131089) conducted at Samsung Medical Center (2013-2021). The primary outcome measure was RFS. Social support was measured using the social and family well-being (SFWB) domain of the Functional Assessment of Cancer Therapy-General. We calculated the changes in SFWB scores before and during treatment and the hazard ratio for RFS by comparing such changes.
Results The mean±standard deviation (SD) age of the patients was 35±3.9 years, and 71.5% and 64.8% of the patients were married and had children, respectively. The mean±SD SFWB score at baseline was 20.5±5.0 out of 26. After cancer treatment, 35.9%, 10.3%, and 53.8% of the participants had increasing, unchanged, and decreasing SFWB scores, respectively. The decreasing SFWB score group had a higher risk of mortality or recurrence than the increasing group. Risk factors for the decreasing score were the presence of children during diagnosis.
Conclusion In this cohort, changes in social support after treatment were associated with RFS in young patients with breast cancer. Health professionals should develop family interventions to help them receive proper social support.
Haeyoung Kim, Su SSan Kim, Ji Sung Lee, Jae Sun Yoon, Hyun Jo Youn, Hyukjai Shin, Jeong Eon Lee, Se Kyung Lee, Il Yong Chung, So-Youn Jung, Young Jin Choi, Jihyoung Cho, Sang Uk Woo, Korean Breast Cancer Society
Cancer Res Treat. 2023;55(2):580-591. Published online December 27, 2022
Purpose This study aimed to evaluate the incidence and prognosis of second non-breast primary cancer (SNBPC) among Korean survivors of breast cancer.
Materials and Methods Data from the Korean National Health Insurance Service were searched to identify women who received curative surgery for initial breast cancer (IBC) between 2003 and 2008 (n=64,340). Among them, patients with the following characteristics were excluded: other cancer diagnosis before IBC (n=10,866), radiotherapy before IBC (n=349), absence of data on sex or age (n=371), or male (n=248). Accordingly, data of 52,506 women until December 2017 were analyzed. SNBPC was defined as a newly diagnosed SNBPC that occurred 5 years or more after IBC diagnosis.
Results The median follow-up time of all patients was 12.13 years. SNBPC was developed in 3,084 (5.87%) women after a median of 7.61 years following IBC diagnosis. The 10-year incidence of SNBPC was 5.78% (95% confidence interval [CI], 5.56 to 6.00). Higher SNBPC incidence was found in survivors with the following factors: old age at IBC diagnosis, low household income, and receiving combined chemotherapy with endocrine therapy, whereas receiving radiotherapy was related to a lower incidence of SNBPC (hazard ratio, 0.89; p < 0.01). Among the patients with SNBPC, the 5-year survival rate was 62.28% (95% CI, 65.53 to 69.02).
Conclusion Approximately 5% of breast cancer survivors developed SNBPC within 10 years after IBC diagnosis. The risk of SNBPC was associated with patient’s age at IBC diagnosis, income level, and a receipt of systemic treatments.
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Cancer Res Treat. 2023;55(2):419-428. Published online November 8, 2022
Purpose We developed a comprehensive return to work (RTW) intervention covering physical, psycho-social and practical issues for patients newly diagnosed and evaluated its efficacy in terms of RTW.
Materials and Methods A multi-center randomized controlled trial was done to evaluate the efficacy of the intervention conducted at two university-based cancer centers in Korea. The intervention program comprised educational material at diagnosis, a face-to-face educational session at completion of active treatment, and three individualized telephone counseling sessions. The control group received other education at enrollment.
Results At 1-month post-intervention (T2), the intervention group was more likely to be working compared to the control group after controlling working status at diagnosis (65.4% vs. 55.9%, p=0.037). Among patients who did not work at baseline, the intervention group was 1.99-times more likely to be working at T2. The mean of knowledge score was higher in the intervention group compared to the control group (7.4 vs. 6.8, p=0.029). At the 1-year follow-up, the intervention group was 65% (95% confidence interval, 0.78 to 3.48) more likely to have higher odds for having work.
Conclusion The intervention improved work-related knowledge and was effective in facilitating cancer patients’ RTW.
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Cancer Res Treat. 2022;54(4):1091-1098. Published online January 10, 2022
Purpose Docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP) regimen is frequently used to treat early and locally advanced human epidermal growth factor receptor 2 (HER2)–positive breast cancer (BC) in neoadjuvant setting. However, large-scaled real-world evidence did not exist.
Materials and Methods We retrospectively reviewed medical records of patients with early or locally advanced HER2-positive BC who underwent neoadjuvant TCHP followed by curative surgery at Samsung Medical Center between January 2016 and August 2020.
