PurposeThis study aimed to determine the incidence of male breast cancer (MBC) and its survival outcomes in Korea, and to compare these results to those for female breast cancer (FBC).Materials and MethodsWe searched the Korea Central Cancer Registry and identified 227,122 breast cancer cases that were diagnosed between 1999 and 2016. Demographic and clinical characteristics and overall survival (OS) rates were estimated according to sex, age, histological type, and cancer stage.ResultsThe 227,122 patients included 1,094 MBC cases and 226,028 FBC cases. Based on the age-standardized rate, the male: female ratio was 0.0055:1. The most common ages at diagnosis were 60-69 years for MBC and 40-49 years for FBC (p < 0.001). Male patients were less likely than female patients to receive adjuvant radiotherapy (7.5% vs. 21.8%, p < 0.001) or adjuvant chemotherapy (40.1% vs. 55.4%, p < 0.001). The 5-year OS rates after diagnosis were 88.8% for all patients, although it was significantly lower for MBC than for FBC (76.2% vs. 88.9%, p < 0.001). In both groups, older age (≥ 60 years) was associated with shorter survival. The 5-year OS rates for the invasive histological types were 75.8% for men and 89.0% for women. The 5-year OS rates in both groups decreased with increasing cancer stage.ConclusionMBC was diagnosed at older ages than FBC, and male patients were less likely to receive radiotherapy and chemotherapy. The survival outcomes were worse for MBC than for FBC, with even poorer outcomes related to older age, the inflammatory histological types, and advanced stage. It is important that clinicians recognize the differences between FBC and MBC when treating these patients.
Background To comprehensively understand the molecular mechanism of tamoxifen resistance (TamR) acquisition by epigenetically regulated genes, it is essential to identify pivotal genes by genome-wide methylation analysis and verify their function in xenograft animal model and cancer patients. Methods The MCF-7/TamR breast cancer cell line was developed and a genome-wide methylation array was performed. The methylation and expression of ELOVL2 was validated in cultured cells, xenografted tumor tissue, and breast cancer patients by methylation-specific PCR, qRT-PCR, Western blot analysis, and immunohistochemistry. Deregulation of ELOVL2 and THEM4 was achieved using siRNA or generating stable transfectants. Tam sensitivity, cell growth, and apoptosis were monitored by colorimetric and colony formation assay and flow cytometric analysis. Pathway analysis was performed to generate networks for the differentially methylated genes in the MCF-7/TamR cells and for the differentially expressed genes in the ELOVL2-overexpressing cells. Results Genome-wide methylation analysis in the MCF-7/TamR cells identified elongation of very-long chain fatty acid protein 2 (ELOVL2) to be significantly hypermethylated and downregulated, which was further verified in the tumor tissues from TamR breast cancer patients (n = 28) compared with those from Tam-sensitive (TamS) patients (n = 33) (P < 0.001). Immunohistochemical analysis of tissues from cancer patients showed lower expression of ELOVL2 in the TamR than TamS tissues. Growth of the MCF-7/TamR cells overexpressing ELOVL2 was retarded in cell culture and also in xenograft tumor tissue. Strikingly, ELOVL2 attenuated resistance to Tam up to 70% judged by the colorimetric and colony formation assay and xenograft mouse model. ELOVL2 contributed to the recovery of Tam sensitivity by regulating a group of genes in the AKT and ERα signaling pathways, e.g., THEM4, which plays crucial roles in drug resistance. Conclusions ELOVL2 was hypermethylated and downregulated in TamR breast cancer patients compared with TamS patients. ELOVL2 is responsible for the recovery of Tam sensitivity. AKT- and ERα-hubbed networks are pivotal in ELOVL2 signaling, where THEM4 contributes to the relaying ELOVL2 signaling. This study implies that deregulation of a gene in fatty acid metabolism can lead to drug resistance, giving insight into the development of a new therapeutic strategy for drug-resistant breast cancer.
