Neutrophil to Lymphocyte Ratio after Treatment Completion as a Potential Predictor of Survival in Patients with Triple-Negative Breast Cancer / 한국유방암학회지

Purpose@#Triple-negative breast cancer (TNBC) has been associated with worse prognosis, and biomarkers are needed to identify high-risk patients who may benefit from clinical trials or escalated treatment after completion of standard treatment. We aimed to assess whether the post-treatment neutrophil-to-lymphocyte ratio (NLR) can reflect patient prognosis and determine the follow-up period that can provide the most feasible data. @*Methods@#In this retrospective analysis involving patients with TNBC, clinicopathological data, including those on peripheral complete blood cell count, were collected. The prognostic powers of serial NLRs obtained at baseline and after treatment completion were compared. Kaplan-Meier curves were generated to compare the overall survival (OS) and distant disease-free survival (DDFS). @*Results@#In total, 210 patients were enrolled. Forty-three (20.5%) events were detected. Twothirds of the events (29/43) were related to breast cancer. Most recurrent breast cancer-related diseases (27/29) were detected within 5 years of the initial diagnosis. In contrast, half of the events due to secondary malignancies or non-breast-related diseases (7/14) occurred 5 years after the initial diagnosis. Comparison of the prognostic performance of NLRs at baseline and at 6, 12, and 24 months after treatment completion revealed the strongest prognostic performance at 6 months after treatment completion (area under the curve = 0.745). The high NLR group (NLR >2.47) showed worse OS (p = 0.006) and DDFS (p < 0.001) than low NLR group. @*Conclusion@#Elevated post-treatment NLR was significantly associated with worse survival in patients with TNBC. We believe that it can be a useful surrogate marker for identifying highrisk patients with TNBC.

Factors Associated with Metastatic Breast Cancer in Patients Who Show Long-Term Stable Disease Status

PURPOSE: This study aimed to analyze the basic clinical characteristics and survival of patients with breast cancer whose disease had been stably maintained for more than 24 months after systemic therapy. METHODS: We retrospectively reviewed the medical records of patients with primary breast cancer who underwent surgery. Among these patients, patients with stage IV disease at diagnosis or those who developed distant metastasis during the follow-up period after surgery were included in this analysis. Patients whose disease remained stable for more than 24 months were classified as the long-term stable disease group. The remaining patients were classified as the control group. RESULTS: A total of 245 patients were eligible for this analysis. Patients in the long-term stable disease group showed a lower rate of histologic type III, a higher rate of hormone receptor positivity, and received less adjuvant chemotherapy. In the long-term stable disease group, the most frequent site of metastasis was the lungs, whereas in the control group, it was the bones. Overall survival was significantly better in the long-term stable disease group than in the control group (p<0.001). In univariate analysis, factors affecting the overall survival rate were the duration from diagnosis to metastasis, the absence of lymphatic infiltration, and the presence of hormone receptors. In multivariate analysis, the duration from diagnosis to metastasis and the absence of lymphatic infiltration were significant factors affecting the overall survival rate. CONCLUSION: Disease progression was observed in many patients even after the disease had been stable for more than 24 months after systemic therapy. Although these patients had better outcomes compared with the others, continuous observation and possible additional treatment might be helpful for some patients.

Phosphorylated S6 Kinase-1 as Predictive Marker of Lapatinib Efficacy in Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer Patients

PURPOSE: The 40S ribosomal protein S6 kinase-1 (S6K1) is a crucial downstream effector of the PI3K/AKT/mTOR pathway. S6K1 overexpression is found in 10% to 30% of breast cancers and is associated with aggressive disease and poor prognosis. Herein, we investigated the relationship between the expression of phosphorylated S6K1 (p-S6K1) and efficacy of lapatinib in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. METHODS: We retrospectively analyzed the data of 36 patients with HER2-positive metastatic breast cancer treated with lapatinib between January 2010 and September 2014. The p-S6K1 expression status of the primary tumor was assessed via immunohistochemistry using a mouse monoclonal antibody. RESULTS: Fourteen of the 36 patients (38.9%) had p-S6K1-positive tumors. The median progression-free survival (PFS) of patients with p-S6K1-positive tumors was significantly longer than that of patients with p-S6K1-negative tumors (13.4 months vs. 7.1 months, p=0.025). In multivariate analysis, p-S6K1 positivity remained an independent, favorable predictive factor for PFS (hazard ratio, 0.32; 95% confidence interval, 0.11–0.97; p=0.044). CONCLUSION: The high expression of p-S6K1 was significantly associated with prolonged PFS, suggesting that p-S6K1 can be a potential biomarker for predicting the efficacy of lapatinib in patients with HER2-positive metastatic breast cancer.