Results Of 447 patients, 316 (70.7%) received breast-conserving surgery and 131 (29.3%) received total mastectomy. In terms of neoadjuvant chemotherapy response, pathologic complete response (pCR) and residual cancer burden (RCB) score were analyzed. The rate of pCR was 64% a class of RCB 0 was observed in 65% of cases, RCB class I in 12%, RCB class II in 14%, and RCB class III in 2%. The 3-year event-free survival rate was 90.6%, BC with pCR occurred in 92.8%, and BC with non-pCR in 86.3% (p=0.016). In terms of distant metastasis, the 3-year distant recurrence-free survival rate was 93.5%; BC with pCR occurred in 95.9% and BC with non-pCR in 89.2% (p=0.013). Mucositis (85.2%), pain (83.2%), and diarrhea (70.5%) were the most common non-hematologic adverse events. In terms of hematologic adverse events, anemia (89.9%) was the most commonly observed adverse events followed by thrombocytopenia (29.8%).
Conclusion Neoadjuvant TCHP therapy had a pCR rate of 64% and a 3-year event-free survival of 90% in real world experience. In terms of toxicity profile, anemia was frequently observed and adequate management including occasional transfusion was required.
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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.
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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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Cancer Res Treat. 2022;54(3):834-841. Published online October 13, 2021
Purpose Little is known about the impact of financial toxicity in disease-free breast cancer survivors. We aim to validate the COmprehensive Score for financial Toxicity in Korean (COST-K) and evaluate financial toxicity among disease-free breast cancer survivors.
Materials and Methods We conducted linguistic validation following a standardized methodology recommended by Functional Assessment of Chronic Illness Therapy multilingual translation (FACITtrans). For psychometric validation, we conducted a cross-sectional survey with 4,297 disease-free breast cancer survivors at a tertiary hospital in Seoul, Korea between November 2018 and April 2019. Survivors were asked to complete the COST-K and European Organization for Research and Treatment of Cancer Quality of Life Core 30 (EORTC QLQ-C30) questionnaires. The test-retest reliability, internal consistency, and validity of the COST-K were assessed using standard scale construction techniques.
Results The COST-K demonstrated good internal consistency, with a Cronbach’s α of 0.81. The test-retest analysis revealed an intraclass correlation coefficient of 0.78. The COST-K had moderate correlation (r=–0.60) with the financial difficulty item of the EORTC QLQ-C30 and week correlation with the items on acute and chronic symptom burdens (nausea/vomiting, –0.18; constipation, –0.14; diarrhea, –0.14), showing good convergent and divergent validity. The median COST-K was 27 (range, 0 to 44; mean±standard deivation [SD], 27.1±7.5) and about 30% and 5% of cancer survivors experienced mild and severe financial toxicity, respectively. Younger age, lower education, lower household income was associated with higher financial toxicity.
Conclusion The COST-K is a valid and reliable instrument for measuring financial toxicity in disease-free breast cancer survivors. Considering its impact on the health-related quality of life, more studies need to be conducted to evaluate financial toxicity in cancer survivors and design interventions.
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Hyung Seok Park, Jai Min Ryu, Ji Soo Park, Seock-Ah Im, So-Youn Jung, Eun-Kyu Kim, Woo-Chan Park, Jun Won Min, Jeeyeon Lee, Ji Young You, Jeong Eon Lee, Sung-Won Kim
Cancer Res Treat. 2020;52(3):680-688. Published online January 28, 2020
Purpose
Recent studies revealed the BRCA1 c.5339T>C, p.Leu1780Pro variant (L1780P) is highly suggested as a likely pathogenic. The aim of this study was to evaluate clinicopathologic features of L1780P with breast cancer (BC) using multicenter data from Korea to reinforce the evidence as a pathogenic mutation and to compare L1780P and other BRCA1/2mutations using Korean Hereditary Breast Cancer (KOHBRA) study data.
Materials and Methods
The data of 54 BC patients with L1780P variant from 10 institutions were collected and the clinicopathologic characteristics of the patients were reviewed. The hereditary breast and/or ovarian cancer–related characteristics of the L1780P variant were compared to those of BC patients in the KOHBRA study.
Results
The median age of all patients was 38 years, and 75.9% of cases showed triple-negative breast cancer. Comparison of cases with L1780P to carriers from the KOHBRA study revealed that the L1780P patients group was more likely to have family history (FHx) of ovarian cancer (OC) (24.1% vs. 19.6% vs. 11.2%, p < 0.001 and p=0.001) and a personal history of OC (16.7% vs. 2.9% vs. 1.3%, p=0.003 and p=0.001) without significant difference in FHx of BC and bilateral BC. The cumulative risk of contralateral BC at 10 years after diagnosis was 31.9%, while the cumulative risk of OC at 50 years of age was 20.0%. Patients with L1780P showed similar features with BRCA1 carriers and showed higher penetrance of OC than patients with other BRCA1 mutations.
Conclusion
L1780P should be considered as a pathogenic mutation. Risk-reducing salpingo-oophorectomy is highly recommended for women with L1780P.
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Cancer Res Treat. 2019;51(2):737-747. Published online September 5, 2018
Purpose
We aimed to analyze the discordance between immunohistochemistry (IHC)-based surrogate subtyping and PAM50 intrinsic subtypes and to assess overall survival (OS) according to discordance.