Purpose: The ACOSOG Z0011 trial has proven the oncological safety of sentinel lymph node biopsy (SLBx) for node negative breast cancer. Accordingly, treatment paradigm including axilla surgery was changed. We retrospectively reviewed breast cancer patients to evaluate the clinical effect of paradigm shift in breast cancer surgery after applying the Z0011 criteria. Methods: All women who underwent breast-conserving surgery at the National Cancer Center between January 1, 2000, and December 31, 2015, were enrolled and classified according to the Z0011 criteria. The primary endpoint of the study was the disease-free survival rates, and the secondary was the adverse events, especially arm lymphedema. Results: Total 361 patients were enrolled the study (271 axillary lymph node dissection [ALND] group, 90 SLBx group). After the Z0011 guideline was adopted in our institute, the use of ALND decreased, and lymph node sampling (removing only a few axillary lymph nodes) replaced ALND. The total mean number of retrieved nodes were more in ALND group (13.02) than SLBx group (3.43). However, there was no difference in the mean number of positive nodes between two groups (2.34 in ALND group vs. 1.12 in SLBx group, P=0.001). During follow-up, 25 patients experienced disease recurrence: 22 from the ALND group and three from the SLBx group. All of died seven patients were from the ALND group. The ALND group had more complications than the SLBx group (P=0.02). Arm edema occurred more frequently in the ALND group (29.5%) than in the SLBx group (5.6%), although without statistical significance (P=0.07). Conclusion: In our study, we concluded that SLBx can be used safely in Z0011-eligible cohort without increased risk of locoregional recurrence. Moreover, we found that omission of ALND is favored to reduce some serious complications such as arm lymphedema.
BACKGROUND The incidence of breast cancer is increasing in Korea. Breast cancer in young Korean women (< 40 years) is rare, but the rate of young age breast cancer incidence in Korea is higher than that in western countries. This study was aimed to evaluate the tumor characteristics of young age breast cancer patients (< 40 years) among Korean women. METHODS Among the Korean women, who were diagnosed with breast cancer from 2010 to 2015, we identified 10,897 cases of nationally representative sample data. The data was made through 10% systematic sampling of the Korea Central Cancer Registry (KCCR). We conducted a chart review survey to collect the data about tumor size, regional lymph node status, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status according to the Collaborative Stage version 2 (CSv2) Data Collection System. We described the number and percentage of the breast cancer stage distribution, tumor grade and intrinsic subtypes by the patient age groups (< 40 years, 40-49 years, 50-59 years, and ≥ 60 years), and evaluated the tumor characteristics in young age breast cancer patients (< 40 years). RESULTS The number of young age breast cancer patients was 1,245 (11.4% of < 40 years vs 35.4% of 40~49 years vs 30.8% of 50~59 years vs 22.4% of ≥ 60 years; P<.001). Young age breast cancer patients were more likely to be diagnosed with larger tumors (T2: 41.6% vs 36.4% vs 36.5% vs 38.4%; T3: 10.1% vs 7.3% vs 6.5% vs 6.2 %; P<.0001), more positive lymph node status (41.2% vs 32.7% vs 35.7% vs 32.5%; P<.0001), and higher tumor grade (grade 3, 26.8% vs 19.4% vs 23.5% vs 22.1%; P<.0001). According to intrinsic subtypes using ER, PR, and HER2, triple negative subtype was found more in young age breast cancer (18.2% vs 11.0% vs 12.2% vs 13.5%; P<.0001). CONCLUSION This study shows that young age breast cancer patients (< 40 years) in Korea have more aggressive tumor including advanced cancer stage at diagnosis, higher tumor grade, and triple negative intrinsic subtype. Therefore, we need to identify high risk group for young age breast cancer (< 40 years) and support their active surveillance. These findings using national cohort provide important information for establishing a national strategy of cancer care to manage young age breast cancer patients. Citation Format: Junyup Kim, So-Youn Jung, Eun-Gyeong Lee, Eun Sook Lee, Han-Sung Kang, See Youn Lee, Jai Hong Han, Heein Jo, Hyun hee Kim, Young-Joo Won, Seri Hong, Jae Jun Lee. Tumor characteristics of young age breast cancer patients using a nationally representative sample of the Korea central cancer registry (KCCR) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-62.
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