The Examination of Ovarian Reserve in Premenopausal Patients with Hormone Receptor Positive Breast Cancer / 이화의대지

The evaluation of menopausal status is an important subject in the field of treatment of hormone receptor positive breast cancer. According to the menopausal status, endocrine therapy should be categorized by individual patient. However, the gonadal injury caused by various therapeutic drugs and its recovery would confuse the interpretation of clinical and biological markers for ovarian reserve. There are some methods to examine the functional ovarian reserve indirectly. Ultrasonography for counting follicles is a relatively reliable procedure, although it is not feasible because of time-labor consumption and high cost. Biological marker from blood samples such as serum follicle stimulating hormone (FSH), serum estradiol (E2), serum inhibin, or anti-Müllerian hormone (AMH) would be a better choice. The examination of serum FSH and E2 is already recommended as biomarkers for measuring functional ovarian reserve in many guidelines. However, there are limitation of serum FSH and E2 in patients with chemotherapy-induced amenorrhea and treated by tamoxifen. AMH is promising biomarker in the field of infertility treatment even in the patients treated by chemotherapy. It might be a possible biomarker to determine the menopausal status for decision-making whether aromatase inhibitor could be applicable or not in hormone positive breast cancer patients with chemotherapy induced amenorrhea or treated by tamoxifen.

The Molecular Subtype Dependent Effect of Concurrent Radiotherapy and Systemic Therapy on Breast Cancer: Analysis of a Human In Vivo Model of Metastatic Brain Lesions

PURPOSE: The molecular subtype of breast cancer is an important predictive factor. Therefore, we investigated the effects of concurrent or serial radiotherapy and systemic therapy on metastatic brain lesions according to the molecular subtype of breast cancer. METHODS: The present retrospective study examined data from 66 patients with breast cancer and metastatic brain lesions, who were treated using radiotherapy between January 1990 and July 2014. Patients were classified into the following three subtypes based on their hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status: HR+/HER2− (luminal A, 13 patients), HR+/HER2+ (luminal B, 21 patients), HR−/HER2+ (HER2, 22 patients), or HR−/HER2− (triple negative, 10 patients). The brain lesions and their responses to treatment were evaluated using brain computed tomography or magnetic resonance imaging. Progression of brain disease was defined by a ≥20% increase in the sum of the lesion's diameters or the development of a new brain lesion. Progression-free survival was calculated from the initiation of radiotherapy to the first instance of brain disease progression or last follow-up. RESULTS: Patients in the HER2 group who had received concur-rent radiotherapy and systemic therapy (mainly HER2-targeted therapy) exhibited significantly better progression-free survival than did patients who had received radiotherapy followed by systemic therapy (p=0.037). However, concurrent radiotherapy and systemic therapy did not significantly improve progression-free survival in the luminal A (p=0.527), luminal B (p=0.462), or triple negative (p=0.558) groups. CONCLUSION: Concurrent radiotherapy and mainly HER2-targeted systemic therapy significantly prolonged progression-free survival in the HER2 group.

Association of BRAF(V600E) Mutation with Poor Clinical Prognostic Factors and Ultrasonographic Findings in Cases of Papillary Thyroid Carcinoma / 대한내분비외과학회지

PURPOSE: This study evaluated the association of the BRAF(V600E) mutation with known prognostic factors and ultrasonographic characteristics in cases of papillary thyroid carcinoma. METHODS: Subjects included 169 patients who received thyroidectomy at Wonju Christian Hospital under the diagnosis of papillary thyroid cancer from February 2010 to October 2011. RESULTS: Of the total patients who received thyroidectomy, there were 128 cases (75,7%) of BRAF(V600E) mutation. Neither age nor sex were associated with the BRAF(V600E) mutation. Tumor size, shape, margin, extrathyroidal extension, central node metastasis and lateral node metastasis were found not to be associated with the BRAF(V600E) mutation. Tumor calcification, echogenicity and vascularity were also not associated with the mutation. CONCLUSION: As debate remains about the association between the BRAF(V600E) mutation and clincopathologic factors and ultrasonographic characteristics in cases of papillary thyroid carcinoma, further study is needed.