Materials and Methods
A total of 607 patients were analyzed. Hormone receptor (HR) expression was evaluated by IHC, and human epidermal growth factor receptor 2 (HER2) expression was analyzed by IHC and/or fluorescence in situ hybridization. PAM50 intrinsic subtypes were determined according to 50 cancer genes using the NanoString nCounter Analysis System. We matched concordant tumor as luminal A and HR+/HER2–, luminal B and HR+/HER2+, HR–/HER2+ and HER2–enriched, and triple-negative breast cancer (TNBC) and normal- or basal-like. We used Ion Ampliseq Cancer Panel v2 was used to identify the genomic alteration related with discordance. The Kaplan-Meier method was used to estimate OS.
Results
In total, 233 patients (38.4%) were discordant between IHC-based subtype and PAM50 intrinsic subtype. Using targeted sequencing, we detected somatic mutation–related discordant breast cancer including the VHL gene in the HR+/HER2– group (31% in concordant group, 0% in discordant group, p=0.03) and the IDH and RET genes (7% vs. 12%, p=0.02 and 0% vs. 25%, p=0.02, respectively) in the TNBC group. Among the luminal A/B patients with a discordant result had significantly worse OS (median OS, 73.6 months vs. not reached; p < 0.001), and among the patients with HR positivity, the basal-like group as determined by PAM50 showed significantly inferior OS compared to other intrinsic subtypes (5-year OS rate, 92.2% vs. 75.6%; p=0.01).
Conclusion
A substantial portion of patients showed discrepancy between IHC subtype and PAM50 intrinsic subtype in our study. The survival analysis demonstrated that current IHC-based classification could mislead the treatment and result in poor outcome. Current guidelines for IHC might be updated accordingly.
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Cancer Res Treat. 2016;48(4):1382-1388. Published online March 11, 2016
Purpose The purpose of this study was to assess the tumor characteristics and long-term clinical outcomes of adjuvant treatments after surgery with a curative aim for patients with breast cancer who are 65 years and older. Materials and Methods Patients with breast cancer who underwent curative surgery from 2000 to 2009 were analyzed (n=4,388). Tumor characteristics and survival outcome were compared by dividing the patients into two age groups (< 65 and ≥ 65 years old). The Kaplan-Meier method was used for comparison of survival rates by log-rank test, and a Cox regression model was used to examine the effect of variables.
Results Among 4,388 patients with invasive breast cancer, 317 patients (7.2%) were 65 years or older and the median age of all patients was 47 years (range, 18 to 91 years). Tumor characteristics were similar between the two age groups, but the older patients were treated less often with adjuvant treatments. During a median follow-up period of 122 months, recurrence-free survival (RFS) was equivalent for patients 65 years and older compared to younger patients, but significantly worse in overall survival (OS) and breast cancer–specific survival (BCSS) (5-year OS, 94.3% vs. 90.5%; p < 0.001 and 5-year BCSS, 94.7% vs. 91.8%; p=0.031). In the multivariate model, age ≥ 65 years old was identified as an independent risk factor for OS and RFS. Conclusion Elderly breast cancer appeared to have worse outcomes with very low prevalence in Korea, despite similar tumor characteristics. More active adjuvant therapies would have a role for aggressive subtypes for fit, elderly patients.
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Purpose TP53, the most frequently mutated gene in breast cancer, is more frequently altered in HER2-enriched and basal-like breast cancer. However, no studies have clarified the role of TP53 status as a prognostic and predictive marker of triple-negative breast cancer (TNBC).
Materials and Methods
We performed p53 immunohistochemistry (IHC), nCounter mRNA expression assay, and DNA sequencing to determine the relationship between TP53 alteration and clinical outcomes of TNBC patients.
Results
Seventy-seven of 174 TNBC patients were found to harbor a TP53 mutation. Patients with missense mutations showed high protein expression in contrast to patients with deletion mutations (positivity of IHC: wild type vs. missense vs. deletion mutation, 53.6% vs. 89.8% vs. 25.0%, respectively; p < 0.001). TP53 mRNA expression was influenced by mutation status (mRNA expression [median]: wild type vs. missense vs. deletion mutation, 207.36± 132.73 vs. 339.61±143.21 vs. 99.53±99.57,respectively; p < 0.001). According to survival analysis, neither class of mutation nor protein or mRNA expression status had any impact on patient prognosis. In subgroup analysis, low mRNA expression was associated with poor prognosis in patientswith a TP53 missense mutation (5-year distantrecurrence-free survival [5Y DRFS]: low vs. high, 50.0% vs. 87.8%; p=0.009), while high mRNA expression with a TP53 deletion mutation indicated poor prognosis (5Y DRFS: low vs. high, 91.7% vs. 75.0%; p=0.316).
Conclusion
Association between TP53 mutation and expression indicates a potential prognostic marker of TNBC; hence both DNA sequencing and mRNA expression analysis may be required to predict the prognosis of TNBC patients.
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Purpose
The aim of the current study is to assess the spectrum of genetic variation in the BRIP1 gene among Korean high-risk breast cancer patients who tested negative for the BRCA1/2 mutation.
Materials and Methods
Overall, 235 Korean patientswith BRCA1/2 mutation–negative high-risk breast cancerwere screened for BRIP1 mutations. The entire BRIP1 gene was analyzed using fluorescent-conformation sensitive gel electrophoresis. In silico analysis of BRIP1 variants was performed using PolyPhen-2 and SIFT.
Results
A total of 20 sequence alterations including 12 exonic and eight intronic variantswere found. Among the 12 exonic variants, 10 were missense and two were silent mutations. No protein-truncating mutation was found among the tested patients. Among the 10 missense variants, four (p.L263F, p.L340F, p.L474P, and p.R848H) were predicted to be pathogenic by both PolyPhen-2 and SIFT, and these variants were found in five patients. Of the four missense variants, p.L263F, p.L474P, and p.R848H localize to regions between the helicase motifs, while p.L340F resides in an iron-sulfur domain of BRIP1.
Conclusion
No protein-truncating mutation in BRIP1 was found among the tested patients. The contribution of BRIP1 variants is thought to be minor in Korean non-BRCA1/2 high-risk breast cancer.
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Mutation status of RAD51C,PALB2 and BRIP1 in 100 Japanese familial breast cancer cases without BRCA1 and BRCA2 mutations Katsutoshi Sato, Mio Koyasu, Sachio Nomura, Yuri Sato, Mizuho Kita, Yuumi Ashihara, Yasue Adachi, Shinji Ohno, Takuji Iwase, Dai Kitagawa, Eri Nakashima, Reiko Yoshida, Yoshio Miki, Masami Arai Cancer Science.2017; 108(11): 2287. CrossRef
Mutational analysis of FANCJ helicase Manhong Guo, Venkatasubramanian Vidhyasagar, Tanu Talwar, Ahmad Kariem, Yuliang Wu Methods.2016; 108: 118. CrossRef
Ji Yun Lee, Sung Hee Lim, Min-Young Lee, Haesu Kim, Moonjin Kim, Sungmin Kim, Hyun Ae Jung, Insuk Sohn, Won Ho Gil, Jeong Eon Lee, Seok Won Kim, Seok Jin Nam, Jin Seok Ahn, Young-Hyuck Im, Yeon Hee Park
Cancer Res Treat. 2015;47(4):765-773. Published online January 13, 2015
Purpose The purpose of this study is to evaluate the role of regular postoperative surveillance to improve the prognosis of patients with breast cancer after curative surgery. Materials and Methods We retrospectively analyzed the medical records of 4,119 patients who received curative surgery for breast cancer at Samsung Medical Center between January 2000 and September 2008. Patients were divided into two groups (group I, regular postoperative surveillance; group II, control group) according to their post-therapy follow-up status for the first 5 years after surgery. Results Among the 3,770 patients selected for inclusion, groups I and II contained 3,300 (87%) and 470 (13%) patients, respectively. The recurrence rates at 5 years for groups I and II were 10.6% and 16.4%, respectively (hazard ratio, 0.85; 95% confidence interval [CI], 0.67 to 1.09; p=0.197). The 10-year mortality cumulative rates were 8.8% for group I and 25.4% for group II (hazard ratio, 0.28; 95% CI, 0.22 to 0.35; p < 0.001). In multivariate analysis for recurrence-free survival (RFS), age over 40 years (p < 0.001), histologic grade 1 (p < 0.001), and pathologic stage I (p < 0.001) were associated with longer RFS but not with follow- up status. Multivariate analysis for overall survival (OS) revealed that patients in group I showed significantly improved OS (hazard ratio, 0.29; 95% CI, 0.23 to 0.37; p < 0.001). Additionally, age over 40 years, histologic grade I, and pathologic stage I were independent prognostic factors for OS. Conclusion Regular follow-up for patients with breast cancer after primary surgery resulted in clinically significant improvements in patient OS.
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Follow-up strategy and survival for five common cancers: A meta-analysis Boris Galjart, Diederik J. Höppener, Joachim G.J.V. Aerts, Christiaan H. Bangma, Cornelis Verhoef, Dirk J. Grünhagen European Journal of Cancer.2022; 174: 185. CrossRef
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Analysis of patient-detected breast cancer recurrence Trishul Kapoor, Sean Wrenn, Peter Callas, Ted A. James Breast Disease.2017; 37(2): 77. 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.
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Primary breast lymphoma (PBL) is a rare disease, particularly in males. Diffuse large B cell lymphoma is the most common PBL, while follicular lymphoma is less common.
Furthermore, primary follicular lymphoma of a male breast is rarely reported. We report a male patient with primary follicular lymphoma of the breast and hepatocellular carcinoma (HCC). A 46-year-old man was diagnosed with liver cirrhosis secondary to chronic hepatitis B infection. Ten years later, he underwent segmentectomy of the liver due to HCC. Another 5 months later, he presented with a painless mass in the right chest wall. The mass was diagnosed as follicular lymphoma of the breast. The stage was IEA and he did not receive adjuvant therapy. Although only a few cases have been reported, lymphoma should be considered as a possible cause of breast mass, even in male patients.
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Cancer Res Treat. 2011;43(2):89-95. Published online June 30, 2011
PURPOSE The aim of the current study was to determine the incidence, clinical presentation, and treatment outcomes of "bone-only metastases" in patients with breast cancer and to analyze the impact of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status on prognosis. MATERIALS AND METHODS Between 1994 and 2007, of 968 patients with metastatic breast cancer who underwent palliative management at Samsung Medical Center, 565 (57%) relapsed with distant metastases. Of the 968, 146 (15%) had bone-only metastases during a median follow-up period of 75 months. Among the 146 patients with bone-only metastases, 122 (84%) were relapsed patients after curative surgery and 24 (26%) were initially metastatic cases. RESULTS The median time from primary surgery to bone-only metastases of the 122 patients was 37 months (95% confidence interval [CI], 27 to 46 months). Bone-only metastases were more common in the HR-positive group than in the other subtypes (85% for HR+; 8.2% for HER2+; 6.8% for triple negative. Among all 146 patients, 75 (51%) were treated with hormone therapy. The median post-relapse progression-free survival was 15 months (95%CI, 13 to 17 months). The median overall survival was much longer in the HR+ patients than the HER2+ and triple negative breast cancer patients with marginal statistical significance (65 vs. 40 vs. 40 months, p=0.077). CONCLUSION Breast cancer patients with "bone-only metastases" had excellent clinical outcomes. Further study is now warranted to reveal the underlying biology that regulates the behavior of this indolent tumor, as it should identify 'favorable tumor characteristics' in addition to 'favorable preferential metastatic site.'
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Analysis of genomics and immune infiltration patterns of epithelial-mesenchymal transition related to metastatic breast cancer to bone Shuzhong Liu, An Song, Yunxiao Wu, Siyuan Yao, Muchuan Wang, Tong Niu, Chengao Gao, Ziquan Li, Xi Zhou, Zhen Huo, Bo Yang, Yong Liu, Yipeng Wang Translational Oncology.2021; 14(2): 100993. CrossRef
Trefoil factor-1 upregulation in estrogen-receptor positive breast cancer correlates with an increased risk of bone metastasis Chiara Spadazzi, Laura Mercatali, Mark Esposito, Yong Wei, Chiara Liverani, Alessandro De Vita, Giacomo Miserocchi, Elisa Carretta, Michele Zanoni, Claudia Cocchi, Alberto Bongiovanni, Federica Recine, Yibin Kang, Toni Ibrahim Bone.2021; 144: 115775. CrossRef
Diagnosis and referral of adults with suspected bony metastases Samantha Downie, Elizabeth Bryden, Fergus Perks, A Hamish RW Simpson BMJ.2021; : n98. CrossRef
Endocrine-Based Treatments in Clinically-Relevant Subgroups of Hormone Receptor-Positive/HER2-Negative Metastatic Breast Cancer: Systematic Review and Meta-Analysis Francesco Schettini, Mario Giuliano, Fabiola Giudici, Benedetta Conte, Pietro De Placido, Sergio Venturini, Carla Rognoni, Angelo Di Leo, Mariavittoria Locci, Guy Jerusalem, Lucia Del Mastro, Fabio Puglisi, PierFranco Conte, Michelino De Laurentiis, Lajos Cancers.2021; 13(6): 1458. CrossRef
Heterogeneity of bone metastases as an important prognostic factor in patients affected by oestrogen receptor-positive breast cancer. The role of combined [18F]Fluoroestradiol PET/CT and [18F]Fluorodeoxyglucose PET/CT Gianluca Bottoni, Arnoldo Piccardo, Francesco Fiz, Giacomo Siri, Federica Matteucci, Andrea Rocca, Oriana Nanni, Manuela Monti, Etienne Brain, Jean Louis Alberini, Bassam Dib, Gian Mauro Sacchetti, Chiara Saggia, Valentina Rossi, Nadia Harbeck, Rachel Wue European Journal of Radiology.2021; 141: 109821. CrossRef
Locoregional therapy in de novo metastatic breast cancer: Systemic review and meta-analysis Daniel Reinhorn, Raz Mutai, Rinat Yerushalmi, Assaf Moore, Eitan Amir, Hadar Goldvaser The Breast.2021; 58: 173. CrossRef
Exosomal miR-19a and IBSP cooperate to induce osteolytic bone metastasis of estrogen receptor-positive breast cancer Kerui Wu, Jiamei Feng, Feng Lyu, Fei Xing, Sambad Sharma, Yin Liu, Shih-Ying Wu, Dan Zhao, Abhishek Tyagi, Ravindra Pramod Deshpande, Xinhong Pei, Marco Gabril Ruiz, Hiroyuki Takahashi, Shunsuke Tsuzuki, Takahiro Kimura, Yin-yuan Mo, Yusuke Shiozawa, Ravi Nature Communications.2021;[Epub] CrossRef
Incidence of Brain Metastases in Nonmetastatic and Metastatic Breast Cancer: Is There a Role for Screening? Adam S. Komorowski, Ellen Warner, Helen J. MacKay, Arjun Sahgal, Kathleen I. Pritchard, Katarzyna J. Jerzak Clinical Breast Cancer.2020; 20(1): e54. CrossRef
Radiation therapy for bone-only metastases in breast cancer patients: A GOCO survey of current clinical practice Marta Bonet, Virginia García, Núria Farré, Manel Algara, Blanca Farrús, Jaume Fernandez, Victoria Reyes, Arancha Eraso, Ana Álvarez, Maria José Cambra, Agustí Pedro, Jordi Vayreda, Claire Lemansky, Françoise Izar, Meritxell Arenas Reports of Practical Oncology & Radiotherapy.2020; 25(1): 113. CrossRef
MicroRNA-429 inhibits bone metastasis in breast cancer by regulating CrkL and MMP-9 Xinxin Zhang, Xiying Yu, Zhenguo Zhao, Zhennan Yuan, Peiqing Ma, Zhibin Ye, Liping Guo, Songfeng Xu, Libin Xu, Ting Liu, Huanmei Liu, Shengji Yu Bone.2020; 130: 115139. CrossRef
Metastatic Presentations of Previously Treated Early-Stage Breast Cancer Patients and Association With Survival Najla Itani, Nicole Grogan, Sarah Mott, Sneha Phadke Clinical Breast Cancer.2020; 20(3): 209. CrossRef
Concordance of real-world versus conventional progression-free survival from a phase 3 trial of endocrine therapy as first-line treatment for metastatic breast cancer Cynthia Huang Bartlett, Jack Mardekian, Matthew James Cotter, Xin Huang, Zhe Zhang, Christina M. Parrinello, Ariel Bulua Bourla, Apar Kishor Ganti PLOS ONE.2020; 15(4): e0227256. CrossRef
International Framework for Red Flags for Potential Serious Spinal Pathologies Laura M. Finucane, Aron Downie, Christopher Mercer, Susan M. Greenhalgh, William G. Boissonnault, Annelies L. Pool-Goudzwaard, Jason M. Beneciuk, Rachel L. Leech, James Selfe Journal of Orthopaedic & Sports Physical Therapy.2020; 50(7): 350. CrossRef
Prognostic Value of Modified IHC4 Score in Patients with Estrogen Receptor-Positive Metastatic Breast Cancer Liang Jin, Kai Chen, Cui Tan, Jianbin Li, Jiayue Luo, Yaping Yang, Yudong Li, Shunying Li, Liling Zhu, Yue Hu, Fengtao Liu, Qiuting You, Min Peng, Zefei Jiang, Qiang Liu The Oncologist.2020; 25(8): e1170. CrossRef
Imaging diagnosis of metastatic breast cancer Filippo Pesapane, Kate Downey, Anna Rotili, Enrico Cassano, Dow-Mu Koh Insights into Imaging.2020;[Epub] CrossRef
Tamoxifen Rechallenge Decreases Metastatic Potential but Increases Cell Viability and Clonogenicity in a Tamoxifen-Mediated Cytotoxicity-Resistant Subline of Human Breast MCF7 Cancer Cells Yung-Chieh Chang, Chun Hei Antonio Cheung, Yao-Lung Kuo Frontiers in Cell and Developmental Biology.2020;[Epub] CrossRef
Treatment effect of palbociclib plus endocrine therapy by prognostic and intrinsic subtype and biomarker analysis in patients with bone-only disease: a joint analysis of PALOMA-2 and PALOMA-3 clinical trials Richard S. Finn, Massimo Cristofanilli, Johannes Ettl, Karen A. Gelmon, Marco Colleoni, Carla Giorgetti, Eric Gauthier, Yuan Liu, Dongrui R. Lu, Zhe Zhang, Cynthia Huang Bartlett, Dennis J. Slamon, Nicholas C. Turner, Hope S. Rugo Breast Cancer Research and Treatment.2020; 184(1): 23. CrossRef
Innovative Options for Bone Metastasis Treatment: An Extensive Analysis on Biomaterials-Based Strategies for Orthopedic Surgeons Ania Naila Guerrieri, Monica Montesi, Simone Sprio, Roberta Laranga, Laura Mercatali, Anna Tampieri, Davide Maria Donati, Enrico Lucarelli Frontiers in Bioengineering and Biotechnology.2020;[Epub] CrossRef
The influence of breast cancer subtype on survival after palliative radiation for osseous metastases Mohamed K. Abdelhakiem, Candice Johnstone, Carmen Bergom, Adam Currey, Jared R. Robbins Cancer Medicine.2020; 9(23): 8979. CrossRef
Racial/ethnic differences in the outcomes of patients with metastatic breast cancer: contributions of demographic, socioeconomic, tumor and metastatic characteristics Jin-Xiao Ren, Yue Gong, Hong Ling, Xin Hu, Zhi-Ming Shao Breast Cancer Research and Treatment.2019; 173(1): 225. CrossRef
Metastatic pattern discriminates survival benefit of primary surgery for de novo stage IV breast cancer: A real-world observational study Kang Wang, Yang Shi, Zhu-Yue Li, Ye-Lei Xiao, Jie Li, Xiang Zhang, Hong-Yuan Li European Journal of Surgical Oncology.2019; 45(8): 1364. CrossRef
The CXCL5/CXCR2 axis is sufficient to promote breast cancer colonization during bone metastasis Ricardo Romero-Moreno, Kimberly J. Curtis, Thomas R. Coughlin, Maria Cristina Miranda-Vergara, Shourik Dutta, Aishwarya Natarajan, Beth A. Facchine, Kristen M. Jackson, Lukas Nystrom, Jun Li, William Kaliney, Glen L. Niebur, Laurie E. Littlepage Nature Communications.2019;[Epub] CrossRef
Single-Agent Oral Vinorelbine as First-Line Chemotherapy for Endocrine-Pretreated Breast Cancer With Bone Metastases and No Visceral Involvement: NORBREAST-228 Phase II Study Guenther G. Steger, Adriana Dominguez, Natalia Dobrovolskaya, Francesco Giotta, Nicole Tubiana-Mathieu, Martin Pecherstorfer, Antonio Ardizzoia, Maria Blasinska-Morawiec, Enrique Espinosa, Gustavo Villanova Clinical Breast Cancer.2018; 18(1): e41. CrossRef
Differential presentation and survival of de novo and recurrent metastatic breast cancer over time: 1990–2010 Judith A. Malmgren, Musa Mayer, Mary K. Atwood, Henry G. Kaplan Breast Cancer Research and Treatment.2018; 167(2): 579. CrossRef
Breast cancer bone metastases: pathogenesis and therapeutic targets Naomi Brook, Emily Brook, Arun Dharmarajan, Crispin R. Dass, Arlene Chan The International Journal of Biochemistry & Cell Biology.2018; 96: 63. CrossRef
Incidence, risk factors and prognostic characteristics of bone metastases and skeletal-related events (SREs) in breast cancer patients: A systematic review of the real world data Hongwei Zhang, Wei Zhu, Ewelina Biskup, Weige Yang, Ziang Yang, Hong Wang, Xiaochun Qiu, Chengjiao Zhang, Guangxia Hu, Guangfu Hu Journal of Bone Oncology.2018; 11: 38. CrossRef
Breast osteoblast-like cells: a new biomarker for the management of breast cancer Manuel Scimeca, Nicoletta Urbano, Rita Bonfiglio, Orazio Schillaci, Elena Bonanno British Journal of Cancer.2018; 119(9): 1129. CrossRef
Post-relapse survival in patients with the early and late distant recurrence in estrogen receptor-positive HER2-negative breast cancer Akiko Ogiya, Kieko Yamazaki, Rie Horii, Tadahiko Shien, Yoshiya Horimoto, Norikazu Masuda, Touko Inao, Mitsuchika Hosoda, Naoko Ishida, Tomofumi Osako, Masato Takahashi, Yumi Endo, Yuichiro Miyoshi, Hiroyuki Yasojima, Nobumoto Tomioka, Hiroko Yamashita Breast Cancer.2017; 24(3): 473. CrossRef
Pattern of metastatic spread and subcategories of breast cancer Catharina Bartmann, Manfred Wischnewsky, Tanja Stüber, Roland Stein, Mathias Krockenberger, Sebastian Häusler, Wolfgang Janni, Rolf Kreienberg, Maria Blettner, Lukas Schwentner, Achim Wöckel, Joachim Diessner Archives of Gynecology and Obstetrics.2017; 295(1): 211. CrossRef
Osteonecrosis of the Jaw in a Breast Cancer Patient Treated with Everolimus and a Single Dose of Zoledronic Acid Claudia Omarini, Maria E. Filieri, Roberta Depenni, Giulia Grizzi, Stefano Cascinu, Federico Piacentini The Breast Journal.2017; 23(5): 610. CrossRef
The critical role of the ZNF217 oncogene in promoting breast cancer metastasis to the bone Aurélie Bellanger, Caterina F Donini, Julie A Vendrell, Jonathan Lavaud, Irma Machuca‐Gayet, Maëva Ruel, Julien Vollaire, Evelyne Grisard, Balázs Győrffy, Ivan Bièche, Olivier Peyruchaud, Jean‐Luc Coll, Isabelle Treilleux, Véronique Maguer‐Satta, Véroniqu The Journal of Pathology.2017; 242(1): 73. CrossRef
Estrogen receptors in breast and bone: from virtue of remodeling to vileness of metastasis I Bado, Z Gugala, S A W Fuqua, X H-F Zhang Oncogene.2017; 36(32): 4527. CrossRef
Which red flags aid the early detection of metastatic bone disease in back pain? Laura Finucane, Susan Greenhalgh, James Selfe Physiotherapy Practice and Research.2017; 38(2): 73. CrossRef
Prognostic utility of FDG PET/CT and bone scintigraphy in breast cancer patients with bone-only metastasis Soyeon Park, Joon-Kee Yoon, Su Jin Lee, Seok Yun Kang, Hyunee Yim, Young-Sil An Medicine.2017; 96(50): e8985. CrossRef
Tolerability of Therapies Recommended for the Treatment of Hormone Receptor-Positive Locally Advanced or Metastatic Breast Cancer Shinji Ohno Clinical Breast Cancer.2016; 16(4): 238. CrossRef
Quality of life and symptom burden in patients with metastatic breast cancer Christine Ecclestone, Ronald Chow, Natalie Pulenzas, Liying Zhang, Angela Leahey, Julia Hamer, Carlo DeAngelis, Gillian Bedard, Rachel McDonald, Anchal Bhatia, Janet Ellis, Eileen Rakovitch, Sherlyn Vuong, Edward Chow, Sunil Verma Supportive Care in Cancer.2016; 24(9): 4035. CrossRef
Evaluation of clinical parameters influencing the development of bone metastasis in breast cancer Joachim Diessner, Manfred Wischnewsky, Tanja Stüber, Roland Stein, Mathias Krockenberger, Sebastian Häusler, Wolfgang Janni, Rolf Kreienberg, Maria Blettner, Lukas Schwentner, Achim Wöckel, Catharina Bartmann BMC Cancer.2016;[Epub] CrossRef
Prolactin receptor in breast cancer: marker for metastatic risk Carrie S Shemanko Journal of Molecular Endocrinology.2016; 57(4): R153. CrossRef
Clinical Characteristics and Outcome of Bone-Only Metastasis in Inflammatory and Noninflammatory Breast Cancers Megumi Kai, Takahiro Kogawa, Diane D. Liu, Tamer M. Fouad, Kazuharu Kai, Naoki Niikura, Limin Hsu, Jie S. Willey, Richard L. Theriault, Vicente Valero, Naoto T. Ueno Clinical Breast Cancer.2015; 15(1): 37. CrossRef
Loading Dose Ibandronate Versus Standard Oral Ibandronate in Patients With Bone Metastases From Breast Cancer Iain R. Macpherson, Caroline Bray, Carol Hopkins, Rosemary A. Hannon, Liz-Anne Lewsley, Diana M. Ritchie, Peter Canney Clinical Breast Cancer.2015; 15(2): 117. CrossRef
Assessing response to treatment of bone metastases from breast cancer: what should be the standard of care? D.K. Woolf, A.R. Padhani, A. Makris Annals of Oncology.2015; 26(6): 1048. CrossRef
Survival time according to the year of recurrence and subtype in recurrent breast cancer Masahiro Nakano, Mamiko Fujisue, Rumiko Tashima, Yasuhiro Okumura, Yasuyuki Nishiyama, Tomofumi Ohsako, Yasuo Toyozumi, Nobuyuki Arima, Reiki Nishimura The Breast.2015; 24(5): 588. CrossRef
Cases of Bone-only Metastasis in Recurrent Breast Cancer Yoko MAEKAWA, Shintaro TAKAO, Koichi HIROKAGA, Mayuko MIKI, Sachiko YOSHIDA Nihon Rinsho Geka Gakkai Zasshi (Journal of Japan Surgical Association).2014; 75(6): 1484. CrossRef
Efficacy of Exemestane in Korean Patients with Metastatic Breast Cancer after Failure of Nonsteroidal Aromatase Inhibitors June Koo Lee, Seock-Ah Im, Daewon Lee, Ji-Yeon Kim, Yoojoo Lim, Eunyoung Lee, Hyeong-Gon Moon, Tae-Yong Kim, Sae-Won Han, Do-Youn Oh, Se-Hoon Lee, Wonshik Han, Dong-Wan Kim, Tae-You Kim, Dong-Young Noh Journal of Breast Cancer.2013; 16(1): 66. CrossRef
Incidence, consequences and treatment of bone metastases in breast cancer patients—Experience from a single cancer centre I. Kuchuk, B. Hutton, P. Moretto, T. Ng, C.L. Addison, M. Clemons Journal of Bone Oncology.2013; 2(4): 137. CrossRef
Zooming in on the schedule of bone-modifying drugs Miguel Martin, Sara López-Tarruella The Lancet Oncology.2013; 14(7): 575. CrossRef
Bone metastases: assessment, management and treatment options Carole Farrell British Journal of Nursing.2013; 22(Sup7): S4. CrossRef
Limites de la scintigraphie osseuse dans le suivi des métastases osseuses du carcinome mammaire : étude du centre tunisien K. Chatti, A. Harrabi, I. Chabchoub, T. Kamoun, R. Sfar, M. Nouira, M.B. Fredj, N. Ayachi, S.B. Ahmed, H. Essabbah Médecine Nucléaire.2012; 36(10): 574. CrossRef